WO2019106573A1

WO2019106573A1 - Composition and methods for treating and preventing bacterial infections

Info

Publication number: WO2019106573A1
Application number: PCT/IB2018/059421
Authority: WO
Inventors: Joshua M. COSTIN; John M. Williams; Dan Li
Original assignee: Hsrx Group, Llc
Priority date: 2017-11-28
Filing date: 2018-11-28
Publication date: 2019-06-06

Abstract

The present invention relates generally to regimes, compositions, and methods of use that treat and/or prevent bacterial infections such as acne. The compositions can contain compounds found in cranberry and/or green tea extract.

Description

COMPOSITION AND METHODS FOR TREATING AND PREVENTING

BACTERIAL INFECTIONS

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 62/591,360, filed November 28, 2017, and U.S. Provisional Patent Application Serial No. 62/611,216, filed December 28, 2017, the entire contents of each of which are hereby incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION

A. Field of the Invention [0002] The present invention relates to formulations containing a mixture of compounds capable of preventing and treating bacterial infections such as acne.

B. Description of Related Art

[0003] Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinization, inflammation, and colonization of hair follicles on the face, neck, chest, and back, typically by the bacterium Propionibacterium acnes. (Liu et al. 2015) (Aubin et al. 2014) (Beylot et al. 2014) (Achermann et al. 2014) (Yu et al. 2015). Acne is a common disease among young people, affecting 85% of people aged 12-24. Although acne usually clears up during adulthood, about 20%-50% of adult females and 40 to 50 million people in the United States are still affected by low-grade and persistent acne. Acne can have a serious impact on quality of life and produce long term self-esteem related mental health problems as well as detrimental facial scarring. (Tan and Bhate 2015) (Ramos-e-Silva, Ramos-e-Silva, and Carneiro 2015).

[0004] The current market leader in over-the-counter (OTC) topical acne treatment is

PROACTIV+®. One of its active ingredients, benzoyl peroxide, is a man-made synthetic drug that is used in most topical acne treatment products. Benzyl peroxide is harsh and abrasive as its mechanism of action is oxidation, which produces heat caused by the oxidation-induced bubbling at the application site. This activity produces uncomfortable to intolerable side effects, such as burning, drying, itching, and peeling of the skin, skin irritation, rash, and/or allergic reactions. Further, use of PROACTIV+® is time-consuming as it requires the utilization of three different topical solutions that must be applied and then either washed off or allowed to absorb. PROACTIV+®’s usage instructions require it to be used for six weeks for maximum efficacy. Accordingly, there is a significant unmet need for an effective, fast acting, and skin friendly acne treatment regimen that contains fewer synthetic chemicals and employs a less difficult application effort while also causing fewer side effects. (“Proactiv” 2017).

SUMMARY OF THE INVENTION

[0005] The present invention provides a solution to the current problems facing treatment and prevention of bacterial infections. The inventors have surprisingly found that a combination of several compounds found in cranberries and/or in green tea can prevent and treat bacterial infection such as acne. Specifically, it is shown herein in clinical studies that a treatment regimen using salicylic acid, a composition containing biomarkers 1 through 11, and a composition containing biomarkers 12 through 23 is capable of treating acne better than the current market leader in over-the-counter (OTC) topical acne treatment PROACTIV+®.

[0006] In one aspect, disclosed in a composition containing any one of, any combination of, or all of eleven biomarkers found in cranberries. In one instance the composition includes biomarker 1 having an accurate mass of 359.3163 amu found in cranberry. In one instance the composition includes any one of, any combination of, or all of, biomarker 2 having an accurate mass of 111.0450 amu, biomarker 3 having an accurate mass of 117.0529 amu, biomarker 4 having an accurate mass of 118.0603 amu, biomarker 5 having an accurate mass of 119.0362 amu, biomarker 6 having an accurate mass of 131.0338 amu, biomarker 7 having an accurate mass of 139.0415 amu, biomarker 8 having an accurate mass of 160.0636 amu, biomarker 9 having an accurate mass of 201.0790 amu, biomarker 10 having an accurate mass of 249.0879 amu, biomarker 11 having an accurate mass of 293.1008 amu, wherein each biomarker is found in cranberry. In some embodiments, the biomarker is: resorcinol; 3-azetidinone: N -nitro; amino oxobutanoic acid; hydroxy oxobutanoic acid; oxobutanedioic acid, 9CI: diamide; salicylic acid; quinolinol; allantoin, tri methyl; citric acid, di-ethyl-ester; and/or grandmarin. The amounts of the ingredients within the composition can vary (e.g., amounts can be as low as 0.000001% to as high as 80% w/w or any range therein). In one instance biomarker 1 has a relative abundance of at least 7.47%, biomarker 2 has a relative abundance of at least 9.41%, biomarker 3 has a relative abundance of at least 9.95%, biomarker 4 has a relative abundance of at least 0.63%, biomarker 5 has a relative abundance of at least 0.18%, biomarker 6 has a relative abundance of at least 27.76%, biomarker 7 has a relative abundance of at least 36.34%, biomarker 8 has a relative abundance of at least 1.22%, biomarker 9 has a relative abundance of at least 16.02%, biomarker 10 has a relative abundance of at least 6.50%, biomarker 11 has a relative abundance of at least 8.16%, wherein the relative abundance is relative abundance as compared to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. In one instance, biomarker 1 has a relative abundance of at most 11.21%, biomarker 2 has a relative abundance of at most 14.12%, biomarker 3 has a relative abundance of at most 14.93%, biomarker 4 has a relative abundance of at most 0.95%, biomarker 5 has a relative abundance of at most 0.27%, biomarker 6 has a relative abundance of at most 41.64%, biomarker 7 has a relative abundance of at most 54.51%, biomarker 8 has a relative abundance of at most 1.83%, biomarker 9 has a relative abundance of at most 24.02%, biomarker 10 has a relative abundance of at most 9.75%, biomarker 11 has a relative abundance of at most 12.24%, wherein the relative abundance is relative abundance as compared to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. In another instance, the composition includes at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or all of biomarkers 1 to 11. In yet another instance, the mass of each biomarker is the mass as determined by a Direct Analysis in Real Time-TOF (DART- TOF) mass spectrometer.

[0007] In another aspect, disclosed is a composition that contains any one of, any combination of, or all of twelve biomarkers found in green tea. In one instance the composition includes any one of, any combination of, or all of biomarker 12 having an accurate mass of 461.1470 amu, biomarker 13 having an accurate mass of 108.0205 amu, biomarker 14 having an accurate mass of 122.0493 amu, biomarker 15 having an accurate mass of 129.0472 amu, biomarker 16 having an accurate mass of 145.0747 amu, biomarker 17 having an accurate mass of 161.0718 amu, biomarker 18 having an accurate mass of 165.0775 amu, biomarker 19 having an accurate mass of 170.0243 amu, biomarker 20 having an accurate mass of 174.0992 amu, biomarker 21 having an accurate mass of 180.0673 amu, biomarker 22 having an accurate mass of 194.0804 amu, and biomarker 23 having an accurate mass of 211.0896 amu, wherein each biomarker is found in green tea. In some instances, the composition further contains salicylic acid. The amounts of the ingredients within the composition can vary (e.g., amounts can be as low as 0.000001% to as high as 80% w/w or any range therein). In one instance biomarker 12 has a relative abundance of at least 2.28%, biomarker 13 has a relative abundance of at least 11.46%, biomarker 14 has a relative abundance of at least 25.67%, biomarker 15 has a relative abundance of at least 90.91%, biomarker 16 has a relative abundance of at least 41.91%, biomarker 17 has a relative abundance of at least 19.70%, biomarker 18 has a relative abundance of at least 94.69%, biomarker 19 has a relative abundance of at least 38.75%, biomarker 20 has a relative abundance of at least 1162.44%, biomarker 21 has a relative abundance of at least 100.06%, biomarker 22 has a relative abundance of at least 3234.90%, biomarker 23 has a relative abundance of at least 25.33%, wherein the relative abundance is relative abundance as compared to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. In one instance biomarker 12 has a relative abundance of at most 3.42%, biomarker 13 has a relative abundance of at most 17.19%, biomarker 14 has a relative abundance of at most 38.51%, biomarker 15 has a relative abundance of at most 136.37%, biomarker 16 has a relative abundance of at most 62.86%, biomarker 17 has a relative abundance of at most 29.56%, biomarker 18 has a relative abundance of at most 142.04%, biomarker 19 has a relative abundance of at most 58.12%, biomarker 20 has a relative abundance of at most 1743.66%, biomarker 21 has a relative abundance of at most 150.09%, biomarker 22 has a relative abundance of at most 4852.36%, biomarker 23 has a relative abundance of at most 38.00%, wherein the relative abundance is relative abundance as compared to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. In another instance, the composition includes at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 of biomarkers 12 to 23. In yet another instance, the mass of each biomarker is the mass as determined by a Direct Analysis in Real Time-TOF (DART- TOF) mass spectrometer.

[0008] In one aspect, disclosed is a composition that contains any one of, any combination of, or all of the eleven biomarkers 1 through 11 found in cranberry and further contains any one of, any combination of, or all of the twelve biomarkers 12 through 23 found in green tea. In some instances, the composition is combined with salicylic acid or additional salicylic acid. The amounts of the ingredients within the composition can vary (e.g., amounts can be as low as 0.000001% to as high as 80% w/w or any range therein). In one aspect, disclosed herein is a kit and/or treatment regime that contains a first composition that contains any one of, any combination of, or all of the eleven biomarkers 1 through 11 found in cranberry and a second composition that contains any one of, any combination of, or all of the twelve biomarkers 12 through 23 found in green tea. [0009] In another aspect, at least one of biomarkers 1 through 23 is synthetically obtained. In yet another aspect, at least one of biomarkers 1 through 23 is obtained from an organism. In one instance, at least one of biomarkers 1 through 23 is obtained from cranberry and/or green tea. In another instance, the composition has at least 90%, preferably at least 95%, or at least 98% batch-to-batch chemical consistency of relative abundance for the biomarkers. In yet another instance, the composition further includes an anti -bacterial agent. In some instances, the anti-bacterial agent is an antibiotic drug. In some instances, the anti bacterial agent is rose oil.

[0010] In one aspect, any of the compositions herein are formulated for topical application. In one instance, the composition is one or more of an emulsion, solution, foam, spreadable solid, soap, serum, etc. In another aspect, any of the composition herein are formulated for oral administration. In one instance, the composition is one or more of a lozenge, a powder, a tablet, a capsule, a delayed release capsule, a quick release capsule, a gel-cap, a gelatin, a liquid solution, and/or a dissolvable film. In some instances, the composition comprising one or more of biomarkers 1 to 11 is formulated for topical administration and the composition comprising one or more of biomarkers 12 to 23 is formulated for oral administration and vice versa. In one instances, any of the compositions herein are formulated for intravenous administration and/or intranasal delivery. In one instance, the composition, kit, regime, or method disclosed herein is capable of treating a bacterial infection. In one instance, the bacterial infection is acne. In one instance, the composition, kit, regime, or method is capable of reducing acne lesions, reducing facial redness, and/or improving the global assessment of the subject.

[0011] In some instances, the compositions contain a topical, oral, nutraceutical, and/or pharmaceutically acceptable carrier. In some instances, the topical, oral, nutraceutical, and/or pharmaceutically acceptable carrier can be a naturally or a non-naturally occurring compound or structure. In some instances, the composition further contains a pH adjuster, structuring agents, inorganic salt, preservative, stabilizer, bulking agent, and/or excipient. In some instances, the preservative, stabilizer, bulking agent, and/or excipient can be a naturally or a non-naturally occurring compound or composition. In some instances, the composition is a topical composition. In some instances, the composition is suitable for oral administration. In some instances, the composition is a nutraceutical composition. In some instances, the composition is a pharmaceutical composition. In some instances, the composition is coated with a polymer. In some instances, the polymer is a naturally or a non-naturally occurring polymer. In some aspects of the invention, the formulated composition can be comprised in a solid nanoparticle, a lipid-containing nanoparticle, a lipid-based carrier, a sealed conduit, a sealed bag, or any combination thereof. In other aspects of the invention, the composition can be formulated for administration by injection.

[0012] In another aspect, the composition may further comprise one or more ingredients described herein. For example, the composition may comprise one or more additional ingredients selected from one or more pH adjusters, structuring agents, inorganic salts, preserving agents, fillers, disintegrating agents, wetting agents, emulsifiers, suspending agents, sweeteners, flavorings, fragrance, antibacterial agents, antifungal agents, lubricating agents, vitamins, polymers, siloxane containing compounds, essential oils, and dispensing agents. Each carrier is acceptable in the sense of being compatible with the other ingredients of the formulation and not injurious to the subject. In some aspects of the invention, the carrier can include at least one hydrophilic polymeric compound selected from the group consisting of a gum, a cellulose ether, an acrylic resin, a carbohydrate carrier, talc, lactose, mannitol, glucose, water, gelatin, a protein-derived compound, polyvinyl pyrrolidone, magnesium stearate, and any combination thereof. The amounts of such ingredients can range from 0.0001% to 99.9% by weight or volume of the composition, or any integer or range in between as disclosed in other sections of this specification, which are incorporated into this paragraph by reference.

[0013] The composition can be stored for one month, 6 months, 12 months, 18 months, or 24 months at room temperature.

[0014] In some instances, the composition contains a dose of the biomarkers contained therein. In some instances, a dose is 1 pg to 10 grams of any one or more of the biomarkers. In some instances, the composition contains a sub-dose of one or more of the biomarkers. In some instances, the composition contains 0.001 mg to 3 g, 0.01 mg to 1 g, 0.1 mg to 500 mg, 1 to 300 mg, 1 to 100 mg, 1 to 10 mg, 1 mg, 2 mg, 3 mg, or 4 mg of any one or more of the biomarkers, or any range therein.

[0015] In one aspect, the composition contains a second anti -bacterial drug. In some instances, the composition does not comprise a second anti -bacterial drug. [0016] Also disclosed is a method of treating or preventing a bacterial infection in a subject. The method comprises administering any one or more of the compositions of the present invention to the subject. Further, there is disclosed a method of administering any one or more of the compositions of the present invention to a subject by administering any one or more of the compositions of the present invention to the subject. In a particular instance, the subject has been diagnosed with a bacterial infection. In a particular instance, the subject has acne. In one instances, the method is for treating a bacterial infection. In one instances, the method is for preventing a bacterial infection. In some instances, the method is for reducing acne lesions, reducing facial redness, and/or improving the global assessment of the subject.

[0017] Also disclosed herein is a treatment and/or prevention regimes for acne. The treatment and/or prevention regime comprises administering any one or more of the compositions of the present invention to the subject. In some instances, the regime includes topical application of a composition containing one or more of biomarkers 1 to 11 found in cranberry. In some instances, the topical application includes topical application of additional salicylic acid. In some instances, the regime includes oral administration of a composition containing one or more of biomarkers 12 to 23 found in green tea. In some instances, the regime includes the topical application of a composition containing one or more of biomarkers 1 to 11 found in cranberry and the oral administration of a composition containing one or more of biomarkers 12 to 23 found in green tea. In some instances, the regime is for reducing acne lesions, reducing facial redness, and/or improving the global assessment of the subject.

[0018] In some instances, the subject is administered a total sum of between 1 and

5,000 mg, preferably between 10 and 1,500 mg, between 50 and 1,000 mg, or between 100 and 500 mg of any one or more of the biomarker(s) during a 24 hour period. In some aspects of any of the methods described herein, the subject is administered any one of the compositions disclosed herein at least once a day. In some instances, the subject is administered any one of the compositions disclosed more than once a day. In some instances, the subject is administered any one of the compositions disclosed herein twice a day. In yet another instance, the composition is administered at least once a day for at least three days. In some aspects, the subject is administered any one of the compositions disclosed herein daily for at least five days. In some aspects, the subject is administered any one of the compositions disclosed herein daily for at least ten days. In some aspects, the subject is administered any one of the compositions disclosed herein daily for at least fourteen days. In some aspects, the subject is administered any one of the compositions disclosed herein daily for at least two weeks, at least a month, at least two months, at least half a year, at least a year, or at least several years. In some aspects, the subject is administered any one of the compositions disclosed herein every other day for at least six days. In some aspects, the subject is administered any one of the compositions disclosed herein every other day for at least ten days. In some aspects, the subject is administered any one of the compositions disclosed herein every other day for at least fourteen days. In some aspects, the subject is administered any one of the compositions disclosed herein every other day for at least two weeks, at least a month, at least two months, at least half a year, at least a year, or at least several years.

[0019] In some instances, the bacterial infection is caused by Propionibacterium acnes (P. acnes). In some instances, the bacterial infection is caused by Escherichia coli ( E . coif), Staphylococcus saprophyticus (S. saprophyticus), Klebsiella , Pseudomonas , and/or Staphylococcus aureus (S. aureus). In some instances, the bacterial infection is caused by a Propionibacterium species, Escherichia species, Klebsiella species, Pseudomonas species, and/or a Staphylococcus species. In some instances, the bacterial infection is acne, a urinary tract infection, an infection of a wound, a skin infection, etc.

[0020] In another aspect, there is disclosed a method of producing any one of the compositions disclosed herein by producing a composition having an at least 90%, preferably at least 95% or at least 98% batch-to-batch chemical consistency of relative abundance for the biomarkers.

[0021] Kits that include the compositions of the present invention are also contemplated. In certain embodiments, the composition is comprised in a container. The container can be a bottle, dispenser, package, or a straw. The container can dispense a predetermined amount of the composition. In certain aspects, the compositions are dispensed as a pill, a tablet, a capsule, a transdermal patch, an edible chew, a cream, a lotion, a gel, spray, mist, dollop, a powder, or a liquid. The container can include indicia on its surface. The indicia can be a word, an abbreviation, a picture, or a symbol. [0022] It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the invention, and vice versa. Furthermore, compositions of the invention can be used to achieve methods of the invention.

[0023] Also contemplated is a product that includes a composition of the present invention. In non-limiting aspects, the product can be a nutraceutical product. In other non limiting aspects, the product can be a pharmaceutical product. The pharmaceutical and/or nutraceutical product can be those described in other sections of this specification or those known to a person of skill in the art. Non-limiting examples of products include a pill, a tablet, an edible chew, a capsule, a cream, a lotion, a gel, a spray, a mist, a dissolving film, a transdermal patch, or a liquid, etc.

[0024] Also disclosed are the following Embodiments 1 to 66 of the present invention. Embodiment 1 is a composition comprising the following biomarkers: biomarker 1 having an accurate mass of 359.3163 amu and having a relative abundance of at least 7.47%; biomarker 2 having an accurate mass of 111.0450 amu and having a relative abundance of at least 9.41%; biomarker 3 having an accurate mass of 117.0529 amu and having a relative abundance of at least 9.95%; biomarker 4 having an accurate mass of 118.0603 amu and having a relative abundance of at least 0.63%; biomarker 5 having an accurate mass of 119.0362 amu and having a relative abundance of at least 0.18%; biomarker 6 having an accurate mass of 131.0338 amu and having a relative abundance of at least 27.76%; biomarker 7 having an accurate mass of 139.0415 amu and having a relative abundance of at least 36.34%; biomarker 8 having an accurate mass of 160.0636 amu and having a relative abundance of at least 1.22%; biomarker 9 having an accurate mass of 201.0790 amu and having a relative abundance of at least 16.02%; biomarker 10 having an accurate mass of 249.0879 amu and having a relative abundance of at least 6.50%; and biomarker 11 having an accurate mass of 293.1008 amu and having a relative abundance of at least 8.16%, wherein the biomarkers are found in cranberry; and wherein the relative abundance is relative to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. Embodiment 2 is the composition of Embodiment 1, wherein the biomarkers contained therein have a relative abundance of at most: biomarker 1 of 11.21%; biomarker 2 of 14.12%; biomarker 3 of 14.93%; biomarker 4 of 0.95%; biomarker 5 of 0.27%; biomarker 6 of 41.64%; biomarker 7 of 54.51%; biomarker 8 of 1.83%; biomarker 9 of 24.02%; biomarker 10 of 9.75%; and biomarker 11 of 12.24%; wherein the relative abundance is relative to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. Embodiment 3 is a composition comprising the following biomarkers: biomarker 1 having an accurate mass of 359.3163 amu and having a relative abundance of at most 11.21%; biomarker 2 having an accurate mass of 111.0450 amu and having a relative abundance of at most 14.12%; biomarker 3 having an accurate mass of 117.0529 amu and having a relative abundance of at most 14.93%; biomarker 4 having an accurate mass of 118.0603 amu and having a relative abundance of at most 0.95%; biomarker 5 having an accurate mass of 119.0362 amu and having a relative abundance of at most 0.27%; biomarker 6 having an accurate mass of 131.0338 amu and having a relative abundance of at most 41.64%; biomarker 7 having an accurate mass of 139.0415 amu and having a relative abundance of at most 54.51%; biomarker 8 having an accurate mass of 160.0636 amu and having a relative abundance of at most 1.83%; biomarker 9 having an accurate mass of 201.0790 amu and having a relative abundance of at most 24.02%; biomarker 10 having an accurate mass of 249.0879 amu and having a relative abundance of at most 9.75%; and biomarker 11 having an accurate mass of 293.1008 amu and having a relative abundance of at most 12.24%, wherein the biomarkers are found in cranberry, and wherein the relative abundance is relative to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. Embodiment 4 is the composition of any of Embodiments 1 to 3, wherein the mass of each biomarker is the mass as determined by a Direct Analysis in Real Time-TOF (DART-TOF) mass spectrometer. Embodiment 5 is the composition of any one of Embodiments 1 to 4, wherein at least one of the biomarker(s) are synthetically obtained. Embodiment 6 is the composition of any one of Embodiments 1 to 5, wherein at least one of the biomarker(s) are isolated from a plant. Embodiment 7 is the composition of Embodiment 6, wherein at least one of the biomarkers(s) are isolated from cranberry. Embodiment 8 is the composition of any one of Embodiments 1 to 7, wherein the composition has an at least 90%, preferably at least 95%, or at least 98% batch-to-batch chemical consistency of relative abundance for the biomarkers. Embodiment 9 is the composition of any one of Embodiments 1 to 8, wherein the composition further comprises a preservative. Embodiment 10 is the composition of any one of Embodiments 1 to 9, wherein the composition further comprises additional salicylic acid. Embodiment 11 is the composition of Embodiment 10, wherein the total salicylic acid of the composition is at least 1% by weight of the composition. Embodiment 12 is the composition of any one of Embodiments 1 to 11, wherein the composition further comprises at least one antibacterial agent. Embodiment 13 is the composition of Embodiment 12, wherein at least one antibacterial agent is rose oil. Embodiment 14 is the composition of any one of Embodiments 1 to 13, wherein the composition is formulated for topical administration. Embodiment 15 is the composition of Embodiment 14, wherein the composition is in a liquid solution, emulsion, powder, or patch. Embodiment 16 is the composition of any one of Embodiments 1 to 13, wherein the composition is formulated for oral administration, administration through injection, and/or intranasal administration. Embodiment 17 is the composition of Embodiment 16, wherein the composition is a lozenge, a powder, a tablet, a gel-cap, a gelatin, a liquid solution, a syrup, an oil, and/or a dissolvable film. Embodiment 18 is the composition of any of Embodiments 1 to 17, wherein the composition is formulated to treat and/or prevent a bacterial infection. Embodiment 19 is the composition of any of Embodiments 1 to 18, wherein the composition is formulated to treat and/or prevent acne. Embodiment 20 is the composition of Embodiment 19, wherein the composition is formulated to reduce acne lesions, reduce facial redness, and/or improve a global assessment of a subject. Embodiment 21 is a composition comprising the following biomarkers: biomarker 12 having an accurate mass of 461.147 amu and having a relative abundance of at least 2.28%; biomarker 13 having an accurate mass of 108.0205 amu and having a relative abundance of at least 11.46%; biomarker 14 having an accurate mass of 122.0493 amu and having a relative abundance of at least 25.67%; biomarker 15 having an accurate mass of 129.0472 amu and having a relative abundance of at least 90.91%; biomarker 16 having an accurate mass of 145.0747 amu and having a relative abundance of at least 41.91%; biomarker 17 having an accurate mass of 161.0718 amu and having a relative abundance of at least 19.70%; biomarker 18 having an accurate mass of 165.0775 amu and having a relative abundance of at least 94.69%; biomarker 19 having an accurate mass of 170.0243 amu and having a relative abundance of at least 38.75%; biomarker 20 having an accurate mass of 174.0992 amu and having a relative abundance of at least 1162.44%; biomarker 21 having an accurate mass of 180.0673 amu and having a relative abundance of at least 100.06%; biomarker 22 having an accurate mass of 194.0804 amu and having a relative abundance of at least 3234.90%; and biomarker 23 having an accurate mass of 211.0896 amu and having a relative abundance of at least 25.33%, wherein the biomarkers are found in green tea, and wherein the relative abundance is relative to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. Embodiment 22 is the composition of Embodiment 21, wherein the biomarkers contained therein have a relative abundance of at most: biomarker 12 of 3.42%; biomarker 13 of 17.19%; biomarker 14 of 38.51%; biomarker 15 of 136.37%; biomarker 16 of 62.86%; biomarker 17 of 29.56%; biomarker 18 of 142.04%; biomarker 19 of 58.12%; biomarker 20 of 1743.66%; biomarker 21 of 150.09%; biomarker 22 of 4852.36%; and biomarker 23 of 38.00%, wherein the relative abundance is relative to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. Embodiment 23 is a composition comprising the following biomarkers: biomarker 12 having an accurate mass of 461.147 amu and having a relative abundance of at most 3.42%; biomarker 13 having an accurate mass of 108.0205 amu and having a relative abundance of at most 17.19%; biomarker 14 having an accurate mass of 122.0493 amu and having a relative abundance of at most 38.51%; biomarker 15 having an accurate mass of 129.0472 amu and having a relative abundance of at most 136.37%; biomarker 16 having an accurate mass of 145.0747 amu and having a relative abundance of at most 62.86%; biomarker 17 having an accurate mass of 161.0718 amu and having a relative abundance of at most 29.56%; biomarker 18 having an accurate mass of 165.0775 amu and having a relative abundance of at most 142.04%; biomarker 19 having an accurate mass of 170.0243 amu and having a relative abundance of at most 58.12%; biomarker 20 having an accurate mass of 174.0992 amu and having a relative abundance of at most 1743.66%; biomarker 21 having an accurate mass of 180.0673 amu and having a relative abundance of at most 150.09%; biomarker 22 having an accurate mass of 194.0804 amu and having a relative abundance of at most 4852.36%; and biomarker 23 having an accurate mass of 211.0896 amu and having a relative abundance of at most 38.00%, wherein the biomarkers are found in green tea, and wherein the relative abundance is relative to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition. Embodiment 24 is the composition of any of Embodiments 21 to 23, wherein the mass of each biomarker is the mass as determined by a Direct Analysis in Real Time-TOF (DART-TOF) mass spectrometer. Embodiment 25 is the composition of any one of Embodiments 21 to 24, wherein at least one of the biomarker(s) are synthetically obtained. Embodiment 26 is the composition of any one of Embodiments 21 to 25, wherein at least one of the biomarker(s) are isolated from a plant. Embodiment 27 is the composition of Embodiment 26, wherein at least one of the biomarkers(s) are isolated from green tea. Embodiment 28 is the composition of any one of Embodiments 21 to 27, wherein the composition has an at least 90%, preferably at least 95%, or at least 98% batch-to-batch chemical consistency of relative abundance for the biomarkers. Embodiment 29 is the composition of any one of Embodiments 21 to 28, wherein the composition further comprises a preservative. Embodiment 30 is the composition of any one of Embodiments 21 to 29, wherein the composition further comprises salicylic acid. Embodiment 31 is the composition of Embodiment 30, wherein the total salicylic acid of the composition is at least 1% by weight of the composition. Embodiment 32 is the composition of any one of Embodiments 21 to 31, wherein the composition further comprises at least one antibacterial agent. Embodiment 33 is the composition of Embodiment 32, wherein at least one antibacterial agent is rose oil. Embodiment 34 is the composition of any one of Embodiments 21 to 33, wherein the composition is formulated for oral administration. Embodiment 35 is the composition of Embodiment 34, wherein the composition is in a lozenge, a powder, a tablet, a gel-cap, a gelatin, a liquid solution, a syrup, an oil, and/or a dissolvable film. Embodiment 36 is the composition of any one of Embodiments 21 to 35, wherein the composition is formulated for topical administration, administration through injection, and/or intranasal administration. Embodiment 37 is the composition of Embodiment 36, wherein the composition is in a liquid solution, emulsion, powder, or patch. Embodiment 38 is the composition of any of Embodiments 21 to 37, wherein the composition is formulated to treat and/or prevent a bacterial infection. Embodiment 39 is the composition of any of Embodiments 21 to 38, wherein the composition is formulated to treat and/or prevent acne. Embodiment 40 is the composition of Embodiment 39, wherein the composition is formulated to reduce acne lesions, reduce facial redness, and/or improve a global assessment of a subject. Embodiment 41 is a composition comprising a combination of a first composition comprising cranberry extract and a second composition comprising green tea extract, the composition formulated to be administered to a subject. Embodiment 42 is the composition of Embodiment 41, wherein the cranberry extract is an aqueous extract and the green tea extract is an aqueous extract. Embodiment 43 is the composition of Embodiment 42, wherein the first composition comprises any one of the compositions of Embodiments 1 to 20. Embodiment 44 is the composition of Embodiment 41, wherein the second composition comprises any one of the compositions of Embodiments 21 to 40. Embodiment 45 is the composition of Embodiment 44, wherein the first composition comprises any one of the compositions of Embodiments 1 to 20 and the second composition comprises the composition of any of Embodiments 21 to 40. Embodiment 46 is a kit comprising: a first composition comprising a cranberry extract formulated to be administered to a subject; and a second composition comprising a green tea extract formulated to be administered to a subject. Embodiment 47 is the kit of Embodiment 46, wherein the cranberry extract is an aqueous extract and the green tea extract is an aqueous extract. Embodiment 48 is the kit of Embodiment 47, wherein the first composition comprises any one of the compositions of Embodiments 1 to 20. Embodiment 49 is the kit of Embodiment 48, wherein the second composition comprises any one of the compositions of Embodiments 21 to 40. Embodiment 50 is the kit of Embodiment 46, wherein the first composition comprises any one of the compositions of Embodiments 1 to 20 and the second composition comprises any one of the compositions of Embodiments 21 to 40. Embodiment 51 is a method of treating a subject at risk for or having a bacterial infection, the method comprising administering any one of the compositions of Embodiments 1 to 45 to the subject, wherein at least one symptom of the bacterial infection is ameliorated in the subject and/or the onset of the bacterial infection is delayed in comparison to the expected onset of the bacterial infection if the patient had not been treated. Embodiment 52 is the method of Embodiment 51, wherein the subject is treated for acne and wherein acne is treated and/or prevented. Embodiment 53 is the method of Embodiment 52, wherein the subject is diagnosed as having acne. Embodiment 54 is the method of any one of Embodiments 51 to 53, wherein the subject is administered a total amount of between 1 and 10,000 mg, between 10 and 5,000 mg, between 50 and 2,500 mg, or between 100 and 1,000 mg of the composition(s) during a 24 hour period. Embodiment 55 is the method of any one of Embodiments 51 to 54, wherein at least one of the composition(s) is administered orally. Embodiment 56 is the method of any one of Embodiments 51 to 55, wherein at least one of the composition(s) is administered topically. Embodiment 57 is the method of any one of Embodiments 51 to 56, wherein any one of the compositions of Embodiments 1 to 20 is administered and a composition comprising green tea extract is also administered. Embodiment 58 is the method of Embodiment 57, wherein the green tea extract is an aqueous extract. Embodiment 59 is the method of Embodiment 57, wherein the composition comprising green tea extract comprises the composition of any of Embodiments 21 to 40. Embodiment 60 is the method of any one of Embodiments 51 to 56, wherein any one of the compositions of Embodiments 21 to 40 is administered and a composition comprising cranberry extract is also administered. Embodiment 61 is the method of Embodiment 60, wherein the cranberry extract is an aqueous extract. Embodiment 62 is the method of Embodiment 60, wherein the composition comprising cranberry extract comprises the composition of any of Embodiments 1 to 20. Embodiment 63 is the method of any one of Embodiments 51 to 56, wherein any one of the compositions of Embodiments 41 to 45 is administered to the subject. Embodiment 64 is the method of any of Embodiments 51 to 63, wherein the compositions of any one of the kits of Embodiments 46 to 50 is administered to the subject. Embodiment 65 is the method of any of Embodiments 51 to 64, wherein acne lesions are reduced, facial redness is reduced, and/or global assessment of a subject is improved. Embodiment 66 is a method of producing a composition of any of Embodiments 1 to 45, wherein the method of producing produces a composition having an at least 90%, preferably at least 95% or at least 98% batch-to-batch chemical consistency of relative abundance for the biomarkers. [0025] “Therapeutic agent” encompasses the compounds specifically claimed herein.

It also encompasses such compounds together with nutraceutical and/or pharmaceutically acceptable salts thereof. Useful salts are known to those skilled in the art and include salts with inorganic acids, organic acids, inorganic bases, or organic bases. Therapeutic agents useful in the present invention are those compounds that affect a desired, beneficial, and often pharmacological, effect upon administration to a human or an animal, whether alone or in combination with other nutraceutical and/or pharmaceutical excipients or inert ingredients.

[0026] The term“biomarker” refers to the compound defined as the biomarker, analogues thereof, derivatives thereof, or salt forms of any analogue or derivative thereof.

[0027] The term “accurate mass” refers to a measured mass of a molecule experimentally determined for an ion of known charge. The units for accurate mass include atomic mass units (amu) and milli unified atomic mass units (mmu). The term“molecular weight” refers to the average weight of the molecule with all of the different isotopic compositions present in a compound but weighted for their natural abundance.

[0028] The term“relative abundance” refers to the abundance of a compound of interest relative to the abundance of a reference compound. In particular aspects, relative abundance is the raw intensity of a mass spectrometry peak for the compound of interest over the raw intensity of a mass spectrometry peak for a reference compound. In one non-limiting instance, the mass spectrometry peaks can be obtained by the use of DART-TOF mass spectrometry. In another particular aspect, the reference compound is a compound that is spiked, or doped, into a sample containing the compound of interest. In yet another particular aspect, the reference compound is a compound that does not exist in the sample previous to its addition to the sample for determining relative abundance. In another particular aspect, the reference compound can be curcumin.

[0029] Accurate mass and relative abundances described herein are based on experiments using particular instruments and particular settings and can change from instrument to instrument. There is variability in each measurement. Thus, the accurate mass and relative abundances are defined as being close to as understood by one of ordinary skill in the art. In one non-limiting embodiment the terms are defined to be within 20%, preferably 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%. In one non-limiting embodiment, the accurate mass has an error of within +/- 20 mmu, preferably 10 mmu, more preferably within 5 mmu, and most preferably within 1 mmu. In one non-limiting embodiment, the relative abundance has an error of +/- 20%, preferably 10%, preferably within 5%, and more preferably within 1%, and most preferably within 0.5%.

[0030] The term“substantially” and its variations are defined as being largely but not necessarily wholly what is specified as understood by one of ordinary skill in the art, and in one non-limiting embodiment substantially refers to ranges within 10%, within 5%, within 1%, or within 0.5%.

[0031] “Patient,”“subject,” or“individual” refers to a mammal ( e.g ., human, primate, dog, cat, bovine, ovine, porcine, equine, mouse, rat, hamster, rabbit, or guinea pig). In particular aspects, the patient, subject, or individual is a human.

[0032] “Inhibiting” or“reducing” or any variation of these terms includes any measurable decrease or complete inhibition to achieve a desired result.

[0033] “Effective” or“effect” or any variation of these terms means adequate to accomplish a desired, expected, or intended result.

[0034] “Treating” or“treat” or any variation of these terms includes any measurable improvement in a disease, condition, or symptom that is being treated or is associated with the disease, condition, or symptom being treated.

[0035] “Preventing” or“prevent” or any variation of these terms means to slow, stop, or reverse progression toward a result. The prevention may be any slowing of the progression toward the result.

[0036] “Analogue” and“analog,” when referring to a compound, refers to a modified compound wherein one or more atoms have been substituted by other atoms, or wherein one or more atoms have been deleted from the compound, or wherein one or more atoms have been added to the compound, or any combination of such modifications. Such addition, deletion or substitution of atoms can take place at any point, or multiple points, along the primary structure comprising the compound.

[0037] “Derivative,” in relation to a parent compound, refers to a chemically modified parent compound or an analogue thereof, wherein at least one substituent is not present in the parent compound or an analogue thereof. One such non-limiting example is a parent compound which has been covalently modified. Typical modifications are amides, carbohydrates, alkyl groups, acyl groups, esters, pegylations and the like.

[0038] A“therapeutically equivalent” compound is one that has essentially the same effect in the treatment of a disease or condition as one or more other compounds. A compound that is therapeutically equivalent may or may not be chemically equivalent, bioequivalent, or generically equivalent.

[0039] “Parenteral injection” refers to the administration of small molecule drugs via injection under or through one or more layers of skin or mucus membranes of an animal, such as a human.

[0040] “Bioavailability” refers to the extent to which the therapeutic agent is absorbed from the formulation.

[0041] “Systemic,” with respect to delivery or administration of a therapeutic agent to a subject, indicates that the therapeutic agent is detectable at a biologically significant level in the blood plasma of the subj ect.

[0042] Controlled release” refers to the release of the therapeutic agent at such a rate that blood (e.g., plasma) concentrations are maintained within the therapeutic range, but below toxic concentrations over a period of time of about one hour or longer, preferably 12 hours or longer. [0043] “Pharmaceutically acceptable carrier” refers to a pharmaceutically acceptable solvent, suspending agent or vehicle for delivering a drug compound of the present invention to a mammal such as an animal or human.

[0044] “Nutraceutical acceptable carrier” refers to a nutraceutical acceptable solvent, suspending agent or vehicle for delivering a compound of the present invention to a mammal such as an animal or human.

[0045] “Pharmaceutically acceptable” ingredient, excipient or component is one that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation and allergic response) commensurate with a reasonable benefit/risk ratio. [0046] “Nutraceutical acceptable” ingredient, excipient or component is one that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation and allergic response) commensurate with a reasonable benefit/risk ratio.

[0047] The term“about” or“approximately” or“substantially unchanged” are defined as being close to as understood by one of ordinary skill in the art, and in one non-limiting embodiment the terms are defined to be within 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%. Further,“substantially non-aqueous” refers to less than 5%, 4%, 3%, 2%, 1%, or less by weight or volume of water.

[0048] The use of the word“a” or“an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean“one,” but it is also consistent with the meaning of“one or more,”“at least one,” and“one or more than one.”

[0049] As used in this specification and claim(s), the words“comprising” (and any form of comprising, such as“comprise” and“comprises”),“having” (and any form of having, such as“have” and“has”),“including” (and any form of including, such as“includes” and “include”) or“containing” (and any form of containing, such as“contains” and“contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0050] The compositions and methods for their use can “comprise,” “consist essentially of,” or“consist of’ any of the ingredients or steps disclosed throughout the specification. With respect to the transitional phase“consisting essentially of,” in one non- limiting aspect, a basic and novel characteristic of the compositions and methods disclosed in this specification includes the compositions’ abilities to treat or prevent bacterial infections, such as acne.

[0051] Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the examples, while indicating specific embodiments of the invention, are given by way of illustration only. Additionally, it is contemplated that changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

[0053] FIG. 1 Patients were PCR positive for P. acnes DNA as demonstrated by amplification curves for 30 patients as well as positive and negative controls.

[0054] FIG. 2 Percent reduction of acne lesion count over the first 28 days of the study for the three treatment arms of the study. [0055] FIG. 3 Percent reduction of facial redness over the first 28 days of the study for the three treatment arms of the study.

[0056] FIG. 4 Percent reduction of Investigator’ s Global Assessment (IGA) over the first 28 days of the study for the three treatment arms of the study.

DETAILED DESCRIPTION [0057] The inventors have surprisingly found that a combination of salicylic acid and several compounds that can be found in cranberries can prevent and treat bacterial infections. In addition, the inventors believe that using the compounds found in cranberries in combination with compounds found in green tea enhance the ability of the combined compounds to treat and prevent bacterial infections. Further, it is expected that the compound will have synergistic effect with other anti -bacterial drugs for prevention and treatment of bacterial infection. Non-limiting examples of bacterial infections include acne. Non-limiting examples of bacteria include P. acnes , E. coli , S. saprophyticus , Klebsiella , Pseudomonas , and/or S. aureus. It is also believed that the compounds and compositions disclosed herein are capable of treating and preventing the symptoms associated with a bacterial infection. Non-limiting examples of symptoms include redness of and around the infected area, inflammation, pain, and lesions. A. Active Compounds

[0058] A folk medicine remedy for urinary tract infection, cranberry ( Vaccinium macrocarpon ), has been used for its juice to treat urinary tract infections (UTIs). However, the efficacy of treatment with cranberry to treat UTIs has recently been called into question. In one clinical study, researchers found no statistically significant reduction in the presence of bacteriuria plus pyuria over a 1 year study monitoring 185 study participants. (Juthani -Mehta et al. 2016).

[0059] In contrast, the compositions disclosed herein are effective in treating and preventing bacterial infections. Specifically, it has now been shown herein that a regimen or composition containing compounds from cranberry combined with salicylic acid can be used to treat and prevent acne. Further, the effects of these compounds may be enhanced further by administration of compounds found in green tea. In some instances, the compositions or regimen can more effectively treat acne than a leading commercial anti-acne medication.

[0060] The composition of the present invention can include one or more of the biomarkers found in cranberry defined by accurate mass of 359.3163 amu, 111.0450 amu, 117.0529 amu, 118.0603 amu, 119.0362 amu, 131.0338 amu, 139.0415 amu, 160.0636 amu, 201.0790 amu, 249.0879 amu, and 293.1008 amu, and combinations thereof.

[0061] The composition of the present invention can include one or more of the biomarkers found in green tea defined by accurate mass of 461.1470 amu, 108.0205 amu, 122.0493 amu, 129.0472 amu, 145.0747 amu, 161.0718 amu, 165.0775 amu, 170.0243 amu, 174.0992 amu, 180.0673 amu, 194.0804 amu, and 211.0896 amu, and combinations thereof.

[0062] In a preferred embodiment, the biomarker or combination of biomarkers has a

90% batch-to-batch chemical consistency of relative abundance for the biomarkers. In another preferred embodiment, the compound or combination of compounds has a 95% and/or 98% batch-to-batch chemical consistency of relative abundance for the biomarkers.

[0063] In some aspects of the invention, the compounds and derivatives and analogues can be made through known synthetic methods. In some aspects of the invention, the compounds can be synthetically obtained by producing the compound according to methods known to one of skill in the art in chemical synthesis. In one instance, the compound is synthesized through organic chemistry methods. [0064] In some aspects of the invention, the compounds can be isolated from extracts of an organism such as fruits, plants, animals, fungi, bacteria, and/or archaea. Non-limiting examples of suitable fruits include cranberry. Non-limiting examples of suitable plants include green tea. The compound(s) can be extracted from the organism using known extraction methods, such as contacting the extract with CO2, contacting the extract with EtOH, or any combination of EtOEfEhO, and/or with any method utilizing a suitable separation media for purification of the extract. Non-limiting examples of separation medias that can be used for purification include ADS (Nankai ETniversity, China), Sephadex (GE Healthcare Life Sciences), and AMBERLITE® (The Dow Chemical Company), etc.

[0065] The extract can include any one of or combination of compounds defined by accurate mass of 359.3163 amu, 111.0450 amu, 117.0529 amu, 118.0603 amu, 119.0362 amu, 131.0338 amu, 139.0415 amu, 160.0636 amu, 201.0790 amu, 249.0879 amu, and/or 293.1008 amu found in cranberries and any combination thereof. The extract can include any one of or combination of compounds defined by accurate mass of 461.1470 amu, 108.0205 amu, 122.0493 amu, 129.0472 amu, 145.0747 amu, 161.0718 amu, 165.0775 amu, 170.0243 amu, 174.0992 amu, 180.0673 amu, 194.0804 amu, and/or 211.0896 amu found in green tea and any combination thereof.

[0066] In some aspects of the invention, one or more of the compounds of the composition and derivatives and analogues thereof can be made through known synthetic methods known by one of skill in the art and one or more of the compounds of the composition and derivatives and analogues thereof may be isolated from other sources, such as, but not limited to, extracts of fruits and plants.

B. Compounds Defined by DART TOF/MS

[0067] The composition of the present invention can include one or more of the compounds defined by accurate mass of about 359.3163 amu, 111.0450 amu, 117.0529 amu, 118.0603 amu, 119.0362 amu, 131.0338 amu, 139.0415 amu, 160.0636 amu, 201.0790 amu, 249.0879 amu, and/or 293.1008 amu found in cranberries and any combination thereof. The composition of the present invention can include one or more of the compounds defined by accurate mass of about 461.1470 amu, 108.0205 amu, 122.0493 amu, 129.0472 amu, 145.0747 amu, 161.0718 amu, 165.0775 amu, 170.0243 amu, 174.0992 amu, 180.0673 amu, 194.0804 amu, and/or 211.0896 amu found in green tea and any combination thereof. The composition of the present invention can include a combination of one or more of the defined compounds from cranberries above and one or more of the defined compounds from green tea above.

[0068] The accurate mass and relative abundances described herein are based on experiments using particular instruments and particular settings and can change from instrument to instrument. There is variability in each measurement. Thus, the accurate mass and relative abundances are defined as being close to as understood by one of ordinary skill in the art. In one non-limiting embodiment the terms are defined to be within 20%, preferably 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%. In one non-limiting embodiment, the accurate mass has an error of within +/- 20 mmu, preferably 10 mmu, more preferably within 5 mmu, and most preferably within 1 mmu. In one non-limiting embodiment, the relative abundance has an error of +/- 20%, preferably 10%, preferably within 5%, and more preferably within 1%, and most preferably within 0.5%.

[0069] In a non-limiting example, the compounds of the present invention can be identified using Direct Analysis in Real Time (DART) Time of Flight/Mass Spectrometry (TOF/MS). Specifically, a JEOL DART™ AccuTOF-mass spectrometer from Jeol USA of Peabody, MA (JMS-T100LC) can be used. Accurate mass can be determined by subtracting the mass of a proton (1.007825 amu) from the measured mass of the ions produced from the sample. The mass of compounds may be determined in a sample by directly introducing the sample to the ion stream by means of a Dip-IT sampler and a Dip-IT sampler holder (IONSENSE™). While no sample preparation is required for a simple analysis with the DART, a chemical doped/spiked solution can be used for quantitation relative to a known quantity. As a non-limiting example, curcumin is not present in cranberry extract or in green tea extract and can therefore be used to create a quantitative chemical profile of the bioactive molecules. The settings for the DART ion source can be the following:

Gas: He

Flow: 2.52 LPM @ 50 PSI

Temperature: 250 C

Needle Voltage: 3000V

Grid Electrode Voltage: 250V

Discharge Electrode Voltage: 400V The settings for the JEOL AccuTOF MS can be the following:

Peaks Voltage: 1000V

Orifice 1 Temperature: 120 C

Detector Voltage: 2600V

Reflectron Voltage: 990.0V

[0070] Samples can be analyzed in six replicates by DART-TOF MS. These six replicates can be analyzed to create a single, averaged, filtered, and statistically significant DART fingerprint of the sample. This processed fingerprint can then be used to determine the presence of the bioactive markers by comparison of masses. Due to the initial discovery and identification of these bioactive markers, a simple mass comparison is sufficient to determine their presence in any extract or mixture of chemicals.

[0071] All MS have a mass tolerance - a range of acceptable reported masses surrounding the predicted [M+H] or [M-H] value. For the AccuTOF, that mass tolerance is less than 20 millimass units (mmu) (predicted mass +/-10 mmu). Given the same sample and ion source, other TOF-MS may have a higher or lower mass tolerance.

[0072] In another non-limiting example, the compounds of the present invention can be determined by DART TOF/MS by using a JEOL DART™ AccuTOF-mass spectrometer from Jeol USA of Peabody, MA (JMS-T100LC) executed in the positive ion mode ([M+H]⁺) using the following settings for the DART ion source: Gas: He

Flow: 3.98 L/min

Needle voltage: 3500 V

Temperature: 300 °C

Electrode 1 Voltage: 150 V

Electrode 2 Voltage: 250 V,

The settings for the JEOL AccuTOF MS can be the following:

Peaks Voltage: 1000V

Orifice 1 Voltage: 20 V

Ring Lens Voltage: 5 V Orifice 2 Voltage: 5 V

Detector Voltage: 2550V

[0073] Calibrations can be performed internally with each sample using a 10%

(weight/volume) solution of PEG 600 from Ultra Chemical of North Kingston, RI that provided mass markers throughout the required mass range of 100-1000 amu. Calibration tolerances can be held to 5 mmu. Samples can be introduced into the DART He plasma using the closed end of a borosilicate glass melting point capillary tube until a signal is achieved in the total-ion chromatogram (TIC). The next sample can then be introduced when the TIC returns baseline levels.

C. Additional Anti-Bacterial Agents

[0074] In some aspects, a second anti-bacterial agent can be combined with the compounds of the compositions disclosed herein. In some instances, the anti-bacterial agent is an anti -bacterial drug. In one embodiment, the compositions disclosed herein further includes at least one additional anti -bacterial agent.

[0075] In some instances, the anti -bacterial agent is rose oil, salicylic acid, benzoyl peroxide, benzoyl peroxide micronized, benzoyl peroxide microspheres, adapalene-benzoyl peroxide, clindamycin HC1, clindamycin phosphate, clindamycin palmitate HC1, clindamycin-tretinoin, clindamycin phosphate-tretinoin, clindamycin-benzoyl peroxide, tetracycline, doxycycline hyclate, doxycycline calcium, doxycycline monohydrate, doxycycline-benzoyl peroxide, minocycline, tretinoin, isotretinoin, tretinoin microspheres, erythromycin, erythromycin stearate, erythromycin ethyl succinate, erythromycin-ethanol, dapsone, adapalene, sulfacetamide sodium, sulfur, sulfacetamide sodium-sulfur, sulfacetamide-sulfur, sulfacetamide sodium-sulfur-urea, azelaic acid, resorcinol-sulfur, salicylic acid-benzoic acid, erythromycin-benzoyl peroxide, benzoyl peroxide-sulfur, benzoyl peroxide-hydrocortisone, salicylic acid-hydrocortisone, tazarotene, sulfur-alcohol, coal tar- salicylic acid, benzoyl peroxide-vitamin E, salicylic acid-benzoyl peroxide-vitamin E, benzoyl peroxide-aloe vera, salicylic acid-ammonium lactate-aloe, sulfacetamide sodium- sulfur-avobenzone-OTN-OCSA, salicylic acid-sulfur, salicylic acid-pyrithione zinc, witch hazel-glycerin-salicylic acid, salicylic acid-urea, bacitracin, ceftriaxone, cephalexin, chlorhexidine, ethanol, fosfomycin, fusidic acid, mupirocin, nitrofurantoin, trimethoprim- sulfamethoxazole, Norgestimate-Ethinyl Estradiol, Drospirenone-Ethinyl Estradiol, Norethindrone-E.Estradiol-Iron, Noreth-Ethinyl Estradiol -Iron, L Norgest/E.Estradiol- E.Estrad, Desog-E.Estradiol/E.Estradiol, Drospirenone-E.Estradiol-Lm.FA, Levonorgestrel- Ethinyl Estrad, Norethindrone-Ethin Estradiol, Estradiol Valerate-Dienogest, Desogestrel- Ethinyl Estradiol, Norgestrel-Ethinyl Estradiol, Levonorg-Eth Estrad Triphasic, Norethindrone Ac-Eth Estradiol, Norethin-E.Estradiol Triphasic, and/or Norethin-Eth Estrad Biphasic.

D. Amounts of Ingredients

[0076] It is contemplated that the compositions of the present invention can include any amount of the ingredients discussed in this specification. The compositions can also include any number of combinations of additional ingredients described throughout this specification ( e.g ., stabilizers, fillers, pharmaceutically and/or nutraceutical acceptable salts, and/or additional pharmaceutical and/or nutraceutical ingredients). The concentrations of the any ingredient within the compositions can vary. In non-limiting embodiments, for example, the compositions can comprise, consisting essentially of, or consist of, in their final form, for example, at least about 0.0001%, 0.0002%, 0.0003%, 0.0004%, 0.0005%, 0.0006%,

0.0007%, 0.0008%, 0.0009%, 0.0010%, 0.0011%, 0.0012%, 0.0013%, 0.0014%, 0.0015%, 0.0016%, 0.0017%, 0.0018%, 0.0019%, 0.0020%, 0.0021%, 0.0022%, 0.0023%, 0.0024%, 0.0025%, 0.0026%, 0.0027%, 0.0028%, 0.0029%, 0.0030%, 0.0031%, 0.0032%, 0.0033%, 0.0034%, 0.0035%, 0.0036%, 0.0037%, 0.0038%, 0.0039%, 0.0040%, 0.0041%, 0.0042%, 0.0043%, 0.0044%, 0.0045%, 0.0046%, 0.0047%, 0.0048%, 0.0049%, 0.0050%, 0.0051%, 0.0052%, 0.0053%, 0.0054%, 0.0055%, 0.0056%, 0.0057%, 0.0058%, 0.0059%, 0.0060%, 0.0061%, 0.0062%, 0.0063%, 0.0064%, 0.0065%, 0.0066%, 0.0067%, 0.0068%, 0.0069%, 0.0070%, 0.0071%, 0.0072%, 0.0073%, 0.0074%, 0.0075%, 0.0076%, 0.0077%, 0.0078%, 0.0079%, 0.0080%, 0.0081%, 0.0082%, 0.0083%, 0.0084%, 0.0085%, 0.0086%, 0.0087%, 0.0088%, 0.0089%, 0.0090%, 0.0091%, 0.0092%, 0.0093%, 0.0094%, 0.0095%, 0.0096%, 0.0097%, 0.0098%, 0.0099%, 0.0100%, 0.0200%, 0.0250%, 0.0275%, 0.0300%, 0.0325%, 0.0350%, 0.0375%, 0.0400%, 0.0425%, 0.0450%, 0.0475%, 0.0500%, 0.0525%, 0.0550%, 0.0575%, 0.0600%, 0.0625%, 0.0650%, 0.0675%, 0.0700%, 0.0725%, 0.0750%, 0.0775%, 0.0800%, 0.0825%, 0.0850%, 0.0875%, 0.0900%, 0.0925%, 0.0950%, 0.0975%, 0.1000%, 0.1250%, 0.1500%, 0.1750%, 0.2000%, 0.2250%, 0.2500%, 0.2750%, 0.3000%, 0.3250%, 0.3500%, 0.3750%, 0.4000%, 0.4250%, 0.4500%, 0.4750%, 0.5000%, 0.5250%, 0.0550%, 0.5750%, 0.6000%, 0.6250%, 0.6500%, 0.6750%, 0.7000%, 0.7250%, 0.7500%, 0.7750%, 0.8000%, 0.8250%, 0.8500%, 0.8750%, 0.9000%, 0.9250%, 0.9500%, 0.9750%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%,

2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%,

4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 5.1%, 5.2%, 5.3%,

5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 6.0%, 6.1%, 6.2%, 6.3%, 6.4%, 6.5%, 6.6%, 6.7%,

6.8%, 6.9%, 7.0%, 7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, 8.0%, 8.1%,

8.2%, 8.3%, 8.4%, 8.5%, 8.6%, 8.7%, 8.8%, 8.9%, 9.0%, 9.1%, 9.2%, 9.3%, 9.4%, 9.5%,

9.6%, 9.7%, 9.8%, 9.9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% or any range derivable therein, of at least one of the ingredients that are mentioned throughout the specification and claims. In non-limiting aspects, the percentage can be calculated by weight or volume of the total composition or relative abundance. A person of ordinary skill in the art would understand that the concentrations can vary depending on the addition, substitution, and/or subtraction of ingredients in a given composition.

E. Additional Components

[0077] The compound of the present invention can be formulated into any suitable composition form for administration to a human or non-human animal patient.

[0078] The composition may consist of the claimed compound or compounds alone or may include the compound or compounds and any suitable additional component, such as one or more pharmaceutically and/or nutraceutical acceptable carriers, diluents, adjuvants, excipients, or vehicles, such as preserving agents, fillers, disintegrating agents, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavoring agents, perfuming agents, antibacterial agents, antifungal agents, lubricating agents and dispensing agents, depending on the nature of the mode of administration and dosage forms. Each carrier must be acceptable in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.

1. Excipients

[0079] Excipients employed in the compositions of the present invention can be solids, semi-solids, liquids or combinations thereof. Preferably, the excipients are solids. Compositions of the invention containing excipients can be prepared by any known technique that comprises, for example, admixing an excipient with the claimed compounds. A pharmaceutical composition of the invention contains a desired amount of the claimed compounds per dose unit and, if intended for oral administration, can be in the form, for example, of a tablet, a caplet, a pill, a hard or soft capsule, a lozenge, a cachet, a dispensable powder, granules, a suspension, an elixir, a dispersion, or any other form reasonably adapted for such administration. If intended for topical application, it can be in the form of an emulsion, solution, powder, patch, spreadable solid, etc. If intended for parenteral administration, it can be in the form, for example, of a suspension or transdermal patch. If intended for rectal administration, it can be in the form, for example, of a suppository. Presently preferred are oral dosage forms that are discrete dose units each containing a predetermined amount of the claimed compounds such as tablets or capsules and topical dosage forms.

2. Carriers / Diluents

[0080] Suitable carriers or diluents illustratively include, but are not limited to, either individually or in combination, lactose, including anhydrous lactose and lactose monohydrate; starches, including directly compressible starch and hydrolyzed starches (e.g., CELUTAB™ and EMDEX™), mannitol, sorbitol, xylitol, dextrose (e.g., CERELOSE™ 2000) and dextrose monohydrate, dibasic calcium phosphate dihydrate, sucrose-based diluents, confectioner's sugar, monobasic calcium sulfate monohydrate, calcium sulfate dihydrate, granular calcium lactate trihydrate, dextrates, inositol, hydrolyzed cereal solids, amylose, celluloses including microcrystalline cellulose, food grade sources of alpha- and amorphous cellulose (e.g., RexcelJ), powdered cellulose, hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC), calcium carbonate, glycine, clay, bentonite, block co-polymers, polyvinylpyrrolidone, and the like. Such carriers or diluents, if present, constitute in total about 5% to about 99.999%, about 10% to about 85%, and 20% to about 80%, of the total weight of the composition. The carrier, carriers, diluent, or diluents selected preferably exhibit suitable flow properties and, where tablets are desired, compressibility.

3. Disintegrant

[0081] Compositions of the invention optionally can include one or more pharmaceutically and/or nutraceutical acceptable disintegrants as excipients. Suitable disintegrants include, but are not limited to, either individually or in combination, starches, including sodium starch glycolate and pregelatinized corn starches, clays, celluloses such as purified cellulose, microcrystalline cellulose, methylcellulose, carboxymethylcellulose and sodium carboxymethylcellulose, croscarmellose sodium, alginates, crospovidone, and gums such as agar, guar, locust bean, karaya, pectin and tragacanth gums. Disintegrants may be added at any suitable step during the preparation of the composition, particularly prior to granulation or during a lubrication step prior to compression. Such disintegrants, if present, constitute in total about 0.2% to about 30%, preferably about 0.2% to about 10%, and more preferably about 0.2% to about 5%, of the total weight of the composition.

4. Binders

[0082] The compositions of the present invention can include binding agents or adhesives particularly for tablet formulations. Such binding agents and adhesives preferably impart sufficient cohesion to the powder being tableted to allow for normal processing operations such as sizing, lubrication, compression and packaging, but still allow the tablet to disintegrate and the composition to be absorbed upon ingestion. Such binding agents may also prevent or inhibit crystallization or recrystallization of a co-crystal of the present invention once the salt has been dissolved in a solution. Suitable binding agents and adhesives include, but are not limited to, either individually or in combination, acacia; tragacanth, sucrose, gelatin, glucose, starches such as, but not limited to, pregelatinized starches, celluloses such as, but not limited to, methylcellulose and carmellose sodium, alginic acid and salts of alginic acid; magnesium aluminum silicate, PEG, guar gum, polysaccharide acids, bentonites, povidone, polymethacrylates, HPMC, hydroxypropylcellulose, and ethylcellulose. Such binding agents and/or adhesives, if present, constitute in total about 0.5% to about 25%, preferably about 0.75% to about 15%, and more preferably about 1% to about 10%, of the total weight of the pharmaceutical composition. Many of the binding agents are polymers comprising amide, ester, ether, alcohol or ketone groups and, as such, can be included in pharmaceutical compositions of the present invention. Polyvinylpyrrolidones is an non-limiting example of a binder used for slow release tablets. Polymeric binding agents can have varying molecular weight, degrees of crosslinking, and grades of polymer. Polymeric binding agents can also be copolymers, such as block co polymers that contain mixtures of ethylene oxide and propylene oxide units. Variation in these units' ratios in a given polymer affects properties and performance. 5. Wetting Agents

[0083] Wetting agents can be used in the compositions of the present invention.

Wetting agent can be selected to maintain the crystal in close association with water, a condition that may improve bioavailability of the composition. Such wetting agents can also be useful in solubilizing or increasing the solubility of crystals. Surfactants can be used as wetting agents. Non-limiting examples of surfactants that can be used as wetting agents in compositions of the invention include quaternary ammonium compounds, for example benzalkonium chloride, benzethonium chloride and cetylpyridinium chloride, dioctyl sodium sulfosuccinate, polyoxyethylene alkylphenyl ethers, poloxamers (polyoxyethylene and polyoxypropylene block copolymers), polyoxyethylene fatty acid glycerides and oils, for example polyoxyethylene (8) caprylic/capric mono- and di glycerides, polyoxyethylene (35) castor oil and polyoxyethylene (40) hydrogenated castor oil, polyoxyethylene alkyl ethers, for example polyoxyethylene (20) cetostearyl ether, polyoxyethylene fatty acid esters, for example polyoxyethylene (40) stearate, polyoxyethylene sorbitan esters, for example polysorbate 20 and polysorbate 80, propylene glycol fatty acid esters, for example propylene glycol laurate, sodium lauryl sulfate, fatty acids and salts thereof, for example oleic acid, sodium oleate and triethanolamine oleate, glyceryl fatty acid esters, for example glyceryl monostearate, sorbitan esters, for example sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate and sorbitan monostearate, tyloxapol, and mixtures thereof. Such wetting agents, if present, constitute in total about 0.25% to about 15%, preferably about 0.4% to about 10%, and more preferably about 0.5% to about 5%, of the total weight of the pharmaceutical and/or nutraceutical composition.

6. Lubricants

[0084] Lubricants can be included in the compositions of the present invention.

Suitable lubricants include, but are not limited to, either individually or in combination, glyceryl behenate, stearic acid and salts thereof, including magnesium, calcium and sodium stearates; hydrogenated vegetable oils, colloidal silica, talc, waxes, boric acid, sodium benzoate, sodium acetate, sodium fumarate, sodium chloride, DL-leucine, PEG (e.g., CARBOWAX™ 4000 and CARBOWAX™ 6000 of the Dow Chemical Company), sodium oleate, sodium lauryl sulfate, and magnesium lauryl sulfate. Such lubricants, if present, constitute in total about 0.1% to about 10%, preferably about 0.2% to about 8%, and more preferably about 0.25% to about 5%, of the total weight of the composition. 7. Other Agents

[0085] Surfactant, emulsifier, or effervescent agents can be used in the compositions.

Emulsifying agents can be used to help solubilize the ingredients within a soft gelatin capsule. Non-limiting examples of the surfactant, emulsifier, or effervescent agent include D-sorbitol, ethanol, carrageenan, carboxyvinyl polymer, carmellose sodium, guar gum, glycerol, glycerol fatty acid ester, cholesterol, white beeswax, dioctyl sodium sulfosuccinate, sucrose fatty acid ester, stearyl alcohol, stearic acid, polyoxyl 40 stearate, sorbitan sesquioleate, cetanol, gelatin, sorbitan fatty acid ester, talc, sorbitan trioleate, paraffin, potato starch, hydroxypropyl cellulose, propylene glycol, propylene glycol fatty acid ester, pectin, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyl 35 castor oil, polysorbate 20, polysorbate 60, polysorbate 80, macrogol 400, octyldodecyl myristate, methyl cellulose, sorbitan monooleate, glycerol monostearate, sorbitan monopalmitate, sorbitan monolaurate, lauryl dimethylamine oxide solution, sodium lauryl sulfate, lauromacrogol, dry sodium carbonate, tartaric acid, sodium hydroxide, purified soybean lecithin, soybean lecithin, potassium carbonate, sodium hydrogen carbonate, medium-chain triglyceride, citric anhydride, cotton seed oil-soybean oil mixture, and liquid paraffin.

F. Vehicles

[0086] Various delivery systems are known in the art and can be used to administer a therapeutic agent or composition of the invention, e.g., encapsulation in liposomes, microparticles, microcapsules, receptor-mediated endocytosis and the like. Methods of administration include, but are not limited to, parenteral, intra-arterial, intramuscular, intravenous, intranasal, and oral routes. The compositions can be provided in the form of tablets, lozenges, granules, capsules, pills, ampoule, suppositories or aerosol form. The compositions can also be provided in the form of suspensions, solutions, and emulsions of the active ingredient in aqueous or non-aqueous diluents, syrups, granulates or powders.

G. Formulation and Administration

[0087] The composition may, for example, be a pharmaceutical composition

(medicament), and over the counter composition (OTC), a nutraceutical, etc. Compositions according to the present invention include formulations suitable for oral or parenteral routes. Non-limiting examples of specific routes include intradermal, subcutaneous, intramuscular, intravenous, local injection, rectal, intranasal inhalation, insufflation, topical (including transdermal, buccal and sublingual), vaginal, parenteral (including subcutaneous, intramuscular, intravenous and intradermal) and pulmonary administration. The formulations can conveniently be presented in unit dosage form and can be prepared by any methods well known in the art. Such methods include the step of bringing into association the active ingredient (or ingredients) with the carrier, which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredient with a suitable carrier, such as liquid carriers or finely divided solid carriers or both, and then if necessary shaping the product. Formulations of the subject invention suitable for oral administration can be presented as discrete units such as capsules, cachets or tablets, each containing a predetermined amount of the active ingredient, or as an oil-in-water liquid emulsion, water-in-oil liquid emulsion, or as a supplement within an aqueous solution, for example, a tea. The active ingredient can also be presented as bolus, electuary, or paste. Useful injectable preparations include sterile suspensions, solutions or emulsions of the compound compositions in aqueous or oily vehicles. The compositions can also contain formulating agents, such as suspending, stabilizing and/or dispersing agent. The formulations for injection can be presented in unit dosage form, e.g., in ampoules or in multidose containers, and can contain added preservatives. Alternatively, the injectable formulation can be provided in powder form for reconstitution with a suitable vehicle, including but not limited to sterile pyrogen free water, buffer, dextrose solution, etc., before use. To this end, the compound compositions can be dried by any art-known technique, such as lyophilization, and reconstituted prior to use.

[0088] Formulations suitable for topical administration in the mouth include lozenges comprising the active ingredient in a flavored basis, usually sucrose and acacia or tragacanth, pastilles that include the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia, mouthwashes that include the active ingredient in a suitable liquid carrier, and chocolate comprising the active ingredients.

[0089] Formulations suitable for topical administration according to the subject invention can be formulated as an ointment, cream, suspension, lotion, powder, solution, paste, gel, spray, aerosol or oil. Alternatively, a formulation can comprise a patch or a dressing such as a bandage or adhesive plaster impregnated with active ingredients, and optionally one or more excipients or diluents. In some embodiments, topical formulations preferably comprise compounds that facilitate absorption of the active ingredients through the skin and into the bloodstream.

[0090] Formulations suitable for intranasal administration, wherein the carrier is a solid, include a coarse powder having a particle size, for example, in the range of about 20 to about 500 microns, which is administered in the manner in which snuff is taken, i.e., by rapid inhalation through the nasal passage from a container of the powder held close up to the nose. Suitable formulations wherein the carrier is a liquid for intranasal administration, such as by the non-limiting examples of a nebulizer, include aqueous or oily solutions of the agent. Formulations preferably can include compounds that facilitate absorption of the active ingredients through the skin and into the bloodstream.

[0091] Formulations suitable for parenteral administration include aqueous and non- aqueous isotonic sterile injection solutions which can contain antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which can include suspending agents and thickening agents, and liposomes or other microparticulate systems which are designed to target the compound to blood components or one or more organs. The formulations can be presented in unit-dose or multi-dose or multi-dose sealed containers, such as for example, ampoules and vials, and can be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions can be prepared from sterile powders, granules and tablets of the kind previously described.

[0092] Liquid preparations for oral administration can take the form of, for example, elixirs, solutions, syrups or suspensions, or they can be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations can be prepared by conventional means with pharmaceutically and/or nutraceutical acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol, or fractionated vegetable oils); and preservatives (e.g., methyl or propyl p hydroxybenzoates or sorbic acid). The preparations can also contain buffer salts, preservatives, flavoring, coloring and sweetening agents as appropriate. [0093] For buccal administration, the compositions can take the form of the non limiting examples of tablets or lozenges formulated in a conventional manner.

[0094] For rectal and vaginal routes of administration, the compound compositions can be formulated as solutions (for retention enemas) suppositories or ointments containing conventional suppository bases such as cocoa butter or other glycerides.

[0095] For nasal administration or administration by inhalation or insufflation, the compound compositions can be conveniently delivered in the form of an aerosol spray from pressurized packs or a nebulizer with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, fluorocarbons, carbon dioxide or other suitable gas. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount. Capsules and cartridges for use in an inhaler or insufflator (for example capsules and cartridges comprised of gelatin) can be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

[0096] For prolonged delivery, the compound compositions can be formulated as a depot preparation for administration by implantation or intramuscular injection. The compound compositions can be formulated with suitable polymeric or hydrophobic materials (e.g., as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, e.g., as a sparingly soluble salt. Alternatively, transdermal delivery systems manufactured as an adhesive disc or patch, which slowly releases the compound compositions for percutaneous absorption, can be used. To this end, permeation enhancers can be used to facilitate transdermal penetration of the compound compositions. Suitable transdermal patches are described in for example, U.S. Pat. No. 5,407,713; U.S. Pat. No. 5,352,456; U.S. Pat. No. 5,332,213; U.S. Pat. No. 5,336,168; U.S. Pat. No. 5,290,561; U.S. Pat. No. 5,254,346; U.S. Pat. No. 5,164,189; U.S. Pat. No. 5,163,899; U.S. Pat. No. 5,088,977; U.S. Pat. No. 5,087,240; U.S. Pat. No. 5,008,110; and U.S. Pat. No. 4,921,475.

[0097] Alternatively, other delivery systems can be employed. Liposomes and emulsions are well-known examples of delivery vehicles that can be used to deliver the compound compositions. Certain organic solvents such as dimethylsulfoxide (DMSO) can also be employed, although usually at the cost of greater toxicity. [0098] It should be understood that in addition to the ingredients particularly mentioned above, the formulations useful in the present invention can include other agents conventional in the art regarding the type of formulation in question. For example, formulations suitable for oral administration can include such further agents as sweeteners, thickeners, and flavoring agents. It also is intended that the agents, compositions, and methods of this invention be combined with other suitable compositions and therapies.

[0099] In one embodiment, the pharmaceutical and/or nutraceutical compositions of the invention can be administered locally to the area in need of treatment; such local administration can be achieved, for example, by local infusion, by injection, or by means of a catheter. In another embodiment, a compound or composition of the invention is administered in a manner so as to achieve peak concentrations of the active compound at sites of the disease. Peak concentrations at disease sites can be achieved, for example, by intravenously injecting of the agent, optionally in saline, or orally administering, for example, a tablet, capsule or syrup containing the active ingredient. H. Other Pharmaceutical and/or Nutraceutical Agents

[00100] Pharmaceutical, over the counter (OTC), and/or nutraceutical formulations of the invention can be administered simultaneously or sequentially with other drugs or biologically active agents. Examples include, but are not limited to antioxidants, free radical scavenging agents, analgesics, anesthetics, anorectals, antihistamines, anti-inflammatory agents including non-steroidal anti-inflammatory drugs, antibiotics, antifungals, antivirals, antimicrobials, anti-cancer actives, antineoplastics, biologically active proteins and peptides, enzymes, hemostatics, steroids including hormones and corticosteroids, etc.

I. Therapeutic Methods And Dosage

[00101] Preferred unit dosage formulations are those containing a daily dose or unit, daily subdose, or an appropriate fraction thereof, of an agent. Therapeutic amounts can be empirically determined and will vary with the pathology being treated, the subject being treated, and the efficacy and toxicity of the agent. Similarly, suitable dosage formulations and methods of administering the agents can be readily determined by those of ordinary skill in the art. [00102] In some embodiments, a therapeutic method of the present invention can include treating a disease, condition, or disorder by administering to a subject having such disease or condition a stable formulation as described herein in an amount effective to treat the disease, condition, or disorder. In some embodiments, the subject is administered a stable formulation comprising the compounds claimed herein. The disease, condition, or disorder can be caused by an bacteria. Further, the disease, condition, or disorder can be acne and related diseases, conditions, and disorders. For prophylactic administration, the composition can be administered to a patient at risk of developing one of the previously described conditions.

[00103] The amount of composition administered will depend upon a variety of factors, including, for example, the particular indication being treated, the mode of administration, whether the desired benefit is prophylactic or therapeutic, the severity of the indication being treated and the age and weight of the patient, etc. Determination of an effective dosage is well within the capabilities of those skilled in the art. In some aspects of the invention, total dosage amounts of a compound composition will typically be in the range of from about 0.0001 or 0.001 or 0.01 mg/kg of patient/day to about 100 mg/kg patient/day, but may be higher or lower, depending upon, among other factors, the activity of the components, its bioavailability, the mode of administration and various factors discussed above. Dosage amount and interval can be adjusted individually to provide plasma levels of the compound(s) which are sufficient to maintain therapeutic or prophylactic effect. For example, the compounds can be administered once per week, several times per week (e.g., every other day), once per day or multiple times per day, depending upon, among other things, the mode of administration, the specific indication being treated and the judgment of the prescribing physician. Skilled artisans will be able to optimize effective local dosages without undue experimentation.

J. Secondary and Combination Treatments

[00104] Certain embodiments provide for the administration or application of one or more secondary or additional forms of therapies or preventative interventions. The type of therapy is dependent upon the type of disease that is being treated or prevented. The secondary form of therapy may be administration of one or more secondary pharmacological agents that can be applied in the treatment or prevention of a bacterial infection. [00105] If the secondary or additional therapy is a pharmacological agent, it may be administered prior to, concurrently, or following administration of the compositions disclosed herein. The interval between administration of the compositions and the secondary or additional therapy may be any interval as determined by those of ordinary skill in the art. For example, the compositions and the secondary or additional therapy may be administered simultaneously, or the interval between treatments may be minutes to weeks. In embodiments where the agents are separately administered, one would generally ensure that a significant period of time did not expire between the time of each delivery, such that each therapeutic agent would still be able to exert an advantageously combined effect on the subject. For example, the interval between therapeutic agents may be about 12 h to about 24 h of each other and, more preferably, within about 6 hours to about 12 h of each other. In some situations, it may be desirable to extend the time period for treatment significantly, however, where several days (2, 3, 4, 5, 6 or 7) to several weeks (1, 2, 3, 4, 5, 6, 7 or 8) lapse between the respective administrations. In some embodiments, the timing of administration of a secondary therapeutic agent is determined based on the response of the subject to the composition.

[00106] Examples of secondary treatments useful with methods disclosed herein are: anti -bacterial drugs. Further, secondary treatments can include treatments for the symptoms of a bacterial infection or the complications caused by a bacterial infection, such as fluid replacement therapy, fever reducers, pain reducers, etc. Secondary treatments can also include dietary supplements such as vitamins C, E and D, calcium, zinc, selenium, curcumin, folate, bioflavonoids, resveratrol, and plant extracts.

K. Kits

[00107] In another aspect of the present invention, kits for treating or preventing a disease, condition or disorder as described herein. For instance, compositions of the present invention can be included in a kit. A kit can include a container. Containers can include a bottle, a metal tube, a laminate tube, a plastic tube, a dispenser, a straw, a pressurized container, a barrier container, a package, a compartment, or other types of containers such as injection or blow-molded plastic containers into which the dispersions or compositions or desired bottles, dispensers, or packages are retained. The kit and/or container can include indicia on its surface. The indicia, for example, can be a word, a phrase, an abbreviation, a picture, or a symbol. [00108] The containers can dispense a predetermined amount of the composition. In other embodiments, the container can be squeezed ( e.g ., metal, laminate, or plastic tube) to dispense a desired amount of the composition. The composition can be dispensed as a spray, an aerosol, a liquid, a fluid, a semi-solid, or a solid. In a preferred embodiment, the composition is dispensed as a tablet or lozenge. The containers can have spray, pump, or squeeze mechanisms. A kit can also include instructions for employing the kit components as well the use of any other compositions included in the container. Instructions can include an explanation of how to apply, use, and maintain the compositions. The compositions can, if desired, be presented in a pack or dispenser device, which can contain one or more unit dosage forms containing the compound compositions. The pack can, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device can be accompanied by instructions for administration.

EXAMPLES

[00109] The present invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of noncritical parameters which can be changed or modified to yield essentially the same results.

EXAMPLE 1

(EXTRACTION OF COMPOUNDS FROM CRANBERRIES AND GREEN TEA)

[00110] The inventors have surprisingly found that a combination of several compounds found in cranberries and a combination of several compounds found in green tea can prevent and treat bacterial infections. The inventors have also found that specific relative concentrations of the compounds act to enhance the ability of the combined compounds to prevent and treat bacterial infections. In addition, the inventors expect that using compounds of the present invention with additional anti -bacterial compounds may enhance the ability of the combined compounds to prevent and treat bacterial infections. The compounds of the present invention were isolated from cranberries and/or green tea. The compounds isolated from cranberries and/or green tea may further be combined with salicylic acid. [00111] Compounds isolated from cranberries: Freeze or sun dried Vaccinium macrocarpon fruits were mixed with purified water, preferably one part dried fruit to two parts purified water, and left to sit for two hours. The mixture was extracted with short chain alcohol, such as food grade ethanol multiple times, at a temperature below 60 °C. After each extraction, the alcohol phase was discarded and the aqueous phase was retained. The aqueous phase was concentrated, for example using a filtration device with a low protein binding cellulose membrane, or alternatively, a polypropylene, Teflon, or Nylon membrane can be used. The purpose of filtration was to remove water from the material. The retentate from the filtration was then concentrated to dryness at a temperature about 40 °C. The dried material was further chromatographed on a column, preferably AMBERLITE® XAD7HP and sephadex LH-20. The fractions were eluted off by 5-90% ethanol or 40-90% acetone. The fraction material was then concentrated to dryness using a suitable drying method, such as rotary evaporator, at a temperature below 50 °C, other suitable drying methodologies include, but are not limited to, vacuum drying and spray drying.

[00112] Compounds isolated from green tea: Dried Camellia sinensis leaves were mixed with purified water, preferably one part dried leaves to three parts purified water, and left to sit for two hours. The mixture was extracted with short chain alcohol, such as food grade ethanol multiple times at a temperature below 60 °C. After each extraction, the alcohol phase was discarded and the aqueous phase was retained. The aqueous phase was concentrated, for example using a filtration device with a low protein binding cellulose membrane, or alternatively, a polypropylene, Teflon, or Nylon membrane can be used. The purpose of filtration was to remove water from the material. The retentate from the filtration was then concentrated to dryness at a temperature below 50 °C. The dried material was chromatographed on a column, preferably AMBERLITE® XAD7HP. The fractions were eluted off by 10 - 80% ethanol or 40- 95% acetone. The fraction material was then concentrated to dryness using a suitable drying method, such as rotary evaporator, at a temperature below 50°C, other suitable drying methodologies include, but are not limited to, vacuum drying and spray drying.

EXAMPLE 2

(CHARACTERIZATION OF COMPOUNDS BY ACCURATE MASS AND RELATIVE ABUNDANCE)

[00113] The compounds of the present invention include biomarker compounds defined by compounds found in cranberry with an accurate mass of 359.3163 amu, 111.0450 amu, 117.0529 amu, 118.0603 amu, 119.0362 amu, 131.0338 amu, 139.0415 amu, 160.0636 amu, 201.0790 amu, 249.0879 amu, and 293.1008 amu. The compounds of the present invention include biomarker compounds defined by compounds found in green tea with an accurate mass of 461.1470 amu, 108.0205 amu, 122.0493 amu, 129.0472 amu, 145.0747 amu, 161.0718 amu, 165.0775 amu, 170.0243 amu, 174.0992 amu, 180.0673 amu, 194.0804 amu, and 211.0896 amu. These compounds may be produced synthetically or isolated from an organism such as, but not limited to, cranberries and/or green tea. The compounds may be characterized by methods known by one of skill in the art.

[00114] Accurate mass and relative abundances described herein are based on experiments using particular instruments and particular settings and can change from instrument to instrument. There is variability in each measurement. Thus, the accurate mass and relative abundances are defined as being close to as understood by one of ordinary skill in the art. In one non-limiting embodiment the terms are defined to be within 20%, preferably 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%. In one non-limiting embodiment, the accurate mass has an error of within +/- 20 mmu, preferably 10 mmu, more preferably within 5 mmu, and most preferably within 1 mmu. In one non-limiting embodiment, the relative abundance has an error of +/- 20%, preferably 10%, preferably within 5%, and more preferably within 1%, and most preferably within 0.5%.

[00115] Methods for Accurate mass: The compounds were characterized and relative abundance was determined using Direct Analysis in Real Time (DART) ion source combined with Time of Flight/Mass Spectrometry (TOF-MS). Specifically, the DART TOF-MS was a JEOL DART™ AccuTOF-mass spectrometer from Jeol USA of Peabody, MA (JMS- T100LC). The mass of the compounds were determined in a cranberry extract or green tea extract sample by directly introducing the sample to the ion stream by means of a Dip-IT sampler and a Dip-IT sampler holder (IONSENSE™).

[00116] The settings for the DART ion source were the following:

Gas: He

Flow: 2.52 LPM @ 50 PSI

Temperature: 250 C

Needle Voltage: 3000V Grid Electrode Voltage: 250V

Discharge Electrode Voltage: 400V

[00117] The settings for the JEOL AccuTOF MS were the following:

Peaks Voltage: 1000V

Orifice 1 Temperature: 120 C

Detector Voltage: 2600V

Reflectron Voltage: 990.0V

[00118] Extract samples were analyzed in six replicates by DART-TOF MS. These six replicates were analyzed to create a single, averaged, filtered, and statistically significant DART fingerprint of the extract. This processed fingerprint was then used to determine the presence of the bioactive markers by comparison of masses. Due to the initial discovery and identification of these bioactive markers, a simple mass comparison was sufficient to determine their presence in any extract or mixture of chemicals. For the AccuTOF, that mass tolerance is less than 20 millimass units (mmu) (predicted mass +/-10 mmu). Given the same extract and ion source, other TOF mass spectrometers may have a higher or lower mass tolerance.

[00119] Methods for Relative Abundance: While no sample preparation is required for a simple analysis with the DART, a curcumin doped/spiked solution was used for determining relative abundance of test compositions through quantitation relative to a known quantity. Standards that are well known and that exist naturally in cranberry and green tea would vary given any number of influences - growing conditions, harvest time, plant health, etc. For purposes of quantifying the biomarkers, the natural variations of naturally occurring standards make it unacceptable to use as a basis for an absolute quantification of the biomarkers. In order to remove that inconsistency, a compound that is not native to cranberry and green tea (in this case, curcumin) was used as the basis for a quantitative chemical profile of the bioactive molecules.

[00120] For determining relative abundance of samples with unknown concentrations of the biomarkers disclosed herein, samples of the disclosed compositions were doped/spiked with curcumin. Samples were then analyzed by the DART-TOF method used above. [00121] Table 1 discloses the relative abundance of the biomarkers disclosed herein found in non-limiting, preferred embodiments of compositions comprising all eleven biomarkers found in cranberries and compositions comprising all twelve biomarkers found in green tea. [00122] Table 1. Relative Abundance of the Biomarkers in Preferred Active

Compositions Determined Using 1 mg/ml of the Cranberry Composition or 1 mg/ml of the Green Tea Composition Spiked with 0.01 mg/ml Curcumin.

EXAMPLE 3

(FORMULATIONS FOR EXAMPLES 4 THROUGH 5)

[00123] A dose-reliable, cranberry extract comprising biomarkers 1 through 11 was produced in general according to the methods described in Example 1. A dose-reliable, green tea extract comprising biomarkers 12 through 23 was produced in general according to the methods described in Example 1.

[00124] For the clinical study of Example 5, the cranberry extract was formulated in a toner for topical administration and the green tea extract was encapsulated in a capsule for oral administration.

EXAMPLE 4

(SAFETY)

[00125] Compositions of Example 1 were tested for safety for human use. In the clinical study of Example 5 and in human pharmacokinetic studies (not shown), no adverse events were attributed to the compositions of Example 1. EXAMPLE 5

(CLINICAL STUDY FOR THE TREATMENT AND PREVENTION OF BACTERIAL INFECTION)

[00126] Inhibition and prevention of acne infection by the compounds of the present invention in a clinical trial was determined. It was found that the compounds of the present invention treat and prevent acne. Specifically, treatment with the compounds of the present invention reduced acne lesions and facial redness and improved an investigator’s global assessment of the subject.

[00127] Briefly, three groups of study volunteers, each containing 30 volunteers received either compositions of the present invention (Arm 1), open-label PROACTIV+® (Arm 2), or received placebo (Arm 3). The volunteers had mild to moderate (a score or 2 to 3) clinically evident facial acne as defined in the acne severity index of Table 2 and were between the ages of > 17 years and < 45 years of age of either gender and could be from any racial/ethnic group. The gender and age breakdown for the study participants is shown in Table 3. Of the 90 participants enrolled in the study, 3 did not finish. Two participants were lost to follow up and one patient from the placebo group terminated the study early. Though there were overall more women enrolled in the study than men, there were roughly equal numbers of men and women between each of the three arms of the study. The average and median ages of study participants in each study arm were equivalent.

[00128] Table 2. Investigator’s Global Assessment / Severity Index.

* Rating score of 2 or 3 is required for study entry [00129] Table 3. Demographics of Study Participants

[00130] Products:

[00131] Arm 1 - Acne Treatment Toner Product containing salicylic acid 1.5%, water, organic cranberry extract of Example 1, organic rose oil, and organic trisodium citrate. Vegicap Capsule containing organic green tea extract of Example 1. One capsule was taken twice a day orally and the topical toner was applied externally twice a day.

[00132] Arm 2 - PROACTIV+® was used open label and as directed by the manufacturer. PROACTIV+® was purchased from PROACTIV+® website and vending machines.

[00133] Step 1 - PROACTIV+® Skin Smoothing Exfoliator containing benzoyl peroxide 2.5%, water, sodium cocoyl isethionate, glycerin, polyethylene, lauryl/myristyl benzoate, linoleic acid, linolenic acid, butylene glycol, dimethicone, ethylhexylglycerin, acrylates/Cl0-30 alkyl acrylate crosspolymer, glycolic acid, sodium hydroxide, phenoxyethanol, and fragrance. One capsule was taken twice a day orally and the topical toner was applied externally twice a day. [00134] Step 2 - Pore Targeting Treatment containing benzoyl peroxide 2.5%, water, ethoxydiglycol, glycerin, prunus amygdalus dulcis (sweet almond) oil, polysorbate 80, polysorbate 60, sorbitan stearate, carbomer, potassium hydroxide, disodium EDTA, and fragrance.

[00135] Step 3 - Complexion Perfecting Hydrator containing salicylic acid 0.5%, water, butylene glycol, cetearyl alcohol, polyacrylate, Scutellaria baicalensis root extract, sophora angustifolia root extract, morns alba root extract, glycyrrhiza glabra (licorice) root extract, arctostaphylos uva ursi leaf extract, kojic acid, zinc gluconate, alpha-glucan oligosaccharide, sodium hyaluronate, bisabolol, allantoin, squalane, safflower oil/palm oil aminopropanediol esters, C12-15 alkyl lactate, caprylic/capric triglyceride, caprylyl glycol, ethylhexylglycerin, glycerin, ethylhexyl palmitate, hydrogenated polydecene, hydroxypropyl cyclodextrin, PPG-5-laureth-5, polyquatemium-l 1, ceteareth-20, aluminum starch octenyl succinate, polysorbate 60, hexylene glycol, PPG-2 myristyl ether propionate, sodium hydroxide, disodium EDTA, phenoxyethanol, fragrance, dimethicone, sodium.

[00136] Arm 3 - Placebo Toner Product containing organic maltodextrin, corn based complex carbohydrate, water, rose oil, and organic food coloring. Vegicap Capsule containing organic maltodextrin.

[00137] Methods: Propionibacterium Acnes PCR - Not all skin breakouts are caused by P. acnes. Therefore, the visual diagnosis of acne infection in study subjects was confirmed by PCR. A randomized PCR analysis of 10 study subjects from each of the three Arms were performed. A 2 inch x 2 inch section of skin where the worst acne was present was swabbed using a sterile flocked swab from Copan (Murrieta, CA) for polymerase chain reaction (PCR) verification of the presence of P. acnes. Samples were frozen at -20 °C for transport to the laboratory where they were frozen at -80 °C until use.

[00138] DNA was extracted from swabs using a QIAamp DNA Mini Kit purchased from Qiagen (Valencia, CA) according to the manufacturer’s protocol. A P. acnes PCR kit was purchased from PrimerDesign Ltd (Southampton, ETC) and used non-quantitatively according to the manufacturer’s protocol. A sampling of 10 patients from each arm of the study was analyzed for the presence of P. acnes DNA.

[00139] Facial Assessments - Facial assessments of acne lesions, acne redness, and global severity were performed at each study visit.. [00140] Acne Lesion Counts - An investigator or qualified staff assessed the subject’s facial acne by counting the number of pustules, papules, and nodulo-cystic lesions from the jaw line to the hairline, including those present on the nose. Lesions involving the eyes and the scalp were excluded from the count. A papule with a pustule on its apex was counted as a pustule.

[00141] Acne Redness Assessment - Subjects were evaluated for any signs of facial erythema using the redness assessment in Table 4. Baseline values were used for comparative purposes against the scores documented at subsequent visits for each treatment group. [00142] Table 4. Ratings for Redness Assessment

[00143] Global Severity Assessment - An investigator assessed the overall status of the subject’s face for acne vulgaris using the Investigator’s Global Assessment (IGA) (Table 5). Subjects needed to have a definite clinical diagnosis of acne vulgaris of severity grade 2 or 3 for entry into the study. For the purposes of this study, a papule was defined as an inflammatory lesion that was small (<5 mm in diameter), solid palpable lesion, usually with inflamed elevation of the skin that does not contain pus. A pustule was defined as an inflammatory lesion that was small (<5 mm in diameter), with inflamed skin swelling that is filled with pus. Nodules were defined as large, hard bumps under the skin’s surface.

[00144] Table 5. Investigator’s Global Assessment / Severity Index

[00145] Results: Briefly, the Arm 1 treatment, Acne Treatment Toner Product containing salicylic acid 1.5%, water, organic cranberry extract of Example 1, organic rose oil, and organic trisodium citrate and Vegicap Capsule containing organic green tea extract of Example 1, outperformed PROACTIV+®, the current market leading acne treatment topical product, and a placebo in a randomized, double blind clinical study on all three parameters tested. Specifically, Arm 1 outperformed in the total acne lesion count (FIG. 2), reducing the unsightly redness caused by acne’s inflammation (FIG. 3), and an Investigator’s Global Assessment (FIG. 4) for acne vulgaris. All Study groups tested PCR positive for P. acnes bacteria in similar amounts at intake (FIG. 1 and Table 6), validating the clinical diagnosis of P. acnes derived acne as well as validating the global severity assessment on the IGA scale, as all study participants were required to score a 2 or 3 for admission into the study (Table 2).

[00146] Propionibacterium Acnes PCR - A random sampling of 10 subjects from each arm at the baseline visit of the study was selected for PCR confirmation of the clinical diagnosis of infection by P. acnes. All 30 samples tested positive for P. acnes DNA by PCR (FIG. 1 and Table 6), confirming the diagnosis. Average CT values for the patients in each arm were roughly equivalent, suggesting that on average, the severity of acne was the same between patients in each of the three arms of the study (Table 6). This is indicative and confirmatory of the narrow criteria for which patients were admitted into the study, requiring a 2 or a 3 on the Investigator’s Global Assessment (Table 2).

[00147] Table 6. Crossing Threshold Values (CT) for P. acnes PCR, Confirming Infection of Patients

[00148] Acne Lesion Counts - The Study Subject Group using the Arm 1 treatment product demonstrated a dramatic reduction of acne lesions (pimples) versus both the placebo and PROACTIV+® treatment Groups (FIG. 2). A baseline for each patient was taken upon enrollment in the study for the number of pustules, papules and nodulo-cystic lesions from the jaw line to the hairline on the face. New counts were performed at days 1, 2, 3, 7, 14, and 28 after commencement of the study. The results are presented in FIG. 2 and show a clear advantage for the Arm 1 treatment product in the percent reduction of acne lesions that began as early as 24 hours and increased throughout the entire 28-day study. PROACTIV+® did not decrease acne lesions greater than placebo until 48 hours after beginning treatment, and even then, never as well as the Arm 1 treatment product. Table 7 reports the increased efficacy of the Arm 1 treatment product over the over the counter (OTC) industry leader for topical acne treatment, PROACTIV+®, displaying up to a 164% improvement over PROACTIV+® in decreased facial acne lesion counts as early as 24 hours after application.

[00149] TABLE 7. Percent Increase in the Reduction of the Acne Lesion Counts with Arm 1 Treatment Product Over PROACTIV+®

[00150] Acne Redness Assessment - The subject in the Arm 1 treatment group experienced a significant early reduction of the severity of facial erythema, a type of inflammation that causes the intense redness associated with acne. The reduction in redness results experienced by the Arm 1 treatment group was demonstrated in the first 24 hours of treatment and superior performance in reduction of acne redness continued to be experienced by the Arm 1 treatment user group throughout the study as compared to either the PROACTIV+® or placebo user groups. Signs of facial erythema were evaluated using the redness assessment in Table 4 at baseline and days 1, 2, 7, 14, and 28. The Arm 1 treatment product decreased erythema over placebo within 24 hours after the start of treatment, whereas PROACTIV+® took 14 days to reduce erythema greater than placebo (FIG. 3). The reduction in erythema was not only faster, but was greater with the Arm 1 treatment product than PROACTIV+®, ranging from 134% to 286% greater of an improvement on the redness assessment (Table 8).

[00151] Table 8. Percent Increase in the Reduction of the Facial Redness Experienced by Users of the Arm 1 Treatment Product over PROACTIV+®

[00152] Global Severity Assessment - The Investigator’s Global Assessment, or IGA, quantifies the severity of acne lesions, either non-inflammatory, or mild, moderate, or severe lesions (see Table 5). In this way, the IGA is a measure of the interaction of acne lesion counts with inflammation. IGA measurements were taken at baseline and days 1, 2, 3, 7, 14, and 28. Arm 1 treatment product outperformed placebo and PROACTIV+® beginning at 24 hours, and maintained an improvement throughout the entirety of the 28-day study (FIG. 4). The increased efficacy is especially apparent when examining the greater reduction in IGA of the Arm 1 treatment product versus PROACTIV+® (Table 9). For the Arm 1 treatment, it is clear that there are significant decreases in IGA as early as 24 hours after application, a 621% greater reduction at one week, and significant improvement that continued through to the end of the study. That PROACTIV+® did not outperform placebo to any significant degree at 28 days is not unexpected, as the PROACTIV+® product use instructions state it can take six weeks (42 days) for their product to perform at its maximum. [00153] Table 9. Percent Increase in the Reduction of IGA for Patients Using Arm 1 Treatment Product Over Patients Using PROACTIV+®

[00154] Conclusions: The Arm 1 treatment product outperformed PROACTIV+® in total acne lesion counts, acne redness reduction, and IGA at a minimum of a 114% increase in effectiveness, increasing up to 621% during the Study (Figures 2-4). Remarkably, the Arm 1 treatment product group had significantly reduced acne symptoms 24 hours after application for each measure - acne lesion counts, acne redness, and IGA. Conversely, PROACTIV+® did not improve the reduction in acne lesions counts over placebo until 48 hours, the reduction of acne redness until 14 days, and IGA until 28 days after application. Moreover, PROACTIV+® never reached the same level of efficacy as the Arm 1 treatment product on any day, using any measure.

[00155] In addition, the Arm 1 treatment achieved these superior results through a simple 2 step treatment - 1 capsule taken twice a day orally and a topical toner applied externally twice a day, versus PROACTIV+®, which has 3 different components that need to be used to wash the face, or absorb onto the face, up to three times a day.

EXAMPLE 6

(SYNERGY)

[00156] Because of the predicted method of action of the compositions disclosed herein containing compounds found in cranberries and/or in green tea, it is believed that the compositions will act synergistically with other antibacterial compounds that act through a separate mechanism. To determine synergism with other compounds/compositions, the compositions disclosed herein can be tested in combination with one or more anti -bacterial treatments and or drugs. The anti -bacterial drugs can include one or more anti-acne drugs. Combination studies can show competitive, additive, or synergistic interactions for treatment and/or prevention of bacterial infection, cell viability, cellular toxicity, side effects, etc. of the combination in cell culture, animal studies, human studies, etc. Non-limiting examples of studies can include those described above and herein as well as those known to one of skill in the art. As a non-limiting example, the combination of the compositions disclosed herein and benzyl peroxide may be tested. As a non-limiting example, the compositions disclosed herein containing compounds found in cranberries and/or in green tea in combination with benzyl peroxide may show synergistic activity against at least acne.

[00157] A non-limiting example of a combination assay that can be performed to determine the competitive, additive, or synergistic interactions of a combination can utilize an interaction matrix commonly used to look at drug interactions and synergy. In one instance, the interaction matrix is used in a prevention and/or treatment study of bacterial infection in cell culture. Briefly, the experiment can have 25 samples: 4 with a first test compound/composition (such as the compositions disclosed herein containing compounds found in cranberries and/or in green tea) alone, 4 with a second test compound/composition (such as benzyl peroxide) alone, 1 with no chemistries, and the remaining 16 can be combinations of the first and second test compounds/compositions. 1 :4 dilutions of the first test compound/composition from a starting concentration (such as 1 mg/ml for the compositions disclosed herein containing compounds found in cranberries and/or in green tea) and 1 :4 dilutions of the second test compound/composition from a starting concentration (such as 1 mg/ml for benzyl peroxide) can be tested. The infection and culture of the bacteria can occur in the constant presence of the inhibitory compounds. In this way, the experiment simulates a patient infected while on prophylactic treatment and tests prevention of infection by the first test compound/composition alone, the second test compound/composition alone, and the combination of the two at a range of concentrations. The data can be analyzed with the methodology of Berenbaum to determine competitive, additive, or synergistic interactions. (Berenbaum 1977).

[00158] All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

REFERENCES

Berenbaum M C. (1977) Synergy, additivism and antagonism in immunosuppression. A critical review. Clin Exp. Immunol. 28(1): 1-18.

Achermann, Yvonne, Elbe J. C. Goldstein, Tom Coenye, and Mark E. Shirtliff. 2014. “Propionibacterium Acnes: From Commensal to Opportunistic Biofilm-Associated

Implant Pathogen.” Clinical Microbiology Reviews 27 (3):419-40. https://doi.org/l0.H28/CMR.00092-l3.

Aubin, G. G., M. E. Portillo, A. Trampuz, and S. Corvee. 2014.“Propionibacterium Acnes, an Emerging Pathogen: From Acne to Implant-Infections, from Phylotype to Resistance.” Medecine Et Maladies Infectieuses 44 (6):24l-50. https://doi.org/l0.l0l6/j.medmal.20l4.02.004.

Beylot, C., N. Auffret, F. Poli, J.-P. Claudel, M.-T. Leccia, P. Del Giudice, and B. Dreno.

2014. “Propionibacterium Acnes: An ETpdate on Its Role in the Pathogenesis of Acne.” Journal of the European Academy of Dermatology and Venereology: JEADV 28 (3):27l-78. https://doi.org/l0. l l l l/jdv. l2224.

Juthani-Mehta, Manisha, Peter H. Van Ness, Luann Bianco, Andrea Rink, Sabina Rubeck, Sandra Ginter, Stephanie Argraves, et al. 2016.“Effect of Cranberry Capsules on Bacteriuria Plus Pyuria Among Older Women in Nursing Homes: A Randomized Clinical Trial.” JAMA 316 (18): 1879-87. https://doi.org/l0.l00l/jama.20l6. l6l4l. Liu, Pei-Feng, Yao-Dung Hsieh, Ya-Ching Lin, Aimee Two, Chih-Wen Shu, and Chun-Ming Huang. 2015.“Propionibacterium Acnes in the Pathogenesis and Immunotherapy of Acne Vulgaris.” Current Drug Metabolism 16 (4):245-54.

“Proactiv.” 2017. Wikipedia. https://en.wikipedia.org/w/index.php?title=Proactiv&oldid=810662042.

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Claims

1. A composition comprising the following biomarkers:

biomarker 1 having an accurate mass of 359.3163 amu and having a relative abundance of at least 7.47%;

biomarker 2 having an accurate mass of 111.0450 amu and having a relative abundance of at least 9.41%;

biomarker 3 having an accurate mass of 117.0529 amu and having a relative abundance of at least 9.95%;

biomarker 4 having an accurate mass of 118.0603 amu and having a relative abundance of at least 0.63%;

biomarker 5 having an accurate mass of 119.0362 amu and having a relative abundance of at least 0.18%;

biomarker 6 having an accurate mass of 131.0338 amu and having a relative abundance of at least 27.76%;

biomarker 7 having an accurate mass of 139.0415 amu and having a relative abundance of at least 36.34%;

biomarker 8 having an accurate mass of 160.0636 amu and having a relative abundance of at least 1.22%;

biomarker 9 having an accurate mass of 201.0790 amu and having a relative abundance of at least 16.02%;

biomarker 10 having an accurate mass of 249.0879 amu and having a relative abundance of at least 6.50%; and

biomarker 11 having an accurate mass of 293.1008 amu and having a relative abundance of at least 8.16%,

wherein the biomarkers are found in cranberry; and

wherein the relative abundance is relative to 0.01 mg/ml curcumin spiked in 1 mg/ml of the composition.

2 The composition of claim 1, wherein the biomarkers contained therein have a relative abundance of at most:

biomarker 1 of 11.21%;

biomarker 2 of 14.12%;

biomarker 3 of 14.93%;

biomarker 4 of 0.95%;

biomarker 5 of 0.27%;

biomarker 6 of 41.64%;

biomarker 7 of 54.51%;

biomarker 8 of 1.83%;

biomarker 9 of 24.02%;

biomarker 10 of 9.75%; and

biomarker 11 of 12.24%;

3. A composition comprising the following biomarkers:

biomarker 1 having an accurate mass of 359.3163 amu and having a relative abundance of at most 11.21%;

biomarker 2 having an accurate mass of 111.0450 amu and having a relative abundance of at most 14.12%;

biomarker 3 having an accurate mass of 117.0529 amu and having a relative abundance of at most 14.93%;

biomarker 4 having an accurate mass of 118.0603 amu and having a relative abundance of at most 0.95%;

biomarker 5 having an accurate mass of 119.0362 amu and having a relative abundance of at most 0.27%; biomarker 6 having an accurate mass of 131.0338 amu and having a relative abundance of at most 41.64%;

biomarker 7 having an accurate mass of 139.0415 amu and having a relative abundance of at most 54.51%;

biomarker 8 having an accurate mass of 160.0636 amu and having a relative abundance of at most 1.83%;

biomarker 9 having an accurate mass of 201.0790 amu and having a relative abundance of at most 24.02%;

biomarker 10 having an accurate mass of 249.0879 amu and having a relative abundance of at most 9.75%; and

biomarker 11 having an accurate mass of 293.1008 amu and having a relative abundance of at most 12.24%,

wherein the biomarkers are found in cranberry, and

4. The composition of any of claims 1 to 3, wherein the mass of each biomarker is the mass as determined by a Direct Analysis in Real Time-TOF (DART-TOF) mass spectrometer.

5. The composition of any one of claims 1 to 4, wherein at least one of the biomarker(s) are synthetically obtained.

6. The composition of any one of claims 1 to 5, wherein at least one of the biomarker(s) are isolated from a plant.

7. The composition of claim 6, wherein at least one of the biomarkers(s) are isolated from cranberry.

8. The composition of any one of claims 1 to 7, wherein the composition has an at least 90%, preferably at least 95%, or at least 98% batch-to-batch chemical consistency of relative abundance for the biomarkers.

9. The composition of any one of claims 1 to 8, wherein the composition further comprises a preservative.

10. The composition of any one of claims 1 to 9, wherein the composition further comprises additional salicylic acid.

11. The composition of claim 10, wherein the total salicylic acid of the composition is at least 1% by weight of the composition.

12. The composition of any one of claims 1 to 11, wherein the composition further comprises at least one antibacterial agent.

13. The composition of claim 12, wherein at least one antibacterial agent is rose oil.

14. The composition of any one of claims 1 to 13, wherein the composition is formulated for topical administration.

15. The composition of claim 14, wherein the composition is in a liquid solution, emulsion, powder, or patch.

16. The composition of any one of claims 1 to 13, wherein the composition is formulated for oral administration, administration through injection, and/or intranasal administration.

17. The composition of claim 16, wherein the composition is a lozenge, a powder, a tablet, a gel-cap, a gelatin, a liquid solution, a syrup, an oil, and/or a dissolvable film.

18. The composition of any of claims 1 to 17, wherein the composition is formulated to treat and/or prevent a bacterial infection.

19. The composition of any of claims 1 to 18, wherein the composition is formulated to treat and/or prevent acne.

20. The composition of claim 19, wherein the composition is formulated to reduce acne lesions, reduce facial redness, and/or improve a global assessment of a subject.

1. A composition comprising the following biomarkers:

biomarker 12 having an accurate mass of 461.147 amu and having a relative abundance of at least 2.28%;

biomarker 13 having an accurate mass of 108.0205 amu and having a relative abundance of at least 11.46%;

biomarker 14 having an accurate mass of 122.0493 amu and having a relative abundance of at least 25.67%;

biomarker 15 having an accurate mass of 129.0472 amu and having a relative abundance of at least 90.91%;

biomarker 16 having an accurate mass of 145.0747 amu and having a relative abundance of at least 41.91%;

biomarker 17 having an accurate mass of 161.0718 amu and having a relative abundance of at least 19.70%;

biomarker 18 having an accurate mass of 165.0775 amu and having a relative abundance of at least 94.69%;

biomarker 19 having an accurate mass of 170.0243 amu and having a relative abundance of at least 38.75%;

biomarker 20 having an accurate mass of 174.0992 amu and having a relative abundance of at least 1162.44%;

biomarker 21 having an accurate mass of 180.0673 amu and having a relative abundance of at least 100.06%;

biomarker 22 having an accurate mass of 194.0804 amu and having a relative abundance of at least 3234.90%; and

biomarker 23 having an accurate mass of 211.0896 amu and having a relative abundance of at least 25.33%,

wherein the biomarkers are found in green tea, and

22. The composition of claim 21, wherein the biomarkers contained therein have a relative abundance of at most:

biomarker 12 of 3.42%;

biomarker 13 of 17.19%;

biomarker 14 of 38.51%;

biomarker 15 of 136.37%;

biomarker 16 of 62.86%;

biomarker 17 of 29.56%;

biomarker 18 of 142.04%;

biomarker 19 of 58.12%;

biomarker 20 of 1743.66%;

biomarker 21 of 150.09%;

biomarker 22 of 4852.36%; and

biomarker 23 of 38.00%,

23. A composition comprising the following biomarkers:

biomarker 12 having an accurate mass of 461.147 amu and having a relative abundance of at most 3.42%;

biomarker 13 having an accurate mass of 108.0205 amu and having a relative abundance of at most 17.19%;

biomarker 14 having an accurate mass of 122.0493 amu and having a relative abundance of at most 38.51%;

biomarker 15 having an accurate mass of 129.0472 amu and having a relative abundance of at most 136.37%;

biomarker 16 having an accurate mass of 145.0747 amu and having a relative abundance of at most 62.86%; biomarker 17 having an accurate mass of 161.0718 amu and having a relative abundance of at most 29.56%;

biomarker 18 having an accurate mass of 165.0775 amu and having a relative abundance of at most 142.04%;

biomarker 19 having an accurate mass of 170.0243 amu and having a relative abundance of at most 58.12%;

biomarker 20 having an accurate mass of 174.0992 amu and having a relative abundance of at most 1743.66%;

biomarker 21 having an accurate mass of 180.0673 amu and having a relative abundance of at most 150.09%;

biomarker 22 having an accurate mass of 194.0804 amu and having a relative abundance of at most 4852.36%; and

biomarker 23 having an accurate mass of 211.0896 amu and having a relative abundance of at most 38.00%,

wherein the biomarkers are found in green tea, and

24. The composition of any of claims 21 to 23, wherein the mass of each biomarker is the mass as determined by a Direct Analysis in Real Time-TOF (DART-TOF) mass spectrometer.

25. The composition of any one of claims 21 to 24, wherein at least one of the biomarker(s) are synthetically obtained.

26. The composition of any one of claims 21 to 25, wherein at least one of the biomarker(s) are isolated from a plant.

27. The composition of claim 26, wherein at least one of the biomarkers(s) are isolated from green tea.

28. The composition of any one of claims 21 to 27, wherein the composition has an at least 90%, preferably at least 95%, or at least 98% batch-to-batch chemical consistency of relative abundance for the biomarkers.

29. The composition of any one of claims 21 to 28, wherein the composition further comprises a preservative.

30. The composition of any one of claims 21 to 29, wherein the composition further comprises salicylic acid.

31. The composition of claim 30, wherein the total salicylic acid of the composition is at least 1% by weight of the composition.

32. The composition of any one of claims 21 to 31, wherein the composition further comprises at least one antibacterial agent.

33. The composition of claim 32, wherein at least one antibacterial agent is rose oil.

34. The composition of any one of claims 21 to 33, wherein the composition is formulated for oral administration.

35. The composition of claim 34, wherein the composition is in a lozenge, a powder, a tablet, a gel-cap, a gelatin, a liquid solution, a syrup, an oil, and/or a dissolvable film.

36. The composition of any one of claims 21 to 35, wherein the composition is formulated for topical administration, administration through injection, and/or intranasal administration.

37. The composition of claim 36, wherein the composition is in a liquid solution, emulsion, powder, or patch.

38. The composition of any of claims 21 to 37, wherein the composition is formulated to treat and/or prevent a bacterial infection.

39. The composition of any of claims 21 to 38, wherein the composition is formulated to treat and/or prevent acne.

40. The composition of claim 39, wherein the composition is formulated to reduce acne lesions, reduce facial redness, and/or improve a global assessment of a subject.

41. A composition comprising a combination of a first composition comprising cranberry extract and a second composition comprising green tea extract, the composition formulated to be administered to a subject.

42. The composition of claim 41, wherein the cranberry extract is an aqueous extract and the green tea extract is an aqueous extract.

43. The composition of claim 42, wherein the first composition comprises any one of the compositions of claims 1 to 20.

44. The composition of claim 41, wherein the second composition comprises any one of the compositions of claims 21 to 40.

45. The composition of claim 44, wherein the first composition comprises any one of the compositions of claims 1 to 20 and the second composition comprises the composition of any of claims 21 to 40.

46. A kit comprising: a first composition comprising a cranberry extract formulated to be administered to a subject; and

a second composition comprising a green tea extract formulated to be administered to a subject.

47. The kit of claim 46, wherein the cranberry extract is an aqueous extract and the green tea extract is an aqueous extract.

48. The kit of claim 47, wherein the first composition comprises any one of the compositions of claims 1 to 20.

49. The kit of claim 48, wherein the second composition comprises any one of the compositions of claims 21 to 40.

50. The kit of claim 46, wherein the first composition comprises any one of the compositions of claims 1 to 20 and the second composition comprises any one of the compositions of claims 21 to 40.

51. A method of treating a subject at risk for or having a bacterial infection, the method comprising administering any one of the compositions of claims 1 to 45 to the subject, wherein at least one symptom of the bacterial infection is ameliorated in the subject and/or the onset of the bacterial infection is delayed in comparison to the expected onset of the bacterial infection if the patient had not been treated.

52. The method of claim 51, wherein the subject is treated for acne and wherein acne is treated and/or prevented.

53. The method of claim 52, wherein the subject is diagnosed as having acne.

54. The method of any one of claims 51 to 53, wherein the subject is administered a total amount of between 1 and 10,000 mg, between 10 and 5,000 mg, between 50 and 2,500 mg, or between 100 and 1,000 mg of the composition(s) during a 24 hour period.

55. The method of any one of claims 51 to 54, wherein at least one of the composition(s) is administered orally.

56. The method of any one of claims 51 to 55, wherein at least one of the composition(s) is administered topically.

57. The method of any one of claims 51 to 56, wherein any one of the compositions of claims 1 to 20 is administered and a composition comprising green tea extract is also administered.

58. The method of claim 57, wherein the green tea extract is an aqueous extract.

59. The method of claim 57, wherein the composition comprising green tea extract comprises the composition of any of claims 21 to 40.

60. The method of any one of claims 51 to 56, wherein any one of the compositions of claims 21 to 40 is administered and a composition comprising cranberry extract is also administered.

61. The method of claim 60, wherein the cranberry extract is an aqueous extract.

62. The method of claim 60, wherein the composition comprising cranberry extract comprises the composition of any of claims 1 to 20.

63. The method of any one of claims 51 to 56, wherein any one of the compositions of claims 41 to 45 is administered to the subject.

64. The method of any of claims 51 to 63, wherein the compositions of any one of the kits of claims 46 to 50 is administered to the subject.

65. The method of any of claims 51 to 64, wherein acne lesions are reduced, facial redness is reduced, and/or global assessment of a subject is improved.

66. A method of producing a composition of any of claims 1 to 45, wherein the method of producing produces a composition having an at least 90%, preferably at least 95% or at least 98% batch-to-batch chemical consistency of relative abundance for the biomarkers.