TECHNICAL FIELD This invention relates to antimicrobial compositions and manufacturing and application methods thereof.

BACKGROUND Public concern about the safety of synthetic, man-made ingredients or components used in personal care products, especially regarding their accumulation and subsequent heath effects, have driven health authorities to reduce the applied concentrations or even ban synthetic ingredients. Alternatives, such as plant substances, have become the focus of much research. Various consumer products, such as cosmetic products, soaps, cleaning products, other personal care products, and medical devices (hereafter also referred to as "products"), include more and more herbs as the demand from the conscious consumer increases for "natural" products that meet desired requirements.

However, such natural personal care products may be susceptible or prone to growth of harmful microbes and bacteria which can lead to user infection. Thus, natural antimicrobial compositions that are effective and may be utilized in personal care products are highly desirable.

DESCRIPTION

The present invention advantageously and surprisingly eliminates or reduces the above-mentioned shortcomings of prior products that may grow harmful microbes utilizing natural components to provide antimicrobial properties for personal care, medical, and/or household products.

Hydrophilic (i.e., water soluble) herbal or plant ingredients can be extracted by chemicals or water, and by various techniques, such as infusion, decoction, and maceration. A resultant liquid including extracted herbal or plant components is hereinafter referred to also as an "extract solution". Lipophilic (i.e., oil soluble) herbal or plant ingredients can be obtained either by pressing the necessary parts, mostly seeds, of the plant to obtain a fixed oil or by distilling out the essential oils of the desired parts, mostly leaves or flowers. An emulsion/dispersion of a fixed and/or essential oil in water (i.e., a fixed oil, an essential oil, or a combination of both) is hereinafter referred to also as an "oil dispersion".

Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping). An infusion is also the name for the resultant liquid or mixture including the solvent and the extracted plant material in the solvent. In one example, an infusion includes the use of simmering water, which is poured over chosen subject or target plants or herbs. The brew is covered for a few minutes to produce an infusion or an extract solution by infusion. In a further example, the heat will release essential oils which are valuable for their concentrated active principles.

Decoction is a method of extraction by boiling of dissolved chemicals from herbal or plant material, which may include stems, roots, bark and rhizomes. Decoction may include first mashing and then boiling the plant in water to extract the plant components or other chemical substances. Decoctions and infusions may produce liquids with differing chemical properties as there are temperature/preparation differences. In one example, a decoction includes putting the plant material in cold water and bringing the mixture to boil. Once the water comes to a boil, the mixture is removed from the heat and covered for a few minutes to produce a decoction or an extract solution by decoction.

Maceration involves extraction by solvent extraction. In one example, a maceration includes placing the plant material in a container of cold water for 24 hours or longer to steep and extracting the active principles to thereby produce a maceration or an extract solution by maceration. As used herein, the term "extract" refers to an active ingredient or fraction isolated from a plant by using a solvent or a solvent system. Also as used herein, the term "extract solution" refers to the solution of the extract solvated in the solvent. The extraction procedure for obtaining any of the plant extracts employed in accordance with the invention, unless otherwise indicated, may be carried out in various ways. For example, an herbal extract solution can be one of an infusion, a decoction, a maceration, or a product from another extraction technique performed on a subject plant by man. In yet another example, the plant parts can be crushed and/or milled and optionally dried before being contacted with the extraction solvent; the extraction can be assisted with shaking, agitating, and/or heating; the extraction can be microwave and/or ultrasound assisted; the solvent can be filtered and reduced under reduced pressure evaporation; the filtered solids may be re-extracted to yield a second crop; and so forth. In the alternatives set forth herein, a water extract of a saponin containing plant is employed as a solvent.

In accordance with one embodiment, an antimicrobial composition comprises: an herbal extract solution having soluble components of a subject plant solvated in an extraction medium, wherein the extraction medium has an antimicrobial property; a plant extract including a natural surface active material (e.g., a saponin component such as a plant extract containing saponin); and/or a cell permeabilizer.

In accordance with another embodiment, an antimicrobial composition comprises: an herbal extract solution having soluble components of a subject plant solvated in an extraction medium, wherein the extraction medium has an antimicrobial property, is between 40 wt% and 90 wt% of the composition, and includes a solvent selected from the group consisting of turpentine, vinegar, honey, and limonene; a soluble component from a saponin plant solvated in water; a cell permeabilizer between 0.1 wt% and 5 wt% of the composition and selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), carvacrol, fulvic acid, propolis, and a combination thereof; glycerin between 16 wt% and 90 wt% of the composition or glycerite between 24 wt% and 99 wt% of the composition; and a micelle inhibitor between 5 wt% and 80 wt% of the composition. In yet another embodiment, a product is provided comprising any of a composition as described in the various embodiments above. The product may be selected from the group consisting of a cosmetic, a preservative formulation, an antimicrobial formulation, a pharmaceutical composition, a medical device, and a disinfectant.

In accordance with yet another embodiment, a method for treating human skin comprises applying, to a skin surface, a suitable composition as described above.

In a further aspect, the invention provides an antimicrobial formulation comprising a composition as described in the various embodiments above. The antimicrobial formulation of the invention may be effective in reducing or eliminating a microorganism population or a biofilm of such microorganisms. According to some embodiments, the antimicrobial formulations of the invention are effective in reducing, inhibiting, eliminating, and/or preventing the growth of bacteria, fungi, yeast, and/or other microbes.

In a further aspect, the invention provides a therapeutic formulation (pharmaceutical composition) comprising a composition as described in the various embodiments above or a mixture of extracts thereof, as defined herein.

The pharmaceutical formulation of the invention may be effective in the treatment and/or prevention of a variety of diseases and disorders. The formulations of the invention may provide instant and/or persistent antimicrobial activity against a wide spectrum of microorganisms, as defined herein. In some embodiments, the disease or disorder to be treated is associated with bacterial infection, fungal infection, or viral infection.

In another aspect of the invention, there is provided the use of a formulation of the invention as herein defined, for the preparation of a pharmaceutical composition for treating or preventing a disease or disorder in a mammal (human or non-human). In some embodiments, the disease or disorder is associated with a bacteria, virus, fungus, yeast, or mold. As used herein, the term "treating" or "treatment" refers to the administering of a therapeutic amount of the composition of the present invention which is effective to ameliorate undesired symptoms associated with a disease, to prevent the manifestation of such symptoms before they occur, to slow down the progression of the disease, slow down the deterioration of symptoms, to enhance the onset of remission period, slow down the irreversible damage caused in the progressive chronic stage of the disease, to delay the onset of said progressive stage, to lessen the severity or cure the disease, to improve survival rate or more rapid recovery, or to prevent the disease from occurring, or a combination of two or more of the above.

The "effective amount" for purposes disclosed herein is determined by such considerations as may be known in the art. The amount must be effective to achieve the desired therapeutic effect as described above, depending, inter alia, on the type and severity of the disease to be treated and the treatment regime. The effective amount is typically determined in appropriately designed clinical trials (dose range studies) and the person versed in the art will know how to properly conduct such trials in order to determine the effective amount. As generally known, an effective amount depends on a variety of factors including the affinity of the ligand to the receptor, its distribution profile within the body, a variety of pharmacological parameters such as half life in the body, on undesired side effects, if any, and on factors such as age, gender, etc.

In yet another aspect, the invention provides a preservative formulation comprising a composition as described in the various embodiments above or a mixture of extracts thereof, as defined herein. The preservative formulation of the invention may be used to reduce, inhibit or completely eliminate pathogen population in a variety of consumer products, such as personal care products, industrial products, food products, therapeutics, and others. The formulation of the invention may be used to replace currently available chemicals which are used as preservatives, some of which are known as toxic to humans and animals, or to reduce their concentration in such products for human or animal use. The preservative formulation may be added to any such product, such as cosmetics and toiletries in aqueous or hydroalcoholic solution, oil-in-water or water-in-oil emulsion, aqueous or anhydrous gels, cream, ointment, lotion, gel, solution and suspension, therapeutics, and over-the-counter pharmaceutical products. The above compositions may have the following alternative components, which may also be combined in various applicable and functioning combinations within the scope of the present invention. The subject plant may be selected from the group consisting of: Quercus infectoria, Quercus pontica, Quercus robur robur, Quercus robur pedunculiflora, Quercus hartwissiana, Quercus macranthera syspirensis, Quercus frainetto, Quercus petraea petraea, Quercus petraea iberica, Quercus petraea pinnatiloba, Quercus vulcanica, Quercus infectoria boissieri, Quercus pubescens, Quercus virgiliana, Quercus cerris, Quercus cerris austriaca, Quercus ithaburensis macrolepis, Quercus brantii, Quercus libani, Quercus trojana, Quercus ilex, Quercus aucheri, Quercus coccifera, and a combination thereof.

The subject plant may also be a plant including salicylates and/or salicin, such as Betula lenta (sweet birch), Gaultheria procumbens (eastern teaberry or wintergreen), and Salix alba (white willowbark).

The herbal extract solution may be one of an infusion, a decoction, a maceration, or a product from another extraction technique performed on the subject plant by man.

The saponin plant may be selected from the group consisting of: Camellia sinensis, Styrax japonica, Acacia concinna, Acacia nilotica, Acorus calamus, Aesculus hippocastanum, Agave Americana, Ailanthus altissima, Akebia quinata, Albizia julibrissin, Aletris farinose, Aleurites fordii, Allium cepa, Allium drummondii, Allium fistulosum, Allium neapolitanum, Allium oleraceum, Allium ramosum, Allium sativum var. sativum, Allium schoenoprasum, Allium sphaerocephalon, Allium tricoccum, Allium tuberosum, Allium ursinum, Allium vineale, Anemone Pulsatilla, Arisaema consanguineum, Asparagus lucidus, Balanites aegyptiacus, Banisteriopsis caapi, Bupleurum falcatum, Calendula officinalis, Camellia oleifera, Capparis spinosa, Capsicum annuum, Castanospermum austral, Caulophyllum thalictroides, Centella asiatica, Ceratonia siliqua, Chrysophyllum cainito, Cissampelos pareira, Coix lacryma- jobi, Colocasia esculenta, Colubrina arborescens, Corchorus olitorius, Cymbopogon citrates, Desmodium, Dianthus caryophyllus, Dictamnus albus, Dioscorea bulbifera, Dodonaea viscose, Elytrigia repens, Eryngium foetidum, Glechoma hederacea, Guaiacum sp., Gypsophila acantholimoides, Gypsophila Achaia, Gypsophila acutifolia, Gypsophila adenophora, Gypsophila adenophylla, Gypsophila albida, Gypsophila altissima, Gypsophila antari, Gypsophila antoninae, Gypsophila arabica, Gypsophila aretioides, Gypsophila arrostii, Gypsophila aucheri, Gypsophila aulieatensis, Gypsophila australis, Gypsophila bicolor, Gypsophila capituliflora, Gypsophila cephalotes, Gypsophila cerastioides, Gypsophila davuhca, Gypsophila desertorum, Gypsophila elegans, Gypsophila fastigiata, Gypsophila glandulosa, Gypsophila glomerata, Gypsophila huashanensis, Gypsophila imbricate, Gypsophila intricate, Gypsophila iranica, Gypsophila krascheninnikovii, Gypsophila libanotica, Gypsophila licentiana, Gypsophila muralis, Gypsophila nana, Gypsophila oldhamiana, Gypsophila pacifica, Gypsophila paniculata, Gypsophila patrinii, Gypsophila perfoliata, Gypsophila petraea, Gypsophila pilosa, Gypsophila repens, Gypsophila rokejeka, Gypsophila ruscifolia, Gypsophila scorzonerifolia, Gypsophila sericea, Gypsophila silenoides, Gypsophila sp., Gypsophila spinosa, Gypsophila stevenii, Gypsophila struthium, Gypsophila tenui folia, Gypsophila tschi liens is, Gypsophila uralensis, Gypsophila venusta, Gypsophila viscose, Gypsophila wendelboi, Gypsophila wilhelminae, Gypsophila xanthochlora, Hibiscus sabdariffa, Hyacinthus orientalis, Hyacinthus orientalis, Hydrangea arborescens, Hypericum perforatum, Lagenaria siceraria, Leonurus cardiac, Lonicera japonica, Manilkara zapota, Medicago sativa, Melia azedarach, Menyanthes trifoliate, Ocimum basilicum, Origanum majorana, Panax japonicas, Panax quinquefolius, Panax quinqufolius, Paullinia cupana, Phragmites australis, Polygala tenuifolia, Portulaca oleracea, Quillaja saponaria, Rosa centifolia, Rosa gallica, Rosa laevigata, Ruscus aculeatus, Salvia officinalis, Sapindus delavayi, Sapindus marginatus, Sapindus mukorossi, Sapindus saponaria, Sapindus trifoliatus, Saponaria officinalis, Sida rhombifolia, Smilax spp, Solanum lycopersicum, Solanum melongena, Solanum nigrum, Taraxacum officinale, Terminalia bellirica, Teucrium chamaedrys, Teucrium marum, Teucrium montanum, Teucrium scordium, Tilia sp., Trigonella foenum-graecum, Vinca minor, Viola tricolor, Yucca schidigera, Zea mays, Zizyphus jujube, another plant including saponin, and a combination thereof. This group may be referred to as a saponin plant list.

The saponin plant is a natural plant which includes saponin that can be extracted into water, at least in part. Accordingly, in some embodiments of the invention, the saponin material is obtained by extraction from a plant source by employing water, and in some embodiments, alcohol, glycerin, a water/alcohol solution, or a water/glycerin solution may be used for extraction. The extraction time may vary without limitation from 1 to 8 hours, at or above room temperature (20Ό - 30Ό), e.g., above 30 , 40^3, 50 , 60 ^< C, or In some embodiments, the extraction is carried out at a temperature between 70 and 1

In some embodiments, the saponin material is obtained from a plant source. The plant source may be selected from the saponin plant list as described above or any mixture thereof. Any part of the plant may be used for extracting the saponin material, including leaves, stems, roots, bulbs, blossom and fruit (including the skin, flesh and seed of the fruit).

In other embodiments, the saponin-containing extract may be obtained from any natural source known to comprise saponins. Such a natural source may be a plant source, some of which are detailed infra, and also from non-plant sources such as marine organisms (e.g., starfish and sea cucumbers). In some embodiments of the invention, the saponins are extracted from a plant source, naturally grown or genetically modified to have high saponin content. The extraction medium may be one of an infusion, a decoction, a maceration, or a product from another extraction technique performed on the saponin plant by man. The extraction medium may be produced from an extraction technique on the saponin plant using 1 weight unit of the saponin plant to 5-10 weight units of water. In other embodiments, the extraction medium is between 30 wt% and 99 wt% of the composition and includes a solvent selected from the group consisting of turpentine, vinegar, honey, and limonene.

The composition may further comprise a film-forming biopolymer, wherein the biopolymer is between 10 wt% and 50 wt% of the composition. In one example, the film-forming biopolymer may be selected from the group consisting of chitosan, pullulan or other polysaccharides, galactomannans, Turkish tragacanth, locust bean gum or other gums, alginates, casein or caseinates, and a combination thereof. This group may be referred to as a biopolymer list. Advantageously, the film-forming biopolymer functions to form the composition as a film on the application surface, such as skin, to provide an increased length of time for the composition to be absorbed by the application surface. In one example, the cell permeabilizer is a cell wall permeabilizer or a cell membrane permeabilizer. In yet another example, the cell wall permeabilizer is between 0.1 wt% and 5 wt% of the composition and includes one of ethylenediaminetetraacetic acid (EDTA), carvacrol, fulvic acid, propolis, potassium alum, and a combination thereof. In yet another example, the cell membrane permeabilizer is between 0.1 wt% and 5 wt% of the composition and includes one of fulvic acid, hummic acid, piperidine, propolis, carvacrol, chitin, chitosan, and a combination thereof.

In one example, the composition may further comprise glycerin between 16 wt% and 90 wt% of the composition or glycerite between 24 wt% and 99 wt% of the composition. In one example, the glycerite is of a Quercus plant species.

In one example, the composition may further comprise a micelle inhibitor that increases a critical micelle concentration level. In yet another example, the micelle inhibitor includes an electrolyte or a polyelectrolyte. In yet another example, the electrolyte or the polyelectrolyte is fulvic acid, alum, or chitosan.

In one example, the composition may further comprise a rheology modifier, wherein the rheology modifier is selected from the group consisting of chitosan, pullulan or other polysaccharides, galactomannans, Turkish tragacanth, locust bean gum or other gums, alginates, casein or caseinates, starch, xantham gum, and a combination thereof.

In yet another example, the composition components may bre formed partially or wholly as a liposome. In yet another example, the subject plant, the extraction medium, the surface active material, and the cell permeabilizer are selected from among host proliferating ingredients. In accordance with other embodiments, an antimicrobial composition is disclosed, comprising:

1 ) A water-soluble plant ingredient with antibacterial and/or antifungal and/or antiviral effect, extracted by a solution that is not needed to be separated after extraction. On the contrary this solution is capable of boosting the antibacterial effect. Such a solution is: a- A plant distillate, ferment or solution that has its own antibacterial and/or antifungal and/or antiviral activity (eg turpentine, vinegar, d-limonen) (antimicrobial component) b-A water solution of a plant ingredient that contains surface active materials, facilitating the penetration of the actives into the microbial cells (eg licorice extract) (microbial cell penetration component) c- a water solution of glycerol that enhances extraction of a wider spectrum of more effective ingredients of plants (eg curcumin or gallnut in a 67% solution of glycerin in water) (extraction enhancer component).

2) The composition may also contain one or more of the following co-actives: a- cell wall permeabilizers or destructors that boost the effect of the antimicrobial components of plants (eg EDTA, carvacrol, fulvic acid) b- Lipophilic antimicrobial ingredients of plants that are applied together with natural plant extracts with surface active materials that achieve better dispersion of them into the water solution, thus increasing their effect (eg gypsophila extract) (dispersion enhancer component) c- Are partially or wholly liposomed for sustained release. d- Containing inactivators of inhibitors: using surface active material containing plants may cause an inhibitory effect for the active materials by forming micelles around them. This decreases the concentration of antimicrobial ingredients in water and thus their efficiency. Inclusion of an electrolyte/polyelectrolyte or other "salting in" additive, overcomes this inhibition by elevating the critical micelle concentration (CMC) levels.

3) A cosmetic, personal care, cleaning compound that contains one of the above.

4) A food product, a beverage or agricultural product that contains any of the above.

5) A topical or mucosal product be it a medical or veterinary product or a medical device, with such antimicrobial composition additionally containing a film forming biopolymer like chitosan, pullulan and the like. Also containing a rheology modifier.

6) The composition can be a water solution, a water emulsion/dispersion, dried form of any one of them, a self emulsifying dried composition or a solution in a non-water natural solvent as in 1 -a above.

In yet another embodiment, an antibacterial solution for treating wounds or other skin problems is provided. The composition terminates bacteria and is cytotoxic on cancer cells while having a positive effect on host cell viability. Advantageously and surprisingly, gallnut is effective against all kinds of bacteria and fungus but does not kill host cells. Instead, gallnut may feed or nourish the skin cells and proliferate the cells. Thus, a gallnut component may be good for anti-aging creams.

A further understanding of embodiments of the present invention can be obtained by reference to certain specific examples and tests of compositions in accordance with the present invention, which are now provided herein for purposes of illustration only and are not intended to be limiting of the present invention to these examples.

EXAMPLES

Antibacterial herbal ingredients extracted into synergetically effective antibacterial natural solvents

Anti-bacterial boosting effect of permeabilizers

Staphylococcus Escherichia

Extracts

aureus coli

Gallnut (70 brix) + 0.1 chitosan 2.87 2.40

Gallnut (70 brix) 2.53 2.13

Candida

Extracts Escherichia coli

albicans

Gallnut (70 brix) +0.2 Carvacrol 2.93 4.40

Gallnut (70 brix) 2.13 2.80

3. Surface active materials increase antibacterial effect

Staphylococcus Escherichia

Extracts

aureus coli

Soaproot (40%) : Gallnut (70 brix) = 1:2 0.76 3.06

Natural soap gel (40%) : Gallnut (70 brix)=l:2 0.8 2.8

Soaproot (40 brix) 0 0

Gallnut (70 brix) 0.7 0.93 It is noted that brix is the amount of substance other than water, such that a notation of 70 brix means 70% substance and 30% water.

Antimicrobials may not be effective because they often need to be dispersed in water. Also, antimicrobials are not effective with emulsifiers used in creams because of the formation of misceles around microbes. Advantageously, it is believed that cell wall permeabilizers allow for destruction of misceles and that adding saponin aids in dispersing the antimicrobial in water and also acts to wash away a microbe cell membrane, thus allowing an antimicrobial to be effective against microbes. Materials and procedure for example tests

PBS (LONZA), 0.25% Trypsin/EDTA (GIBCO), DMEM (GIBCO), FBS (GIBCO) PENICILLIN/STREPTOMYCIN (GIBCO), xCELLigence system (ACEA), 96 E-plate. Real Time Cell Analysis

The xCELLigence technology is an advanced real-time cell analysis (RTCA) system that allows monitoring of cell growth in real-time with the help of a label-free cell based assay that measures the variations of impedance occuring in the culture media. The microelectrodes that are equipped in the base of cell culture wells, determine and record the changes in the electronic impedance of cultured cells by their attached sensors. The plates that are equipped with microelectrodes, are special cell culture plates called E-Plates and based on the cell status, the measured electrical impedance is called CI. The electrode impedance is exhibited and set down as the CI value to exemplify the differences in cell number, adhesion degree, cellular morphology and viability.

Real Time Cell Analysis is a label free, impedance-based, real time assay. It provides continuous measurement for cells. HaCaT cell line was expanded in DMEM (GIBCO), 10% FBS (GIBCO) and subjected to tissue culture 96 E-Plate (5x10 ³ cells per well) that was used to generate dynamic real-time data with measuring electrical impedance across interdigitated micro-electrodes on the bottom of the plate. After 24 hrs, several compunds were prepared at various concentrations and applied to the E-plate. The results were followed at real time by the xCelligence system. ANALYSIS OF ANTIMICROBIAL ACTIVITY

Staphlococcus aureus®, Escherichia co , Pseudomonas aeruginosa, Candida albicans Antimicrobial analyzes were performed according to disk diffusion method. The production of microorganisms for studies and the process of transferring petri dishes carried out in the making of experiments is as follows:

Production of Microorganisms:

The antimicrobial properties of plant extracts were made according to the Kirby-Bauer Disk Diffusion test protocol. (Source: Hudzicki J. Kirby-Bauer disk diffusion susceptibility test protocol. American Society for Microbiology; Washington, DC: Dec 8, 2009)

In this test method, all the tested bacteria were replicated in an incubator at 37 ° C overnight by single colony plating. Then, 1 imL of liquid medium was added to a 2 imL eppendorf tube and bacteria were produced for 2 to 3 hours at 37 ° C in a shaking incubator for seeding. Concentrations of the bacteria for seeding were optimized according to the 0,10 - 0,5 Mc Farland measurement at 625 nm wavelength in the UV Spectrophotometer. This measure corresponds to a bacterial concentration of about 2x108 CFU / ml.

Inoculation:

The microorganisms produced in the liquid medium were seeded with the help of spreading technique on agar medium using a sterile inoculating cotton swab (Hudzicki, 2009). Then, the appropriate antimicrobial disks with a diameter of 6 mm were placed on the surface of the agar, using forceps to dispense each antimicrobial disk one at a time.

Reporting of the Experiment:

10 μί of each extract and antibiotic were added to the filter paper disc. The discs were seeded in culture at a known concentration by spreading with bacterial strains, ensuring that the extracts were absorbed. The disk placed petri dishes were incubated at 37 ° C. After 24 hrs, the diameter of the zone was measured (in centimeters). Products of Composition

In accordance with one embodiment, a product is provided comprising any of a composition as described in the various embodiments above. The product may be selected from the group consisting a preservative formulation, an antimicrobial formulation, a pharmaceutical composition, a cosmetic and a personal care product, a disinfectant, a food product, a beverage product, an agricultural product, a veterinary product, a medical product, and a medical device.

For example, the present invention provides a cosmetic or cleansing formulation comprising a composition as described in the various embodiments above. The cosmetic or cleansing formulations according to the invention are typically formulated in a form adapted for topical application comprising a cosmetically or dermatologically acceptable medium, namely a medium which is suitable for application onto the skin of a subject (human or non-human). The medium may be in the form of aqueous or hydroalcoholic solution, an oil-in-water or water-in-oil emulsion, a microemulsion, aqueous or anhydrous gels, serum, or else a dispersion of vesicles, a patch, cream, spray, salve, ointment, lotion, gel, solution, suspension, or any other known cosmetically acceptable form. The formulation may alternatively be formulated for application to the human skin (including mucosal regions via a mucous membrane or mucosa), hair, eyelashes, eyebrows, or nails.

In addition, the formulation may contain other additives such as an emollient, moisturizer, thickener, emulsifier, neutralize^ coloring agent, a fragrance, absorber or filter, and/or gelling agent, a sun screen agent (e.g., UV absorbing agents), electrolytes, proteins, antioxidants, anti-pollution additives and chelating agents.

The formulation may also further comprise at least one active ingredient such as peptide active ingredients, vegetable extracts, anti-age agents, anti-wrinkle agents, soothing agents, radical scavengers, UV absorbing agents, agents stimulating the synthesis of dermal macromolecules or the energy metabolism, hydrating agents, antibacterial agents, anti-fungal agents, anti-inflammatory agents, anesthetic agents, agents modulating cutaneous differentiation, pigmentation or de-pigmentation, agents stimulating nail or hair growth. In a further aspect, the antimicrobial formulation of the invention may be effective in reducing or eliminating a microorganism population or a biofilm of such microorganisms. According to some embodiments, the antimicrobial formulations of the invention are effective in reducing, inhibiting, eliminating, and/or preventing the growth of bacteria, fungi, yeast, viruses and/or other microbes. Such formulations may also contain cell wall permeabilizers for the targeted microbes selected from EDTA, Chitosan or other cationic surfactants. In a further aspect, the invention provides a therapeutic formulation (pharmaceutical composition) comprising a composition as described in the various embodiments above or a mixture of extracts thereof, as defined herein.

The pharmaceutical formulation of the invention may be effective in the treatment and/or prevention of a variety of diseases and disorders. The formulations of the invention may provide instant and persistent antimicrobial activity against a wide spectrum of microorganisms, as defined herein. In some embodiments, the disease or disorder to be treated is associated with bacterial infection, fungal infection, or viral infection.

In another aspect of the invention, there is provided the use of a formulation of the invention as herein defined, for the preparation of a pharmaceutical composition for treating or preventing a disease or disorder in a mammal (human or non-human). In some embodiments, the disease or disorder is associated with a bacteria, virus, fungus, yeast, or mold.

As used herein, the term "treatment" refers to the administering of a therapeutic amount of the composition of the present invention which is effective to ameliorate undesired symptoms associated with a disease, to prevent the manifestation of such symptoms before they occur, to slow down the progression of the disease, slow down the deterioration of symptoms, to enhance the onset of remission period, slow down the irreversible damage caused in the progressive chronic stage of the disease, to delay the onset of said progressive stage, to lessen the severity or cure the disease, to improve survival rate or more rapid recovery, or to prevent the disease from occurring, or a combination of two or more of the above.

The "effective amount" for purposes disclosed herein is determined by such considerations as may be known in the art. The amount must be effective to achieve the desired therapeutic effect as described above, depending, inter alia, on the type and severity of the disease to be treated and the treatment regime. The effective amount is typically determined in appropriately designed clinical trials (dose range studies) and the person versed in the art will know how to properly conduct such trials in order to determine the effective amount. As generally known, an effective amount depends on a variety of factors including the affinity of the ligand to the receptor, its distribution profile within the body, a variety of pharmacological parameters such as half life in the body, on undesired side effects, if any, on factors such as age, gender, etc. In yet another aspect, the invention provides a preservative formulation comprising a composition as described in the various embodiments above or a mixture of extracts thereof, as defined herein. The preservative formulation of the invention may be used to reduce, inhibit or completely eliminate pathogen population in a variety of consumer products, such as personal care products, industrial products, food products, therapeutics, and others. The formulation of the invention may be used to replace currently available chemicals which are used as preservatives, some of which known as toxic to humans and animals, or at reduce their concentration in such products for human or animal use. The preservative formulation may be added to any such product, such as cosmetics and toiletries in aqueous or hydroalcoholic solution, oil-in-water or water-in-oil emulsion, aqueous or anhydrous gels, cream, ointment, lotion, gel, solution and suspension; therapeutics and over-the-counter pharmaceutical products.

In accordance with one embodiment, a method for treating human skin is provided, the method comprising applying, to a skin surface, any of a composition as described in various embodiments above.

Although the present invention and disclosure are not limited to this theory, it is believed the extraction of natural ingredients is enhanced significantly by the permeabilization or rupture of cell walls and cell membranes by natural extraction enhancers of the present disclosure (extraction media including saponin). Cell rupture enhances extraction, and/or can enhance antibacterial, antiviral, and/or antifungal effects of a co-existing preservative by membrane rupture of pathogenic organisms. Advantageously, these natural extraction enhancers cause no or negligible negative effects in the targeted areas of the body. Extracted natural ingredients can be delivered into relevant levels of skin or other parts of the body by the employment of transdermals or cell membrane permeabilization agents that are called delivery agents. In the integrated method of the present disclosure, products that have both properties, as an extraction enhancer as well as a delivery agent, are employed. It is noted that the herbal extract infusion may be used without separation from herbal residue, or the herbal residue after physical filtering may be used without separation from the extraction medium. Furthermore, an herbal extract solution enables the incorporation of desired ingredients of plants into the product without the need for an external solvent and subsequent solvent removal.

The foregoing examples have been provided merely for the purpose of explanation and are in no way to be construed as limiting of the present invention. While the present invention has been disclosed with reference to embodiments, the words used herein are intended to be words of description and illustration, rather than words of limitation. While the present invention has been described with reference to particular materials and embodiments, the present invention is not intended to be limited to the particulars disclosed herein. Rather, the present invention extends to all functionally equivalent structures, materials, and uses, such as are within the scope of the appended claims. Changes may be made, within the purview of the appended claims, as presently stated and as may be amended, without departing from the scope and spirit of the present invention. All terms used in this disclosure should be interpreted in the broadest possible manner consistent with the context.