Background of the Invention

Like other species of the genus Candida, Candida albicans is a diploid fungus that grows both as yeast and filamentous cells. More specifically, C.albicans is a dimorphic fungus, which has both a yeast-like growth habit and a filamentous form consisting of both hyphae and pseudohypae. C. albicans exists as part of the normal microbial flora in humans, but can produce opportunistic infections ranging from topical infections such as oral thrush to life-threatening disseminated mycoses. In response to changes in its environment, C.albicans can transition from budding yeast to its filamentous morphology. The filamentous morphology is important for its virulence and causes both skin and mucosal infections. Quorum sensing has been identified as a phenomenon contributing to

C.a/b/cans'morphogenic transition from its conidial to filamentous form.

Quorum sensing systems have been found to coordinate virulence and biofilm development of pathogenic microorganisms. Manipulation of quorum sensing systems has been recently considered a promising strategy for developing antimicrobial agents since the manipulation of quorum sensing systems only inhibits the virulence but not the growth of microorganisms.

Generally, essential oils are volatile aromatic oils derived from plants through distillation. Essential oils have been found to act as a quorum sensing inhibitor to decrease the rate that C.albicans transitions from budding yeast to the filamentous form.Terpenes, such as sesquiterpenes (e.g., farnesol), are among the primary chemical constituents of most essential oils, and are derived from units of isoprene. This high terpenein essential oils may contribute to the ability to attenuate germ tube formation in C.albicans.

While essential oils are known to be environmentally friendly and effective in combating microorganisms, they nevertheless suffer from significant problems. For example, essential oils are highly volatile and unstable in the presence of oxygen, which ultimately limits their effectiveness in most applications in which wipes are commonly employed (e.g., food service wipes). Attempts to overcome this problem often involve the use of a larger amount of the essential oils to prolong antimicrobial activity. Regrettably, this often leads to another problem in that high concentrations of essential oils can cause damage to certain types of food products, such as fruit.

As such, a need currently exists for an improved formulation that is safe, stable, and capable of being used as a quorum sensing inhibitor of C. albicans in a practical manner.

Sum mary of the Invention

Methods are generally provided for adjusting the solubility of a botanical oil in water, along with the resulting modified botanical oil and related products (e.g., treatment compositions, wipes, absorbent articles, etc.). In one embodiment, the method includes reacting the botanical oil to form a reactive product (e.g., having a hydroxyl group); and attaching a hydrophilic end group (e.g., a carboxylic acid, a carboxylic acid salt, a sugar, etc.) on the reactive product to form a modified botanical oil. The modified botanical oil generally, in most embodiments, has a greater solubility in water than the botanical oil (e.g., a solubility in water of about 10 grams per 100 grams of water or greater, such as completely soluble in water). The botanical oil includes, in one particular embodiment, an essential oil, such as those essential oils that include at least one terpene compound.

Attaching the hydrophilic end group on the reactive product can be achieved by attaching a functional end group to the reactive product; andreacting the functional end group to form a hydrophilic end group on the reactive product. For example, reacting the botanical oil to form a reactive product can be achieved by reducing aldehyde groups within the botanical oil to form the hydroxyl group (e.g., via reaction of the botanical oil with an alcohol and a reducing agent, such as borohydride. As such, in one embodiment, the functional end group is a carboxylic acid end group, which may be attached to the reactive product via an ester and an alkane chain. Alternatively, attaching the functional end group to the reactive product can includereacting the hydroxyl group of the reactive product to a dicarboxylic acid (e.g., succinic acid). In yet another embodiment, the reactive product can include a carboxylic acid, which may be formed via oxidizing carbonyl groups within the botanical oil.

The modified botanical oil formed according to the method discussed above is also generally provided. For example, the modified botanical oil can include a botanical oil reduction product having a hydrophilic end group, wherein the modified botanical oil hasa solubility in water of about 10 grams per 100 grams of water or greater.

Wipes, such as webs formed from a plurality of fibers, are also generally provided, and can be coated with a treatment composition that includes such a modified botanical oil.

Absorbent articles are also generally provided that include a liquid

impermeable outer cover;a liquid permeable bodyside liner; an absorbent body disposed between the outer cover and bodyside liner; anda treatment composition applied to the bodyside liner. The treatment composition generally includes a modified botanical oil, as discussed above.

Other features and aspects of the present invention are discussed in greater detail below.

Brief Description of the Drawi ngs

A full and enabling disclosure of the present invention, including the best mode thereof, directed to one of ordinary skill in the art, is set forth more

particularly in the remainder of the specification, which makes reference to the appended figures in which:

Fig. 1 is a perspective view of an exemplary feminine care absorbent article; Fig. 2 is a cross-sectional view of the article of Fig. 1 taken along the lines indicated in Fig. 1 ;

Fig. 3 shows a graph of the growth and percentage of singlet cells of C. albicansSC53-\ 4 in YPD and mGSB broths incubated at 30° C according to the Examples;

Fig. 4 shows the effect of farnesol (100 μΜ) and tyrosol (100 μΜ) on the lag phase of C. albicansSC53 ^' \ 4 in YPD medium at 37 ^Q Caccording to the Examples; and

Fig. 5 shows a diagram for synthesized water soluble compounds from artemisa oil according to the Examples.

Repeat use of references characters in the present specification and drawings is intended to represent the same or analogous features or elements of the invention.

Detailed Description of Representative Embodi ments Reference now will be made in detail to various embodiments of the invention, one or more examples of which are set forth below. Each example is provided by way of explanation of the invention, not a limitation of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations may be made in the present invention without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment, may be used on another embodiment to yield a still further embodiment. Thus, it is intended that the present invention covers such

modifications and variations as come within the scope of the appended claims and their equivalents.

Methods are generally provided for modifying a botanical oil to be more hydrophilic, along with the resulting modified oil. Uses of such modified oils are also generally provided in a treatment composition (e.g., a lotion) and as an additive to a wipe and/or an absorbent article. In one particular embodiment, the modified oil can generally act as a quorum sensing inhibitor to decrease the rate that Candida albicans, and other species of the genus Candida, transitions from budding yeast to the filamentous form. Although referred to hereafter with respect to Candida albicans, the presently disclosed compositions, methods, and modified botanical oils are also applicable to other species of yeast within the genus

Candida (e.g., C. glabrata, C. rugosa, C. parapsilosis, C. tropicalis, C. dubliniensis, and C. oleophila).

Thus, the modified oil can serve as an inhibitor of infection by Candida albicans, and other species of the genus Candida, on the skin of the user, when applied within a lotion, via a wipe, or when included on an absorbent article in a manner that can contact or be in close proximity to the skin of the wearer.

I.Methods of Modifying a Botanical Oil

A. Botanical Oil

Botanical oils are generally employed as the starting material in the presently provided methods. Prior to modification, the botanical oils are generally soluble in lipids, but are not soluble in water. As used herein, the term "botanical oil" refers to oils extracted or derived from a plant, as well as synthetically prepared oils engineered to mimic the composition of an oilextracted or derived from a plant. Additionally, the term "botanical oil" is intended to encompass isolated

compositions and purified compositions extracted from such oils. In one embodiment, the botanical oil may be an "essential" oil, including thoseessential oils extracted from a plant or synthetically prepared. Likewise, the botanical oil may also be isolated or purified from an essential oil, or it may simply be made synthetically to mimic a compound derived from a plant (e.g.,

synthetically made thymol). Essential oils are derived from herbs, flowers, trees, and other plants, and are typically present as tiny droplets between the cells of the plants and may be extracted by methods known to those of skill in the art (e.g., steam distillation, enfleurage (i.e., extraction using fat(s)), maceration, solvent extraction, or mechanical pressing). Examples of suitable essential oils for use in the present invention may include, for instance, anise oil, artemisia oil, lemon oil, orange oil, oregano oil, rosemary oil, wintergreen oil, thyme oil, lavender oil, clove oil, hops oil, tea tree oil, citronella oil, wheat oil, barley oil, lemongrass oil, cedar leaf oil, cedar wood oil, cinnamon oil, fleagrass oil, geranium oil, sandalwood oil, violet oil, cranberry oil, eucalyptus oil, vervain oil, peppermint oil, gum benzoin oil, basil oil, fennel oil, fir oil, balsam oil, mint oil, ocmeaoriganum oil,

Hydastiscarradensis oil, Berberidaceaedaceae oil, Ratanhiae and Curcuma longa oil, sesame oil, macadamia nut oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, pimento berries oil, rose oil, bergamot oil, rosewood oil, chamomile oil, sage oil, clary sage oil, cypress oil, sea fennel oil, frankincense oil, ginger oil, grapefruit oil, grape seed oil, jasmine oil, juniper oil, lime oil, mandarin oil, marjoram oil, myrrh oil, neroli oil, patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine oil, rape seed oil, rose otto oil, spearmint oil, spikenard oil, vetiver oil, or ylangylang oil. Still other essential oils known to those of skill in the art are also contemplated as being useful within the context of the present invention.

As indicated above, isolates and/or derivatives of essential oils may also be employed as the botanical oil to be modified. Most particularly suitable botanical oils generally include a combination of different terpenes, such as monoterpenols (e.g., linalool, terpineol, borneol, iso-borneol, terpinen-4-ol, nerol, lavandulol, etc.), terpene esters (e.g., linalyl acetate, geranyl acetate, neryl acetate, octane-3-l acetate, lavandulyl acetate, etc.), monoterpenes (e.g., myrcene, pinene, camphene, ocimene, phellandrene, etc.), terpenoid oxides (e.g., eucalyptol), sesquiterpenes (e.g., caryophyllene, farnesene, germacrene, humulene, etc.), ketones (e.g., camphor, octanone-3, cryptone, etc.), and the like. Most of these compounds define at least one chemical group that can be formed into a reactive species (e.g., via a reduction reaction, an oxidation reaction, etc.). For example, these compounds can define a hydroxyl group, a carbonyl group (e.g., an aldehyde end group), or a carboxylic acid group.

For example, botanical oils that include monoterpene phenols are suitable for use in particular embodiments of the present invention. The monoterpene phenols may be isolated and purified from plant oil extracts, or made synthetically by known methods. Thymol (isopropyl-cresol) is one particularly suitable monoterpene phenol, which is a crystalline substance that has a boiling point of about 238 °C at atmospheric pressure. Carvacrol (isopropyl-o-cresol), an isomer of thymol, is another suitable compound. Carvacrol is a liquid with a boiling point of about 233 °C at atmospheric pressure. Thymol and carvacrol, as well as isomers thereof, may be derived from plant oil extracts or synthesized. For example, carvacrol may be synthesized by the reaction of nitrous acid with 1 -methyl-2- amino-4-propyl benzene.

In addition to being employed in an isolated or pre-synthesized form, botanical oils (and particularly essential oils) containing the monoterpene phenols as major constituents may be employed, with the final concentrations of the monoterpene phenols being within the ranges provided herein. The term "major constituent" in this context generally refers to those essential oils having

monoterpene phenols in an amount of more than 50 wt.%.

Particularly suitable essential oils may also contain other constituents, such as non-aromatic terpene compounds. In one particular embodiment, the botanical oil includes a non-aromatic terpene compounds in an amount of about 10 wt. % to about 75 wt. %. Without wishing to be bound by any particular theory, it is believed that such non-aromatic terpene compounds can serve as a quorum sensing inhibitor to decrease the rate that Candida albicans transitions from budding yeast to the filamentous form.

B. Reacting the Botanical Oil to Form a Reactive Product

The botanical oil can be reacted to form a more reactive product. For example, the botanical oil can be subjected to a reduction reaction or an oxidation reaction. According to this reaction, the resulting reactive product can include a more uniform reactive end group, such as an hydroxyl group or acid group, across the components of the reactive product. For example, at least about 50% by weight of the components of the reactive product formed from the botanical oil can include the reactive end group.

In one particular embodiment, carbonyl groups (e.g., aldehyde groups) on the components of the botanical oilcan be reacted to form hydroxyl end groups via a reduction reaction or carboxylic acid end groups via an oxidation reaction.

In one particular embodiment, a reduction reaction can be utilized to reduce the carbonyl groups on the components of the botanical oil(e.g., aldehyde groups) to hydroxyl groups (-OH). In such reduction reactions, a reducing agent transfers electrons to another substance; i.e., it reduces others, and is thus itself oxidized. Because it "donates" electrons, it is also called an electron donor. Electron donors can also form charge transfer complexes with electron acceptors.One particularly suitable class of reducing agents include hydride transfer reagents, such as NaBH ₄ and LiAIH ₄ , which primarily result in the reduction of carbonyl compounds to alcohols. For example, a reduction reaction that reacts an alkyl alcohol (e.g., methanol, ethanol, propanol, etc.)with a reducing agent can be utilized to convert the carbonyl group to a hydroxyl group. Such reducing agentsare particularly suitable for forming a reactive product from the botanical oil, since such a reducing agent does not substantially attack any carbon-carbon double bonds in the chain of the components of the botanical oil.

For example, monoterpenols, sesquiterpenes, and ketones generally react with NaBH and/or with LiAIH to form a hydroxyl group from the carbonyl group. Similarly, terpene esters can generally react with LiAIH ₄ to form a hydroxyl group from the carbonyl group. The carbonyl group on monoterpenes can be converted to a hydroxyl group by reaction via an oxymercuration reaction (e.g., mercuric acetate and NaBH ₄ ), via a strong acid catalysis, or via reaction with BH ₃ + H ₂ 0 ₂ . Epoxides, such as terpenoid oxides, can be converted to alcohols having a hydroxyl group via mild acid cleavage, mild base cleavage, or through reaction with Grignard reagents.

Other reagents can also be used to to reduce carbonyl groups to hydroxyl groups, such as DIBAL-H (diisobutylaluminum hydride) or lithium tri-tert- butoxyaluminum hydride, reduction by sodium metal in alcohol solvent, hydrogenation over catalysts (e.g., CuCr ₂ 0 ₄ ), Grignard reagents, etc.

According to these reduction reactions, at least about 50% by weight of the components of the reactive product formed through reduction of the botanical oil can define an hydroxylend group, such as at least about 75% by weight of the

components.

Alternatively, an oxidation reaction can be utilized to oxidize the carbonyl groups on the components of the botanical oil (e.g., aldehyde groups) to carboxylic acids(-COOH).AIcohols can be oxidized by KMn0 ₄ and OH ^" , concentrated HNO ₃ , Chromic acid, or CrO ₃ and pyridine. Aldehydes andketones can be oxidized with KMnO ₄ and an acid, dichromate, silver(l) and copper(l) solutions such as the Tollens reagent. Alkenes (monoterpenes&sesquiterpenes) can be oxidized with more stringent conditions such as KMnO ₄ and acid and heat or H ₂ CrO ₄ .

According to these oxidation reactions, at least about 50% by weight of the components of the reactive product formed through oxidation of the botanical oil can define a carboxylic acid end group, such as at least about 75% by weight of the components.

C. Attaching a Functional End Group to the Reactive Product

In one embodiment, a functional end group can be attached to the

components of the reactive product, since the same reactive end group is present on at least a majority of the components of the reactive product. For example, in embodiments where the reactive product includes an hydroxylend group (i.e., the reactive product is an alcohol)across a majority of the components of the reactive product, a carboxylic acid functional molecule can be reacted with the hydroxylend group through an esterification reaction. In addition to the carboxylic group, the carboxylic acid functional molecule can also include a functional end group (e.g., a second carboxylic acid end group, a halide end group, etc.). As such, following the esterification reaction, the functional end group is covalently attached to the components of the reactive product via an ester group and optionally an alkane chain (e.g., having 1 to about 8 carbon atoms).

In one particular embodiment, the carboxylic acid functional molecule is a dicarboxylic acid, such asoxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, tartaric acid, etc. As such, following the

esterification reaction, a carboxylic acid functional group is covalently attached to the components of the reactive product via an ester group and an alkane chain (e.g., having 1 to about 8 carbon atoms).

In embodiments where the reactive product includes a carboxylic acid end group across a majority of the components of the reactive product, an alcohol functional molecule can be reacted with the carboxylic acid end group through an esterification reaction. In one embodiment, the alcohol functional molecule can be a hydroxy acid that includes both ahydroxyl end group and a carboxylic acid end group. In such an embodiment, following the esterification reaction, a carboxylic acid functional group is covalently attached to the components of the reactive product via an ester group and an alkane chain (e.g., having 1 to about 8 carbon atoms).

D. Attaching a Hydrophilic End Group to the Reactive Product

A hydrophilic end group can then be attachedto the reactive product. For example, in embodiments where a functional end group has been attached to the reactive product, the functional end group can be reacted to form a hydrophilic end group on the reactive product. Suitable hydrophilic end groups can be attached according to any reaction.

In one particular embodiment, the hydrophilic end group can include a carboxylic acid salt (e.g., -COO ^" M ⁺ , where M is a cation such as Na ⁺ , K ⁺ , etc.). In an alternative embodiment, the hydrophilic end group can include a sugar. For example, the sugar can be a monosaccharide end group (e.g., glucose, fructose, galactose, xylose, ribose, etc) or a disaccharide end group (e.g., sucrose).

E. Modified Botanical Oil

According to these methods, a modified botanical oil is formed that is soluble in water.By adding the polar, hydrophilic end groups, the modified botanical oil becomes much more like a non-ionic surfactant comprised of a hydrophobic tail and a hydrophilic head group (the added end group). With this chemical structure, the modified botanical oil is prone to acting like a surface active agent (surfactant) and can thusly organize in micelles, bilayers, or any of the other known surfactant phases. While the modified oil is generally water soluble, micelles may form in the water solution. However, no separate phase is detected in the solution.

For example, the modified botanical oil can have a solubility in water of about 10 grams per 100 grams of water or greater. In one particular embodiment, the modified botanical oil includes abotanical oil reduction product having a hydrophilic end group, as discussed above.

In one embodiment, the hydrophilic end group contains at least one hydroxyl group (-OH) along the chain. Additionally, the hydrophilic end group can be attached via at least one ester linkage. Without wishing to be bound by any particular theory, it is believed that the presence of polar groups, such as hydroxyl group(s) and/or ester linkage(s), increases the solubility of the modified botanical oil in water.

When applied to C. albicans, the modified botanical oil can, in certain embodiments, have a percentage of cells with germ tubes formed (GTF%) of less than about 50%, such as less than about 25%.

Il.Treatment Composition

The modified botanical oil can be included within a treatment composition, which can be, for example, applied to the skin of a user. For example, the treatment composition may be administered to the skin of the user in a variety of forms, such as a lotion, cream, jelly, liniment, ointment, salve, oil, foam, gel, film, wash, coating, liquid, capsule, tablet, concentrate, etc.

The manner in which the treatment composition is formed may vary as is known to those skilled in the art. In one embodiment, for example, the modified botanical oil may be initially blended with a solvent, such as water and/or an organic solvent. Organic solvents can be present, such as alcohols, such as methanol, ethanol, n-propanol, isopropanol, butanol, and so forth; triglycerides; ketones (e.g., acetone, methyl ethyl ketone, and methyl isobutyl ketone); esters

(e.g., ethyl acetate, butyl acetate, diethylene glycol ether acetate, and

methoxypropyl acetate); amides (e.g., dimethylformamide, dimethylacetamide, dimethylcaprylic/capric fatty acid amide and N-alkylpyrrolidones); nitriles (e.g., acetonitrile, propionitrile, butyronitrile and benzonitrile); sulfoxides or sulfones (e.g., dimethyl sulfoxide (DMSO) and sulfolane); and so forth. The combination of the ingredients may be facilitated through agitation (e.g., stirring) and control of the temperatures of each mixture. Conventional homogenization techniques may, for instance, be employed to stabilize the treatment composition.

The resulting treatment composition may contain a discontinuous oil phase dispersed within a continuous solvent phase. Nevertheless, due to the stability imparted by the hydrophilic end group on the modified botanical oil, a relatively small amount of botanical oils may be employed and still achieve the desired quorum sensing inhibition of C. albicans. More particularly, the coating solution may employ modified botanical oils in an amount of from about 0.01 wt.% to about 15 wt.%, in some embodiments from about 0.05wt.% to about 10 wt.%, and in some embodiments, from about 0.1 wt.% to about 5 wt.%. For example, in one particular embodiment, the coating solution may employ modified botanical oils in a relatively small amount, while still achieving the desired quorum sensing inhibition, such as inan amount of from about 0.01 wt.% to about 1 wt.% (e.g., about 0.05 wt. % to about 0.5 wt. %).

Other additives may also be incorporated into the treatment composition. For example, the composition may contain a preservative or preservative system to inhibit the growth of microorganisms over an extended period of time. Suitable preservatives may include, for instance, alkanols, disodium EDTA

(ethylenediaminetetraacetic acid), EDTA salts, EDTA fatty acid conjugates, isothiazolinone, phenoxyethanol, phenethyl alcohol, caprylyl glycol, 1 ,2-hexanediol, benzoic esters (parabens) (e.g., methylparaben, propylparaben, butylparaben, ethylparaben, isopropylparaben, isobutylparaben, benzylparaben, sodium

methylparaben, and sodium propylparaben), benzoic acid, propylene glycols, sorbates, urea derivatives (e.g., diazolindinyl urea), and so forth. Other suitable preservatives include those sold by Sutton Labs, such as "Germall 1 15"

(amidazolidinyl urea), "Germall II" (diazolidinyl urea), and "Germall Plus"

(diazolidinyl urea and iodopropynylbutylcarbonate). Another suitable preservative is Kathon CG®, which is a mixture of methylchloroisothiazolinone and

methylisothiazolinone available from Dow Chemical; Mackstat H 66 (available from Rhodia, part of the Solvay Group). Still another suitable preservative system is a combination of 56% propylene glycol, 30% diazolidinyl urea, 1 1 % methylparaben, and 3% propylparaben available under the name GERMABEN® II from Ashland.

The pH of the composition may also be controlled within a range that is considered more biocompatible. For instance, it is typically desired that the pH is within a range of from about 3 to about 9, in some embodiments from about 4 to about 8, and in some embodiments, from about 5 to about 7. Various pH modifiers may be utilized in the composition to achieve the desired pH level. Some examples of pH modifiers that may be used in the present invention include, but are not limited to, mineral acids, sulfonic acids (e.g., 2-[N-morpholino] ethane sulfonic acid), carboxylic acids, and polymeric acids. Specific examples of suitable mineral acids are hydrochloric acid, nitric acid, phosphoric acid, and sulfuric acid. Specific examples of suitable carboxylic acids are lactic acid, acetic acid, citric acid, glycolic acid, maleic acid, gallic acid, malic acid, succinic acid, glutaric acid, benzoic acid, malonic acid, salicylic acid, gluconic acid, and mixtures thereof.

Specific examples of suitable polymeric acids include straight-chain poly(acrylic) acid and its copolymers (e.g., maleic-acrylic, sulfonic-acrylic, and styrene-acrylic copolymers), cross-linked polyacrylic acids having a molecular weight of less than about 250,000, poly(methacrylic) acid, and naturally occurring polymeric acids such as carageenic acid, carboxymethyl cellulose, and alginic acid. Basic pH modifiers may also be used in some embodiments of the present invention to provide a higher pH value. Suitable pH modifiers may include, but are not limited to, ammonia; mono-, di-, and tri-alkyl amines; mono-, di-, and tri-alkanolamines; alkali metal and alkaline earth metal hydroxides; alkali metal and alkaline earth metal silicates; and mixtures thereof. Specific examples of basic pH modifiers are ammonia; sodium, potassium, and lithium hydroxide; sodium, potassium, and lithium metasilicates; monoethanolamine; triethylamine; isopropanolamine;

diethanolamine; and triethanolamine. When utilized, the pH modifier may be present in any effective amount needed to achieve the desired pH level.

To better enhance the benefits to consumers, other optional ingredients may also be used. For instance, some classes of ingredients that may be used include, but are not limited to: antioxidants (product integrity); anti-reddening agents, such as aloe extract; astringents-cosmetic (induce a tightening or tingling sensation on skin); colorants (impart color to the product); deodorants (reduce or eliminate unpleasant odor and protect against the formation of malodor on body surfaces, by, for example, absorption, adsorption, or masking); fragrances

(consumer appeal); opacifiers (reduce the clarity or transparent appearance of the product); skin conditioning agents; skin exfoliating agents (ingredients that increase the rate of skin cell turnover such as alpha hydroxy acids and beta hydroxyacids); skin protectants (a drug product which protects injured or exposed skin or mucous membrane surface from harmful or annoying stimuli); and viscosity modifiers (e.g., thickeners to increase viscosity).

Ill.Wipe

In one embodiment, the treatment composition can be applied to a wipe prior to use. Such wipes may be used to reduce microbial or viral populations on a hard surface (e.g., sink, table, counter, sign, and so forth) or surface on a user/patient (e.g., skin, mucosal membrane, such as in the mouth, nasal passage, stomach, vagina, the areasurrounding the vaginal opening, etc., wound site, surgical site, and so forth). The wipe may provide an increased surface area to facilitate contact of the composition with microorganisms. In addition, the wipe may also serve other purposes, such as providing water absorption, barrier properties, etc. The wipe may also eliminate microorganisms through shear forces imparted to the surface.

The wipe may be formed from any of a variety of materials as is well known in the art. For example, the wipe can include a nonwoven fabric, woven fabric, knit fabric, wet-strength paper, or combinations/laminates thereof. Materials and processes suitable for forming such substrate are well known to those skilled in the art. For instance, some examples of nonwoven fabrics that may be used as the wipe in the present disclosure include, but are not limited to, spunbonded webs (apertured or non-apertured), meltblown webs, bonded carded webs, air-laid webs, coform webs, hydraulically entangled webs, and the like. In addition, nonwoven fabrics can contain synthetic fibers (e.g., polyethylenes, polypropylenes, polyvinyl chlorides, polyvinylidene chlorides, polystyrenes, polyesters, polyamides, polyimides, etc.); cellulosic fibers (softwood pulp, hardwood pulp,

thermomechanical pulp, etc.); or combinations thereof.

In one particular embodiment, the wipe includes a fibrous web that contains absorbent fibers. For example, the wipe may be a cellulose based paper product containing one or more paper webs, such as facial tissue, bath tissue, paper towels, napkins, and so forth. The paper product may be single-ply in which the web forming the product includes a single layer or is stratified (i.e., has multiple layers), or multi-ply, in which the webs forming the product may themselves be either single or multi-layered. Normally, the basis weight of such a paper product is less than about 120 grams per square meter ("gsm"), in some embodiments less than about 80 gsm, in some embodiments less than about 60gsm, and in some embodiments, from about 10 to about 60 gsm.

Any of a variety of materials can also be used to form the paper web(s) of the product. For example, the material used to make the paper product may include absorbent fibers formed by a variety of pulping processes, such as kraft pulp, sulfite pulp, thermomechanical pulp, etc. The pulp fibers may include softwood fibers having an average fiber length of greater than 1 mm and

particularly from about 2 to 5 mm based on a length-weighted average. Such softwood fibers can include, but are not limited to, northern softwood, southern softwood, redwood, red cedar, hemlock, pine (e.g., southern pines), spruce (e.g., black spruce), combinations thereof, and so forth. Hardwood fibers, such as eucalyptus, maple, birch, aspen, and so forth, can also be used. In certain instances, eucalyptus fibers may be particularly desired to increase the softness of the web. Eucalyptus fibers can also enhance the brightness, increase the opacity, and change the pore structure of the web to increase its wicking ability. Moreover, if desired, secondary fibers obtained from recycled materials may be used, such as fiber pulp from sources such as, for example, newsprint, reclaimed paperboard, and office waste. Further, other natural fibers can also be used in the present invention, such as abaca, sabai grass, milkweed floss, pineapple leaf, bamboo, algae, and so forth. In addition, in some instances, synthetic fibers can also be utilized.

If desired, the absorbent fibers (e.g., pulp fibers) may be integrated with synthetic fibers to form a composite. Synthetic thermoplastic fibers may also be employed in the nonwoven web, such as those formed from polyolefins, e.g., polyethylene, polypropylene, polybutylene, etc. ; polytetrafluoroethylene; polyesters, e.g., polyethylene terephthalate and so forth; polyvinyl acetate; polyvinyl chloride acetate; polyvinyl butyral; acrylic resins, e.g., polyacrylate, polymethylacrylate, polymethylmethacrylate, and so forth; polyamides, e.g., nylon; polyvinyl chloride; polyvinylidene chloride; polystyrene; polyvinyl alcohol; polyurethanes; polylactic acid; polyhydroxyalkanoate; copolymers thereof; and so forth. Because many synthetic thermoplastic fibers are inherently hydrophobic (i.e., non-wettable), such fibers may optionally be rendered more hydrophilic (i.e., wettable) by treatment with a surfactant solution before, during, and/or after web formation. Other known methods for increasing wettability may also be employed, such as described in U.S. Patent No. 5,057,361 to Savovitz, et al., which is incorporated herein by reference. The relative percentages of such fibers may vary over a wide range depending on the desired characteristics of the composite. For example, the composite may contain from about 1 wt.% to about 60 wt.%, in some embodiments from 5 wt.% to about 50 wt.%, and in some embodiments, from about 10 wt.% to about 40 wt.% synthetic polymeric fibers. The composite may likewise contain from about 40 wt.% to about 99 wt.%, in some embodiments from 50 wt.% to about 95 wt.%, and in some embodiments, from about 60 wt.% to about 90 wt.% absorbent fibers.

Composites, such as described above, may be formed using a variety of known techniques. For example, a nonwoven composite may be formed that is a "coform material" that contains a mixture or stabilized matrix of thermoplastic fibers and a second non-thermoplastic material. As an example, coform materials may be made by a process in which at least one meltblown die head is arranged near a chute through which other materials are added to the web while it is forming. Such other materials may include, but are not limited to, fibrous organic materials such as woody or non-woody pulp such as cotton, rayon, recycled paper, pulp fluff and also superabsorbent particles, inorganic and/or organic absorbent materials, treated polymeric staple fibers and so forth. Some examples of such coform materials are disclosed in U.S. Patent Nos. 4,100,324 to Anderson, et al. ;

5,284,703 to Everhart, et al. ; and 5,350,624 to Georqer, et al. ; which are

incorporated herein by reference. Alternatively, the nonwoven composite may be formed by hydraulically entangling staple length fibers and/or filaments with high- pressure jet streams of water. Various techniques for hydraulically entangling fibers are generally disclosed, for example, in U.S. Patent Nos. 3,494,821 to Evans and 4,144,370 to Boulton, which are incorporated herein by reference.

Hydraulically entangled nonwoven composites of continuous filaments (e.g., spunbond web) and natural fibers (e.g., pulp) are disclosed, for example, in U.S. Patent Nos. 5,284,703 to Everhart, et al. and 6,315,864 to Anderson, et al.. which are incorporated herein by reference. Hydraulically entangled nonwoven composites of staple fiber blends (e.g., polyester and rayon) and natural fibers (e.g., pulp), also known as "spunlaced" fabrics, are described, for example, in U.S. Patent No. 5,240,764 to Haid, et al., which is incorporated herein by reference.

Regardless of the materials or processes utilized to form the wipe, the basis weight of the wipe is typically from about 20 to about 200 gsm, and in some embodiments, between about 35 to about 100 gsm. Lower basis weight products may be particularly well suited for use as light duty wipes, while higher basis weight products may be better adapted for use as industrial wipes.

The wipe may assume a variety of shapes, including but not limited to, generally circular, oval, square, rectangular, or irregularly shaped. Each individual wipe may be arranged in a folded configuration and stacked one on top of the other to provide a stack of wet wipes. Such folded configurations are well known to those skilled in the art and include c-folded, z-folded, quarter-folded

configurations and so forth. For example, the wipe may have an unfolded length of from about 2.0 to about 80.0 centimeters, and in some embodiments, from about 10.0 to about 25.0 centimeters. The wipes may likewise have an unfolded width of from about 2.0 to about 80.0 centimeters, and in some embodiments, from about 10.0 to about 25.0 centimeters. The stack of folded wipes may be placed in the interior of a container, such as a plastic tub, to provide a package of wipes for eventual sale to the consumer. Alternatively, the wipes may include a continuous strip of material which has perforations between each wipe and which may be arranged in a stack or wound into a roll for dispensing. Various suitable

dispensers, containers, and systems for delivering wipes are described in U.S. Patent Nos. 5,785,179 to Buczwinski, et al.: 5,964,351 to Zander; 6,030,331 to

Zander; 6,158,614 to Havnes. et al. : 6,269,969 to Huang, et al. : 6,269,970 to

Huang, et al. ; and 6,273,359 to Newman, et al.. which are incorporated herein by reference.

The treatment composition may be impregnated into the wipe during its formation or simply coated onto all or a portion of a surface of the wipe using known techniques, such as printing, dipping, spraying, melt extruding, coating (e.g., solvent coating, powder coating, brush coating, etc.), foaming, and so forth. Due to the increased solubility in water, the modified botanical oil allows the treatment composition to be more compatible for application to the wipe using such

conventional coating techniques.

In one embodiment, for example, the coating is applied to the wipe by dipping, spraying, or printing. In one embodiment, a benefit can be achieved by applying the treatment composition in a film-like pattern that is discontinuous over the surface of the wipe. The pattern may, for example, cover only from about 5% to about 95%, in some embodiments from about 10% to about 90%, and in some embodiments, from about 20% to about 75% of a surface of the wipe. Such patterned application may have various benefits, including enhanced softness and drape, improved absorbency, etc.

If desired, the wipe may be dried at a certain temperature to drive the solvents from the solution and form a concentrate. Such concentrates generally have a very high stability in storage. To use the wipe, water or an aqueous solution may simply be added, thereby releasing the botanical oil and optionally re- emulsifying the concentrate. Drying may be accomplished using any known technique, such as an oven, drying rolls (e.g., through-air drying, Yankee dryer), etc. The temperature at which the wipe is dried generally depends on the time period over which it is dried, but is typically at least about 20°C, and in some embodiments, from about 30 °C to about 100°C. Drying may occur either before or after the solution is applied to the wipe. The solvent content of the resulting concentrate is thus typically less than about 5 wt.%, in some embodiments less than about 2 wt.%, and in some embodiments, less about 1 wt.%.

The solids add-on level of the treatment composition is typically from about 2to about 100%, in some embodiments from about 10% to about 80%, and in some embodiments, from about 15% to about 70%. The "solids add-on level" is determined by subtracting the weight of the untreated substrate from the weight of the treated substrate (after drying), dividing this calculated weight by the weight of the untreated substrate, and then multiplying by 100%. Lower add-on levels may provide optimum functionality of the substrate, while higher add-on levels may provide optimum antimicrobial efficacy. In such embodiments, the treatment composition typically contains modified botanical oils in an amount of from about 0.05 wt.% to about 50 wt.%, in some embodiments from about 1 wt.% to about 40 wt.%, and in some embodiments, from about 5 wt.% to about 30 wt.%.

In addition to being employed as a treatment composition, the modified botanical oil may also be in the form of a liquid. This may be accomplished by simply not drying the solution after it is applied to the wipe. While the solids addon level of such "wet wipes" generally remain within the ranges noted above, the total amount of the solution employed in such "wet wipes" (including any solvents) depends in part upon the type of wipe material utilized, the type of container used to store the wipes, the nature of the solution, and the desired end use of the wipes. Generally, however, each wet wipe contains from about 150 wt.% to about 600 wt.%, and desirably from about 300 wt.% to about 500 wt.% of the solution on the dry weight of the wipe.

In one embodiment, the liquid component of the wet wipe may include water, a surfactant or surfactant system, a preservative, an optional pH modifier (e.g., buffering agent), and the modified botanical oil. For instance, the liquid component can be at least 95% by weight water (e.g., about 97.5% to about 99% by weight), about 0.25 to about 1 .5 % by weight of a surfactant(s) (e.g., sodium lauryl glucose carboxylate, lauryl glucoside, sodium lauroylsarcosinate, a polysorbate surfactant such as polysorbate 20, or combinations thereof), about 0.05% to about 1 .0% by weight of a preservative(s) (e.g., methylisothiazolinone, sodium benzoate, or mixtures thereof), up to about 1 .5% by weight of an pH modifier (e.g., malic acid), and up to about 2.5% by weight of the modified botanical oil (e.g., about 0.01 % by weight to about 0.5 % by weight).

The present inventors have discovered that the treatment composition including the modified botanical oil may inhibit (e.g., reduce by a measurable amount or to prevent entirely) transition of Candida albicans from budding yeast to the filamentous form by serving as a quorum sensing inhibitor.

IV.Absorbent Articles

Referring to Figs. 1 and 2, a typical feminine care absorbent article 10, such as a pad or liner, is shown. The article 10 includes longitudinal ends 24 and 26 and opposed longitudinal sides 28 and 30, and is designed to extend through the wearer's crotch region between the legsupon the inside surface of an

undergarment. Fig. 2 is a cut-away view of the article 10. In this view, it can be seen that the article 10 includes a substantially liquid impermeable outer cover 12, and an absorbent structure in superposed relation to the outer cover 12. The absorbent structure may include various layers and/or components. The topmost component defines a bodyfacing surface 1 6 that is disposed against the wearer's skin. In the illustrated embodiment, the absorbent structure includes a porous, liquid permeable bodyside liner 14 defining the bodyfacing surface 16, and an absorbent body 18, such as an absorbent pad, disposed between the outer cover 12 and bodyside liner 14. The bodyside liner 14 is generally superimposed and coextensive with the outer cover 12, but may cover an area which is larger or smaller than the area of the outer cover 12. The body side liner 14, outer cover 12, and absorbent body 18 are integrally assembled together employing suitable attachment means, such as adhesive, ultrasonic bonds, thermal bonds, etc. In the shown embodiment, the bodyside liner 14 and outer cover 12 are bonded together and to the absorbent body 18 with an adhesive, such as a hot melt, pressure- sensitive adhesive. The bodyside liner 14 is bonded to the outer cover 12 around the periphery of the article 10 to form a periphery margin area 13. In other embodiments, the outer cover 12 and bodyside liner 14 may have a periphery that is continuous with the edge of the absorbent body 18.

The outer cover 12 is desirably formed of a breathable material which permits vapors to escape from the absorbent body 18 while still preventing liquid exudates from passing through the outer cover 12. For example, in one particular embodiment, the outer cover 12 is formed by a microporous film/nonwoven laminate including a spunbond nonwoven material laminated to a microporous film. . Suitable materials for the outer cover 12 are well known to those skilled in the art and many such materials are described, for example, in detail in U.S. Pat. No. 6,149,934of Krzvsik, et al. Reference is also made to U.S. Pat. No. 5,879,341 of Odorzvnski, et al. : U.S. Pat. No. 5,843,056 of Good, et al. : and U.S. Pat. No. 5,855,999 of McCormack. which are incorporated by reference herein, for descriptions of suitable breathable materials for the outer cover 12.

The bodyside liner 14 presents the bodyfacing surface 1 6 which is

compliant, soft, and nonirritating to the wearer's skin. The bodyside liner 14 helps to isolate the wearer's skin from liquids held in the absorbent body 18. Further, the bodyside liner 14 may be less hydrophilic than the absorbent body 18 to present a relatively dry surface to the wearer, and may be sufficiently porous to be liquid permeable so that liquid readily penetrates its thickness to be absorbed by the absorbent body 18. A suitable bodyside liner 14 may be made from a wide selection of materials, such as porous foams, reticulated foams, apertured plastic films, natural fibers, synthetic fibers, or any combination thereof. Various woven and nonwoven fabrics can be used for the bodyside liner 14. For example, the liner 14 may be composed of a meltblown or spunbonded web of polyolefin fibers. The bodyside liner 14 may also be a bonded-carded web of natural and/or synthetic fibers. The liner may be composed of a substantially hydrophobic material which, optionally, may be treated with a surfactant, a wetting agent, or otherwise processed to impart a desired level of wettability and hydrophilicity. The liner can be treated with a surfactant that includes a skin wellness treatment. This treatment can be applied in conjunction with asurfactant(s) or as a separate treatment.

The absorbent body 18 may comprise a matrix of hydrophilic fibers, such as a web of cellulosic fluff, alone or mixed with particles of a high-absorbency material commonly known as "superabsorbent material." The wood pulp fluff may be exchanged with synthetic, polymeric, meltblown fibers or with a combination of meltblown fibers and natural fibers. The superabsorbent particles may be substantially homogeneously mixed with the hydrophilic fibers or may be non- uniformly mixed. The fluff and superabsorbent particles may be selectively placed into desired zones of the absorbent body 18 to better contain and absorb body exudates. Alternatively, the absorbent body 18 may include a laminate of fibrous webs and/or fibrous webs and superabsorbent materials or other suitable means of maintaining a superabsorbent material in a localized area.

The high absorbency material can be selected from natural, synthetic, and modified natural polymers and materials. The high absorbency materials can be inorganic materials, such as silica gels, or organic compounds, such as

crosslinked polymers. The term "crosslinked" refers to any means for effectively rendering normally water-soluble materials substantially water insoluble but swellable. Such means can include, for example, physical entanglement, crystalline domains, covalent bonds, ionic complexes and associations, hydrophilic associations such as hydrogen bonding, and hydrophobic associations or Van der Waals forces.

Examples of synthetic, polymeric, high absorbency materials include the alkali metal and ammonium salts of poly(acrylic acid) and poly(methacrylic acid), poly(acrylamides), polyvinyl ethers), maleic anhydride copolymers with vinyl ethers and alpha-olefins, polyvinyl pyrolidone), polyvinyl morpholinone), polyvinyl alcohol), and mixtures and copolymers thereof. Further polymers suitable for use in the absorbent core include natural and modified natural polymers, such as hydrolyzed acrylonitrile-grafted starch, acrylic acid grafted starch, methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, and the natural gums, such as alginates, xanthum gum, locust bean gum, and the like. Mixtures of natural and wholly or partially synthetic absorbent polymers can also be useful in the present invention. Such high-absorbency materials are well known to those skilled in the art and are widely commercially available.

The high absorbency material may be in any of a wide variety of geometric forms. As a general rule, it is preferred that the high absorbency material be in the form of discrete particles. However, the high absorbency material may also be in the form of fibers, flakes, rods, spheres, needles, or the like. As a general rule, the high absorbency material is present in the absorbent body in an amount of from about 5 to about 90 weight percent based on total weight of the absorbent body.

A hydrophilic wrap sheet may be employed to help maintain the structural integrity of the absorbent body 18. For example, the hydrophilic wrap sheet may be a tissue wrap sheet, a nonwoven wrap sheet, a nonwoven laminate wrap sheet, etc. The wrap sheet is typically placed about the absorbent body over at least two major facing surfaces thereof and composed of an absorbent cellulosic material, such as creped wadding or a high wet-strength tissue. The wrap sheet can be configured to provide a wicking layer which helps to rapidly distribute liquid over the mass of absorbent fibers constituting the absorbent body 18. Another layer or layers can be incorporated between the liner 14 and the absorbent body 18, such as a surge layer and/or transfer layer, etc.

According to embodiments of the present invention, the treatment composition can be included on or within the absorbent article 10, particularly on areas of the article 10 that may come into close proximity to the skin of the wearer. For example, the treatment composition can be applied on or within the bodyfacing surface 1 6 of the bodyside liner 14, such as by using the application techniques discussed above with reference to wipes.

In one embodiment, the treatment composition can be applied substantially uniformly on the entire bodyfacing surface 1 6. Alternatively, the treatment composition can be applied as discrete localized deposits on the bodyfacing surface 1 6 of the article, which may be, for example, the bodyfacing surface 16 of the bodyside liner 14, as discussed in greater detail below. It should be appreciated that the invention is not limited to an article having a bodyside liner 14. For example, in certain embodiments, the article may not include a liner 14 and the bodyfacing surface may be defined by an absorbent layer of material. In this case, the treatment composition would be applied directly on or within the absorbent layer, the surge layer, and/or the transfer layer (if present).

The amount of treatment composition may vary widely within the scope of the invention. For example, if a bodyside liner is used, it may be desired that the treatment composition be present at an add-on weight of between about 0.5% to about 50% of the weight of the bodyside liner 14. It is desired that the treatment composition remain substantially on the bodyfacing surface 1 6 where it can contact and/or transfer to the wearer's skin to provide the desired skin health benefit.

The treatment composition may be in addition to an overall skin wellness treatment applied uniformly to the bodyside liner 14. For example, the liner 14 may be treated with a surfactant that includes a skin wellness additive, or a skin wellness additive may be applied in an additional process. Any of the skin wellness additives discussed herein with respect to the treatment composition may be applied as a separate overall treatment to the liner 14.

The invention is not limited to any particular treatment composition. The treatment composition may include any combination of emollients, and may also include one or more waxes. A viscosity enhancer may also be included. The treatment composition may include other ingredients as well.

The emollients act as lubricants to reduce the abrasiveness of the bodyside liner to the skin and, upon transfer to the skin, help to maintain the soft, smooth and pliable appearance of the skin. Suitable emollients which can be incorporated into the treatment composition include oils such as petroleum based oils,

vegetable based oils, mineral oils, natural or synthetic oils, silicone oils, lanolin and lanolin derivatives, kaolin and kaolin derivatives and the like and mixtures thereof; esters such as cetylpalmitate, stearylpalmitate, cetyl stearate, isopropyl laurate, isopropyl myristate, isopropyl palmitate and the like and mixtures thereof; glycerol esters; ethers such as eucalyptol, cetearylglucoside, dimethyl

isosorbicidepolyglyceryl-3 cetyl ether, polyglyceryl-3 decyltetradecanol, propylene glycol myristyl ether and the like and mixtures thereof; alkoxylated carboxylic acids; alkoxylated alcohols; fatty alcohols such as octyldodecanol, lauryl, myristyl, cetyl, stearyl and behenyl alcohol and the like and mixtures thereof; and the like and mixtures thereof. For example, a particularly well suited emollient is petrolatum. Other conventional emollients may also be added in a manner which maintains the desired properties of the treatment composition set forth herein.

To provide the improved stability and transfer to the skin of the wearer, the treatment composition may include from about 5 to about 95 weight percent, desirably from about 20 to about 75 weight percent, and more desirably from about 40 to about 60 weight percent of the emollient.

The wax in the treatment composition, when included, can primarily function as an immobilizing agent for the emollient and any active ingredient. In addition to immobilizing the emollient and reducing it's tendency to migrate, the wax in the treatment composition provides a tackiness to the lotion formulation which improves the transfer to the skin of the wearer. The presence of the wax also modifies the mode of transfer in that the treatment composition tends to fracture or flake off instead of actually rubbing off onto the skin of the wearer which can lead to improved transfer to the skin. The wax may further function as an emollient, occlusive agent, moisturizer, barrier enhancer and combinations thereof.

Suitable waxes which can be incorporated into the lotion formulation include animal, vegetable, mineral or silicone based waxes which may be natural or synthetic such as, for example, bayberry wax, beeswax, C30 alkyl dimethicone, candelilla wax, carnauba, ceresin, cetyl esters, esparto, hydrogenated cottonseed oil, hydrogenated jojoba oil, hydrogenated jojoba wax, hydrogenated

microcrystalline wax, hydrogenated rice bran wax, Japan wax, jojoba butter, jojoba esters, jojoba wax, lanolin wax, microcrystalline wax, mink wax, montan acid wax, montan wax, ouricury wax, ozokerite, paraffin, PEG-6 beeswax, PEG-8 beeswax, rezowax, rice bran wax, shellac wax, spent grain wax, spermaceti wax,

steryldimethicone, synthetic beeswax, synthetic candelilla wax, synthetic

carnaubawax, synthetic Japan wax, synthetic jojoba wax, synthetic wax, and the like and mixtures thereof. For example, a particularly well suited wax includes about 70 weight percent ceresin wax, about 10 weight percent microcrystalline wax, about 10 weight percent paraffin wax and about 10 weight percent cetyl esters (synthetic spermaceti wax). To provide the improved transfer to the skin of the wearer, the treatment composition may include from about 5 to about 95 weight percent, desirably from about 25 to about 75 weight percent, and more desirably from about 40 to about 60 weight percent of the wax. Treatment compositionswhich include an amount of wax less than the recited amounts tend to have lower viscosities which

undesirablely leads to migration of the lotion. Whereas, treatment compositions which include an amount of wax greater than the recited amounts tend to provide less transfer to the wearer's skin.

A viscosity enhancer may be added to the treatment composition to increase the viscosity to help stabilize the formulation on the bodyfacing surface 1 6 of the bodyside liner 14 and thereby reduce migration and improve transfer to the skin. Desirably, the viscosity enhancer increases the viscosity of the treatment composition by at least about 50 percent, more desirably at least about 100 percent, even more desirably by at least about 500 percent, yet even more desirably by at least about 1000 percent, and even more desirably by at least about 5000 percent. Suitable viscosity enhancers which can be incorporated into the treatment composition include polyolefin resins, lipophilic/oil thickeners, ethylene/vinyl acetate copolymers, polyethylene, silica, talc, colloidal silicone dioxide, zinc stearate, cetylhydroxy ethyl cellulose and other modified celluloses and the like and mixtures thereof.

To provide the improved transfer to the skin of the wearer, the treatment composition may include from about 0.1 to about 25 weight percent, desirably from about 5 to about 20 weight percent, and more desirably from about 10 to about 15 weight percent of the viscosity enhancer for reduced migration and improved transfer to the wearer's skin.

If it is desired that the treatment composition treat the skin, it can also include an active ingredient such as a skin protectant. Skin protectants may be a drug product which protects injured or exposed skin or mucous membrane surface from harmful or irritating stimuli. Suitable active ingredients, in addition to those mentioned above as suitable emollients, which can be incorporated into the lotion formulation include, but are not limited to, allantoin and its derivatives, aluminum hydroxide gel, calamine, cocoa butter, dimethicone, cod liver oil, glycerin, kaolin and its derivatives, lanolin and its derivatives, mineral oil, shark liver oil, talc, topical starch, zinc acetate, zinc carbonate, and zinc oxide and the like, and mixtures thereof. The treatment composition may include from about 0.10 to about 95 weight percent of the active ingredient depending upon the skin protectant and the amount desired to be transferred to the skin.

In order to better enhance the benefits to the wearer, additional ingredients can be included in the treatment composition. For example, the classes of ingredients that may be used and their corresponding benefits include, without limitation: antifoaming agents (reduce the tendency of foaming during processing); antimicrobial actives; antifungal actives; antiseptic actives; antioxidants (product integrity); astringents - cosmetic (induce a tightening or tingling sensation on skin); astringent - drug (a drug product which checks oozing, discharge, or bleeding when applied to skin or mucous membrane and works by coagulating protein); biological additives (enhance the performance or consumer appeal of the product); colorants (impart color to the product); deodorants (reduce or eliminate unpleasant odor and protect against the formation of malodor on body surfaces); other emollients (help to maintain the soft, smooth, and pliable appearance of the skin by their ability to remain on the skin surface or in the stratum corneum to act as lubricants, to reduce flaking, and to improve the skin's appearance); external analgesics (a topically applied drug that has a topical analgesic, anesthetic, or antipruritic effect by depressing cutaneous sensory receptors); film formers (to hold active ingredients on the skin by producing a continuous film on skin upon drying); fragrances (consumer appeal), silicones/organomodified silicones (protection, tissue water resistance, lubricity, tissue softness), oils (mineral, vegetable, and animal); natural moisturizing agentsor natural moisturizing factors (NMF) and other skin moisturizing ingredients known in the art; opacifiers (reduce the clarity or transparent appearance of the product); powders (enhance lubricity, oil adsorption, provide skin protection, astringency, opacity, etc.); skin conditioning agents;

solvents (liquids employed to dissolve components found useful in the cosmetics); and surfactants (as cleansing agents, emulsifying agents, solubilizing agents, and suspending agents).

The present invention may be better understood with reference to the following examples.

EXAMPLE 1 In vitro models were developed for screening quorum sensing inhibitory compounds/products against Candida albicansSC53 ^' \ 4 to identify potential quorum sensing inhibitors. Potential quorum sensing inhibitory compounds/products were not only sourced from commercial analogs of quorum sensing molecules, natural antifungal botanicals and antifungal drugs, but also by developing water soluble products by modifying essential oils and thymol.

Generally, these Examples presented the following key findings:

1 . An in vitro model was established for screening quorum sensing inhibitory compounds against C. albicansSC53 ^' \ 4 using germ tube formation;

2. Multiple water-soluble products formed from essential oils were synthesized and screened by thegerm tube formation/ ^' n vitro model;

4. A C. elegansin vitro model was established for screening quorum sensing inhibitory compounds against C. albicansSC53 ^' \ 4;

5. Multiple water-soluble products formed from essential oils were synthesized and screened by the C.elegansin vitro model;

Test Methods

In these examples, the YPD agar consisted of 10.0 g of peptone, 5.0 g of Yeast extract, 10.0 g of glucose, 10.0 g of agar, and between 500 ml_ and 1 L of deionized water, which was prepared by mixing all ingredients and then sterilizing via autoclave at 1 15° C for 30 min.

The YPDbroth consisted of 10.0 g of peptone, 5.0 g of Yeast extract, 10.0 g of glucose, and betweenSOOmL and 1 L of deionized water, which was prepared by mixing all ingredients and then sterilizing via autoclave at 1 15° C for 30 min.

The mGSBbroth consisted of 1 .0 g of peptone, 2.0 g of KH ₂ P0 ₄ , 1 .0 g of (NH ₄ ) ₂ S0 ₄ , 0.05 g of MgS0 ₄ -7H ₂ 0, 0.05 g CaCI ₂ '2H ₂ 0, and 1 .0 L of deionized water, which was prepared by mixing all ingredients and then sterilizing via autoclave at 121 ° C for 15 min. After cool down, a filter sterilized 30ml 50% glucose solution (w/v) and 0.4 ml GPP vitamin stock was added, which contained the following (per 100 ml of 20% ethanol): 2 mg of biotin,20 mg of thiamine-HCI, and 20 mg of pyridoxine-HCI.

The NGM agar consisted of 2.5 g of peptone, 3.0 g of NaCI, 17 g of agar, and 975 ml_ of deionized water, which was prepared by mixing all ingredients and then sterilizing by autoclave at 121 ° C for 15 min. After cool down, sterilized 25 ml of KPO ₄ buffer(400 mMKH ₂ PO ₄ and100mMK ₂ HPO ₄ ),0.1 % 1 M MgSO ₄ (v/v), 0.1 % 1 M CaCI ₂ (v/v), filter sterilized 100 mg/ ml streptomycin, and 0.1 %5 mg/ ml cholesterol in ethanol (v/v) were added.

The M9 buffer consisted of 3.0 g of KH ₂ PO ₄ , 6.0 g of Na ₂ HPO ₄ , 5.0 g of NaCI, and 1 L of deionized water, which was prepared by mixing all ingredients and then sterilizing by autoclave at 121 ° C for 15 min. After cool down, 1 ml_ of filter sterilized 1 M MgSO was added.

1 . Development of in vitro screening model

a) Develop protocols for preparation of single cell suspensions of C. albicans

The growth of Candida albicansSC53 ^' \ 4 in two media, Yeast Extract

Peptone Dextrose broth(commonly known as YPD broth), and modified glucose salts biotin broth (commonly known as mGSB broth), was examined during incubation at 30° C. Fig. 3 shows that SC5314 reached stationary phase after24 h incubation at 30° C in both media. The percentage of singlet cells decreased initially, and then increased after 24 h in both media. The percentage of singlet cells in YPD broth exceeded80% after 48 h; whereas that in mGSB broth was around 60-70% after 30 h -54 h incubation.

Based on the results in Fig. 3, single cell suspensions of SC5314 was prepared as follows. Stock culture of C. albicansSC53 ^' \ 4 was streaked onto YPD agar (YPDA) and incubated at 30° C overnight. Single colonies were subcultured in YPD broth (YPDB) and incubated at 30° C, 200 rpm overnight. Overnight culture in YPDB was subcultured in YPD broth again and incubated at 30° C, 200 rpm 48 h. Cells were collected by centrifugation (4000 g 10 min) at 4° C, washed three times with sterile water, and then resuspended in sterile water at a final concentration of 10 ⁹ colony-forming unit/ml(cfu/ml). The suspension was stored at 4° C at least 1 d, then subcultured into YPDB to a final concentration of 10 ⁶ cfu/ml. After 48 h incubation, cell suspension was examined under the microscope for single cell percentage. When the single cell percentage exceeded 80%, cells were collected andwashed three times with water, then resuspended in water to a final

concentration of 10 ⁹ cfu/ml, and stored at 4° C for no more than a month.

b) Develop protocols for determination of the percentage of cells with germ tubes formed (GTF%) Germinated yeast cells generally tend to aggregate, making it difficult to count the total number of cells during the in vitro screening. To disaggregate the cells, various approaches were attempted, such as vortexing with glass beads, sonication, addition of dithiothreitol (0.1 mM to 0.4 mM) and glutathione (reduced, 5 mM to 25 mM), and storage at various temperatures (4 ^Q C, 15 ^Q C, 20 ^Q C, 25 ^Q C). Good disaggregation was observed only for storage at 15 ^Q C for 20 h, as seen microscopically.

Two approaches were taken to determine the percentage of cells with germ tubes formed (GTF%). One way was to count the total cells at the start of incubation, and count the ungerminated cells after incubation, then calculate the GTF% as (1 - ungerminated cells/ total cells at 0 h) ^* 100. Another way was to store the samples at 15° C for 20 h after incubation, then count the germinated cells and total cells after disaggregation, then calculated the GTF% as (germinated cells/ total cells after storage) ^* 100. No significant difference was observed for the GTF% of C. albicans in a screening medium (1 1 mM imidazole buffer, 3

mMMgSO4, and 2.6 mM N-acetyl-D-glucosamine) determined by the two methods. Therefore, for practical purposes,the GTF% was determined by the first method, that is, GTF% = (1 - ungerminated cells/ total cells at 0 h) ^* 100, for the in vitro screening discussed herein.

c) Select screening media for in vitro screening

A screening medium, containing 1 1 mM imidazole buffer, 3 mMMgSO4, and 2.6 mM N-acetyl-D- glucosamine (GlcNAc) has been used to study the effect of farnesol analogs on the germ tube formation of C. albicans. Here, the germ tube formation of C. albicans in modified screening media was assessed with various concentrations of imidazole buffer (10 mM, 30 mM, and 50 mM) and MgSO4 (0.5 mM, 1 .5 mM, and3 mM). Table 1 shows that the GTF% decreased as the concentration of imidazole bufferincreased; whereas the GTF% increased as the concentration of MgSO4 increased. It took 2 h to3 h for the GTF% to reach above 80%. For practical purposes, the screening medium, containing 1 1 mM imidazole buffer, 0.5 mMMgSO4, and 2.6 mM N-acetyl-D- glucosamine (GlcNAc) was adopted for in vitro screening the quorum sensing inhibitory effect of farnesol compounds and botanicals.

Table 1 : Effect of concentrations of imidazole buffer and MgSO4 on the germ tube formation(GTF%) of C. albicans cells at 37° C in screening media (pH 6.5) with 2.6 mM N-acetyl-D- glucosamine

Table 1 :

Imidazole 2+ ^G ' ^F

buffer ^g ^ ^ 2 h 2.5 h 3 h

0.5 mM 32.0 84.8

10 mM 1.5 mM 34.4 88.8

3.0 mM 38.0 86.8

0.5 mM 29.2 54.8 82.8

30 mM 1.5 mM 39.2 66.8 84.4

3.0 mM 34.0 64.0 92.4

0.5 mM 18.8 38.4 65.2 76.4

50 mM 1.5 mM 22.8 41.2 66.8 80.0

3.0 mM 10.0 62.0 68.8 85.6

Note: GTF% was calculated as the 1-(ungerminated cells/total cells at 0 h}% d) Effect of quorum sensing molecules on lag phase of C. albicans

Fig.4 shows that 100 μΜ farnesol or 100 μΜ tyrosol had little effect on the growth of C. albicansSC53^ 4 in YPD broth at 37° C for 6 h. Those results confirm no increase of cells occurred during the period of the in vitro screening.

Synthesis of Modified Essential Oils

Fig.5 shows a diagram for synthesizing water soluble products, #1

(withCOONa) and #2 (with D-Glucose), from Artemisia oil. The same process was applied to lavender oil, tea tree oil and thymol to obtain other five water soluble products: lavender oil, tea tree oil and thymol with COONa, and lavender oil and tea tree oil with D-Glucose.

Table 2 shows the effect of water soluble products from essential oils and thymol on the germ tube formation (GTF%) of C. albicansSC53 ^' \ 4.

Table 2 GTF%

Water soluble product

(mean ± SEM, n=3)

Artemisia oil + D-glucose 1.3 ± 0.9

Artemisia oil + D-glucose (1 :1 dilution) 58.0 ± 1.0

Tea tree oil + D-glucose 97.7 ± 1.2

Lavender oil + D-glucose 96.0 ± 2.1

Artemisia oil + COONa 4.3 ± 2.2

Artemisia oil + COONa (1 :5 dilution} 21.7 ± 0.9

Tea tree oil + COONa 12.3 ± 7.9

Lavender + COONa 53.6 ± 7.9

Thymol oil with COONa 18.3 ± 4.7

Thymol oil with COONa (1 :10 dilution) 50.3 ± 2.2

Thymol (1 mM) 43.7 ± 5.2

Control 80.6 ± 0.5

Note: all products were tested at 85% or its dilutions unless otherwise indicated Table 3 shows the effect of essential oil and plant extracts on the germ tube formation (GTF%) of C. albicansSC53^ 4.

Table 3

GTF%

Essential oil & plant extracts (mean ± SEM, n=2)

0.025% 0.250%

Artemisia oil 66.2 ± 2.1 2.8 ± 2.8

Eucalyptus oil 57.0 ± 1.5 6.8 ± 2.1

Tea tree oil 56.5 ± 3.1 3.9 ± 2.5

Lavender oil 41.1 ± 1.1 2.1 ± 2.1

Orange oil 61.8 ± 2.7 40.1 ± 0.1

Ginger oil 58.3 ± 1.4 8.5 ± 1.1

Rape seed oil Not tested 83.1 ± 1.3

Cedar oil Not tested 88.3

Grape seed extract Not tested 38.5 ^*

Hawthorn fruit extract Not tested 100

ginger extract Not tested 100

Control 82.8 ± 0.6

'.Grape seed extract changed the morphology of yeast cells

C. Elegans In vitro Screeni ng Caenorhabditiselegansg\p4;seM was used as the model for in vitro screening. Breger et al. (Breger, J. ; Fuchs, B. B. ; Aperis, G.; Moy, T. I., Ausubel, F. M., Mylonakis, E. ; "Antifungal chemical compounds identified using a C. elegans pathogenicity assay." PLoS Pathogens 3: 1 68-178; 2007) reported that the glp-4 mutation rendered the strain incapable of producing progeny at 25° C, and the sek- 1 mutation enhanced the sensitivity of the strain to various pathogens, thereby decreasing the time for screening assays. It was observed that no progenies was produced by the Caenorhabditiselegansg\p4;seM strain after 3 d incubation at 25° C.

The synchronization of C. elegans was achieved by collecting the eggs and arresting the larvae at L1 stage. The commonly used bleach treatment was able to release the eggs from the adult worms. However, it was observed that the released eggs were not always able to hatch after treated with sodium hypochlorite (0.2, 0.3, 0.4, 0.5, 0.7or 1 %) for 3-5 min. A modified egg laying method was developed to synchronize worms to L1 stage. In brief, stock cultures of C.

e/egansglp4;sek1 , maintained on NGM plates, were subcultured onto NGM plates with OP50 and incubated at 15° C for 6-9 days. Then a chunk (1 cm ² ) of agar with gravid adults was subcultured again onto Nematode Growth Media (NGM) plates with OP50 and incubated at 15° C. After incubation of 3-7 days, the worms were gently washed off with 3 ml of M9 buffer on the rotating platform (100 rpm). The plate was tilted on its lid to allow the liquid and worms to drain to one side of the plate. The liquid and worms were aspirated off. The plate was washed again with M9 buffer three more times to remove OP50 as much as possible. After washing, the plate was incubated at 25° C overnight to let the eggs hatch overnight. Since there was no OP50, the larvae were arrested at the L1 stage.

The live C. e/egansglp4;sek1 was quite curvy; whereas the dead C.

e/egansglp4;sek1 tended to be straight, and in most cases the dead worms with the hyphae of C. albicans pieced through the body. The curvy shape and

movement after shaking were used as the criteria for live.

Results of initial screening showed that the death rate of C.

e/egansglp4;sek1 infected with C.a/£>/cansSC5314 increased over time (Table 4). The presence of 0.1 % tea tree oil reduced the death rate slightly. The higher concentration of tea tree oil resulted in a higher death rate of the worm. This implies that the tea tree oil at higher concentrations may be toxic to the worm.

Table 4 shows the death rate of C. e/egansglp4;sek1 infected with C.

albicansSC53 ^' \ 4 during incubation in 96 well plates

Table 4:

% change in the death rate compared to the control

Compounds Concentration - day 1 day 4 day 5

Tea tree oil 0.15% 28 12 4

0.20% 70 16 6

Death rate of c&ntFoi <%) 3S 72 ei

Water soluble products were synthesized and had inhibitory effect on the quorum sensing of C. albicans in vitro.

Experimental

1 . Maintenance of Candida albicansSC53 ^' \ 4

Candida albicansSC53-\ 4 was streaked onto YPD agar (YPDA) and incubated at 30° C overnight. Single colonies were subcultured in YPD broth (YPDB) and incubated 30° C, 200 rpm overnight. Glycol stocks of overnight culture in YPDB were prepared, and stored in -20 °C.

2. Maintenance of Caenorhabditiselegans

Caenorhabditiselegansg\p4;seM was maintained by subculturing on E.

CO//OP50 on NGM plates at 15 ^Q C for 7 days. Those can be stored at 15° C for up to 2 months.

3. In vitro screening of compounds and botanicals

The in vitro screening assay was based on the N-acetylglucosamine (GlcNAc)-triggered differentiation assay (Hornby et al., "Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol;" Applied and

Environmental Microbiology 67:2982-2992; 2001 ), which included 0.56ml of 0.1 M imidazole buffer (pH 6.5), 0.15 ml of 0.1 M MgS04, 0.13 ml of O.I MGIcNAc, and 4.1 6 ml of sterilized water. Bioassays of quorum sensing candidates were conducted by the addition of the chemical, as a solution in 100% methanol, to the bioassay media; the final concentration of methanol was no greater than 1 %.

4. In w ^' froscreening of compounds and botanicals

The In vitro screening assay, based on the method of Tampakakis et al (Tampakakis, E. ; Okoli, I. ; Mylonakis, E. ; "A C. elegans- based, whole animal, in vivo screen for the identification of antifungal compounds." Nature Protocols 3:1925-1931 ; 2008), is described as follows:

a) Preparation of worms

L1 worms, which were prepared by the modified egg-laying method, were collected by centrifugation at 675 g for 30 s at room temperature, and the supernatant was removed. Worms were resuspended in M9 buffer and inoculated on NGM agar plates with OP50, -1000 worms per plate. After 2-3 days incubation at 25 ^Q C, the worms were washed off with M9 buffer for the in vitro screening assay. b) Preparation of C. albicans

Stock cultures of C. albicansSC53 ^' \ 4 was subcultured into 3 ml of YPD broth and incubated at 30 °C. Then the overnight culture in broth was spread onto YPD agar, and incubated at 30° C. The 24 h old lawn of SC5314 was used to feed worms for 2 h at 25° C. The control were worms fed on OP50.

c) In vitro screening assay

The worms were washed off the YPD plates and washed twice with M9 buffer. The worms were resuspended in screening media, M9 buffer with 0.3% Tween 80. The worm suspension (50 μΙ) was dispensed into the wells of 96-well plates, 20-30 worms/well. Aliquots (50 μΙ) of compounds in screening media were added to wells, 5 wells each compound. The 96 well plates were incubated at 25° C for up to 5 days. Live and dead worms were counted during incubation, and the death rates of worms were calculated.

EXAMPLE 2

Chemical modification was performed on five essential oils and a terpene control. The effect of essential oils and their carboxylated and glycosylated products against the quorum sensing of Candida albicansSC53 ^' \ 4 by an in vitro screening assay was also investigated. The five essentials oils were Artemisia oil, lavender oil, tea tree-oil, ginger oil and eucalyptus oil; and the terpene control was 1 -decene that had no hydroxyl (-OH) functional group.

The key findings of this work are highlighted as follows:

1 . Carboxylated and glycosylated products were obtained for all five essential oils, and the yields ranged from 2.1 to 10.6. No product was observed for 1 -decene after carboxylation or glycosylation.

2. All five essential oils and their products (at concentration of 0.1 % or 0.2%), except for tea tree oil-D-glucose, inhibited the germ tube formation of (GTF%) of C. a/k/cansSC5314 without affecting its viability.

3. The inhibitory effect of carboxylated and glycosylated products was no greater than their oil at equivalent concentrations of 0.1 % or 0.2%.

Chemical modification

Carboxylated and glycoxylated products were obtained for five essential oils (Table 5). No product was observed for 1 -decene, the terpene control, after carboxylation and glycoxylation modification. Table 5 shows the yields of chemical modification of essential oils.

Table 5

Raw materia! Carboxylation yield (%) Glycosylatton yieid (%)

Artemisia oif 2.1 6.9

Lavender oif 4.4 10.6

Eucalyptus oi! 2.5 3.5

Ginger oil 6.2 6.8

Tea tree oil 3.3 2.5

1-Deceoe No product No product

(CAS 872-05-9)

In vitro screeni ng of essential oils and thei r products The germ tube formation of (GTF%) of C. albicansSC53 ^' \ 4 was reduced in the presence of all five essential oil and their products, except for tea tree oil-D- glucose, at concentrations of 0.1 % or 0.2% (Table 6). The viability of C. albicans was not affected by those conditions.

At the equivalent concentration of 0.1 %, the inhibitory effect of both carboxylated and glycosylated products of Artemisia oil, lavender oil, ginger oil was not significantly different from that of their oil; whereas the inhibitory effect of both carboxylated and glycosylated products of tea tree oil and eucalyptus oil was significantly lower than that of their oil. All essential oils at 0.1 % had equal to or greater than the inhibitory effect of 100 mMfarnesol (0.0022%).

At the equivalent concentration of 0.2%, the inhibitory effect of both carboxylated and glycosylated products of ginger oil and the glycosylated product of eucaplytus oil was not significantly different from that of their oil; the inhibitory effect of both carboxylated and glycosylated products of tea tree oil and the carboxylated product of eucalyptus oil was significantly lower than that of their oil.

For samples that had no greater inhibitory effect than 100 mMfarnesol when the tested concentration was 0.1 %, the inhibitory effect improved significantly when the concentration of the samples was increased to 0.2%. For samples that had greater inhibitory effect than 100 mMfarnesol, the inhibitory effect was similar for both 0.1 % and 0.2%.

Table 6

<5TF% _eortrol - G t F% _saropte

sam les (mean ± SD _; n=3)

0.1%

Artemisia oi! 59.3 ± 8.8 ³ Not. tested

Artemisia oil -COONa 41,9 ± 8.8 ^A Mot tested

Artemisia oii-D-gluccse 67.5 ± 15.2 ^A Not tested

Lavender oil 48.0 ± 0.8 ³ Not tested

Lavender oil-COONa 61.3 ± 8.2 ^A Not tested

Lavender oil-D-g!ucose 29.6 ± 21.9 ³ 72.2 ± 8.6 ^*

tree oil 69.7 ± 9.7 81.0 ±4.3 *

tree oil-COONa 17.6 ±6.5 61 ± 7.5 -- ^'

tree oif-D-g!ucose 0 ^£

Ginger a\\ 25.3 ±13.2 ³ 65.0 ± 5.2

Ginger oil-COONa 10.8 ± 7.6 ^a 58.1 ± 5.6

Ginger oii-D-glucose 0* 72.6 ±1.4

Eucalyptus oil 57.0 ± 19.8 ³ 78.3 ± 5.8

Eucalyptus oti-COONa 0 ^S 46.3 ± 6.0 ^{5 1}

Eucalyptus osf-D-g!ucose 12.8 ±5.8" 71..3 ± S.Q

1-Decene 0 35.2 ± 5.2 ^*

Letters s-c indicate sictt iesm differences iP<0.Q5 in reducSon of GTF% etween

oil and their products. * indicates significant difference between ihe 0.1% and 0.2% of one sampte.

Results show the carboxylated and glycoxylated products of essential oils inhibiting the quorum sensing of C. albicans in vitro. Experi mental : Chemical modification

a) Protocols for synthesizing Artemisia oil-COONa and Artemisia oil- Glucose products

1 . Add 8 g of Artemisia oil, 100 ml of anhydrous ethanol, and 4 g of sodium borohydride into a 250 ml round bottom flask, connected the flask with a drying tube. Stir the mixture overnight at room temperature.

2. Remove ethanol under reduced pressure.

3. Add 100 ml of methylene dichloride to dissolve the solid, wash with 100 ml of deionized water twice and then 100 ml of saturated sodium chloride solution once. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

4. Remove the solvent under reduced pressure, obtained 4.69 g of the reduced Artemisia oil product.

5. Add the 4.69 g of the reduced product, 100 ml of anhydrous

tetrahydrofuran (THF), 4.0 g of 1 -(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC ), 1 .0 g of 4- dimethylamiopryidine (DMAP) and 5.0 g of succinic acid into a round bottom flask, connect the flask with a drying tube. Place the flask in ice bath, and stir the mixture overnight at room temperature.

6. Remove the solid by filtration under reduced pressure, collect the filtrate. 7. Remove the solvents under reduced pressure. Add 100 ml of acetic ether to dissolve, wash with 100 ml of deionized water three times. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

8. Remove the solvent under reduced pressure. Obtained 6.5 g of the raw product of carboxylated Artemisia oil.

9. Transfer 3 g of the raw product of carboxylated Artemisia oil and 50 ml of deionized water to a round bottom flask.

10. Add saturated sodium bicarbonate solution till pH reaches pH 8.

1 1 . Wash with 50 ml of petroleum ether twice, collect the aqueous phase, and adjust the pH with 10% HCI to ~ pH 6.

12. Extract with 50 ml of acetic ether twice, collect the acetic ether phase.

13. Remove the residual water using anhydrous sodium sulfate, then collect the filtrate by filtration under reduced pressure. 14. Remove the acetic ether under reduced pressure. Obtained 0.0789 g of the final product of Artemisia oil-COOH.

15. Transfer 3.5 g of the raw product of carboxylated Artemisia oil in a round bottom flask. Add 100 ml of THF, 3.0 g of EDC, 1 .0 g of DMAP and 2.57 g of glucose. Place the flask in an ice bath. Stir the mixture overnight at room

temperature.

16. Remove the solid by filtration under reduced pressure, and collect the filtrate.

17. Remove the solvents under reduced pressure. Add 100 ml of deionized water to dissolve, extract with 100 ml of acetic ether three times. Collect the acetic ether phase. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

18. Remove the solvents under reduced pressure. Obtained the raw product of glycosylated Artemisia oil.

19. Add 50 ml of deionized water to dissolve the solid. Wash with 50 ml of petroleum ether twice, collect the aqueous phase.

20. Extract with 40 ml of butyl alcohol twice, collect the butyl alcohol phase. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

21 . Remove the solvents under reduced pressure. Obtained 0.2955 g of the final product of Artemisia oil-D-glucose.

b) Protocols for synthesizing Lavender oil-COONa and Lavender oil- Glucose products

1 . Add 10 g of Lavender oil, 187.5 ml of anhydrous ethanol, and 4 g of sodium borohydride into a 250 ml round bottom flask, connected the flask with a drying tube. Stir the mixture overnight at room temperature.

2. Remove ethanol under reduced pressure.

3. Add 120 ml of methylene dichloride to dissolve the solid, wash with 100 ml of deionized water twice and then 100 ml of saturated sodium chloride solution once. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

4. Remove the solvent under reduced pressure, obtained 7.55 g of the reduced Lavender oil product. 5. Add the 7.55 g of the reduced product, 100 ml of THF, 4.0 g of EDC, 1 .0 g of DMAP and 5.0 g of succinic acid into a round bottom flask, connect the flask with a drying tube. Place the flask in ice bath, and stir the mixture overnight at room temperature.

6. Remove the solid by filtration under reduced pressure, collect the filtrate.

7. Remove the solvents under reduced pressure. Add 100 ml of acetic ether to dissolve, wash with 100 ml of deionized water three times. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

8. Remove the solvent under reduced pressure. Obtained 8.56 g of the raw product of carboxylated Lavender oil.

9. Transfer 5.06 g of the raw product of carboxylated Lavender oil and 100 ml of deionized water to a round bottom flask.

10. Add saturated sodium bicarbonate solution till pH reaches pH 8.

1 1 . Wash with 50 ml of petroleum ether twice, collect the aqueous phase, and adjust the pH with 10% HCI to ~ pH 6.

12. Extract with 80 ml of acetic ether twice, collect the acetic ether phase.

13. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

14. Remove the acetic ether under reduced pressure. Obtained 0.2617 g of the final product of Lavender oil-COOH.

15. Transfer 3.5 g the raw product of carboxylated Lavender oil in a round bottom flask. Add 100 ml of THF, 3.0 g of EDC, 1 .0 g of DMAP and 2.57 g of glucose. Place the flask in ice bath. Stir the mixture overnight at room temperature.

16. Remove the solid by filtration under reduced pressure, collect the filtrate.

17. Remove the solvents under reduced pressure. Add 100 ml of deionized water to dissolve, extract with 100 ml of acetic ether three times. Collect the acetic ether phase. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

18. Remove the solvents under reduced pressure. Obtained the raw product of glycosylated Lavender oil.

19. Add 100 ml of deionized water to dissolve the solid. Wash with 50 ml of petroleum ether twice, collect the aqueous phase. 20. Extract with 40 ml of butyl alcohol twice, collect the butyl alcohol phase. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

21 . Remove the solvents under reduced pressure. Obtained 0.4326 g of the final product of Lavender oil-D-glucose.

c) Protocols for synthesizing Tea tree oil-COONa and Tea tree oil-Glucose products

1 . Add 8 g of Tea tree oil, 100 ml of anhydrous ethanol, and 4 g of sodium borohydride into a 250 ml round bottom flask, connected the flask with a drying tube. Stir the mixture overnight at room temperature.

2. Remove ethanol under reduced pressure.

3. Add 100 ml of methylene dichloride to dissolve the solid, wash with 100 ml of deionized water twice and then 100 ml of saturated sodium chloride solution once. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

4. Remove the solvent under reduced pressure, obtained 5.76 g of the reduced Tea tree oil product.

5. Add the 5.76 g of the reduced product, 100 ml of THF, 4.0 g of EDC, 1 .0 g of DMAP and 5.0 g of succinic acid into a round bottom flask, connect the flask with a drying tube. Place the flask in ice bath, and stir the mixture overnight at room temperature.

6. Remove the solid by filtration under reduced pressure, collect the filtrate.

7. Remove the solvents under reduced pressure. Add 100 ml of acetic ether to dissolve, wash with 100 ml of deionized water three times. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

8. Remove the solvent under reduced pressure. Obtained 4.47 g of the raw product of carboxylated Tea tree oil.

9. Transfer 2 g of the raw product of carboxylated Tea tree oil and 50 ml of deionized water to a round bottom flask.

10. Add saturated sodium bicarbonate solution till pH reaches pH 8.

1 1 . Wash with 50 ml of petroleum ether twice, collect the aqueous phase, and adjust the pH with 10% HCI to ~ pH 6. 12. Extract with 50 ml of acetic ether twice, collect the acetic ether phase.

13. Remove the residual water using anhydrous sodium sulfate, then collect the filtrate by filtration under reduced pressure.

14. Remove the acetic ether under reduced pressure. Obtained 0.1 18 g of the final product of Tea tree oil-COOH.

15. Transfer 2.47 g the raw product of carboxylated Tea tree oil in a round bottom flask. Add 100 ml of THF, 3.0 g of EDC, 1 .0 g of DMAP and 2.57 g of glucose. Place the flask in ice bath. Stir the mixture overnight at room temperature.

16. Remove the solid by filtration under reduced pressure, and collect the filtrate.

17. Remove the solvents under reduced pressure. Add 100 ml of deionized water to dissolve, extract with 100 ml of acetic ether three times. Collect the acetic ether phase. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

18. Remove the solvents under reduced pressure. Obtained the raw product of glycosylated Tea tree oil.

19. Add 50 ml of deionized water to dissolve the solid. Wash with 50 ml of petroleum ether twice, collect the aqueous phase.

20. Extract with 40 ml of butyl alcohol twice, collect the butyl alcohol phase. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

21 . Remove the solvents under reduced pressure. Obtained 0.1452 g of the final product of Tea tree oil-D-glucose.

d) Protocols for synthesizing Ginger oil-COONa and Ginger oil-Glucose products

1 . Add 5 g of Ginger oil, 100 ml of anhydrous ethanol, and 2 g of sodium borohydride into a 250 ml round bottom flask, connected the flask with a drying tube. Stir the mixture overnight at room temperature.

2. Remove ethanol under reduced pressure.

3. Add 100 ml of methylene dichloride to dissolve the solid, wash with 100 ml of deionized water twice and then 100 ml of saturated sodium chloride solution once. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure. 4. Remove the solvent under reduced pressure, obtained the reduced Ginger oil product.

5. Add the reduced Ginger oil product, 100 ml of THF, 2.0 g of EDC, 0.5 g of DMAP and 2.5 g of succinic acid into a round bottom flask, connect the flask with a drying tube. Place the flask in an ice bath, and stir the mixture overnight at room temperature.

6. Remove the solid by filtration under reduced pressure, collect the filtrate.

7. Remove the solvents under reduced pressure. Add 50 ml of acetic ether to dissolve, wash with 100 ml of deionized water three times. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

8. Remove the solvent under reduced pressure. Obtained the raw product of carboxylated Ginger oil.

9. Transfer the raw product of carboxylated Ginger oil to a round bottom flask, add 100 ml of deionized water to dissolve. Add saturated sodium

bicarbonate solution till pH reaches pH 8.

10. Wash with 50 ml of petroleum ether twice, collect the aqueous phase, and adjust the pH with 10% HCI to ~ pH 6.

1 1 . Extract with 100 ml of acetic ether twice, collect the acetic ether phase. 12. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

13. Remove the acetic ether under reduced pressure. Obtained 0.3101 g of the final product of Ginger oil-COOH.

14. Add 10 g of Ginger oil, 180 ml of anhydrous ethanol, and 4 g of sodium borohydride into a 250 ml round bottom flask, connected the flask with a drying tube. Stir the mixture overnight at room temperature.

15. Remove ethanol under reduced pressure.

16. Add 100 ml of methylene dichloride to dissolve the solid, wash with 100 ml of deionized water twice and then 100 ml of saturated sodium chloride solution once. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

17. Remove the solvent under reduced pressure, obtained 5.82 g of the reduced Ginger oil product. 18. Add the 5.82 g of the reduced product, 100 ml of THF, 4.0 g of EDC, 1 .0 g of DMAP and 5.0 g of succinic acid into a round bottom flask, connect the flask with a drying tube. Place the flask in ice bath, and stir the mixture overnight at room temperature.

19. Remove the solid by filtration under reduced pressure, and collect the filtrate.

20. Remove the solvents under reduced pressure. Add 50 ml of acetic ether to dissolve, wash with 100 ml of deionized water three times. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

21 . Remove the solvent under reduced pressure. Obtained 4.89 g of the raw product of carboxylated Ginger oil.

22. Transfer 2.445 g the raw product of carboxylated Ginger oil in a round bottom flask. Add 100 ml of THF, 3.0 g of EDC, 1 .0 g of DMAP and 2.57 g of glucose. Place the flask in ice bath. Stir the mixture overnight at room temperature.

23. Remove the solid by filtration under reduced pressure, collect the filtrate.

24. Remove the solvents under reduced pressure. Add 100 ml of deionized water to dissolve, extract with 100 ml of acetic ether three times. Collect the acetic ether phase. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

25. Remove the solvents under reduced pressure. Obtained the raw product of glycosylated Ginger oil.

26. Add 50 ml of deionized water to dissolve the solid. Wash with 50 ml of petroleum ether twice, collect the aqueous phase.

27. Extract with 40 ml of butyl alcohol twice, collect the butyl alcohol phase.

Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

28. Remove the solvents under reduced pressure. Obtained 0.3386 g of the final product of Ginger oil-D-glucose.

e) Protocols for synthesizing Eucalyptus oil-COONa and Eucalyptus oil-

Glucose products

1 . Add 10 g of Eucalyptus oil, 180 ml of anhydrous ethanol, and 4 g of sodium borohydride into a 250 ml round bottom flask, connected the flask with a drying tube. Stir the mixture overnight at room temperature.

2. Remove ethanol under reduced pressure.

3. Add 100 ml of methylene dichloride to dissolve the solid, wash with 100 ml of deionized water twice and then 100 ml of saturated sodium chloride solution once. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

4. Remove the solvent under reduced pressure, obtained 5.21 g of the reduced Eucalyptus oil product.

5. Add the 5.21 g of the reduced product, 100 ml of THF, 4.0 g of EDC, 1 .0 g of DMAP and 5.0 g of succinic acid into a round bottom flask, connect the flask with a drying tube. Place the flask in an ice bath, and stir the mixture overnight at room temperature.

6. Remove the solid by filtration under reduced pressure, and collect the filtrate.

7. Remove the solvents under reduced pressure. Add 100 ml of acetic ether to dissolve, wash with 100 ml of deionized water three times. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

8. Remove the solvent under reduced pressure. Obtained 3.61 g of the raw product of carboxylated Eucalyptus oil.

9. Transfer 1 .61 g of the raw product of carboxylated Eucalyptus oil to a round bottom flask, and add 100 ml of deionized water. Add saturated sodium bicarbonate solution till pH reaches pH 8.

10. Wash with 50 ml of petroleum ether twice, collect the aqueous phase, and adjust the pH with 10% HCI to ~ pH 6.

1 1 . Extract with 50 ml of acetic ether twice, collect the acetic ether phase.

12. Remove the residual water using anhydrous sodium sulfate, then collect the filtrate by filtration under reduced pressure.

13. Remove the acetic ether under reduced pressure. Obtained 0.1 129 g of the final product of Eucalyptus oil-COOH.

14. Transfer 2 g the raw product of carboxylated Eucalyptus oil in a round bottom flask. Add 100 ml of THF, 3.0 g of EDC, 1 .0 g of DMAP and 2.57 g of glucose. Place the flask in ice bath. Stir the mixture overnight at room temperature. 15. Remove the solid by filtration under reduced pressure, collect the filtrate.

16. Remove the solvents under reduced pressure. Add 100 ml of deionized water to dissolve, extract with 100 ml of acetic ether three times. Collect the acetic ether phase. Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

17. Remove the solvents under reduced pressure. Obtained the raw product of glycosylated Eucalyptus oil.

18. Add 50 ml of deionized water to dissolve the solid. Wash with 50 ml of petroleum ether twice, collect the aqueous phase.

19. Extract with 40 ml of butyl alcohol twice, collect the butyl alcohol phase.

Remove the residual water using anhydrous sodium sulfate, and collect the filtrate by filtration under reduced pressure.

20. Remove the solvents under reduced pressure. Obtained 0.192 g of the final product of Eucalyptus oil-D-glucose.

While the invention has been described in detail with respect to the specific embodiments thereof, it will be appreciated that those skilled in the art, upon attaining an understanding of the foregoing, may readily conceive of variations and equivalents to these embodiments. Accordingly, the scope of the present invention should be assessed as that of the appended claims and any equivalents thereto.