AU2008100919A4 - Method for and Composition of Excipient Suitable for Use in Herbal Formulations and Formulations Derived Therefrom - Google Patents

Description

19/09 2008 FRI 14:30 FAX Smoorenburg Pinl IP AUSTRALIA R003/046 PU00002 Regulation 3.28

AUSTRALIA

Patents Act 1990

ORIGINAL

COMPLETE SPECIFICATION INNOVATION PATENT Application No.

Lodged: 19 September 2008 Innovation Title: METHOD FOR AND COMPOSITION OF EXCIPIENT SUITABLE FOR USE IN HERBAL FORMULATIONS AND FORMULATIONS DERIVED THEREFROM The following statement is a full description of this innovation, including the best method of performing it known to the Applicant, GreenTaste Pty Ltd: COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:30 FAX Smoorenburg Pinl IP AUSTRALIA Q004/046 00 2 METHOD FOR AND COMPOSITION OF EXCIPIENT SUITABLE FOR USE IN SHERBAL FORMULATIONS AND FORMULATIONS DERIVED THEREFROM FIELD OF INVENTION The present invention relates to the field of human and animal health, nutrition and wellbeing. In one form, the present invention relates to liquid formulations comprising excipients suitable for application in the ingestion of substances. It will be convenient to hereinafter describe the invention in relation to foods, beverages, supplements, active ingredients, excipients, natural or 00 synthetic, in their application to therapy, prevention, treatment, nutrition and diagnosis, however it should be appreciated that the present invention is not limited to that use, only.

BACKGROUND ART Throughout this specification the use of the word "inventor" in singular form may be taken as reference to one (singular) inventor or more than one (plural) inventor of the present invention.

Consumers have embraced the benefits of herbal medicine and nutritional supplements to the extent that the current widespread use is based on a combination of "mass market" acceptance, advice from complementary medicine practitioners and nutritionists, and an increasing endorsement from conventional medicine practitioners. Such acceptance is now driving practitioner and consumer/client expectations for more effective, better tasting and/or more efficacious forms of preventative healthcare and self-medication. Accordingly, herbal medicine is considered a major contributor to consumer health in Australia and the benefits are marketed through professional practitioner, retail and direct marketing channels.

Traditional liquid herbal formulations have an established market base through complementary health practitioners and a small market base in retail and direct marketing channels. In each of these marketing channels consumer acceptance is limited due to presence of alcohol, usually ethanol and/or glycerol, and taste characteristics that limit acceptance and compliance. Furthermore, the presence of alcohol in such formulations is contraindicated in a significant proportion of consumers with gastrointestinal or liver disease; who are pregnant; who have certain religious beliefs; who have a predisposed genetic susceptibility COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:30 FAX Smoorenburg Pini IP AUSTRALIA R005/046 00 3 to alcohol; who are taking certain other drugs; who have a history of alcoholism; e( d who are operating machinery, transport vehicles or aircraft under strict blood alcohol regulations; who are convalescing from medical intervention, or who are children.

Some compositions of liquid herbal medicines have attempted to reduce or overcome the issue of alcohol content in the formulations by substituting alcohol in the form of ethanol with another alcohol, glycerol. In these cases glycerol has _been used as a preservative and also as a taste modifier due to its artificial sweet 00 taste. Nonetheless, glycerol is also an alcohol, presents a glycaemic load, and for some has an unpleasant "mouth feel" and artificial taste.

The perceptions and effects of ingesting excipients of natural and nonanimal origin are of importance to consumers. Furthermore, in many existing products the source of glycerol is usually not disclosed to consumers and while glycerol from vegetable sources can be obtained, it is expensive and often mixed or substituted by glycerol produced as a by-product of biodiesel production or as a by-product from saponification of animal fat in soap making.

It is considered that the advantages of substituting glycerol for ethanol are that it has allowed removal of ethanol and provided for a degree of taste substitution in the formulations. However, there are significant disadvantages of using glycerol, in particular, the expense and often uncertain origin. Moreover, glycerols, being a form of alcohol, do not mean the resultant formulations are entirely free from alcohol. Glycerols also have an artificial taste. Furthermore, medicines based on botanical and fungal extracts are complex mixtures of chemical components, many of which are subject to oxidation and other chemical instabilities. Neither alcohols nor glycerol provide the required antioxidant and molecular stabilising properties. In contrast, components specifically conferring anti-oxidant properties enhance the stability of botanical and fungal extracts.

Other compositions of liquid herbal medicines have retained either an alcohol such as ethanol or, have used glycerol for their preservative function and added flavours (natural or synthetic) and/or fruit juice concentrates to address the unpleasant taste profile/s. The formulations which have added fruit concentrates and/or flavours have achieved a greater degree of taste modification, however, fruit concentrates, extracts, pulps, balms and flavours are very sensitive to COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:30 FAX Smoorenburg Plnl IP AUSTRALIA R006/046 00 4 oxidation and this sensitivity has an impact on the reliability of their taste Sproperties.

Also there may be a necessity for adding a benzoate for the preservation function, which is considered a significant disadvantage. Benzoates are found naturally in certain fruits and spices but are considered to have potential health implications that may be contrary to the fundamental benefits of health promoting herbal formulation(s).

Honey has occasionally been attempted as an alternative to alcohol or 00 glycerol, or in combination with reduced concentrations of alcohol and/or glycerol, but suffers from major drawbacks. At too low a concentration the sugar in honey can support fermentation by contaminating yeasts. At levels providing antimicrobial activity honey presents a high glycaemic load that is contraindicated in consumers with metabolic disorders, and limits flexibility with taste modification of herbal characteristics due to its dominating taste at such concentrations.

Generally, it can be stated therefore that three great disadvantages of current liquid herbal medicines exist; firstly, the presence of alcohol (including glycerol) in formulations which results in both health contra-indications and unpleasant taste contributing in turn to poor consumer compliance, secondly, the lack of acceptable alternative compositions to replace benzoate preservatives when required, and thirdly, the lack of specific antioxidants to stabilise actives as well as flavour-modifying juice extracts, concentrates, pulps, balms, sera and flavours.

It was previously known that licorice, stevia or other strong or sweet tasting herbs could be included as a taste modifier. If licorice or other naturally strong tasting herbs are added for taste modification effects, then either alcohol or benzoates are commonly added for preservative function. However, licorice for example is a valued active ingredient for specific indications and should not be used as a general excipient. Thus, due to its active constituents, licorice presents taste and compliance issues and importantly compromises regulatory status by using the "active" licorice as an "excipient", per se. Generally, while the liquid herbal product category is currently a relatively small niche, growth has been limited due to lack of innovation and the disadvantages of current offerings based COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:31 FAX Smoorenburg Pinl IP AUSTRALIA Q007/046 00 c on formulations containing alcohol, honey, glycerol and/or licorice, or benzoates C as taste-masking and/or preservative excipients.

The discussion throughout this specification comes about due to the realisation of the inventor and/or the identification of certain related art problems by the inventor and, moreover, any discussion of documents, devices, acts or knowledge in this specification is included to explain the context of the invention.

It should not be taken as an admission that any of the material forms a part of the C prior art base or the common general knowledge in the relevant art in Australia or 00 elsewhere on or before the priority date of the disclosure and claims herein.

SUMMARY OF INVENTION It is an object of the embodiments described herein to overcome or alleviate at least one of the above noted drawbacks of the related art or to at least provide a useful alternative to related art.

In a first aspect of embodiments described herein there is provided a composition of matter comprising an excipient for use in formulating ingestible substances wherein the excipient comprises one or a combination of: an organoleptic modifier of botanical origin; a herbal stabiliser; a herbal antimicrobial agent; an antifungal agent In one preferred form, the composition of matter may further comprise sorbate present in an acidic environment of less than about pH 6.5 and, in one alternate form, the antimicrobial agent may comprise benzoate.

Preferably, the organoleptic modifier comprises a selection of one or more of: botanical concentrates; botanical extracts; botanical sera; botanical juices; botanical pulps; essential oils; natural botanical flavours; synthetic botanical flavours.

The organoleptic modifier may be present in a concentration ranging from about 1% to about 99%.

The herbal stabiliser preferably comprises a botanical extract having antioxidant properties. The herbal stabiliser may be present in a concentration ranging from about 1:1 extract ratios to about 2 parts per million.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:31 FAX Smoorenburg Pinl IP AUSTRALIA Q008/046 00 6 C The herbal antimicrobial agent is preferably present in a concentration 0 ranging from about 1:1 extract ratios to about 2 parts per million The antifungal agent may be of botanical origin and is preferably present in a concentration ranging from about 1:1 extract ratios to about 10 parts per million.

In a second aspect the present embodiments provide a liquid herbal Sformulation comprising an excipient wherein the excipient comprises one or a Scombination of: a botanical stabiliser, and; a hops extract.

SIn a third aspect of embodiments, there is provided a liquid herbal 00 formulation comprising an excipient wherein the excipient comprises one or a combination of: a botanical stabiliser selected from one of rosemary extract, sage, thyme, vitamin E and witchhazel; an antimicrobial agent selected from one of a hops extract, alpha acids, beta acids, and benzoate, and; an antifungal agent selected from one of apple, cinnamon, cranberry, ginger, peppermint, sorbic acid, tea tree, and sorbate in an acid environment of less than about The botanical stabiliser is preferably rosmarinic acid that may be provided as a standardised rosemary extract. In preferred forms, a botanical stabiliser is provided by rosemary extract standardised to not less than about 4.5% rosmarinic acid and may be water soluble and/or deodorized.

The hops extract may comprise beta acids, which may be purified from hops. Preferably, the beta acids are present in a concentration of about and, in preferred forms the beta acids may comprise lupulone, colupulone, and adlupulone.

A liquid herbal formulation in accordance with preferred embodiments may further comprise sorbate wherein the sorbate is preferably present in a concentration of about 0.01% to about 1%.

In an alternate form, one embodiment provides a liquid herbal formulation as noted above in which the beta acids may be substituted, in whole or in part, with antimicrobially active benzoate.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:31 FAX Smoorenburg Pini IP AUSTRALIA 9009/046 00 7 N In another aspect of embodiments described herein there is provided a Smethod of manufacturing a liquid herbal formulation, the method comprising the steps of: mixing an excipient composition comprising one or a combination of an organoleptic modifier of botanical origin; a herbal stabiliser, a herbal antimicrobial Sagent and an antifungal agent of botanical origin in an aqueous solution; mixing at least one therapeutically active substance in an aqueous Ssolution; 00 combining the mixed excipient composition and the at least one mixed therapeutically active substance to a predetermined volumetric concentration in an aqueous solution.

The method preferably further comprises the steps of: separately weighing a predetermined required quantity of all ingredients, which may be listed as Parts A, B, C, D and E and storing these in suitable containers. In this example, Part A constitutes the active herbal ingredients (vitamin, pharmaceutical etc), Part B constitutes the antifungal agent, which preferably further comprises a predetermined amount of purified water at a pH of not more than about 6.5. Part C constitutes the organoleptic modifier(s), Part D constitutes the botanical stabiliser components. Part E may preferably constitute the antimicrobial agent and a predetermined amount of water at a pH of not less than about 7.

Preferably, the following blending steps are utilised: For Part B as described in the example above, the method may further comprise the step of heating the purified water to a temperature equal to or greater than about 25C then add the antifungal agent and mix until dissolved.

Check that the pH at no time exceeds about The method may further comprise the steps of: mixing Part E (the antimicrobial) with a pre-determined amount of purified water; mixing Part D (the herbal stabiliser) with a pre-determined amount of purified water; mixing components of Part C together.

blending each of these Parts B, D and E in turn with Part C, the organoleptic components.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:31 FAX Smoorenburg Pinl IP AUSTRALIA [010/046 00 8 i.e. with mixing commenced, add Parts B, D and E to Part C and mix until 0D blended evenly.

Slowly add Part A to mixture until all constituents are evenly dissolved.

Bring volume up to specified volume with additional purified water, all the time ensuring that the pH is less than approximately For formulations involving actives in Part A that are particularly "tarry" or hydrophobic e.g Hypericum perforatum, mixer speeds need to be high enough to Sensure a homogenous mixture.

0 Preferably, the method steps are performed at ambient temperature in the range of about 4°C about 300C.

In yet a further aspect of embodiments described herein there is provided a method of manufacturing an excipient composition for use in the formulation of ingestible substances, the method comprising the steps of segregating the above noted excipients into Parts B and C and processing each excipient in accordance with the above noted blending steps individually in isolation.

Other aspects and preferred forms are disclosed in the specification andlor defined in the appended claims, forming a part of the description of the invention.

In essence, embodiments of the present invention stem from the realization that natural extracts and/or compounds that are used in the sugar, food and beverage industries primarily for their taste modifying and preservative properties and being acceptable to regulatory authorities, practitioners and consumers can provide, in newly devised combinations, a substitute for alcohol or other active excipients in herbal formulations.

Advantages provided by the present invention comprise the following: Formulations in accordance with embodiments of the invention have a base of natural excipients, standardised concentrates or extracts thereof, or purified compounds of natural origin to preserve the active constituents in the absence of alcohol. Preferred formulations contain no added alcohol or glycerol, no sucrose, glucose or artificial sweeteners, no colours, no artificial flavours and no gluten. Accordingly, the relevant active constituents are fully active and the efficacy of traditional extracts is retained in the presence of the organoleptic modifiers; COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:31 FAX Smoorenburg Pinl IP AUSTRALIA [011/046 00 O 9 Preferred formulations contain specific components that are capable of slowing or preventing oxidation of other components in the formulation that are part of the active and organoleptic modifier function. Such components may comprise excipients with chemical properties exhibited by polyphenols, tannins, vitamins and thiols, all being examples of compound classes that inhibit oxidative reactions by being oxidized Sthemselves.

Preferred formulations may use stabilisers, antimicrobial and antifungal 00 Sexcipients in a form containing the most effective natural constituents in a C1 10 concentrated or purified form, thereby minimising unwanted components or interference with the active constituents; S The formulations of preferred embodiments are designed to be naturally pleasant tasting and palatable without undue masking of the taste of the herbal constituents or compromising gastrointestinal tract response to bitter principles and other active constituents; The components in the formulations of preferred embodiments are naturally occurring, and fully acceptable to regulatory authorities such as the Australian Therapeutic Goods Administration; Health contra-indications associated with alcohol, glycerol and honey are eliminated due to their absence, improving practitioner recommendation and consumer compliance, and increasing market penetration of the liquid herbal formulation market; Sweetening agents are not required due to elimination of alcohol and effective taste modification from the organoleptic taste modifiers; No licorice or other strong or sweet tasting herbs are used as a tastemasking and compromising excipient; Simplified manufacturing process provides high margins due to low costs of blending/mixing and packaging of herbal preparations; Elimination of the use of alcohol and other common additives in liquid therapeutic formulations and therefore also the contraindications and disadvantages associated with these.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:32 FAX Smoorenburg Pinl IP AUSTRALIA @012/046 00 0 010 Taste profiles of formulations are significantly improved by using natural excipients all of botanical origin.

Preservatives derived from plant origins are used for product stability.

Further scope of applicability of embodiments of the present invention will become apparent from the detailed description given hereinafter. However, it Sshould be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the 0 disclosure herein will become apparent to those skilled in the art from this detailed 0 10 description.

BRIEF DESCRIPTION OF THE DRAWINGS Further disclosure, objects, advantages and aspects of preferred and other embodiments of the present application may be better understood by those skilled in the relevant art by reference to the following description of embodiments taken in conjunction with the accompanying drawings, which are given by way of illustration only, and thus are not limitative of the disclosure herein, and in which: Figures la and lb are a graphical illustration of a High Pressure Liquid Chromatograpy (HPLC) elution profile for components in a dry extract of Siberian Ginseng and corresponding components detected in liquid compositions according to a preferred embodiment of the invention; Figure 2a and 2b are a graphical illustration of a High Pressure Liquid Chromatograpy (HPLC) elution profile for components in a dry extract of Panax Ginseng and corresponding components detected in liquid compositions according to a preferred embodiment of the invention; Figure 3a and 3b are a graphical illustration of a High Pressure Liquid Chromatograpy (HPLC) elution profile for components in a dry extract of St John's Wort and corresponding components detected in liquid compositions according to a preferred embodiment of the invention; Figures 3c and 3d are graphical representations of a mass spectrogram of components in a dry extract of St John's Wort and corresponding components detected in liquid compositions according to a preferred embodiment of the invention; COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:32 FAX Smoorenburg Pinl IP AUSTRALIA 1013/046 00 11 SFigure 3e is a graphical representation of a High Pressure Liquid Chromatograpy (HPLC) elution profile for components in a dry extract of St John's V) Wort and corresponding components detected at 520 nm in liquid compositions according to a preferred embodiment of the invention.

DETAILED DESCRIPTION For the purposes of this description, it is to be noted that, although it may be common in the art for usage of the term "herbal" to refer to herbal formulations Sand herbal medicines that predominantly include herbs, it is to be taken herein 00 that such compositions, in accordance with the present embodiments, may be derived not only from herbs per se but also from other botanical or fungal components and may further comprise nutritional supplements. Accordingly, compositions of the present embodiments may be derived from ingredients that may comprise herbs, spices, fruits, vegetables, fungi such as mushrooms and yeast as well as constituents of nutritional supplements such as, for example, vitamins, mineral salts, oils, glucosamine, etc. Accordingly, use of the term "herbal" in the appended claims is not limiting the claims to a particular botanical element or plant. Further, the term "herb" as used herein and in the appended claims may be taken as giving the same meaning as "herbal extract" or "active herbal constituent". "Complementary medicine" as used herein may also be taken as reference to "herbal medicine" and /or "nutritional medicine".

In preferred aspects of the present invention, the inventor has provided commercially useful solutions for the herbal medicine and associated pharmaceutical industry which offer liquid herbal formulations that are a) free from alcohol, b) stable using novel plant based preservatives and c) selectively taste modified. Furthermore, the use of glycerol in formulations has been addressed where the inventor has recognised that the taste aspect of glycerol is a question of degree. For instance, it may be better than alcohol and may also be influenced by the herbal constituents being used in formulations.

Preferred embodiments make use of excipients of botanical origin such as concentrates/juices/sera/pulps and essential oils to significantly enhance the taste profile of the formulations.

Preferred formulations in accordance with embodiments of the present invention desirably use herbal antimicrobial agents to replace the addition of COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:32 FAX Smoorenburg Pinl IP AUSTRALIA R014/046 00 0 12 benzoate/s which may confer unwanted health and/or consumer acceptance consequences. Although certain embodiments described herein may also include benzoate(s) as a preferred antimicrobial preservative.

A further preferred aspect of formulations according to embodiments of the invention is the use of herbal or vitamin stabilizers to preserve properties of the formulation.

It is highly preferable not to use excipient botanical extracts, such as C licorice, stevia, marshmallow and others as part of the therapeutic claims of the 00 formulation or to have such excipients at a level where they are conferring unwanted therapeutic or other side-effects.

In a preferred embodiment, botanical extracts with a known preservative property as exemplified in Appendix 2 are specifically identified and where possible concentrates are used that retain the active preservative constituents but reduce or eliminate other interfering constituents. For example, rosemary (Rosmarinus officinalis) is a known stabilising preservative. One of its constituents, rosmarinic acid is a highly effective natural antioxidant for the food, beverage and cosmetic industry. While crude herb extract can be used, it has a strong characteristic odour and the content of the specific components has not been optimized. In the case of using rosemary as a stabilizer, preferred embodiments use water soluble, deodorized rosemary extract standardised to not less than about 4.5% rosmarinic acid. It is considered that this has not been used before for liquid herbal formulations. For the purposes of this description, a stabilizer comprising rosemary is to be taken as reference to substances comprising rosemary extract derived from the plant source and standardised to contain rosmarinic acid.

Another example is provided by the antimicrobial action of hops (Humulus lupulus). Hops have been widely used in the brewing industry for their characteristic taste properties. More recently, the antibacterial activity of concentrated hops extracts has been used in the food, beverage and sugar industries. One of the constituents in hops, beta acids (comprising lupulone, colupulone and adlupulone), has properties similar to sodium benzoate and has been suggested as a substitute for this preservative in the food and beverage industries. While crude hops extracts can be used as an antimicrobial, they have COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:32 FAX Smoorenburg Pini IP AUSTRALIA 1015/046 00 13 a very bitter taste and other constituents that confer pharmacological activities. In 0) the case of using hops as an antimicrobial excipient a preferred embodiment uses beta acids extracted from hops and standardized to about 10% w/w. At the concentrations used in the preferred embodiments any bitterness or aroma is negligible. It is considered that this has not been used before for liquid herbal formulations. For the purposes of this description, a hops extract is to be taken as reference to substances comprising one or a combination of the following: a Sbase of hops, in particular beta fraction; hop extracts as may be known in the art, 0 0 in particular THIAA (tetrahydro-iso-alpha acid), RHO (dihydro-iso-alpha acid), isomerised hop extract (IHE), isomerised hop boiler extract, hop emulsion, beta emulsion One preferred embodiment is based on a unique approach to addressing five component areas when developing formulations for liquid medicines. An aim is to ensure effective formulations that achieve required taste modifications and profiles, and microbial and chemical stability in the absence of alcohol and without the addition of glycerol, honey, sugar, licorice, artificial sweeteners and other preservatives such as benzoates, which have undesirable attributes.

Preferred formulations are based on specific consideration of the following five component areas: 1. Herbal or pharmaceutical active(s) The choice of botanical, fungal, nutritional, that is herbal in this context or pharmaceutical actives depends on the therapeutic indication and label claims being sought. All dose levels and herb, nutritional supplement or drug specifications are chosen for the purpose of therapeutic claims and whenever possible, standardised extracts and components are preferred. It is also to be taken that herbal or pharmaceutical actives, in this context, may comprise nutritional supplements as may be known by the person skilled in the art.

2. Taste and organoleptic modifiers Taste and organoleptic modifiers of botanical, fungal or nutritional origin are chosen to achieve the desired level of taste modification or masking as well as modifying mouth feel. The type and amount of modifier depends on the herb, drug or their combinations to be included in the formulation and the quantity of the herbal extract or drug. Aligning the taste properties of the herbal extract(s) or drug(s) and modifiers is an COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:33 FAX Smoorenburg Pinl IP AUSTRALIA 016/046 00 14 Simportant aspect of achieving formulations acceptable to both practitioners and consumers. Whenever possible, standardised taste and organoleptic modifiers are preferred.

3. Stabiliser(s) Potential changes in formulation stability due to oxidation and changes in degree of polymerisation are minimised through the addition of specific botanical or nutritional extracts having anti-oxidant activity.

Whenever possible standardised stabilisers are preferred and antioxidant activity Sis due to the presence of, but not limited to, phenolic acid, carnosolic acid, 00 rosmarinic acid, camosic acid, caffeic acid, ursolic acid, betulinic acid, rosmaridiphenol and rosmanol. An example of standardisation is to use rosmarinic acid as a reference in the botanical stabiliser extract.

4. Antimicrobial(s) Potential endogenous or exogenous microbial contamination is managed through the addition of botanical extracts with strong anti-microbial action. Whenever possible, standardised and concentrated antimicrobials are preferred.

Food grade antifungal The spectrum of antimicrobial preservative activity is increased through specifically addressing the challenge potentially presented by yeast and fungal contamination through the addition of a food grade antifungal agent of natural origin.

Each of the above five components may be included in a preferred herbal formulation. When combined, these components may then be used to develop formulations containing single or multiple herbal, nutritional or pharmaceutical active ingredients.

An aim of preferred embodiments is to eliminate entirely the need for alcohol in the formulations (including its occasional substitute glycerol).

The elimination of alcohol from liquid herbal formulations means they can be prescribed and consumed by consumers who currently fall into the main contraindicated groups for whom alcohol is inappropriate including infants and children, the elderly, those with disturbed gastrointestinal tract function and/or liver damage, those convalescing from surgery, those requiring "zero" blood alcohol levels for equipment and vehicle operation, alcoholics, and those who are opposed to alcohol consumption.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:33 FAX Smoorenburg Pini -4 IP AUSTRALIA @017/046 00 O A significant issue for many consumers and their subsequent compliance Swith treatment or therapy is the unacceptable taste of liquid herbal medicines in r their current formulations. This poor taste arises from excipients such as alcohol, and excessive licorice, and the therapeutic herbal extracts themselves. A major challenge in the formulation of liquid herbal medicines has been the removal of Salcohol, which exacerbates the unpleasant taste of liquid formulations and heightens the need for powerful excipients to mask alkaloids, tannins and other potentially unpleasant tasting compounds in herbal extracts.

00 According to preferred embodiments, compliance may be enhanced through effective taste-modification with natural botanical extracts, juices, concentrates, pulps, sera as exemplified in Appendix 1 rather than the clumsy and suboptimal taste masking attempted through use of glycerol, licorice extract or honey. While a minority of consumers accept that the characteristic tastes of herbal extracts and alcohol are a part of treatment with complementary medicines, the majority of consumers find the taste unacceptable with the consequence that the compliance required for effective treatment with herbal medicines is significantly compromised.

Preservatives are necessary in all forms of liquid herbal extracts, without which the shelf-life of the medicines is compromised. Formulations according to preferred embodiments contain natural preservatives of botanical origin that ensure antimicrobial activity and allow development of formulations having an appropriate and acceptable shelf-life. The preferred excipients are highly effective preservatives conferring stabilisation and antimicrobial activities to the formulation, The preferred preservatives used are recognised safe preservatives used in the food and beverage industry. Such preferred formulations contain rosmarinic acid, beta acids and sorbate as preservatives.

It is advantageous to identify key parameters and quantities of specific classes of excipients that can be used to create a successful formulation. Once a particular herb extract(s), vitamin or drug(s) and/or herbal or pharmaceutical active is determined to form the basis for a formulation, the following is used to define the precise excipients and their quantities.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:33 FAX Smoorenburg Pini IP AUSTRALIA Q018/046 00 16 1. Taste and organoleptic modifiers The preferred taste and organoleptic modifiers are based on botanical concentrates, extracts, sera, juices, and pulps and essential oils and natural or nature identical fruit flavours.

Typically these are selected on a case by case basis from more than 200 potential modifiers. The specific choice depends on the purpose of the Sformulation, for example practitioner dispensed, retail sale or veterinary Sapplications, and the degree of taste modification that is required with respect to Seach active ingredient and active ingredient concentration. Typical modifiers are 00 listed in Appendix I 2. Stabiliser excipient(s) Typically, the stabilising component is based on a botanical extract with strong anti-oxidant properties such as rosemary extract, grape seed extract and other anti-oxidant extracts. Preferred stabilisers are listed in Appendix 2. The concentration of stabiliser used in a formulation depends on a) its impact on taste and organoleptic feel, b) any potential therapeutic effect or side effect conferred on the formulation, and c) the requirements for stabilisation related to specific herbal extracts and excipients.

Depending on the type and amount of active herb, vitamin or drug, the stabiliser would be added in concentrations ranging from 1:1 extract ratios to quantities as low as 2 parts per million. The stabilising properties are ideally conferred by, but not limited to, the presence of phenolic acid, camosolic acid, rosmarinic acid, carnosic acid, caffeic acid, ursolic acid, betulinic acid, rosmaridiphenol and rosmanol.

3. Antimicrobial excipients(s) Typically, the antimicrobial component is based on a botanical extract with strong antimicrobial properties such as hops extract, ginger extract and other antimicrobial herbal extracts that are not part of the therapeutic claims. Typical sources of antimicrobials are listed in Appendix 3.

The concentration of antimicrobial used depends on a) the requirement for antimicrobial action, b) estimated microbial load (qualitative and quantitative), c) any potential therapeutic effect or side effect conferred on the formulation and d) the impact on taste modification. Depending on the type and amount of active herb, vitamin or drug the antimicrobial would be added in concentrations ranging from 1:1 extract ratios to 2 parts per million. The antimicrobial activity can be conferred by a variety of components in botanical extracts described in Appendix COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:33 FAX Smoorenburg Pinl IP AUSTRALIA 1019/046 00 17 cN 3 and can be specifically exemplified by beta acids from hops. In an alternative J form, one preferred embodiment provides for benzoates to be included as an antimicrobial in the presence of a preferred antifungal as a substitute for ethanol in liquid botanical formulations.

4. Antifungal excipient(s) Formulations may also include addition of a specific antifungal excipient to provide additional protection from potential growth of yeast and fungal spores. Typical sources of antifungals are listed in Appendix S4. The concentration of antifungal used depends on the anticipated fungal load 00 and is up to that concentration permitted by regulatory authorities. The preferred antifungal excipient is sorbic acid and its salts and preferably, the sorbate is present in an acidic environment of less than about pH In one preferred form, beta acids may be provided in a concentration range of about 0.1% to about 10% and are combined with sorbates in a concentration range of about 0.01% to about In accordance with this embodiment, a synergistic effect is observed between the beta acids and sorbate enabling antifungal activity of the sorbates at the lower noted concentrations.

Many different single and multiple herb formulations have been created as exemplified in Examples 1, 2, 3, 6, 7, 8, 9, and Appendix 5. The degree of taste modification can be varied according to the desired active taste profile, for example but not limited to, the components listed in Appendix 1 without the need for adding artificial sweeteners or agents All formulations can be achieved using excipients of natural origin or derivation.

The inventor has worked with all the major herbal extracts used in consumer and practitioner products in Australia and has not observed drawbacks to the use of the preferred embodiments with respect to the major herbal extracts.

Manufacturing requires a simple three stage process, preferably at ambient temperature; a) mixing of each of four groups of excipients in water, b) mixing of actives together, where more than one are present and c) combining excipients and actives to volume with water. As an exemplary production method, manufacturing at approximately the 200 litre batch scale has been used to produce products in their final presentation form. Standard stock batch size is considered to be at least 2,000 litres.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:34 FAX Smoorenburg Pinl IP AUSTRALIA @020/046 00 0 18 Unlike other products, each formulation produced in accordance with 1) preferred embodiments comprises a distinct fruit flavour profile that best suits the Sactive constituents and also where possible reflects the functionality of the actives. It should be noted that there are two distinct markets for such formulations and these are diametrically opposed in terms of purpose for Sformulation. The retail market formulations need to reflect distinct functionality and concomitant flavour profiles in order to distinguish purpose. For the Spractitioner market the reverse is true. Each single (one active herbal constituent 00 only) herbal formulation for the practitioner market needs to be as uniform as possible within the group of formulations to enable inter-mixing by the practitioner for individualised prescription. The taste profile should remain as consistent as possible; a microcosm of a broader formulation which is made up at the point of sale for the consumer. Retail products by contrast need to be well differentiated from each other in both active constituents and flavour profile. Wherever possible the flavour profile should reflect functionality of formulation.

Examples of formulations: Example 1: Formulation for energy Each L of formulation contains extracts equivalent to the following: Eleutherococcus senticosus (Siberian ginseng) dry root 99.9g Schisandra chinensis (wu wei zi) 99.9g Glycyrrhiza glabra (licorice) dry rhizome 33.3 Panax ginseng (Korean ginseng) dry root 79.92g Withania somnifera (Winter Cherry) dry root 99.9g Apple juice concentrate 600g Lime juice concentrate 100g Lime flavour 1.25g West Indian Lime Oil (distilled) 1g Potassium sorbate Hops extract standardised to 10% beta acids 0.1g Rosemary extract standardised to NLT 4.5% rosmarinic acid 0.1g where "NLT" means "not less than".

Water to make 1 L COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:34 FAX Smoorenburg Pinl IP AUSTRALIA Q021/046 00 0 19 CI Example 2: Formulation for mood d Hypericum perforatum (St John's Wort) dry herb 133.2g Withania somnifera (winter cherry) dry root 66.6g Matricaria recutita (chamomile) dry flower 133.2g Passiflora incarnate (passionflower) dry herb 99.9g Zingiber officinale (ginger) dry root 13.26g Apple juice concentrate 450g SPassionfruit pulp .200g 00 Lemon serum 0 010 Passionfruit flavour Lemon oil distilled 2g Potassium sorbate Hops extract standardised to 10% beta acids 0.lg Rosemary extract standardised to NLT 4.5% rosmarinic acid 0.1g where "NLT" means "not less than" Water to make 1L Example 3: Formulation for female function Black cohosh formulation Cimicifuga racemosa (black cohosh) dried rhizome/root 74.07g Apple juice concentrate 150g Pear juice concentrate 100g Lemon serum Lemon oil Potassium sorbate Hops extract standardised to 10% beta acids 0.1g Rosemary extract standardised to NLT 4.5% rosmarinic acid 0.lg where "NLT" means "not less than".

Purified water to make 1L Detailed analyses of both specific actives in formulations of preferred embodiments of the invention have been undertaken by the Centre for Phytochemistry and Pharmacology at Southern Cross University (Lismore, NSW).

This research shows that products formulated using the preferred embodiments retain the identified actives and that the formulations did not modify or eliminate COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:34 FAX Smoorenburg Pini IP AUSTRALIA 1022/046 00 the presence of the key compounds. This preservation of the active herbal compounds after exposure to the taste and organoleptic modifiers is an important functional advantage for preferred embodiments of the invention.

Analyses using High Performance Liquid Chromatography and Mass Spectrometry (LC-MS) demonstrate that the active compounds in botanical extracts are unaltered by the preferred formulations and show quantitative equivalence after formulation. This is considered an important observation with Srespect to bioavailability.

0 0 The analytical evidence from the Centre for Phytochemistry, Southern 0 10 Cross University has established molecular integrity of specific active chemical components. For example, key entities in Echinacea are quantitatively present and detectable after formulation in accordance with preferred embodiments.

Successful accelerated stability tests examining microbiological contamination, appearance and flavour/aroma preservation have been undertaken for several formulations containing from one up to nine herbal extracts.

Example 4: Siberian Ginseng Figures la and lb illustrate the similarity in High Pressure Liquid Chromatograpy (HPLC) profile for components in a dry extract of Siberian Ginseng and components detected in liquid compositions according to preferred embodiments described herein.

LC (HPLC) data was obtained on an Agilent 1100SL LC-MSD. The LC was fitted with an Aqua C18, 125A, 5u, 150 x 4.6 mm if column (Phenomenex) at a column temperature of 40°C. The mobile phases consisted of A: 0.005% TFA in MilliQ water; B: 0.005% TFA in acetonitrile. The photodiode array detector was set to detection at 210 nm and 280 nm and scan (190 600 nm) spectral data with peakwidth at >0.1 min. The system data was controlled by Agilent Chemstation software.

Figure la shows a strong quantitative and qualitative similarity between elution profiles of the dry herbal extract active ingredient and its components recovered from the liquid formulation the subject of this preferred embodiment.

The main difference is seen in the specifically added preservatives the subject of this invention that elute at approximately 5.5 and approximately 10 minutes.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:34 FAX Smoorenburg Pinl IP AUSTRALIA Q023/046 00 21 Figure 1b presents a Total Ion Chromatograph (TIC) showing strong 0 similarity between profiles of drug actives and components recovered from the liquid formulation for Siberian Ginseng extract.

Example 5: Panax Ginseng Figures 2a and 2b illustrate the similarity in HPLC for components in a dry extract of Panax Ginseng and components detected in liquid compositions according to preferred embodiments described herein.

LC data were obtained on an Agilent 1100SL LC-MSD. The LC was fitted 0 with an Aqua C18, 125A, 5u, 150 x 4.6 mm if column (Phenomenex) at a column temperature of 40C. The mobile phases consisted of A: 0.005% TFA in MilliQ water; B: 0.005% TFA in acetonitrile. The photodiode array detector was set to detection at 210 nm and 280 nm and scan (190 600 nm) spectral data with peakwidth at >0.1 min. The system data was controlled by Agilent Chemstation software. Figures 2a and 2b show the strong similarity between elution profiles of the dry herbal extract and components recovered from the liquid formulation embodied in this embodiment. Critical to the quality of ginseng is the ginsengosides that elute between about 10.5 and about 16 minutes and these are all substantially unaffected by the liquid formulation. The additional component eluting in the liquid formulation at about 10 min is the introduced preservative.

Example 6: St John's Wort Figures 3a to 3e illustrate the similarity in HPLC and MS profile for components in a dry extract of St John's Wort and components detected in liquid compositions described herein.

LC-Mass Spectrometer (MS) data was obtained on an Agilent 1100SL LC- MSD. The LC was fitted with an Aqua C18, 125A, 5u, 150 x 4.6 mm if column (Phenomenex) at a column temperature of 40C. The mobile phases consisted of A: 0.005% TFA in MilliQ water; B: 0.005% TFA in acetonitrile. The photodiode array detector was set to detection at 210 nm and 280 nm and scan (190 600 nm) spectral data with peakwidth at >0.1 min. The SL1100 Series Mass Spectrometer Detector was in scan mode (100 1350 amu) using chemical ionisation as follows: ionisation voltage: 150 V (+ve mode) and 175 V (-ve mode); capillary voltage: 2000V; corona current: 8uA (both modes); drying gas flow: COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:34 FAX Smoorenburg Pinl IP AUSTRALIA I024/046 00 22 N L/min; drying gas temperature: 300C; vaporiser temperature: 320C; nebuliser qj pressure: 20 psig. The system data was controlled by Agilent Chemstation software.

Figures 3a and 3b illustrate the qualitative and quantitative recovery of components in St John's Wort detected at 280 nm and with respect to Total Ion Content (TIC). This recovery is also reflected in the Mass Spectrograms presented jn Figures 3c and 3d showing the recovery of the hypericin C components (MW around 520) and the quercetin glycosides (MW around 303)..

00 Figure 3e illustrates the recovery of the important hypericin components eluting after approximately 26, 28 and 31 minutes as detected at 520 nm and having a molecular weight of 522, 520 and 520 respectively. The suite of quercetin glycosides and aglycones eluting between about 7 and about 11 minutes as seen in Figure 3e was similar for the dry herbal extract (lower trace) and the components recovered from the liquid formulation (upper trace). These data illustrate the continued chemical integrity of key components of herbal actives after formulation according to this embodiment.

Example 7: Accelerated tests at 40°C showed the following formulation comprising two different active herbal extracts to be stable with respect to microbiological contamination, preservative levels, density, appearance, odour and aroma for more than 18 months. This composition comprises benzoate and sorbate as effective replacements for alcohol to result in stability equivalent to a three year shelf life at ambient temperature. Total aerobic microbial, yeast and mould plate count of less than 10 colony forming units per gram of formulation complied with British Pharmacopoeia standards and, appearance, odour, density and pH parameters demonstrated stability.

Composition per Litre wow% Eleutherococcus senticosus (siberian ginseng) 10:1 dry root extract 1.00 Paullinia cupana (guarana)5:1 dry rhizome 0.67 Apple juice concentrate Lime flavour 0.52 Potassium sorbate 0.25 Sodium benzoate 0.25 COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:35 FAX Smoorenburg Pini IP AUSTRALIA I025/046 00 8 23 SCitric acid 0.30 Purified water 71.99 Example 8: Accelerated stability tests at 30°C including aerobic plate count, yeast and mould, preservative efficacy revealed the following composition containing five Sdifferent active herbal extracts to be stable for more than 12 months. This composition contained rosmarinic acids, beta acids and sorbate as effective Sreplacements for alcohol.

00 Composition per Litre Eleutherococcus senticosus (siberian ginseng) 15:1 dry root extract Glycyrrhiza glabra (licorice) 4:1 dry rhizome 6.25g Panax ginseng (Korean ginseng) 10:1 dry root Schisandra chinensis (wu wei zi) 4:1 dry berry 12.5g Withania somnifera (winter cherry) dry root Apple juice concentrate 400g Lime juice concentrate 100g Lime flavour (Natural) Lime oil Ig Potassium sorbate Rosmarinic acids standardised to NLT 4.5% 0.07g Beta acids standardised to 10% 0.075g Purified water to make 1L where "NLT" means "not less than".

Microbiological analyses demonstrated that this formulation was stable.

Aerobic microbial and yeast and mould plate counts of less than 10 colony forming units per gram, and preservative efficacy challenge testing for fungi, yeast, mould and bacteria conform with the British Pharmacopoeia standard.

Example 9: Stability tests at 30°C including aerobic plate count, yeast and mould, preservative efficacy revealed the following composition containing six different active herbal extracts to be stable for 12 months. This composition contained rosmarinic acids, beta acids and sorbate as effective replacements for alcohol and has an effective shelf life at ambient temperature of more than two years.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:35 FAX Smoorenburg Pinl IP AUSTRALIA Q026/046 00 8 24 c Compositionper Litre SAvena sativa (Green oats) 3.5:1 Matricaria recutita (chamomile) 5:1 dry flower Passiflora incarnata (passionflower) 5.5:1 dry herb 4.55g Hypericum perforatum (St John's Wort) 6:1 herb tops 12.5g SWithania somnifera (winter cherry) 10:1 dry root 6.25g Zingiber officinale (ginger) 10:1 dry root 0 Apple juice concentrate 4 400g oO Lemon serum 0 010 Xanthan gum Potassium sorbate Beta acids standardised to 10% 0.

0 Rosmarinic acids standardised to NLT 4.5% 0.075g Passionfruit flavour (Natural) Lemon oil 1g Passionfruit pulp 300g Water to make 1L where "NLT" means "not less than".

Microbiological analyses demonstrated that this formulation was stable.

Aerobic microbial and yeast and mould plate counts of less than 10 colony forming units per gram, and preservative efficacy challenge testing for fungi, yeast, mould and bacteria conform with the British Pharmacopoeia standard.

Experience has shown that the compositions of preferred embodiments and the methods used to produce the compositions is reproducible and amenable to scaling with simple manufacturing steps at ambient temperature.

While this invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modification(s). This application is intended to cover any variations uses or adaptations of the invention following in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth.

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:35 FAX Smoorenburg Pinl IP AUSTRALIA Z027/046 00 CAs the present invention may be embodied in several forms without departing from the spirit of the essential characteristics of the invention, it should Sbe understood that the above described embodiments are not to limit the present invention unless otherwise specified, but rather should be construed broadly within the spirit and scope of the invention as defined in the appended claims.

_The described embodiments are to be considered in all respects as illustrative only and not restrictive.

_Various modifications and equivalent arrangements are intended to be 0 included within the spirit and scope of the invention and appended claims.

Therefore, the specific embodiments are to be understood to be illustrative of the many ways in which the principles of the present invention may be practiced. By way of example, in the following claims and where present, means-plus-function clauses are intended to cover structures as performing the defined function and not only structural equivalents, but also equivalent structures. For example, although a nail and a screw may not be structural equivalents in that a nail employs a cylindrical surface to secure wooden parts together, whereas a screw employs a helical surface to secure wooden parts together, in the environment of fastening wooden parts, a nail and a screw are equivalent structures.

"Comprises/comprising" when used in this specification is taken to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof." Thus, unless the context clearly requires otherwise, throughout the description and the claims, the words 'comprise', 'comprising', and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to".

COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:35 FAX Smoorenburg Pinl Ip AUSTRALIA Q028/046 00 8 26 N Appendix 1: Exemplary sources of taste and/or organoleptic modifying Sconcentrates, extracts, sera, juices, pulps, essential oils, natural flavours and synthetic flavours.

Acai, Acerola, Aloe vera, Aniseed, Apple, Apricot, Aronia, Avocado, Banana, Barley, Basil, Beetroot, Bilberry, Blackberry, Black cherry, Blackcurrant, Blood Sorange, Blueberry, Boysenberry, Brambleberry, Capsicum (green,) Capsicum (red,) Carrot, Celery, Cherry (sour), Cherry (sweet), Cinnamon, Citrus, Clove, SCoconut, Cranberry, Cumquat, Custard Apple, Date, Dragon fruit, Durian, 00 Elder(berry), Elderberry (flower), Eucalyptus, Feijoa, Fig, Ginger, Gooseberry, Grape, Grapefruit, Grapefruit pink, Guava, Honeydew, Illawara plum, Juniperberry, Kakadu plum, Kiwi, Lemon, Lemonbarley, Lemongrass, Lemonlime, Lemon myrtle, Lemon verbena, Licorice, Lime, Longan, Lychee, Mandarin, Mango, Melon, Menthol, Mixed Berry, Mulberry, Nectarine, Noni, Orange, Papaya, Passionfruit, Pawpaw, Peach, Pear, Peppermint, Pineapple, Pinelime, Plum, Pomegranate, Prune, Quince, Raisin, Raspberry, Redcurrant, Rhubarb, Rockmelon, Rosehip, Rosemary, Rubini, Spearmint, Spinach, Starfruit, Strawberry, Sultana, Tamarind, Tangerine, Teatree, Thyme, Tomato, Tropical blends, Tutti-frutti, Vanilla, Watermelon, Wheatgrass, Wildberry Appendix 2: Exemplary sources of botanical stabilisers Aloe, Artichoke, Bilberry, Blueberry, Buckwheat, Carotene, Cat's Claw, Ciderberry, Cranberry, Curcumin, Fennel, Ginger, Gingko, Grape seed, Hawthorn, Lavender, Lemon, Lemon balm, Licorice, Lycopene, Marjoram, Melissa, Mint, Olive, Oregano, Peppermint, Perilla, Pine bark, Pomegranate, Rosemary, Sage, St Mary's Thistle, Tea, Thyme, Turmeric, Vitamin

E,

Witchhazel Appendix 3: Exemplary sources of antimicrobial activities Andrographis, Apple, Arnica, Basil, Bearberry, Benzoates/benzoic acid, Berberis, Chamomile, Chaste tree, Chelidonium, Cinnamon, Citrus seed, Clove, Cranberry, Eyebright, Fennel, Feverfew, Forsythia, Garlic, Ginger, Hops, Hydrastis, Lemongrass, Licorice, Melilotus, Myrrh, Onion, Pau d'arco, Peppermint, Plums, Rosemary, Sage, Scutellaria, Thyme, Turmeric COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:35 FAX Snoorenburg PInI IP AUSTRALIA Q0I29/046 00 27 CIAppendix 4: Exemplary sources of antifungal activities Apple, Arnica, Cardemon, Chaste Tree, Cheledonium, Cinnamon, Citrus Seed, Clove, Cranberry, Cumin, Ginger, Nettle, Oregano, Pau d'arco, Peppermint, Plums, Rowan, Sorbates/sorbic acid, Tea Tree Appendix 5: Exemplary single active. component formulations Single active formulations: Achillea millefolium Yarrow flowers __Adhatoda vasica Adhatoda 00 Albizzia lebek Albizia Allium sativa/ ursinum garlic leaf/bulb Aloe vera/spp. Aloe sap Althaea officinalis Marshmallow root Andrographis paniculata andrographis root Anemarrhena asphodeloides Zhi mu root 'Anemone pulsatilla Pulsatilla Angelica sinensislpolymorpha Dong quai root Anthemis nobilis Chamomile flower Arctium lappa Burdock root Armoraceia rusticana Horseradish root Aronia melanocarpa Chokeberry fruit Aspalathus linearus Roolbos herb Asparagus lucidus Asparagus root Asparagus racemosus Shatavari root Astragalus membranaceous Astragalus root Atractylodes macrocephala Atractylodes root Avena sativa Oats seed/leaf Bacopa monniera Brahmi whole plant Beta vulgaris Beet root Boswellia serrata Boswellia gum Bupleurum falcatumn Bupleurum root Calendula officinalis Calendula/Marigold flowers Camellia sinensis Green tea leaf Capsicum annuum Capsicum fruit COMS ID No: ARCS-206804 Received by 113 Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:36 FAX Smoorenburg Pini IP AUSTRALIA R~030/046 00 00 Caulophylum thalictroides Centella asiatica Chamomilla recutita Cimicifuga racemosa Cinnamomum cassia Citrus aurantium Citrus reticulate Cnidium monieri Codonopsis pilosula Cordyceps sinensis Corydalis ambigua/fabacea Cranberry Crataegus monogyna/spp.

Crataegus monogyna/spp.

Crataegus pin natifida Crataeva spp Curcuma longa Cynara scolymus Dioscorea villosa Echinacea angustifolia Echinacea pallid Echinacea purpurea Eleutherococcus senticosus Epiloium parviflorum Epimedium sagittatumn Equisetum arvense Euphrasia officinalis Filipendula ulmaria Foeniculum vulgare Fucus vesiculosis Ganoderma lucidum Gentiana lutea Ginkgo biloba Blue cohosh Gotu kola Chamomile Black cohosh Cinnamon Bitter orange Chen pi Libidium Codonopsis Cordyceps Corydalis Hawthorn Hawthorn English hawthorn Varuna Turn eric Artichoke Wild yam Echinacea Echinacea Echinacea Siberian ginseng Epilobium Horny goat weed Horsetail Eyebright Meadowsweet Fennel kelp Reishi mushroom Gentian Ginkgo rhizome/roots leaf flowers rhizome/roots bark fruit peel fruit root mycelium tuber leaves berry fruit rhizome leaf rhizome root aerial parts aerial parts root herb leaf stem aerial parts flowers/I eaves sprout whole plant fruit root leaf COMS ID No: ARCS-206804 Received by 113 Australia: lime 14:36 Date 2008-09-19 19/09 2008 FRI 14:36 FAX Smoorenburg Pini IP AUSTRALIA Q~031/046 00 00 Glycine max Glycyrrhiza glabra Gymnema sylvestre Harpagophytum procumbens Hoodia gordonil Humufus lupulus Hydrastis Canadensis Hypericumn perforatum hnula helenjumn Juniperus communis Lentinula edodes Leonurus cardiac Ligusticum wallichi Lycium barbarum Magnolia officinalis Malpighia gibra Medicago sativa Mentha piperita Momordica charantia Morus alba Ocimomum tenuiflorum Olea europea Paeonia lactiflora/spp Panax ginseng Panax notoginseng Panax pseudoginseng Passiflora incarnata Perilla frutescens Petroselinum crispum Piper longum Piper nigrum Plantago asiatica Prunus Aficana soybean Licorice Gymenma Devils claw Hoodia Hops Golden seal St John's Wort Elecampane Juniper Shiitake Motherwort Cnidiumn Goji berry Magnolia Ace rola Alfalfa peppermint Bitter melon Mulberry Basil Olive Peony Korean ginseng Tienchi ginseng Sanchi ginseng Passionflower Perilla Parsley long pepper black pepper Plantago Pygeum seed root leaf tuber stem strobiles root aerial parts root berry mycelium aerial parts root fruit bark fruit sprout leaf fruit leaf whole plant leaf root root root root leaf seed/leaf leaf fruit fruit whole plant bark COMS ID No:ARCS-206804 Received by IP Australia: ime 14:36 Date 2008-09-19 19/09 2008 FRI 14:36 FAX Smoorenburg PIni IP AUSTRALIA Q03 2/046 00 00 Punica granatum Rehrnannia glutinosa Rhod iota rosea Ribes nigrumn Rosa canina Rosmarinus officinalis Rubus idaeus/spp Salix alba Salvia miltiorrhiza Salvia officinalis Sambucus nigra Schisandra chinensis Scuteilaria baicalensis Serenoa serrulata/repens Silybum maria num Smilax officinalis Stevia rebaudiana Tanacetum partheniumn Taraxacumn officinale Thymus vulgaris Tribulus terrestris Trifolium pratense Trigonella foenum-graecumn Turnera diffusa Uncarla tomentose Urtica dioica Vacciniumn myrtilus Valeriana officinalislspp Verbena officinalis Viburnum opulus Vitex agnus-castus Vitis vinifera/spp.

Withania somnifera Pomegranate seed Rehmnannia Rhodiola root Blackcurrant fruit Rosehip fruit Rosemary leaf Raspberry leaf leaf White willow bark Sage root Sage leaf Elderberry fruit Schisandra berry Baical skullcap root Saw palmetto fruit St Mary's thistle/Milk thistle seed Sarsaparilla leaf Stevia leaf Feverfew aerial parts Dandelion moot/leaf Thyme leaf Tribulus fruit Red clover aerial parts Fenugreek seed Damiana leaf Cat's claw Nettle leaf berry Valerian root Vervain aerial parts Cramp bark bark Chaste tree berry Grape fruit Withania root COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:36 FAX Sfloorenburg Pini IP AUSTRALIA Q~033/046 00 Zanthoxyllumn clava-herculislspp.

Zingiber officinalis Zizyphus spinosa.

Prickly ash Ginger Zizyphus bark root COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19

Claims (4)

1. A composition of matter comprising an excipient for use in formulating ingestible substances wherein the excipient comprises one or a combination of: an organoleptic modifier of botanical origin; Sa herbal stabiliser; a herbal antimicrobial agent; San antifungal agent. 00

2. A composition of matter as claimed in claim 1 further comprising sorbate present in an acidic environment of less than about pH 6.5 and wherein the antimicrobial agent comprises benzoate.

3. A liquid herbal formulation comprising an excipient wherein the excipient comprises one or a combination of: a botanical stabiliser selected from one of rosemary extract, sage, thyme, vitamin E and witchhazel; an antimicrobial agent selected from one of a hops extract, alpha acids, beta acids, and benzoate, and; an antifungal agent selected from one of apple, cinnamon, cranberry, ginger, peppermint, sorbic acid, tea tree, and sorbate in an acid environment of less than about

4. A method of manufacturing a liquid herbal formulation, the method comprising the steps of: mixing an excipient comprising one or a combination of an organoleptic modifier, a herbal stabiliser and, a herbal antimicrobial agent in an aqueous solution; mixing at least one therapeutically active substance in an aqueous solution; combining the mixed excipient and mixed therapeutically active substance to a predetermined volumetric concentration in an aqueous solution. COMS ID No: ARCS-206804 Received by IP Australia: Time 14:36 Date 2008-09-19 19/09 2008 FRI 14:36 FAX Smoorenburg PIni 4. IP AUSTRALIA i0J03 5/046 00 33 A liquid herbal preparation comprising a composition of matter as claimed in claim I or 2 or a formulation as claimed in claim 3. 00 COMS ID No: ARCS-206804 Received by IP Australia: lime 14:36 Date 2008-09-19