WO2010075611A1

WO2010075611A1 - Composition comprising proanthocyanidin, proteolytic enzyme and aloe vera/agave species substance

Info

Publication number: WO2010075611A1
Application number: PCT/AU2010/000005
Authority: WO
Inventors: Victor Patrick Davidson
Original assignee: Bio - Enhancements Pty Ltd
Priority date: 2009-01-05
Filing date: 2010-01-04
Publication date: 2010-07-08

Abstract

A composition comprising a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species, the composition being free of papain. Use of the composition for improving athletic performance, for improving health and wellbeing, for use as a sports isotonic drink or for the treatment of a condition selected from multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver disease and kidney disease.

Description

COMPOSITION COMPRISING PROANTHOCYANIDIN, PROTEOLYTIC ENZYME AND ALOE VERA/AGAVE SPECIES SUBSTANCE

Technical Field

The present invention relates to a composition containing proanthocyanidin and to uses of the composition.

Background of the Invention

Proanthocyanidin, sometimes referred to as procyanidin, oligomeric proanthocyanidin (OPC), Pycnogenol®, leukocyanidin or leucoanthocyanin is an oligomeric or polymeric species derived from flavonoids such as catechins. It has been linked with health effects associated with its antioxidant and vasodilatory effects. There is however a need for an improved composition of proanthocyanidin which provides bettei bioavailability for the active ingredients. There is also a need for an improved understanding of the range of health benefits which may be addressed by means of such compositions.

Object of the Invention

It is the object of the present invention to at least partially address at least one of the above needs.

Summary of the Invention

Disclosed herein is a composition comprising:

• a proanthocyanidin;

• a proteolytic enzyme; and

• a substance derived from Aloe Vera and/or from a plant of the Agave species.

The proteolytic enzyme may have one or more, optionally all, of the following properties:

• anti-inflammatory activity, optionally by multiple mechanisms;

• lack of undesirable side effects such as hypersensitivity (allergic) reactions, hypotension (low blood pressure), tachycardia (rapid heart rate), vision loss, which have been attributed to papain;

• capable of enhancing absorption into a patient of other substances, e.g. antibiotics;

• capable of modulating the immune system - it may be capable of adjusting components (e.g. hormones etc.) of the immune system to desired or normal levels;

• immunostimulatory properties - effectiveness in the treatment and/or management of autoimmune disorders;

• capable of preventing or inhibiting platelet aggregation and blood clotting;

• anti-oedema activity; • anti-tumour activity;

• effectiveness in reduction of swelling;

• capability to maintain its biological activity in both the acid (e.g. stomach) and the alkaline (e.g. small intestine) environments;

• not broken down in the digestive tract (i.e. absorbed intact, enabling systemic or whole body effects).

The proteolytic enzyme may comprise bromelain. The composition should not contain papain.

In a first aspect of the invention there is provided a composition comprising:

• a proanthocyanidin;

• a proteolytic enzyme; and

• a substance derived from Aloe Vera and/or from a plant of the Agave species; wherein said composition does not comprise papain.

The following options may be used in conjunction with the first aspect, either separately or in any suitable combination.

The proanthocyanidin may be oligomeric. It may be obtained from a source selected from the group consisting of bark of a French Maritime Pine tree, grape seed and bark of a Pinus radiata tree. It may be, or may comprise, an extract from the bark of the French Maritime Pine tree.

The proteolytic enzyme may have any one or more, optionally all, of the properties listed above. It may be a digestive enzyme. It may be, or may comprise, bromelain. It may be such that it does not cause (or may be such that it is not capable of causing) hypersensitivity reaction. It may have anti-inflammatory activity.

The substance derived from Aloe Vera and/or from a plant of the Agave species may be, or may comprise, an extract of Aloe Vera or of a plant of the Agave species. It may be, or may comprise, a juice of Aloe Vera or of a plant of the Agave species, or a concentrate thereof. It may be, or may comprise, a powder obtained by drying a juice of Aloe Vera or of a plant of the Agave species. It may be, or may comprise, an Aloe Vera extract. It may be Aloe Vera juice. It may be Aloe Vera juice concentrate. It may be a powder obtained by drying Aloe Vera juice. The plant of the Agave species may be Century Plant, American Aloe, False Aloe, Flowering Aloe, Spiked Aloe or Maguey. The substance may be, or may comprise, a combination of substances from these different plants. The ratio of the amount of proanthocyanidin to the amount of proteolytic enzyme in the composition maybe between about 1 and about 1.5 (i.e. about 1:1 to about 1.5:1) on a weight basis.

The proanthocyanidin and the proteolytic enzyme in combination may be present in an amount about 1 to about 1.5% on a weight/weight or a weight/volume basis relative to the substance derived from Aloe Vera and/or from a plant of the Agave species.

The composition may be acidic. It may be pH about neutral. The composition may additionally comprise an organic acid, preferably a non-toxic organic acid such as a food acid. The organic acid may comprise, or may be, acetic acid. The composition may have a pH of about 2 to about 7, or about 3 to 7, 4 to 7, 5 to 7, 2 to 5 or 3 to 6, e.g. about 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 or 7.

The composition may additionally comprise a saccharide. The saccharide may be a fructan. The saccharide may comprise sucrose, maltodextrin, inulin or a combination of any two or all of these.

In an embodiment there is provided a composition comprising:

• an oligomeric proanthocyanidin;

• bromelain; and

• Aloe Vera juice; wherein the ratio of proanthocyanidin to bromelain is between about 1 and about 1.5 on a weight basis and the proanthocyanidin and bromelain in combination are present in an amount about of 1 to about 1.5% on a weight/volume basis relative to the Aloe Vera juice, and wherein said composition does not comprise papain.

In another embodiment there is provided a composition comprising:

• an oligomeric proanthocyanidin;

• bromelain;

• Aloe Vera juice;

• acetic acid; and

• a fructan, for example inulin; wherein the ratio of proanthocyanidin to bromelain is between about 1 and about 1.5 on a weight basis, the proanthocyanidin and bromelain in combination are present in an amount of about 1 to about 1.5% on a weight/volume basis relative to the Aloe Vera juice, the vinegar is present in a ratio of about 10 to about 15% relative to the Aloe Vera juice and the fructan is present in an amount about 1 to about 2 times that of the combined proanthocyanidin and bromelain by weight, and wherein said composition does not comprise papain.

In another embodiment there is provided a composition comprising:

• an oligomeric proanthocyanidin;

• bromelain;

• Aloe Vera juice;

• acetic acid; and

• an oligosaccharide, for example maltodextrin; wherein the ratio of proanthocyanidin to bromelain is between about 1 and about 1.5 on a weight basis, the proanthocyanidin and bromelain in combination are present in an amount of about 1 to about 1.5% on a weight/volume basis relative to the Aloe Vera juice, the vinegar is present in a ratio of about 10 to about 15% relative to the Aloe Vera juice and the oligosaccharide is present in an amount about 10 to about 50 times that of the combined proanthocyanidin and bromelain, and wherein said composition does not comprise papain.

The preparation may be suitable for ingestion, e.g. oral ingestion, by a patient.

In a second aspect of the invention there is provided the use of a composition according to the first aspect for improving athletic performance or for improving health and wellbeing or as an isotonic drink. There is also provided the use of the composition for the treatment of multiple sclerosis or cancer and/or for management of symptoms and/or signs therof. There is further provided the use of the composition for treatment of one or more of diabetes, hypercholesterolemia, asthma, heart disease, liver disease and kidney disease and/or for management of symptoms and/or signs therof. In all of the above cases the preparation should be administered internally, e.g. by mouth. In the context of the present specification, liver disease and kidney disease should be taken to encompass liver disfunction and kidney disfunction respectively.

In a third aspect of the invention there is provided a method for treating a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver disease and/or disfunction and kidney disease and/or disfunction, said method comprising administering to a patient in need thereof a composition according to the first aspect. The administering may comprise orally administering. There is also provided a method for management of symptoms and/or signs of said condition, said method comprising administering to a patient in need thereof a composition according to the first aspect. In a fourth aspect of the invention there is provided a process for making a composition for improving athletic performance or for improving health and wellbeing or for use as a sports isotonic drink or for the treatment of a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver disease and/or disfunction and kidney disease and/or disfunction, said process comprising combining a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species, wherein said proteolytic enzyme is not papain.

The proteolytic enzyme may have anti-inflammatory activity. It may not cause hypersensitivity reaction. It may be bromelain. The combining may also comprise combining said components with a water soluble organic acid. The organic acid may be acetic acid. The acetic acid may be in the form of glacial acetic acid. It may be in the form of vinegar. The process may be such that no papain is added.

In a fifth aspect of the invention there is provided the use of a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species for the manufacture of a medicament for improving athletic performance or for improving health and wellbeing or for use as a sports isotonic drink or for the treatment of a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver disease and/or disfunction and kidney disease and/or disfunction, or for management of symptoms and/or signs of said condition, or for any two or more of these applications, wherein said enzyme is not papain. The proteolytic enzyme may have anti-inflammatory activity. It may not cause hypersensitivity reaction. It may be bromelain.

In a sixth aspect of the invention there is provided a process for preparing a composition, said method comprising combining a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species. The combining may be such that it does not comprise addition of papain. The invention also comprises a composition made by this process.

Brief Description of the Drawings

A preferred embodiment of the present invention will now be described, by way of an example only, with reference to the accompanying drawings wherein: Figure 1 shows an MRI taken on 15 Aug 2001 - see Example 5; and Figure 2 shows an MRI taken on 3 Nov 2003 - see Example 5. Detailed Description of the Preferred Embodiments

The composition of the present invention is a very strong antioxidant. The particular combination of components used in the composition, particularly in the quantities described herein, causes a cascade of physiological events which increases the bioavailability of those components and thereby improves the potency of the composition. This thereby provides the beneficial effects that have been observed following ingestion of the composition. The inventor considers that beneficial effects on blood cholesterol levels, diabetes, injury repair and further athletic parameters may arise from use of the present composition. The compositions of this invention have been used in the treatment of multiple sclerosis and demyelination, several oncological conditions, fatigue syndromes and physiological recuperation. In the context of the present specification, where reference is made to "treatment" of a condition, this may refer to administration of the composition to a patient for the purpose of managing and/or alleviating and/or relieving symptoms and/or signs of the condition in said patient. It may refer to administration of the composition to the patient for the purpose of at least partially curing the condition. It may refer to administration of the composition to the patient for both of these purposes. In some cases the treatment may not result in a change in the pathology of a condition, but rather may rely only on the potential to change the experience of symptoms of a condition and/or signs of that condition.

The composition may be made from natural ingredients, optionally only from natural ingredients. The proanthocyanin, the proteolytic enzyme and the substance derived from Aloe Vera and/or from a plant of the Agave species may all be natural ingredients. As many people prefer to use products, particularly health and wellbeing promoting products, that are derived from natural sources, this feature may be a benefit of the present composition. The composition may in some embodiments contain no synthetic ingredients. In certain embodiments of the invention, the proteolytic enzyme serves to improve bioabsorption of the proanthocyanin and of one or more compounds present in the substance derived from Aloe Vera and/or from a plant of the Agave species.

The composition may be substantially non-toxic. In particular it may be substantially non-toxic to humans, or to the subject to whom it is administered. In this context, "non-toxic" indicates that at the normal dose at which the composition is administered in order to obtain the desired effect, it does not cause adverse effects (e.g. death) to the subject to whom it is administered. The composition may be orally administrable. It may not cause a hypersensitivity reaction in said subject. It may contain no enzymes that cause a hypersensitivity reaction when administered to a subject. It will be recognised that certain individuals may have sensitivity to substances which do not cause hypersensitivity reactions in the vast majority of people and which are not generally regarded as sensitisers. In the present context therefore, where reference is made to a substance not causing a hypersensitivity reaction, it should be taken to indicate that the substance will not cause a hypersensitivity reaction in the majority of individuals, e.g. in at least about 95% of the population, or at least about 99, 99.5 or 99.9% of the population. The composition of the present invention comprises a proanthocyanidin, a proteolytic enzyme having anti-inflammatory activity and a substance derived from Aloe Vera and/or from a plant of the Agave species.

Proanthoevanidin: The proanthocyanidin may be obtained, e.g. extracted, from a plant source. The plant may be for example a pine tree (the proanthocyanidin may be obtained from the bark thereof), grape (the proanthocyanidin may be obtained from the seeds and or the skins), bilberry, cranberry, black currant, chokeberry (particularly the berries, preferably of the black chokeberry), tea or some other plants. The proanthocyanidin may be oligomeric. It may be obtained from a source selected from the group consisting of bark of a French Maritime Pine tree, grape seed and bark of a Pinus radiata tree. It may be an extract from the bark of the French Maritime Pine tree.

Proteolytic enzyme: Proteolytic (or digestion) enzymes break down or hydrolyse proteins e.g. during digestion. They therefore occur naturally in the digestive tract of animals where they are partially responsible for the digestive process. They may also occur inside cells, especially in lysosomes. The proteolytic enzyme may be, or comprise a protease or proteinase. The proteolytic enzyme may for example be bromelain. Bromelain is a mixture of proteases with other substances including peroxidase, acid phosphatase, protease inhibitors and calcium. The proteases in bromelain include stem bromelain (EC 3.4.22.32) and fruit bromelain (EC 3.4.22.33 ). The proteolytic enzyme is not papain. The composition contains no papain. The FDA (US Food and Drug Administration) has warned companies to stop marketing topical drug products containing papain by 4 November, 2008. The FDA has said "No topical drug product containing papain has been approved by the FDA." According to the FDA's statement on the subject, "These unapproved products have put consumers health in jeopardy, from reports of permanent vision loss with unapproved balanced salt solutions to a serious drop in blood pressure and increased heart rate from the topical papain products. Topical drug ointments containing papain are used to remove dead or contaminated tissue in acute and chronic lesions, such as diabetic ulcers, pressure ulcers, varicose ulcers and traumatic infected wounds. The FDA has received reports of serious adverse events in patients using products containing papain. Reports include hypersensitivity (allergic) reactions that lead to hypotension (low blood pressure) and tachycardia (rapid heart rate). In addition, patients may be allergic to papaya, the source of papain. Therefore, patients with latex sensitivity may be at increased risk of suffering an adverse reaction. Substance derived from Aloe Vera and/or from a plant of the Agave species: Aloe Vera taken orally has been found to improve blood glucose levels in diabetics, and to lower blood lipids in hyperlipidaemic patients. It has also been found to be useful in reducing inflammation in patients with ulcerative colitis, and it may also find application as an immunostimulant for treatment (e.g. management of symptoms and/or signs) of cancers. Extracts of Aloe Vera have been shown to exhibit antibacterial and antifungal activities. They have been shown to contain a variety of biologically active substances including acetylated mannans, polymannans, anthraquinone C-glycosides, anthrones, anthraquinones and lectins. The substance derived from Aloe Vera may be a solid or it may be a liquid. It may be a dried extract or dried juice (e.g. a freeze dried extract). It may comprise Aloe Vera juice or Aloe Vera juice concentrate. It may comprise any one or more, optionally all, of the biologically active substances listed above. It may additionally or alternatively comprise a substance derived from a plant of the Agave species (e.g. a juice, juice concentrate, dried juice etc.). Suitable such plants include Century Plant, American Aloe, False Aloe, Flowering Aloe, Spiked Aloe or Maguey. The substance may be combination of individual substances, each of which may be obtained from one or more of the above mentioned plants. It may comprise a substance (e.g. a plant extract or plant derived substance) having similar or equivalent biological activity to Aloe Vera juice.

The proanthocyanidin may be present in an amount approximately the same as the amount of proteolytic enzyme or greater than the amount of proteolytic enzyme. The ratio of the amount of proanthocyanidin to the amount of proteolytic enzyme may be about 1 to about 1.5 on a weight basis, or about 1 to 1.2, 1.2 to 1.5 or 1.2 to 1.4, e.g. about 1, 1.1, 1.2, 1.3, 1.4 or 1.5. The proanthocyanidin may represent about 0.2 to about 0.3 wt% of the composition, or about 0.2 to 0.25, 0.25 to 0.3 or 0.22 to 0.27 wt%, e.g. about 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29 or 0.3 wt%. The amount of proteolytic enzyme may be about 0.15 to about 0.25 wt% of the composition, or about 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.25 or 0.25 wt% of the composition. The proanthocyanidin and the proteolytic enzyme in combination may be present in an amount about 1 to about 1.5% on a weight/weight or a weight/volume basis relative to the substance derived from Aloe Vera and/or from a plant of the Agave species, or about 1 to 1.3, 1.2 to 1.5 or 1.2 to 1.4%, e.g. about 1 , 1.1 , 1.2, 1.3, 1.4 or 1.5%.

The substance derived from Aloe Vera and/or from a plant of the Agave species may be present in the composition between about 10 and about 50%, or about 10 to 40, 10 to 30, 20 to 50, 30 to 50 or 20 to 40%, e.g. about 10, 15, 20, 25, 30, 35, 40, 45 or 50 % on a w/v or v/v basis. It may be present in a smaller quantity, e.g. about 1 to about 5% (particularly in a composition that is diluted from a pre-prepared concentrate), or about 1 to 3, 3, to 5 or 2 to 4%, for example about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5% (w/w or w/v). The quantity will depend on whether a juice, extract, juice concentrate or powdered juice is used, as well as on which plant said substance is derived from. It may be present at about 5 to about 10%, or about 5 to 8 or 7 to 10%, e.g. about 5, 6, 7, 8, 9 or 10%.

In the proportions stated above it should be recognised that the substance derived from Aloe Vera and/or from a plant of the Agave species is commonly an extract or a juice of a plant or a concentrate of such an extract. As such it commonly comprises significant amounts of water. It may comprise about 0.1 to about 20% solids, the remainder being essentially water. It may comprise about 0.1 to 10, 0.1 to 5, 0.1 to 2, 0.1 to 1, 1 to 20, 2 to 20, 5 to 20, 10 to 20, 1 to 10, 1 to 5, 0.5 to 5 or 0.5 to 2% solids, e.g. about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% solids. In the event that the substance is a concentrate, or a dried extract, the ratios defined herein may be adjusted to account for the loss of water from the original extract or juice.

The composition may additionally comprise an organic acid. The organic acid may be, or may comprise, a water soluble organic acid. It may comprise acetic acid or propanoic acid or a mixture of these. It may be a non-toxic or low toxicity organic acid. The organic acid may be present in a matrix. For example acetic acid may be present as a component of vinegar, which may be used in making the composition. It may be added to the composition in the form of glacial acetic acid. The organic acid may be present at up to about 0.25% w/v of the composition, or up to about 0.2, 0.15, 0.1, 0.05, 0.025 or 0.01%, e.g. about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.24 or 0.25%. It may be added to the composition in the form of vinegar which is between about 0.4 and 0.6% acetic acid by volume. Commonly if the composition is to be used as a food, the organic acid may be added in the form of vinegar. However if the composition is to be made as a medication, it may be advantageous to add the organic acid as an appropriate amount of glacial acetic acid so as to meet requirements of the TGA (Therapeutic Goods Administration) for OTC (over the counter) medications manufactured in a GMP (good manufacturing practice) facility.

Some of the embodiments of the inventions will be concentrates, which may be diluted before use. The concentrations of the active components will be correspondingly higher in such concentrates. The concentrates may be diluted between about 2-fold and about 50-fold before use. Suitable dilution ratios (defined as the ratio of the volume of concentrate to the volume of the diluted composition) are from about 2 to about 50, or about 2 to 20, 2 to 10, 2 to 5, 5 to 50, 10 to 50, 20 to 50, 5 to 20, 5 to 10, 10 to 20 or 5 to 15, e.g. about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45 or 50. The dilution ratio may be dependent on the desired application for the diluted composition as well as the nature of the concentrate and the concentration of individual components in the concentrate. The stated concentrations of components may vary from the stated ranges depending on whether the composition is a concentrate or is a diluted version of the composition.

The composition may additionally comprise a saccharide or more than one saccharide, each of which may be a monosaccharide (e.g. glucose), a disaccharide (e.g. sucrose), an oligosaccharide or a polysaccharide (e.g. inulin, maltodextrin). The saccharide may comprise sucrose, maltodextrin, inulin or a combination of any two or all of these. The amount of saccharide may depend on the nature of the saccharide. The (or each) saccharide may, if present, be present at up to about 10% w/v, or up to about 5, 2, 1, 0.5, 0.2 or 0.1%, e.g. about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10% w/v, in the composition. Commonly monosaccharides and disaccharides (if present) will be present in larger amounts, e.g. about 2 to about 10%, whereas oligosaccharides and polysaccharides (if present) will be present in smaller amounts e.g. up to about 2%.

The composition may additionally comprise any one or more, optionally all, of the following:

• a sodium salt, for example sodium chloride, equivalent to about 0.01 to about 0.5% sodium w/v, or about 0.01 to 0.2, 0.01 to 0.1, 0.01 to 0.05, 0.05 to 0.5, 0.1 to 0.5, 0.2 to 0.5, 0.05 to 0.2 or 0.1 to 0.2%, e.g. about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45 or 0.5% sodium; • a potassium salt, for example potassium chloride, equivalent to about 0.01 to about 0.2% potassium w/v, or about 0.01 to 0.1, 0.01 to 0.05, 0.05 to 0.2 or 0.1 to 0.2%, e.g. about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15 or 0.2% potassium;

• water, preferably purified (for example filtered, microfϊltered, reverse osmosis treated, ultrafiltered, deionised, distilled, carbon filtered, sterilised, UV treated or water treated by any two or more of these) — purified water may represent up to about 75% of the composition, or up to about 60% or up to about 50%, and may for example represent about 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70 or 75% of the composition;

• one or more flavourings for example a berry flavour (e.g. strawberry, raspberry, blueberry etc.) in a quantity sufficient to provide the composition with an acceptable or pleasing flavour;

• one or more preservatives, for example sodium benzoate and/or potassium sorbate (each, or in combination, suitably about 50 to about lOOmicrograms/ml, e.g. about 50, 60, 70, 80, 90 or 100 micrograms/ml).

Suitable compositions according to the invention include: Composition A

Oligomeric proanthocyanidin 2-3 g

Proteolytic enzyme 1.5-2.5g

Aloe Vera extract 300-40Og

Purified water to 1 litre total volume of composition Composition B

Oligomeric proanthocyanidin 2-3g

Bromelain 1.5-2.5g

Vinegar 30-50ml or about l-3ml glacial acetic acid

Aloe Vera juice 300-400ml

Sodium chloride 2-4 grams

Inulin plant sugar 5-10 grams

Flavouring

Preservatives

Purified water to 1 litre total volume of composition Composition C

Sodium chloride 100-200 mg Potassium chloride 50-100mg

Sucrose 25-50 grains

Maltodextrin 5-15 grams

Oligomeric proanthocyanidin 100-200 mg

Bromelain 100-150 mg

Aloe Vera extract 15-25 ml

Vinegar 2-3 ml

Flavouring

Food acids

Purified water to 600ml total volume of composition

The composition described may be used for improving athletic performance or for improving health and wellbeing or as a sports isotonic drink, or for the treatment (e.g. management of symptoms and/or signs) of multiple sclerosis or cancer. The composition may be used to improve one or more (optionally all) of endurance, strength, power and speed in subjects engaged in sporting, athletic or other physical activity. In order to achieve these effects, a suitable quantity of the composition should be ingested between about 1 and about 3 hours (e.g. about 1, 1.5, 2, 2.5 or 3 hours) prior to commencing the activity. It should be ingested in an amount of about 10 to about 1000ml, or about 10 to 500, 10 to 250, 10 to 100, 10 to 50, 50 to 1000, 100 to 1000, 250 to 1000, 500 to 1000, 50 to 500, 50 to 250, 100 to 500 or 100 to 300ml, e.g. about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900 or 1000ml. The resulting improvement in performance (e.g. as described above) may be about 10 to about 50%, or about 10 to 25, 20 to 50, 15 to 30 or 15 to 25%, e.g. about 10, 15, 18, 20, 25, 30, 35, 40, 45 or 50%. The amount ingested may be sufficient to achieve this improvement.

The composition may be used to improve general wellbeing in a subject. In order to achieve this, a quantity of the composition of about 20 to about 100ml should be ingested daily, or about 20 to 50, 50 to 100, 30 to 70 or 40 to 60ml, e.g. 20, 30, 40, 50, 60, 70, 80, 90 or 100ml. Alternatively a smaller amount may be ingested more frequently (e.g. twice or 3 times daily) or a larger amount may be ingested less frequently (e.g. every 2, 3 or 4 days).

The subject may be a human subject. The subject may be a non-human subject, for example a non-human mammal. The non-human mammal may be a non-human primate (e.g. a monkey or an ape). It may be a non-human placental mammal. It may be a domesticated animal. It may be a wild animal. The subject may be a bird. The composition may be used for treatment (e.g. management of symptoms and/or signs) of a condition in the subject (said subject being any of the above). It may be used for a therapeutic purpose in any of the above (e.g. in a non-human subject). It may be used for a non-therapeutic purpose (e.g. improving athletic performance or for improving health and wellbeing or for use as a sports isotonic drink) in any of the above.

The composition may be used to improve, ameliorate or arrest the progress of a serious illness such as cancer and/or multiple sclerosis, hi order to achieve this, a quantity of the composition of about 100 to about 500ml should be ingested daily, or about 100 to 250, 200 to 500 or 150 to 300ml, e.g. about 100, 150, 200, 250, 300, 350, 400, 450 or 500ml daily. Once improvement in the condition is observed, this may be reduced to about 20 to about 100ml daily, or about 20 to 50, 50 to 100, 30 to 70 or 40 to 60ml, e.g. 20, 30, 40, 50, 60, 70, 80, 90 or 100ml daily for maintenance of the improvement. Alternatively a smaller amount may be ingested more frequently (e.g. twice or 3 times daily) or a larger amount may be ingested less frequently (e.g. every 2, 3 or 4 days). The reduced daily dose may be continued for an extended period. The extended period may be at least about 3 months, or at least 4, 5, 6, 9 or 12 months (or about 3 months to 10 years, or about 6 months to 10 years, 1 to 10 years, 2 to 10 years, 5 to 10 years, 3 to 12 months, 3 to 6 months, 4 to 12 months or 4 to 8 months, e.g. about 3, 4, 5, 6, 7, 8, 9, 10 or 11 months, or about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 years, or more than 10 years). The reduced daily dose may be continued indefinitely.

The composition may be a solution. It may be a suspension. It may be an emulsion. It may be a microemulsion. It may be more than one of these. For example some components may be dissolved in the composition and others may be emulsified. In the event that the composition is an emulsion or a suspension, the particle/droplet size may be between about 0.1 and 100 microns in mean diameter or about 0.1 to 10, 0.1 to 1, 1 to 100, 10 to 100 or 1 to 10 microns, e.g. about 0.1, 0.2, 0.5, 1, 2, 5, 10, 20, 50 or 100 microns. The emulsion/suspension may be a stable emulsion (i.e. it may resist settling/separation) or it may be an unstable emulsion. The composition may be clear, hazy, cloudy or opaque. The composition may be a dark red/brown colour. It may be some other colour, depending on the details of the composition, for example on the nature and quantity of any flavouring components used. The composition may be fully in solution. It is however preferable that the composition be shaken or otherwise agitated shortly prior to consumption in order to ensure that any undissolved matter is evenly distributed throughout the composition. The composition may be stable at room temperature, or at a temperature below room temperature. It may be stable at about 5, 10, 15 or 2O⁰C. In this context, stable indicates that the composition retains at least about 90% of its activity with respect to the desired application when stored, optionally stored in the dark, for a period of at least about 1 week, or at least about 1 month, or at least about 6 months, or at least about 1 year, or at least about 18 months or at least about 2 years. The composition may be stable for the above periods when stored unopened. It may be stable for the above periods when stored in the dark. Once opened, it is advisable to refrigerate the composition so as to reduce degradation of one or more components therein.

The composition of the invention may be made by combining a proanthocyanidin, a proteolytic enzyme having anti-inflammatory activity and a substance derived from Aloe Vera. Other substances as described above may also be combined to form the composition. Suitable amounts and/or ratios of the components are described above. When making the composition, the components in general do not react with each other. Consequently the order of addition of the different components is not critical, and any convenient order may be used. One or more premixes of components may be prepared and combined in order to form the final composition. The combining may be accompanied and/or followed by agitation. The agitation may comprise any one or more of stirring, shaking, mixing, swirling, sonicating or ultrasonicating, either sequentially or simultaneously. The combining may comprise dissolving and/or emulsifying one or more components of the composition.

The composition may be used to obtain a range of health benefits, for example for improving athletic performance or for improving health and wellbeing or for use as a sports isotonic drink or for the treatment (e.g. management of symptoms and/or signs) of multiple sclerosis or cancer or for any two or more of these applications. It may be used for making a medicament for obtaining those health benefits. The composition or medicament may be administrated (or administrable) orally. It may be an orally acceptable composition or medicament. It may be in the form of a drink which the patient drinks in order to obtain the health benefits.

The invention also comprises a process for preparing the composition. In this method a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species are combined. The combining is preferably such that it does not comprise addition of papain.

The components used in the method may be as described in the composition of the first aspect. The combining may comprise dissolving and/or suspending and/or emulsifying. It may comprise agitating, for example mixing, stirring, swirling, sonicating etc. The addition of components may be in any desired order. Thus for example the proanthocyanidin and the enzyme may be combined and then added to the substance derived from Aloe Vera and/or from a plant of the Agave species, or the enzyme may be combined with the substance and then the proanthocyanidin added to the resulting mixture. Dilution with water, if required, may be conducted following preparation of the initial composition or it may be conducted as the composition is prepared. Thus for example the substance derived from Aloe Vera and/or from a plant of the Agave species may be diluted in a desired quantity of water (or a portion thereof) and the proanthocyanidin and enzyme added to form a diluted form of the composition. Other components of the composition (e.g. salts, flavours, acid etc.) if required may also be added at any desired point in the preparation. Commonly each addition is accompanied by agitation as described above. Thus for example if enzyme is to be added to Aloe Vera juice, the juice would be stirred while the enzyme is added. In some instances it may be desired to add one or more of the components in solution or in suspension. In this case the process may additionally comprise dissolving or suspending that component in a suitable solvent, e.g. water. Example 1: a base concentrate

The following components were combined in the quantities shown below to produce 1 litre of composition.

1. Oligomeric proanthocyanidin — 2.5 grams

2. Proteolytic enzyme - 2.1 grams

3. Aloe Vera extract - 350 ml

4. Purified water - to 1 litre total volume of composition Description of components:

1. Oligomeric proanthocyanidin - available from the following sources: a. Extract from the bark of the French Maritime Pine tree (corporate trade name Pycnogenol®) - this is a preferred option; or b. Grape seed extract; or c. Extract from the bark of the Pinus radiate tree (which is produced in NZ under a trade mark Enzogenol™)

2. Proteolytic enzyme - suitable examples include bromelain, which may be for example extracted from pineapple; and/or

3. Aloe Vera extract,e.g. as a pure juice or powder concentrate The preferred proteolytic enzyme in this composition is Bromelain. This enzyme provides faster digestion and further anti-inflammatory properties. Papain is not used in the composition, and the inventor considers that compositions containing bromelain in the absence of papain are as effective as those containing papain in speeding up the digestion.

This composition may be used for athletic performance, health and wellness applications. It may be used as a concentrate, for dilution prior to ingestion by a subject Example 2

The components and quantities described below were used to produce 1 litre of the composition.

1. Oligomeric proanthocyanidin (Pycnogenol®) — 2.5 grams

2. Bromelain — 2.1 grams

3. Vinegar 40ml or a sufficient quantity of glacial acidic acid to provide the same level of acidity

4. Aloe Vera juice 350ml or powdered Aloe Vera extract in sufficient quantity to provide a similar level of Aloe Vera derived solids

5. Sodium chloride - 3 grams

6. Inulin plant sugar - 7 grams

7. purified water - 610ml

8. Flavouring

9. Preservatives

This composition may be used as a sports drink or as a general wellness drink. It may be used as a concentrate, for dilution prior to ingestion by a subject. Example 3

A 600ml isotonic drink was prepared using:

1. Sodium chloride - 170 mg

2. Potassium chloride - 83mg

3. Sucrose - 35grams

4. Maltodextrin - 9.5 grams

5. Pycnogenol ® - 150 mg

6. Bromelain - 126 mg

7. Aloe Vera extract - 21 ml

8. Vinegar - 2.4 ml

9. Purified water

10. Flavouring 11. Food acids

This formulation may be used as an isotonic drink for physical activities. Example 4

Randomised control double blind^'trials were conducted on elite athletes using the composition of Example 1 and a placebo, which was a fruit juice with a similar taste to that of the test composition, but contained no bromelain. The study used 12 athletes of whom 6 were controls and 6 were test subjects. The athletes each consumed 150ml of the product or of the placebo 2 hours prior to the commencement of the physical tests. The physical tests involved a repeat running sprint test over 20m. This test is known in the industry as the "Yoyo Test". In this test, athletes repeatedly sprint a 2x20m course in a specified time. A 5 second rest is allowed between each sprint, and the time allowed for each sprint reduces over time. The number of sprints completed until the athlete can no longer complete the sprint in the allowed time is taken as a measure of endurance.

The placebo test group (control) improved 1.09% while the test group which consumed the product improved 6.14%. The following day those athletes on the placebo were still fatigued from the tests while those on the product had recovered. Other Applications

Formulations according to the invention have been found to be highly beneficial in people with diagnosed multiple sclerosis, and some cancer sufferers have shown marked improvements in their condition associated with consumption of the composition of Example 1. Example 5 Case History 1 Presentation

DV, a 47 year old married male, attended his dentist for routine work in August 2001. DV was a horse trainer by occupation and spent significant time with these animals. That night he felt unwell and on the following day awoke with numbness over the right side of his face and a dull right-sided headache. During the course of the day he became aware of unsteadiness on his feet and by the next morning complained of vertigo and vomiting.

The unsteadiness progressed over the next two weeks, necessitating that he use a walking stick for balance and he was referred to a neurologist by his GP. He smoked about 25 cigarettes per day at the time, did not drink alcohol and had no regular medications. He had no history of significant illness and had been otherwise well. He had no neck pain nor complaint of weakness. Examination

On examination he had no audible bruits over the head or neck. He was unable to walk heel to toe, but there were no other objective findings. He was however noted to have appeared anxious. Other examination was unremarkable. Investigation

A Magnetic Resonance Imaging (MRI) scan was performed to exclude posterior fossa stroke, sequelae of vertebral artery dissection or demyelination. The MRI scan showed an extensive area of abnormal signal intensity from the right side of the medulla superiorly into the inferior cerebellar peduncle and right brachium pontus, with some mass effect. The findings are reported to be consistent with demyelination. Other studies showed that vertebral artery and cerebral vasculature were normal. Visual evoked response testing was performed, showing abnormal delay of the central field response for the right eye, strongly suggestive of Multiple Sclerosis.

An MRI of DV taken on 15 August 2001 is shown in Fig. 1. The radiologist noted as follows: "Extensive area of abnormal signal intensity extending from the right side of the medulla, superiorly, into the inferior cerebellar peduncle and the right brachium Pontus. There is considerable associated mass effect. The appearances are felt most likely to represent a focus of demyelination." Progress

There was some mild improvement over the next two weeks but ataxia remained and he was unable to return to work as a result.

After two months he still had a broad based gait but otherwise was not considered to have severe ataxia any more, and this considered to be the case over the next few months. Some four months after the initial episode he was noted to have "annoying right sided paraesthesia" (numbness) and was prescribed Amitriptyline lOmg nocte.

His instability of gait remained a problem, and the facial numbness remained annoying, but his neurologist was of the view that his neurological status had plateaued and considered that it remained stable subsequently, other than occasional complaints of lightheadedness, "feeling poorly", and experiencing a number of falls, none of which seemed to be associated with any change in the neurological signs. DV, however, became reliant on the walking stick and resorted to a wheelchair to avoid the falls. There was no period where the symptoms and signs abated completely, but nor was there significant progression of the condition. Management

Other than the Amitriptyline, DV was not prescribed medications. However in 2003 he commenced taking an herbal preparation that included pine bark and aloe. The preparation was as described in the present specification, and comprised Pycnogenol®, an extract of aloe or some product of agave, a digestive enzyme and such additives as made the product palatable. After some six months of daily intake of this preparation he noticed some improvement in his instability. He returned to the neurologist to seek confirmation as to whether there was any objective evidence of change.

Although the neurologist could not confirm change in physical examination, a repeat MRI scan was arranged, some 26 months after the original. The scan showed no areas of abnormal signal density, no evidence of demyelination either in the site of the original lesion or in any other area.

An MRI of DV taken on 3 November 2003 is shown in Fig. 2. The radiologist noted as follows: "The previously demonstrated lesion has resolved completely and the examination is now within normal limits".

Over the next short period, DV noted that his symptoms had virtually resolved. He was no longer unsteady and no longer had facial numbness. He has not required either a walking stick or wheelchair since and affirms that he is symptom free and has been over the next 6 years, other than for a short period when he was not taking the herbal preparation and he states that he felt increasingly unwell and a little unsteady over that period. Discussion

The elimination of the symptoms and the disappearance of radiological signs of disease associated with the taking of a herbal preparation, and the subsequent reappearance of symptoms on cessation of the "medication", warrant investigation as to whether the effects can be replicated in others. Due to the limited options for multiple sclerosis management the potential is significant. Example 6 Case History 2 Presentation MC is a 70 year old retired female medical practitioner. She first presented to her doctor prior to 1992 with symptoms of progressive weakness in all limbs and has subsequently developed severe dysarthria. She has had multiple sclerosis, permanent, for about 20 years. By early 2009 she was in assisted living, wheelchair bound, with almost no strength in her lower limbs and unable to hold a pencil with between her fingers. She remained with very severe dysarthria. Her symptoms do not fluctuate. Examination

On examination she had no strength in any of her limbs and speech was almost unintelligible. Investigation

Due to the long standing diagnosis and symptomatology strongly suggestive of Multiple Sclerosis, no additional investigations were done at this time. Progress

For years her symptoms had become progressively more severe and they had been extreme for the last decade. She was living in assisted accommodation and was severely dysarthric, wheelchair bound due to profound lower limb weakness and with no fine use of her upper limbs. Her ability to communicate verbally was extremely limited. Subjectively it was difficult to understand most, if not all, of her verbal communication. Management

In early 2009 her GP approached her with the prospect of trying an herbal preparation that included pine bark and aloe. This approach was on the recommendation of another GP who had seen some fairly remarkable results for another patient taking the same mixture. MCs doctor was himself approached because an objective medical practitioner with an open mind towards the use of herbal remedies was sought. The doctor had no other interests beyond those of his patient. The preparation was as described in the present specification, and comprised Pycnogenol®, an extract of aloe or some product of agave, a digestive enzyme and such additives as made the product palatable.

After some four months of daily intake of this preparation both the patient and her GP noticed some improvement, especially in her dysarthria. Conversation was still difficult but for those familiar with her speech it had become possible to understand speech with far less difficulty, and strangers were able to adjust to her speech within some minutes.

After her sixth month on the mixture her speech was substantially improved. While the formation of the sounds was still imperfect, communication was relatively clear. She remains wheelchair bound but now has sufficient strength in her fingers that she is able to hold and control a pencil.

She has remained with substantial diminution of symptoms for 7 months, other than for a short period of two weeks when she was unable to obtain supply and so was not taking the herbal preparation. For that short period she noted some worsening of symptoms but these again resolved to their prior level within days of restarting the mixture. Discussion

The marked reduction of symptoms in a patient who had become disabled over a decade was of enormous relief to the patient and somewhat of a surprise to her treating doctor. There were no unwanted side-effects to taking the herbal preparation. The subsequent deterioration of symptoms on cessation of the mixture was also interesting. It is to be hoped that similar outcomes will be seen in others. Due to the limited options for multiple sclerosis management the potential is significant.

Examples 5 and 6 are adapted from clinical reports authored by Dr Stan Goldstein MB₅BS; MHA (Assoc. Prof., Conjoint, University of New South Wales, School of Community Medicine and Public Health).

Claims

Claims:

1. A composition comprising:

• a proanthocyanidin;

• a proteolytic enzyme; and

2. The composition of claim 1, wherein said proanthocyanidin is oligomeric.

3. The composition of claim 1 or claim 2 wherein said proanthocyanidin is obtained from a source selected from the group consisting of bark of a French Maritime Pine tree, grape seed and bark of a Pinus radiata tree.

4. The composition of claim 3 wherein the proanthocyanidin is an extract from the bark of the French Maritime Pine tree.

5. The composition of any one of claims 1 to 4 wherein the proteolytic enzyme is bromelain.

6. The composition of any one of claims 1 to 5 wherein the substance derived from Aloe Vera and/or from a plant of the Agave species is Aloe Vera juice or a powder obtained by drying said juice.

7. The composition of any one of claims 1 to 6 wherein the ratio of the amount of proanthocyanidin to the amount of proteolytic enzyme is between about 1 and about 1.5 on a weight basis.

8. The composition of any one of claims 1 to 7 wherein the proanthocyanidin and the proteolytic enzyme in combination are present in an amount about 1 to about 1.5% on a weight/weight or a weight/volume basis relative to the substance derived from Aloe Vera and/or from a plant of the Agave species.

9. The composition of any one of claims 1 to 8 additionally comprising an organic acid.

10. The composition of claim 9 wherein the organic acid is acetic acid.

11. The composition of any one of claims 1 to 10 additionally comprising a saccharide.

12. The composition of claim 11 wherein the saccharide comprises sucrose, maltodextrin, inulin or a combination of any two or all of these.

13. Use of a composition according to any one of claims 1 to 12 for improving athletic performance or for improving health and wellbeing or as a sports isotonic drink.

14. Use of a composition according to any one of claims 1 to 12 for the treatment of a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver disease and kidney disease.

15. A method for treating a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver disease and kidney disease, said method comprising administering to a patient in need thereof a composition according to any one of claims 1 to 12.

16. A process for making a composition for improving athletic performance or for improving health and wellbeing or for use as a sports isotonic drink or for the treatment of multiple sclerosis or cancer, said process comprising combining a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species, wherein said enzyme is not papain.

17. Use of a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species for the manufacture of a medicament for improving athletic performance or for improving health and wellbeing or for use as a sports isotonic drink or for the treatment of a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver disease and kidney disease, wherein said enzyme is not papain.

18. A process for preparing a composition, said process comprising combining a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species, wherein said combining does not comprise addition of papain.

19. Use of a composition according to any one of claims 1 to 12 for symptom relief of a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver dysfunction and kidney dysfunction.

20. A method for management of symptoms and/or signs of a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver dysfunction and kidney dysfunction, said method comprising administering to a patient in need thereof a composition according to any one of claims 1 to 12.

21. Use of a proanthocyanidin, a proteolytic enzyme and a substance derived from Aloe Vera and/or from a plant of the Agave species for the manufacture of a medicament for the management of symptoms and/or signs of a condition selected from the group consisting of multiple sclerosis, cancer, diabetes, hypercholesterolemia, asthma, heart disease, liver disease and kidney disease, wherein said enzyme is not papain.