NZ336856A - Dietary supplements comprising extract from green lipped mussel and one from deer velvet, Enzogenol and shark cartilage to treat inflammation - Google Patents

Abstract

Described is a composition for administration to animals suffering from arthritis, inflammation or chronic joint pain. The composition contains: at least one anti-inflammatory agent selected from: green-lipped mussel extract (GLME) and shark cartilage; with at least one enhancing agent selected from: a bark product or extract exhibiting antioxidant properties and shark cartilage. The composition must include one member from each group and the selected members must be different.

Description

PATENTS FORM NO. 5 Fee No. 4: $250.00 PATENTS ACT 1953 COMPLETE SPECIFICATION After Provisional No: 336856/500630/505875 Dated: 21 July 1999/27 October 1999/21 July 2000 COMPOSITIONS ADDRESSING INFLAMMATION AND/OR DEGENERATIVE DISORDERS I/WE Bomac Laboratories Limited, a New Zealand company of corner Wiri Station Road and Hobill Avenue, Manukau City, Auckland, New Zealand hereby declare the invention for which I/We pray that a patent may be granted to me/us, and the method by which it is to be performed to be particularly described in 11 ,i r ii , t , Intellectual Property and by the following statement: Office of NZ 21 JUL 2000 REQUXfiiJ, ef: 18045/4 COMPOSITIONS ADDRESSING INFLAMMATION AND/OR DEGENERATIVE DISORDERS Technical Field The present invention is directed to compositions for addressing degenerative disorders 5 and inflammation. Preferred embodiments of the invention comprises a sustained slow-acting composition which, when continually administered, exhibit anti-inflammatory effects though various embodiments may also exhibit analgesic effects, gastro-protective effects, a reduction in host-cell damage associated with inflammation, and may reduce cancerous tumours through antiangiogenesis. Differing embodiments may exhibit a 10 number, or all, of these effects to varying degrees depending upon the degree and balance of synergism resulting from the selected components and ratios.

Background Art The present invention was developed with the needs and problems associated with domestic animals in mind. In particular, domestic pets receive significantly more 15 attention from humans than domesticated commercial species (e.g. livestock). The care and attention lavished on domestic pets also means that they tend to live to a significantly greater age than most commercially bred species and are thus more likely to exhibit the problems associated with old age. Such problems include cancer, and debilitating degenerative diseases.

In addition, animals are also susceptible to inflammation associated with various causes such as tissue damage or injury and, as for their human counterparts, some animals may also experience gastro-intestinal irritation from commonly used anti-inflammatories. As many domesticated pets are regarded by owners as family members, owners are often keen to address the various maladies that their pets exhibit In most cases the solution is a curative remedial action after the problem has presented itself. While this may be effective for temporary afflictions such as acute infectious inflammation, longer term afflictions such as cancer and debilitating degenerative ailments have associated degenerative or other effects which are not usually fully reversible and quite often any remedial action is merely to attempt to control the further 30 spread of the affliction, or to ameliorate its effects on the animal. In some instances a partial improvement may be obtained, though there are problems associated with 2 addressing an affliction after it has firmly established itself. As for humans, early diagnosis is often associated with a better prognosis for recovery or control.

Accordingly, a" number of afflictions such as cancer or debilitating degenerative ailments (e.g. arthritis) may be more effectively controlled if preventative measures are taken. 5 For instance there is evidence indicating that cartilage protecting agents may help protect against the occurrence of degenerative joint diseases and associated complaints. While there are varying forms of joint diseases, in general the complaint is accompanied by degeneration of cartiligenous material at the joints. The sooner action is taken against such degeneration, then the less the effects of the complaint will be. Thus, while 10 an animal may still remain susceptible to joint related afflictions, preventative measures may protect against development of the complaint to any appreciable degree.

Similarly, inflammation at the joint is a factor in some degenerative joint diseases and thus some protection may also be provided by preventing inflammation in affected areas.

There are also a number of different types of cancers, though in particular the present invention is more focussed on those accompanied by tumourous growths. In many instances these tumours may be relatively benign though any tumourous growth is potentially serious. Again there is a link between early prognosis and recovery or effective control of the cancer and thus any preventative measure which can hinder the 20 early growth or development of tumours will be of use.

For most animals, there is a limited number of products available which can be safely administered to afford a preventative or curative action towards these types of afflictions. Most animal remedies are based on pure chemicals for addressing a particular diagnosed chemical imbalance. Many of these contain side effects, and even 25 for those that don't, it is generally not a recommended practice for their regular continued administration.

For domestic pets, there have been on-going improvements in food formulations, though again the primary emphasis has been on presenting a tailored balance of nutrients for different animals. A number of more recent formulations have addressed the elimination 30 of problem components, or have altered the foodstuff characteristics to counter known problems in pets - for example, altering the pH of certain pelletised cat foods to avoid 3 urinary tract problems in adult cats. Most focus on various vitamins and minerals and may also increase or reduce specific amino acids present in the foodstuff. Some products have become quite specialised and one American product is specifically formulated for dogs undergoing chemotherapy, and includes high levels of n-3 fatty 5 acids, which inhibit tumour growth.

However, there is a general need for a composition which can be administered on a regular basis to both healthy and afflicted animals and which can address one or more of a number of known, common, problems such as indicated above. Accordingly it is one aspect of the present invention to provide a composition, in a dosage form, or an 10 alternate form, which can be administered regularly and in with relative safety to most domesticated pets, and particular mammalian species. At the very least, it is an object of the present invention to provide the public with a useful alternative to what is currently available.

Further aspects and advantages of the present invention will become apparent from the 15 ensuing description which is given by way of example only.

Disclosure of Invention According to one aspect of the present invention there is provided a composition for administration to animals including a combination of: (a) at least one anti-inflammatory agent selected from the group comprising i) green-lipped mussel extract (GLME) and/or a pharmacologically active green lipped mussel product, and ii) shark cartilage; with (b) at least one enhancing agent selected from the group of: i) a bark product or extract exhibiting antioxidant properties, and 25 ii) shark cartilage; and wherein for a composition including just one member from each group, the selected members must be different.

According to a further aspect of the present invention there is provided a composition for administration to animals including a combination of: (a) at least one anti-inflammatory agent selected from the group comprising 4 i) green-lipped mussel extract (GLME) and/or a pharmacologically active green lipped mussel product, and ii) shark cartilage; with (b) at least one enhancing agent selected from the group of: i) a bark or plant product or extract exhibiting any one of antioxidant, anti- arthritic, and anti-inflammatory properties, and ii) shark cartilage; and wherein for a composition including just one member from each group, the selected members must be different.

According to another aspect of the present invention there is provided a composition, substantially as described above, which includes either or both of a green-lipped mussel extract (GLME) and a pharmaceutically active green lipped mussel product, in combination with any one or more of: shark cartilage, pharmacologically active shark extract, and chondroitin sulphate.

According to another aspect of the present invention there is provided a composition substantially as described above which includes an anti-inflammatory agent in combination with a chondroitin compound.

According to another aspect of the present invention there is provided a composition substantially as described above which includes as the anti-inflammatory agent either or 20 both of shark cartilage and pharmacologically active shark cartilage extract in combination with any one or more of: Enzogenol™, Pycnogenol™, a bark extract equivalent to Enzogenol™ or Pycnogenol™, chondroitin sulphate, and a chondroitin compound.

According to another aspect of the present invention there is provided a composition 25 substantially as described above which includes, as an enhancing agent, Pycnogenol™.

According to another aspect of the present invention there is provided a composition substantially as described above which includes one or more anti-oxidants other than Enzogenol or equivalent bark extracts.

According to another aspect of the present invention there is provided a composition 30 substantially as described above in which an anti-oxidant is vitamin E.

According to another aspect of the present invention there is provided a composition substantially as described above in which includes deer velvet or a pharmacologically active extract thereof.

According to another aspect of the present invention there is provided a composition 5 substantially as described above in which includes additional glycosaminoglycans than those present in the selected anti-inflammatory or enhancing agents.

According to another aspect of the present invention there is provided a composition substantially as described above in which green-lipped mussel extract (GLME) and/or a pharmacologically active green lipped mussel product in sufficient amount to provide 10 gastro-intestinal protection against irritation by other components in the composition.

According to another aspect of the present invention there is provided a composition substantially as described above which also includes any one or more of the following components: a vitamin, glycine, lysine, methionine, glutamic acid, tyrosine, and compounds 15 providing in a pharmacologically acceptable form one or more of the following elements: manganese, zinc, iron, magnesium, selenium, calcium, copper, potassium, cobalt.

According to another aspect of the present invention there is provided a composition substantially as described above which includes one or more pharmacologically active 20 substances.

According to another aspect of the present invention there is provided a composition substantially as described above in which a pharmacologically active substance is an anti-inflammatory other than those listed in claim 1.

According to another aspect of the present invention there is provided a composition 25 substantially as described above formulated to be suitable for addressing any one or more of the following conditions in animals: inflammation, arthritis, chronic joint pain.

According to another aspect of the present invention there is provided a composition substantially as described above in any one or more of the following forms: as a bolus or tablet, in a capsule, as a slow release implant, as a liquid composition, as a 30 gel, and as a paste. 6 According to another aspect of the present invention there is provided a composition substantially as described above formulated for use with non-human mammals.

According to a further aspect of the present invention there is provided a method for addressing joint problems in non-human animals consisting of the administration of a 5 composition as claimed in any one of the preceding claims.

According to another aspect of the present invention there is provided a method substantially as described above in which the method of administration is oral.

According to a further aspect of the present invention there is provided the use of any two or more of: i) green-lipped mussel extract (GLME) and/or a pharmacologically active green lipped mussel product, ii) shark cartilage and/or pharmacologically active shark cartilage extract; and iii) Enzogenol™, and/or equivalent bark extract. in the preparation of a composition for use in addressing any one or more of: 15 a) inflammation; b) degenerative joint complaints; c) other cartiligenous degeneration; d) gastrointestinal sensitivity or irritation; e) cancerous tumours; The present invention has been developed with the needs of domesticated pets, and primarily mammalian species, in mind though it is also envisaged that the present invention is applicable to commercially bred species. However, while tablets or foodstuffs may be regularly administered or fed to pets or stabled animals, the problems associated with regular administration to sheep, cattle, and other livestock, may preclude 25 regular use of the present invention with those species. However this does not mean that the present invention is detrimental, and therefore cannot be administered to such species or animals.

Preferred embodiments of the present invention focus around the use of three components, or equivalents thereof. These comprise green lipped mussel extract 30 (GLME), shark cartilage and enzogenol ™. Each of these components alone is known to exhibit a number of useful properties, though it has been found that varying 7 combinations of these components can yield a significant improvement in the effectiveness of these components alone, and also render the resulting combination useful for addressing a number of complaints.

For instance, green lipped mussel extract (GLME) comprises extractions from the 5 shellfish species perna canaliculus, a mollusc found on the shores of New Zealand. This is a convenient means for including active components from the green lipped mussel, though other forms of green lipped mussel and its products (preferably pharmacologically active) can be used. This mollusc has been found to contain a number of components exhibiting anti-inflammatory activity and includes small 10 amounts of glycosaminoglycans which have been shown to be beneficial for maintaining the integrity of cartilage and bone. Accordingly, green lipped mussel extract has been used for alleviating arthritic complaints, including degenerative joint diseases.

Green lipped mussel extract (GLME) where used in various embodiments of the present invention is preferentially that obtained from extraction processes from live, or recently 15 killed mussels. Procedures such as outlined in granted patents to the inventor Stuart J McFarlane may be followed, though the product may preferentially be obtained from McFarlane Laboratories NZ Ltd., of New Zealand.

The same inventor has also pursued further patent applications directed to extracting specific targeted compounds from green lipped mussels, and re-combining or using 20 these in other preparations. An example is the disclosure of US 4,455,298 (NZ 188489). Such extracts are also considered to be among the acceptable substitutes for green lipped mussel extract (GLME) for use in the present invention.

Shark cartilage has also been used by persons suffering from disorders such as cancer and arthritis and there it appears that it is useful in addressing these complaints. 25 Identified active components include chondroitin sulphate, and glycosaminoglycans. Various shark cartilage products may be used, though preferentially include or retain active quantities of these components.

A further component which can be considered is a bark or plant extract exhibiting antioxidant properties. Preferably the antioxidant activity exceeds that of vitamin E. 30 One product which has been mentioned is enzogenol ™, a proprietary composition manufactured by Enzo Nutraceuticals Limited, of Christchurch, New Zealand, and 8 comprises an extract from the bark of Pinus radiata which is rich in anti-oxidants. Other bark products exist with pycnogenol™, another proprietary product being an acceptable alternative. There is evidence establishing that oxidant and free radical damage can be addressed by this formulation. Both oxidant and free-radical damage 5 have been shown to be involved in both premature ageing, and in particular, joint disease. Equivalent products to enzogenol ™ or pycnogenol™ may be substituted, though the preference is for these products as they contain components other than antioxidants that may further enhance the properties of the product.

As previously indicated, it has been indicated that a significant useful improvement can 10 be made by combining two or more of the three listed components. The selected combination will have some effect on the focus and activity of the resulting combination, and this will become more apparent from the following description.

One possible combination is green lipped mussel (GLM, and preferably an extract) with shark cartilage. This combination is of use as an anti-inflammatory, though in particular 15 is useful for addressing arthritic complaints and degenerative joint problems. For instance, green lipped mussel and its preferred extracts include glycosaminoglycans which help protect cartilage and bone. Preferred GLM extracts also exhibit an antiinflammatory effect. Most arthritic complaints and degenerative joint disorders are known to involve an associated inflammation in the joint region and thus extracts of 20 GLM that have demonstrated effectiveness in these type of disorders have been at least partly attributable to the anti-inflammatory characteristics.

Shark cartilage contains higher levels of glycosaminoglycans which augment the cartilage protective effects of GLM products and extracts alone. This is further augmented by the presence of chondroitin sulphate, another cartilage protecting 25 component. The collagen also present in shark cartilage further enhances the effectiveness of the combination.

Shark cartilage also possess some antiangiogenetic properties which also affords the combination and additional properties in addressing cancer tumour formation. It is also considered that the same property may also further enhance the ability of the 30 combination to address, both preventatively, and curatively (to varying degrees) joint and cartilage problems - particularly mobility related ailments. 9 Enhancing agents such as enzogenol ™, pycnogenol ™ or equivalent bark extracts, may also be combined with either or both of GLME and shark cartilage. Both GLME and shark cartilage possess anti-inflammatory properties. The combination with enzogenol ™, with its anti-oxidant and anti-free radical properties, enhances the 5 usefulness of these antiinflammatories in addressing a number of disorders, and preventing the formation of other problems. For instance, inflammation is generally the consequence of a defensive action of the body and in some instances is accompanied by a significant amount of oxidants in the inflamed regions. These oxidants often include nitrous oxide, varying peroxides and a number of other substances which exhibit a 10 strong localised anti-microbial effect. However, the effectiveness of their action is not always confined to foreign bodies. These oxidants produced by the body are also known to exhibit a negative effect on the host's own cells, and it is known that some oxidant species can disrupt host cell DNA sequences. Current theories consider this to be the first transformational change to occur in a number of forms of cancer, and thus 15 addressing this problem will represent a preventative technique towards the establishment of a number of forms of cancer.

Anti-oxidants, such as those provided in enzogenol™, can reduce damage to the host's own cells, but without any significant decrease in the effectiveness of remaining oxidants in addressing microbial invaders and other foreign material. In some respects 20 the anti-oxidants may be considered to have a regulating effect and tend to mop up excess oxidants which have been produced beyond the actual needs of the body.

Accordingly, the combination of a bark based anti-oxidant product with an antiinflammatory, produces a substantially enhanced useful overall effect in reducing not only the amount of inflammation, but negative side effects associated with 25 inflammation. Other factors may be at work though the use of products such as pycnogenol ™ or enzogenol™ appear to confer the desired characteristics.

Further, the reduction in likelihood of an oxidant induced cancer transformation, coupled with the antiangiogenetic properties of shark cartilage, renders this a useful combination for reducing the probability of cancer formation.

Further , it will be appreciated that the combination of all three can yield a highly useful product which can help simultaneously address a number of afflictions which affect animals, and which become more prevalent in older animals.

Another anti-oxidant which may be used in varying embodiments of the present invention is vitamin E. Other anti-oxidants are also known, and both these and/or vitamin E may be used in varying embodiments including these combining GLM products and extracts with shark cartilage. However, preferred embodiments would 5 include a bark based antioxidant as the preferred anti-oxidant of choice, though it should be also appreciated that not all uses of varying embodiments will focus on inflammation and its side-effects, and thus lower levels of additional anti-oxidant activity may be provided.

Other enhancing agents include plant based products exhibiting antioxidant properties, 10 though may additionally, or alternatively, exhibit anti-inflammatory or anti-arthritic properties. In this later case, the preference is still to include an antioxidant, or to select a material also exhibiting antioxidant properties. One possibility is to include these other enhancing agents in combination with a bark based antioxidant such as enzogenol™ or pycnogenol™. As a gauge of antioxidant activity, pharmacological 15 activity comparable to or exceeding vitamin E is desirable, or alternatively an activity comparable to enzogenol™ or pycnogenol™.

As can be appreciated, the varying combinations which have been described provide enhanced activity and properties over the individual components. The result is a range of embodiments which may be used in a number of similar roles, but which may exhibit 20 slightly enhanced activity in one role over another.

Some of these components possess other useful properties which may extend the usefulness of various combinations. For instance, GLM products and extracts are known to be useful in preventing, alleviating, or treating gastro-intestinal irritation. Accordingly, compositions of the present invention which include GLM and/or its 25 extracts may also be used as a carrier for, or as part of, compositions containing irritant substances just as GLME alone is used in such a role. This further extends the usefulness and flexibility of embodiments of the present invention.

For instance, many current fast-acting anti-inflammatories are irritating to the stomach. While embodiments of the present invention generally include sufficient anti-30 inflammatory activity, when administered over sustained periods, to preclude the use of most existing pharmaceutical anti-inflammatories, there may be instances where the user may wish or need to include one of these existing faster acting compounds. Including 11 such a substance in such embodiments of the present invention may not only reduce the amount of the added anti-inflammatory which needs to be included, but the counter irritant effects of GLME can help reduce the side-effects from the administration of an added anti-inflammatory which may cause irritation.

There are a number of other pharmaceuticals which exhibit irritant properties, and the co-administration, or co-compounding, of embodiments of the present invention with those substances is also a technique within the scope of the present invention. In particular, embodiments of the present invention may find use for administration during chemotherapy which tends to have a number of significant negative side effects.

Embodiments of the present invention may also include other substances which are known to have a beneficial effect. One such substance is deer velvet for which a large amount of anecdotal, but little clinical, evidence exists of its effectiveness. The little clinical work which has been performed suggests that deer velvet administered orally can address problems associated with high blood pressure, as well as having both 15 immuno-stimulatory and anti-inflammatory properties. The inclusion of deer velvet would therefore augment such properties already existing in various embodiments of the present invention.

It is also envisaged that varying embodiments may also include manganese ascorbate and/or S-adenosylmethionine (aka S-adenosyl-L-methionine 1,4 butane disulfonate). 20 This latter compound is also known to promote joint mobility, while the former is involved in the biosynthesis of glycosaminoglycans. These can enhance the action of other components in preferred embodiments of the invention addressing debilitating joint ailments.

As mentioned previously, the present invention may take varying forms. It is envisaged 25 that a common form of the invention is as an oral dosage form. This may be as a pill, tablet, capsule, etc. Liquid formulations may also be produced, as may other types of solid formulations. In particular, an animal foodstuff is envisaged. Each of these different forms may be prepared according to standard existing techniques, and which include the components of the various embodiments of the present invention. 12 Best Modes for Carrying out the Invention Example 1: Compositions for adult dogs This comprises a tablet (or similar dosage form) or dietary foodstuff which includes green lipped mussel extract in combination with shark cartilage. Ideally, the 5 composition also includes a range of vitamins and trace minerals in a balanced proportion, ideal for targeted animal range. Different embodiments may contain different ratios, depending upon the size, type, or age of the animal.

Example la: Constituents In this embodiment, a dosage form, which may take the form of a pellet, capsule or 10 tablet etc, may contain: Green Lipped Mussel Extract 50 - 200 mg Shark cartilage 50 - 200 mg Vitamin mix-optional but where included: 200 ± 200 mg Which may, for example, consist of: Vitamin A 2000-3000 iu Vitamin D3 300-500 iu Vitamin E -30 iu Vitamin K3 0.5-0.75 mg Thiamine (Vitamin Bl) 1-1.5 mg Riboflavin 2-3 mg Pyridoxine 0.5-0.75 mg Panthothenic acid 2-3 mg Niacin 7-10.5 mg Biotin 0.1-0.75 mg Vitamin B12 22-150 |ig Folic acid 0.1-0.15 mg Iron 12-20 mg Copper 1.5-2.5 mg Cobalt 0.25-0.4 mg Manganese 3-5 mg 13 Zinc 25-40 mg Iodine 0.5-0.75 mg Selenium 0.075-0.125 mg Calcium 10-20 mg Manganese ascorbate optional S-adenosylmethionine optional The dosage form may also be incorporated into a food product, such as a pellet, which can be administered for consumption by the animal. Such dosage forms could also be seeded throughout pelletised animal foods -10 lower dosage forms may be prepared for such applications.

For the embodiment above, a typical suggested once daily dosage is: up to 15 kg 1 tablets -30 kg 2 tablets over 30 kg 3 tablets This example is illustrative only. The vitamin mix is illustrative of a typical balance for adult dogs, but can be varied (and components added or eliminated) in different embodiments for other species and ages.

Example IB In this embodiment, a dosage form, which may take the form of a pellet, capsule or 20 tablet etc, may contain: Green Lipped Mussel (preferably dried or powdered) or extract thereof: 50 - 200 mg Shark cartilage (preferably dried or powdered) or chondroitin sulphate 25 or condroitin containing substance 50 - 200 mg Vitamin mix (as above in Example 1 A) optional The dosage form may also be incorporated into a food product, such as a pellet, which can be administered for consumption by the animal. Such dosage forms could also be 14 seeded throughout pelletised animal foods - lower dosage forms may be prepared for such applications.

For the embodiment above, a typical suggested once daily dosage is: up to 15 kg 1 tablets 15 - 30 kg 2 tablets over 30 kg 3 tablets This example is illustrative only. The vitamin mix is illustrative of a typical balance for adult dogs, but can be varied (and components added or eliminated) in different embodiments for other species and ages.

Example 2 This comprises a dosage form combining green lipped mussel with an anti-oxidant, and is of particular use for preventing or addressing inflammation.

In this embodiment a typical dosage form may contain: Green lipped mussel extract 15 (or pharmacologically active green lipped mussel product) 50 - 200 mg ENZOGENOL™ or PYCNOGENOL™ 5 ± 2 mg Anti-inflammatory plant extract (optional) 0 - 500 mg Vitamin mix (see example la) 200 ± 200 mg.

As for Example 1, the dosage form may take different forms, including capsules, tablets, pellets, and even liquid forms. Liquid forms would generally include an acceptable carrier, and may include inert oils such as comestible vegetable oils, and fish oils.

Example 3 This example combines shark cartilage with a bark based antioxidant. While this 25 combination is useful for addressing inflammation, it is directed more to the prevention, and/or addressing arthritic complaints and degenerative joint diseases and afflictions.

In this embodiment the dosage form may contain: Shark cartilage 50 - 200 mg Example 5a: Constituents Each tablet contains: Green Lipped Mussel Extract Deer Velvet Shark Cartilage 175 ±75 mg 25 ± 10 mg 100 ± 50 mg Enzogenol (™) or pycnogenol™ 5 ± 2 mg Vitamin mix (see example la) 200 ± 200 mg Suggested once daily dosage as per example la.

May be fed in conjunction with Example la formulation. Can be administered directly 10 into the mouth or added to the food.

Example 6: for cats The preferred embodiment for cats will include green lipped mussel extract. This acts in the role of an anti-inflammatory to improve mobility, as well as relief from sore and arthritic joints. Again, preferred embodiments of this range will also include a balanced 15 range of vitamins and trace minerals for cats.

Example 6a: Constituents Each tablet contains: Green Lipped Mussel Extract (or pharmacologically active 20 green lipped mussel product - quantity of such products may need to be varied according to activity) 175 ± 75 mg Either or both of: i) enzogenol™ or pycnogenol 5 ± 2 mg ii)shark cartilage - 175 mg Taurine 100 ± 50 mg 70 ± 20 mg Potassium gluconate 17 ENZOGENOL™ or PYCNOGENOL™ Anti-arthritic and/or anti-inflammatory Plant extract (optional: 2-10 mg 0 - 500 mg Vitamin mix (see example la) preferably including adenosylmethionine and manganese ascorbate. 200 ± 200 mg.

Dosages and varying dosage forms, are as for the preceding examples.

Example 4 This embodiment includes deer velvet in addition to the compositions of any of the 10 preceding examples. To a formulation as described in any of examples 1 through 3, there is also included deer velvet in the amount of 25 ±10 mg. Preferably this is dried deer velvet, which has been prepared by a method avoiding substantial degradation of included natural components.

Dosing and administration is as per Example 1 herein.

Example 5: for older or arthritic animals, or animals exhibiting mobility problems These embodiments may also be in dosage forms, or foodstuffs. This range of embodiments are targeted at older animals, and particularly those that may be showing joint problems or arthritis.

These embodiments combine green lipped mussel extract with shark cartilage or 20 extracts thereof. Ideally, the shark cartilage, or any extract thereof, should include glycosaminoglycans. These two active components act as powerful anti-inflammatories, and provide anti-inflammatory action over the use of the green lipped mussel extract alone.

Optionally but ideally also, deer velvet or extract thereof is included in the these 25 formulations.

Ideally also, these embodiments will also include ENZOGENOL (proprietary formulation of anti-oxidants). 16 Thiamine hydrochloride Yeast Dextrose (as a tableting agent) Vitamin mix (see example la) optional ± 10 mg 50 ± 20 mg This composition can provide some additional benefit for cats. Taurine, an essential dietary ingredient in cats, is fundamental in preventing heart and eye disease. Taurine is also an important part of bile in the cat's digestive system. Potassium Gluconate helps prevent hypocalcaemia, a common diet related deficiency in cats.

Thiamine helps prevent diseases related to thiamine deficiency such as diarrhoea, kidney 10 disease and polioencephomalcia. Yeast provides a rich source of B vitamins and other natural products. Dextrose is included as a tableting agent, instead of the more commonly used lactose, because many cats are lactose intolerant.

Suggested once daily dosage 2.5 kg >2.5 kg 2 tablets 1 tablets Can be administered directly into the mouth or added to the food.

It is also possible to use the compositions of examples 1 through 5 for cats.

Example 7 Trials were conducted using tablets on a number of different breeds of dog.

Analysis of tablets used in trial Active ingredients: per tablet Green lipped mussel extract Shark cartilage enzogenol™ 175mg lOOmg 5mg The natural ingredients contain traces of the following vitamins and minerals: Vitamin C Vitamin D3 Tyrosine Potassium 18 Vitamin B1 Cobalt Manganese Zinc Iron Magnesium Selenium Calcium Vitamin B2 Niacin Vitamin B6 Vitamin B12 Glutamic acid Glycine Lysine Methionine Copper The trial was an open assessment. The effect of the treatment was based on the owner's subjective observation of the dogs mobility and vitality. The patients chosen for treatment were dogs with lameness and/or diminished mobility due to pain from chronic arthritis. The recommended dose was 1 tablet per 10 kg bodyweight. The results of the trails are summarised in table 1. The effect is described as 0 : no effect, 1+ : some 15 improvements, 2+ : good effect and 3+ : very good effect.

From table 1 it appears, that the recorded effect of the product in 12 out of 16 cases is good or very good. Typically there was seen improvement of mobility within 5 to 14 days, and especially it was noted by the clients that the dogs showed more vitality and improved well-being. This was most remarkable in geriatric patients.

The initial effect stabilises after 1 to 2 months. The owner also gets used to the better mobility of his dog. A certain depot-effect seems to be built up, which may last for weeks or months. Therefore it is recommended that there is a somewhat (50%) lower maintenance dose after initial dosing for approximately 2 months. After this period further improvement cannot be expected and the dog will stay in status quo.

It appears from table 1, that the indications mainly have been arthritis in different joints like elbow, knee, spondylosis etc. Clinically we have in a few cases observed diminished crepitation in arthritic joints, probably due to better lubrication. We have also observed better vitality in many cases.

During the trial were used tablets from 3 different batches. There was no noted 30 difference as to quality or effect. 19 Table 1: Race, indication, effect and number of glasses consumed in 16 dogs treated for joint pain # » Race Years Indication Dose/Day" Effect Kg Used glasses of 100 Labrador 11 Arthroses+skin 3 3+ 34 Labrador 14 Elbow arthrosis 3 3+ 26 Labrador 12 Hip dysplasia 2 3+ 22 4 Lab / schaefer 13 Hip dysplasia/ knee 2 3+ Fox terrier 14 Shoulder arthrosis 1 1+ 8 1* Dachshund 14 Spondylosis 1 3+ 8 3 Shetl. sheepdog 14 Elbow arthrosis 1 0 12 O** Finsk Spids Spondylosis 2 3+ 18 3 Weimaraner 6 Cruc.rupt.chron. 3 2+ 26 1 Border Collie 0.5 Cruc.rupt.acute 1 2+ 12 2 Labrador 0.4 Hip dysplasia 1 3+ 18 3 Golden Retriever 8 Knee arthros., skin 3 2-3+ 32 4 Rottweiler 4 Elbow arthrosis 3 2 38 4 Schaefer 14 Spondylosis 3 2+ 32 3 Labrador Elbow arthrosis 3 1+ 28 6 Boxer 6 Spondylosis 3 1+ 31 2 * Euthanised after 1 month due to Cushing syndrome.

** Medication stopped after 1 week due to polydipsia.

Generally there were no observed adverse side-effects. One dog showed polyuri and polydipsia after 1 week treatment. The owner stopped treatment with the trial product and the symptoms disappeared. The dog was not examined as to the cause of the PU/PD, so the condition might have been due to other reasons.

Conclusion Chronic arthritis is very difficult to treat. The clinical response has been so positive, that this composition should be considered in future treatment of chronic arthrosis, of patients with loss of vitality and unspecified stiffness of joints or diminished mobility. For many dogs treatment with NASDD or corticosteroids is problematic and in these 10 cases many clients will prefer a natural, alternative treatment when a positive effect can be observed.

Example 7 Following are the results of further efficacy tests performed using various embodiments of the present invention 21 No.

Dog Breed Sex Age (year) Weight (kg) Intake (tabs) Symptom Evaluation 1.

Beagle M(n) 9 18.0 2 Disk herniation No effect 2.

Akita M 11 31.8 3 Knee arthritis Remarkably effective 3.

Miniature Dachshund M(n) 9 8.3 1 Coxa aplasia Effective 4.

Mix M 11 9.8 1 Patella luxation Remarkably effective .

Yorkshire Terrie F 13 2.2 1 Coxa aplasia Slightly effective 6.

Sheltie M 13 11.8 1 Coxa aplasia Effective 7.

Mix F(h) 11 17.4 2 Knee arthritis No effect 8.

Sheltie F(h) 11 12.0 2 Arthritis Effective 9.

Sheltie F 7 11.8 1 Osteoarthritis of spine Remarkably effective .

Pomeranian F(h) 4.7 1 Coxa aplasia No effect 11.

Chow Chow F 3 38.2 3 Carpus Arthritis Remarkably effective 12.

Mix F 3 29.7 2 Traumatic Patella luxation Remarkably effective 13.

Pekinese F 14 .6 1 Coxa aplasia No effect 14.

Mix F 6 13.2 1 Knee Arthritis Effective .

Sheltie F 8 17.0 2 Arthritis No effect 16.

Pomeranian F 3 3.7 1 Patella luxation Effective 17.

Maltese F(h) 4.7 1 Arthritis Remarkably effective 18.

Bernese Mountain dog F 1 .00 3 Arthritis Remarkably effective 19.

Mix M 13.2 1 Left hind foot lameness Remarkably effective No.

Dog Breed Sex Age (year) Weight (kg) Intake (tabs) Symptom Evaluation .

Shiba M 12 .5 2 Osteoarthritis of spine Exacerbation 21.

Chihuahua M(n) 2 1 Arthritis Remarkably effective 22.

Mix F(h) 12 13.3 1 Patella luxation No effect 23.

Golden retriever F 26.8 2 Ligament rupture Judgement impossible 24.

Dachshund F(h) 8 4.3 1 Arthritis Slightly effective .

Mix F(h) 12 8.7 1 Osteoarthritis of spine Remarkably effective 26.

Mix M(n) 12 .7 2 Osteoarthritis of spine Judgement impossible 27.

Mix F(h) 9 19.9 2 Coxalgia Remarkably effective 28.

Pug F 8 7.2 1 Osteoarthritis of spine No effect 29.

Maltese F 18 3.0 1 Left shoulder subluxation Remarkably effective .

Pomeranian F(h) 11 6.0 1 Both hip arthritis deformans Remarkably effective 31.

Mix F(h) 9 13.2 1 Both hip arthritis deformans Remarkably effective 32.

Shih Tzu M(n) 6 8.3 1 Right patella luxation Remarkably effective -3ir Z2-. 33.

Miniature Pinscher M 17 1.7 1 Left elbow arthritis deformans Judgement impossible 34.

Pomeranian M(n) 7 6.3 1 Left shoulder subluxation Remarkably effective .

Mix F 12 14.1 1 Right hip and knee subluxation Effective 36.

Cavalier King Charles Spaniel F 3 7.9 1 Left knee subluxation Effective Remarkably effective 48% Effective 21% Slightly effective 6% Exacerbation 3% No effect 21% Judgement impossible 3 cases

Claims (19)

THE CLAIMS DEFINING THE INVENTION ARE:

1. A composition for administration to animals including a combination of: (a) at least one anti-inflammatory agent selected from the group comprising i) green-lipped mussel extract (GLME) and/or a pharmacologically active green lipped mussel product, and ii) shark cartilage; with (b) at least one enhancing agent selected from the group of: i) a bark product or extract exhibiting antioxidant properties, and ii) shark cartilage; and wherein for a composition including just one member from each group, the selected members must be different.

2. A composition for administration to animals including a combination of: . (a) at least one anti-inflammatory agent selected from the group comprising i) green-lipped mussel extract (GLME) and/or a pharmacologically active green lipped mussel product, and ii) shark cartilage; with (b) at least one enhancing agent selected from the group of: i) a bark or plant product or extract exhibiting any one of antioxidant, anti-arthritic, and anti-inflammatory properties, and ii) shark cartilage; and wherein for a composition including just one member from each group, the selected members must be different.

3. A composition as claimed in either claim 1 or claim 2 which includes either or both of a green-lipped mussel extract (GLME) and a pharmaceutically active green lipped mussel product, in combination with any one or more of: shark cartilage, pharmacologically active shark extract, and chondroitin sulphate.

4. A composition as claimed in either claim 1 or claim 2 which includes an antiinflammatory agent in combination with a chondroitin compound. i21^- Intellectual Propertv Office of NZ 20 DEC 2000 received

A composition as claimed in either claim 1 or claim 2 which includes as the antiinflammatory agent either or both of shark cartilage and pharmacologically active shark cartilage extract in combination with any one or more of: Enzogenol™, Pycnogenol™, a bark extract equivalent to Enzogenol™ or Pycnogenol™, chondroitin sulphate, and a chondroitin compound.

A composition as claimed in any one of the preceding claims which includes vitamin E.

A composition as claimed in any one of the preceding claims which includes deer velvet or a pharmacologically active extract thereof.

A composition as claimed in any one of the preceding claims which includes additional glycosaminoglycans than those present in the selected anti-inflammatory or enhancing agents.

A composition as claimed in any one of the preceding claims which green-lipped mussel extract (GLME) and/or a pharmacologically active green lipped mussel product in sufficient amount to provide gastro-intestinal protection against irritation by other components in the composition.

A composition as claimed in any one of the preceding claims which also includes any one or more of the following components: a vitamin, glycine, lysine, methionine, glutamic acid, tyrosine, and compounds providing in a pharmacologically acceptable form one or more of the following elements: manganese, zinc, iron, magnesium, selenium, calcium, copper, potassium, cobalt.

A composition as claimed in any one of the preceding claims which includes one or more pharmacologically active substances.

A composition as claimed in any one of the preceding claims formulated to be suitable for addressing any one or more of the following conditions in animals: inflammation, arthritis, chronic joint pain.

A composition as claimed in any one of the preceding claims in any one or more of the following forms: Intellectual Property Office of NZ 1 5 FEB 2001 received as a bolus or tablet, in a capsule, as a slow release implant, as a liquid composition, as a gel, and as a paste.

14. A composition as claimed in any one of the preceding claims formulated for use with non-human mammals.

15. A method for addressing joint problems in non-human animals consisting of the administration of a composition as claimed in any one of the preceding claims.

16. A method as claimed in claim 15 in which the method of administration is oral.

17. The composition of any one of claims 1 through 14 substantially as described herein with reference to the contained examples.

18. A method for addressing joint problems, substantially as described herein with reference to the contained examples.

19. The use of any two or more of: i) green-lipped mussel extract (GLME) and/or a pharmacologically active green lipped mussel product, ii) shark cartilage and/or pharmacologically active shark cartilage extract; and iii) an antioxidant bark extract, in the preparation of a composition for use in addressing any one or more of: a) inflammation; b) degenerative joint complaints; c) other cartiligenous degeneration; d) gastrointestinal sensitivity or irritation; e) cancerous tumours. Bomac Laboratories Limited by its Agents jtagual Property uftice of NZ 1 5 FEB 2001 received END