AU2005200953B2 - Pet food for maintenance of joint health and alleviation of arthritic symptoms in companion animals and method of manufacturing same - Google Patents

Description

P001 Section 29 Regulation 3.2(2)

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT Application Number: Lodged: Invention Title: Pet Food for maintenance of joint health and alleviation of arthritic symptoms in companion animals and method of manufacturing same The following statement is a full description of this invention, including the best method of performing it known to me us: PET FOOD FOR MAINTENANCE OF JOINT HEALTH AND ALLEVIATION OF ARTHRITIC SYMPTOMS IN COMPANION ANIMALS AND MAETHOD OF MANUFACTURING SAME FIELD OF THE INVENTION The present invention relates to pet food manufacture for companion animals, and more particularly to pet foods that include a Perna Canaliculus preparation in an amount that will provide a daily pet diet for the maintenance of joint health and for the alleviation of arthritic symptoms in companion animals such as dogs and cats.

BACKGROUND OF THE INVENTION The connective tissues of humans and non-human animals are constantly subject to stresses and strains from mechanical forces that can result in afflictions, such as arthritis (both rheumatoid and osteoarthritis), joint inflammation and stiffness. This is true for both humans and non-human animals, and particularly as they age. The underlying causes of rheumatoid arthritis and/or osteoarthritis are different such that rheumatoid arthritis is characterized as an autoimmune disease affecting both the joints and systemic immune functions, whereas osteoarthritis results from deterioration of the articular cartilage which may result in local inflammation of the joints. While a greater portion of humans with arthritis have rheumatoid arthritis, most of the arthritis occurring in companion animals is osteoarthritis.

In osteoarthritis or degenerative joint disease, increased stress in the joints results in loss of the integrity of the cartilage matrix and the resulting damage causes the accelerated destruction of cartilage components and synovial fluid.

The connective tissues are naturally equipped to repair themselves by manufacturing and remodeling prodigious amounts of collagen (a chief component of connective tissue) and proteoglycans-the other major component of connective tissues. With aging, there is a decreased ability to restore and synthesize normal collagen structures. This results in pain, deformity and limitation of joint motion.

In dogs, osteoarthritis is a disorder of the synovial joints which is characterized by degeneration of the articular cartilage and by formation of new bone at the joint margins. Hardening of the underlying subchondral bone may w~ also be a feature of osteoarthritis and in some cases, a variable degree of synovial inflammation may be present at some time during the progression of the disease.

The treatment of connective tissue afflictions in both humans and nonhuman animals can be quite problematic. A simple decrease in the stresses to which the connective tissue is subject is often not usually an option.

Consequently, treatment is often directed at controlling the symptoms of the afflictions and not their causes, regardless of the stage of the degenerative process. Presently, steroids such as corticosteroids and other anti-inflammatory materials, such as high doses of aspirin are widely used for the treatment of these afflictions in humans. In veterinary medicine, hyaluronic acid and polysulfonated gylcosaminoglycan are used, particularly for equines to reduce connective tissue pain and swelling. While these materials often relieve the pain and swelling associated with maladies arising from connective tissue problems, almost all drugs eventually lose their effectiveness.

Natural products derived from plants and food have frequently been the source of effective drugs, and in recent years there has been an increased interest in the analysis of these natural products, especially where a clinical benefit is claimed.

Compounds that have been identified in foods and may be of clinical benefit are the orally administered chondro-protective agents, glucosamine and chondrotin sulphate, which in the body, are normal constituents of articular cartilage. There are studies to suggest that these agents might be effective in humans in the treatment of osteoarthritis. However, there are few reports in the veterinary literature of the clinical efficacy of these oral chondro-protective agents in dogs and other animals.

In the category of natural food products, it has been found that certain marine organisms contain compounds that when fed to animals aid in the treatment of inflammation. One of these marine organisms is Perna Canaliculus (New Zealand Green Lipped Mussel or GLM) in which its anti-inflammatory activity was first identified in a clinical study on leukaemia.

Initial assessment of the anti-inflammatory activity of Perna Canaliculus was first attempted using a polyarthritis model in rats. (Cullen et al. 1975.) These I 1g- II1 studies, however, failed to show the presence of any significant anti-inflammatory activity in the mussel preparation. In contrast, Miller and Ormrod (1980), using a carrageenan-induced paw edema assay (Winter et al. 1962), were able to show that mussel preparations, when administered intraperitoneally, gave a significant reduction to the swelling of a carrageenan-inducted rat paw edema.

Subsequently, they fractionated a non-dialysable, water-soluble fraction from the mussel preparation that possessed the anti-inflammatory activity. The aqueous extract showed a dose-dependent anti-inflammatory activity when administered intraperitoneally which could not be detected upon oral administration of the mussel powder. It was suggested that the water-soluble fraction therefore contained an irritant component possessing apparent anti-inflammatory activity.

Rainsford and Whitehouse (1980) also reported that freeze-dried powder preparations of the whole mussel (excluding shell) given orally to rats showed some modest antiinflammatory activity in the carrageenan-induced paw edema assay, and that this material strikingly reduced the gastric ulcerogenicity of several non-steroidal antiinflammatory drugs in rats and pigs. In another study, Korthauer and Delatorre (1992) found that the oral administration of aglycosaminoglycan extracted from Pema Canaliculus to 26 dogs with arthritis at mg/kg daily for eight weeks alleviated the signs of lameness or faulty posture in a high proportionate number of dogs in the study.

Macrides and Kalafatis, the named inventors of WO 96/05164 for an antiinflammatory preparation, have established that lipid fractions from Pema Canaliculus (in contrast to earlier work on aqueous fractions) are a rich source of compounds which in semi-purified extracts, have shown a measure of antiinflammatory activity when tested in appropriate model systems. In WO 96/05164, a purified active fraction isolated from a lipid extract of Pema Canaliculus or Mytilus Edulis, has an active component that has been shown to have anti-inflammatory properties. From this active component, a substantially pure form of 17eicosatetraenoic acid (an omega 3 fatty acid) has been isolated and pharmaceutically acceptable esters, amides and salts thereof have been identified. This compound may be a major constituent of the active fraction isolated from the lipid extract of Pema Canaliculus. The lipid extract when fed orally has been shown to reduce inflammation in rats (Whitehouse et al. 1996).

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ilII While the exact mechanism of Perna Canaliculus on arthritic symptoms is unknown, it is thought to be partly due to the presence of a unique eicosatetraenoiec acid (ETA) as well as other unique fatty acids that appear to alter the production of inflammatory agents in the body via the lipoxygenase pathway.

As previously discussed, the lipid extract of Perna Canaliculus contains a high percentage of these fatty acids and the powder form contains small amounts of the same fatty acids as well as other nutrients such as complex proteins, glycosaminoglycans, vitamins, minerals and amino acids, that may act in synergism to regenerate damaged articular cartilage and synovial fluid. In understanding the ideology of the two main types of arthritis, the lipid extract may be more affective in treating animals and/or individuals with rheumatoid arthritis since studies have shown that omega-3 fatty acids can reduce synovial and systematic inflammatory response (Volker et al. 1996). As for the powder form, it may be more beneficial in treating individuals with osteoarthritis since it also contains glycosaminoglycans and other nutrients that might potentially help to regenerate articulate cartilage in the joints. These compounds may also help to maintain joint health in animals not yet exhibiting arthritic symptoms.

Based on the apparent effectiveness of a Perna Canaliculus extract as an anti-inflammatory agent, it would be beneficial to provide a commercially processed.mammal pet food product that incorporates a quantity of a Perna Canaliculus preparation in an amount that will assist in the maintenance of joint health and the alleviation of arthritic symptoms in mammal companion animals selected from the group consisting of dogs and cats.

Similarly, it would be advantageous to devise at least one method or process of manufacturing commercial-grade, processed cat or dog food products for the maintenance of joint health and the alleviation of arthritic symptoms in such mammal companion animals, wherein the effectiveness and bio-availability or activity of a Perna Canaliculus preparation is maintained in the finished, processed food product.

It would also be beneficial if a feeding regime for dog and cat companion animals could be devised, that is simple to implement in seeking to maintain joint health and/or alleviate arthritic symptoms in such companion animals.

r SUMMARY OF THE INVENTION In accordance with a first aspect of the present invention, there is provided a commercial-grade, processed cat or dog pet food product that includes a Perna Canaliculus preparation in a predetermined amount such as to assist in the maintenance of joint health and the alleviation of arthritic symptoms in cat or dog pet animals, wherein the pet food product includes a basal pet food composition that has been cooked or thermally treated and processed at elevated temperatures to achieve shelf-life stability, the pet food composition providing the or part of a daily diet to the dog or cat, and a predetermined amount of an active Pera Canaliculus preparation comprising powdered Pera Canaliculus flesh or a lipid extract of Pera Canaliculus, the predetermined amount being selected such that either a dosage range of generally 0.18 to 114 mg of powdered Perna Canaliculus per kg of animal body weight per day is administered to the pet animal, or the pet food product incorporates about 1.5 to 1000 mg of powdered Perna Canaliculus per 400 kcal of pet food product, or a dosage range of generally 1.0 to 13 mg of Pera Canaliculus lipid extract per kg of animal body weight per day is administered to the companion animal, or the pet food product incorporates about 10.0 to 100 mg of Pera Canaliculus lipid extract per 400 kcal of pet food product.

In the context of the present invention and its different aspects also mentioned below, it is to be understood that the expressions 'commercially processed pet food' or 'commercial-grade, processed pet food' are distinct from and a different matter composition when compared to pet food diets that may be prepared by merely combining or co-mingling food items or substances which are known to be readily consumed by a cat or dog, such as meat cut-offs, offal, cooked vegetables, cereals and the like, and adding to it, shortly before or at the time of feeding of the pet animal, a food supplement containing powdered Perna Canaliculus of such type as sold under the brands 'Seatone SF-4' by Healtheries of New Zealand Limited, 'Canosan' by Boehringer Ingelheim, Germany, or similar food supplements.

Such food additives are specifically formulated and manufactured into administration dosage forms which use inert carrier substrates that have no or extremely limited nutritional values to the animal (ie are not regarded as food per w .r l I 1I se) but enable the active Perna Canaliculus ingredient to be admixed into a pet food diet prior to consumption, and otherwise ensure that the active compound can remain substantially unaffected during storage. Shelf-life for the active compounds present in the Perna Canaliculus preparation is for example achieved by cold-pelleting grain and fibre source material with, freeze-dried Perna Canaliculus powder.

Consequently, such food additives or supplements do not answer the definition of a pet food product as understood herein, wherein a basal pet food composition (which is intended to cover the nutritional requirements of the pet animal) incorporates the active Perna Canaliculus ingredient at the point of manufacture of the product, and which is formulated and packaged to provide a thermally processed, ready-to-eat, pre-packaged and shelf-stable eg main meal administration format.

In accordance with the present invention, the basal pet food compositions include formulations typically used in the manufacture of canned pet food, dry pet food kibbles, semi-moist chewy bites, treats and other commercial-grade, industrially manufactured pet food.

In accordance with a second aspect of the present invention there is provided a process for manufacturing a pet food product for cats or dogs as per the first aspect of the present invention described above, wherein thermal processing of the pet food composition after incorporation of the predetermined amount of the active preparation of Perna Canaliculus is conducted at temperatures below a predetermined temperature where the arthritis-alleviating and joint-health supporting functionality (or activity) of the Perna Canaliculus preparation is substantially degraded, preferably below about 700C.

Additional steps may be employed in order to ensure that the activity of the active constituents of the Perna Canaliculus preparation is maintained throughout the process of manufacture, for example by the addition of suitable anti-oxidant systems that stabilize the Perna Canaliculus composition.

In yet a further aspect of the present invention there is provided a process for maintaining joint health and alleviating arthritic symptoms in cat and dog animals by feeding such companion animals a daily diet comprising the pet food product of the first aspect of the invention.

O Other features and advantages of different aspects of the present invention C will become apparent from the following description of presently preferred embodiments of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT The first aspect of the present invention is embodied in commercially t' packaged, processed pet food products such as wet and semi-moist pet food sold in pouches, trays and cans, and dry kibbles sold in boxes or bags. However, it is also feasible to incorporate an effective amount of an active preparation of Perna tr 10 Canaliculus for maintaining joint health and alleviating arthritic symptoms in dogs and cats in so-called pet food treats and a pet drinks.

A "preparation" of Perna Canaliculus as the term is used herein, is intended to cover a powdered (eg freeze-dried) form of the entire Perna Canaliculus mollusc without its shell, or a concentrated extract of the lipid portion of the Pema Canaliculus.

Although the underlying mechanism in alleviating arthritic symptoms by extracts of Perna Canaliculus (Green Lipped Mussel; GLM hereinafter) have not been well characterized, it has been shown that preparations of GLM in both the powder and lipid form are efficacious in alleviating arthritic symptoms in dogs.

Even though both the powder and lipid extracts have been found to be effective, the Green Lipped Mussel powder (GLMP) may be a more efficacious treatment for osteoarthritic animals because it helps address both a cause (regeneration of cartilage and synovial fluid) and effect (anti-inflammatory effects) of osteoarthritis.

A compound or composition is said to be "acceptable" if its administration can be tolerated by a recipient mammal. Such an agent is said to be administered in an "effective amount" if the amount administered is physiologically significant.

An agent is physiologically significant if its presence results in technical change in the physiology of a recipient mammal. For example, in the alleviation of arthritic symptoms in companion animals, an agent which slows the progression of the disease and/or symptoms or completely treats the disease and/or symptoms, would be considered effective.

Normally, administration dosages may vary depending upon known factors such as the pharmacodynamic characteristics of the particular active ingredient In I. =r

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and its mode and route of administration; the age, sex, health and weight of the companion animal; nature and extent of symptoms; kind of concurrent treatment, frequency of treatment and the effect desired. The dosages referred to herein are the dosages determined from studies.

Where the GLM preparation is in powdered form, ie GLMP, a daily dosage (effective amount) in a range of about 0.18 to 114 mg of active GLMP/kg of animal body weight/day is efficacious in alleviating arthritic symptoms in dogs and cats and likewise would also maintain joint health. More preferably, a dosage range of 1.8 to 85 mg of GLMP/kg of animal body weight/day, and most preferably, a dosage range of 9 to 58 mg of GLMP/kg of body weight/day would be efficacious in maintaining joint health and alleviating arthritic symptoms in these animals. This dosage equates, for example, to a 22 kg dog receiving 0.45 g/day or 0.02 g/kg of body weight/day of GLMP. The dosage level for a cat would be the amount required to reach a level of 0.02 g/kg of body weight/day of GLMP.

Using as a reference the caloric value of a pet food composition, the amount of active GLMP that is necessary per 400 kcal of a pet food product to be efficacious in maintaining joint health and alleviating arthritic symptoms in cat and dog companion animals, and most particularly dogs, is generally 1.5 mg to 1000 mg of GLMP/400 kcal of pet food. More preferably an amount of 15 mg to 750 mg of GLMP/400 kcal and most preferably, an amount of 75 mg to 520 mg of GLMP/400 kcal of a pet food product is required to be efficacious in the maintenance of joint health and alleviating arthritic symptoms in such companion animals.

Where the GLM preparation is a lipid extract of GLM, a daily dosage (effective amount) of the lipid extract of about 1.0 to 13 mg/kg of body weight/day and a most preferred dosage of 4.6 to 5.1 mg/kg of body weight/day is efficacious in alleviating arthritic symptoms in cat and dog companion animals and likewise would also maintain joint health. A dosage related to the caloric value of a pet food composition in mg/400 kcal is about 10.0 to 100 mg of the lipid extract/400 kcal of pet food and more preferably, 33 to 40 mg of the lipid extract/400 kcal of a pet food product to be efficacious in the maintenance of joint health and alleviating arthritic symptoms.

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O As is known to the skilled pet food manufacturer and formulator, there are C' a variety of commonly known pet food products. In the area of cat and dog food, there is wet pet food, semi-moist pet food, dry pet food and pet treats. Drinks for Spets are also available such as milk drinks for cats. Wet pet food generally has a C 5 moisture content above 65%. Semi-moist pet food typically has a moisture content between 20-65% and can include humectants such as propylene glycol, t' potassium sorbate, and other ingredients to prevent microbial growth (bacteria and mold). Dry pet food (kibble) generally has a moisture content below 20% and its processing typically includes extruding, drying and/or baking in heat. Pet treats q -10 can typically be semi-moist chewable treats; dry treats in any number of forms; 0chewable bones; baked, extruded or stamped treats; confection treats; or other kinds of treats.

A basal semi-moist cat or dog food composition that may be used in preparing a pet food product embodiment in accordance with the invention will generally include ingredients such as cereal grains, meats, fats, vitamins, minerals and functional ingredients such as vitamins and minerals that are blended together, cooked and would then usually be packaged in pouches or cans. It will be appreciated that the specific formulation of ingredients may vary and is known to one skilled in the art.

In a basal dry cat or dog pet food composition that may be used in preparing a pet food product embodiment in accordance with the invention, the ingredients generally would include cereal grains, meats, poultry, fats, vitamins, minerals and other functional ingredients. The ingredients are mixed and put through an extruder-cooker. Thereafter, the product is cut or shaped and subsequently dried. After drying, flavours, fats and other functional ingredients can be coated or sprayed onto the dried product. The spray used is of a kind that is known to one skilled in the art of producing dry pet food.

Basal wet pet food compositions, usually for subsequent canning, and pet treats compositions can be equally produced in a manner known to one skilled in the art, depending upon the kind of wet pet food product and treat desired, and the GLMP or a GLM lipid portion preparation may be added to the basal food composition prior to canning or packaging to obtain a pet food product embodiment in accordance with the invention, as is described below.

ml I'll I. illl Generally speaking, the procedure for and timing of adding the GLMP or GLM lipid portion preparation to the basal pet food composition (such as described above generically) will depend upon the type of processing usually required to or employed in the manufacture the specific type of pet food, eg wet pet food, semi-moist food, kibbles, treats, etc.

The anti-arthritic activity of the Perna Canaliculus extract has been shown to be sensitive to moisture, heat and light. Experimentation has demonstrated that extrusion cooking, which usually is employed in the manufacture of dry kibbles, of pet food compositions incorporating the Perna Canaliculus extract at above 100 degrees C destroys its activity. Activity for joint health maintenance and arthritic symptoms alleviation is only maintained with. processing temperatures below about 70 degrees C. Consequently, in the manufacturing of semi-moist as well as other pet food products, where the GLMP or GLM lipid portion is usually admixed into the pet food composition formula prior to thermal processing, the temperature of processing after mixing should be restricted to temperatures below those usually employed in extrusion cooking and such as to otherwise prevent degradation of the GLM's activity.

For example, with semi-moist treats, during manufacture thereof, at no time do processing temperatures usually exceed 50 -70 degrees C. Therefore, the active GLMP or GLM lipid portion can be added to the treat formulation and mixed thereinto at any time and be subjected to thermal processing together with the other ingredients. However, if the processing temperature required to obtain a finished pet food generally exceeds about 70 degrees C, then the active GLMP or lipid portion would be coated onto a 'finished' pet food composition, ie once high temperature thermal processing steps have been concluded.

For example, a commercial-grade, processed semi-moist pet food embodiment of the present invention can be formed by adding to a basic semimoist pet food formulation described above, about 10 by weight of GLMP. In a typical semi-moist pet food, 4.5 grams of food provide a caloric value of approximately 2910 kcal/kg, which will deliver a GLMP dosage range of 9 to 58 mg of GLMP/kg/day.

While a composition and process for producing a semi-moist pet food product has been generally described, it should be appreciated that other semii I moist pet food compositions and manufacturing processes are known to one skilled in the art, and such can be used to produce a semi-moist pet food product containing GLMP or a GLM lipid extract preparation.

To produce an embodiment of a dry pet food product in accordance with the subject invention, kibbles are manufactured as described generically above, and GLMP is added to the kibble product in a spraying process after the kibbles have been dried. The GLMP or lipid extract preparation is added to the surface of the product at low temperatures in conjunction with other surface spray ingredients. This is achieved by incorporating GLMP into a suitable spray formulation in an amount that would provide a final concentration of GLMP in a range of generally between 0.06% w/w and 4.2% w/w. A spray mixture having this amount of GLMP provides an inclusion level of generally 10% w/w of the GLMP. The dry, extruded kibble composition is spray-coated with the GLMP spray mixture such that the final product has an inclusion level of GLMP that is generally about 1 w/w or below. A typical dry kibble formula will have a caloric value of about 3300 kcal/kg, which would then equate to such spray-coated kibbles providing a GLMP dosage range of generally between 75 mg to 520 mg/400 kcal.

While ingredients used in and a process employed for manufacturing a dry pet food product have been described above, it should be appreciated that different dry pet food formulas and other manufacturing processes are known to one skilled in the art, and these can be used to produce a dry pet food product suitable for subsequent coating with a GLMP or a GLM lipid extract coating preparation.

In the case of pet food products having relevant moisture content, ie higher water activity, eg wet and semi-moist pet food compositions, it is desirable to also stabilize the added GLMP preparation against degradation effects associated with water content, eg oxidation. This can be achieved by the addition of antioxidant systems composed of an organic acid and tocopherols, such as tartaric acid and vitamin E.

In accordance with the manufacturing process aspects of the present invention, it is important that the anti-arthritic activity of the relevant compounds that are present in the Perna Canaliculus preparation (powdered or lipid extract) V I 3

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I a' I i is maintained throughout the manufacturing process in the pet food products by using the low temperature processing regime outlined above, and employ where necessary other (eg antioxidation) stabilization criteria. For example, other methods may be used to protect the active Pema Canaliculus compounds from degradation during processing, such as encapsulation or new processing technology.

Thus, as described, the present invention can be embodied in a pet food product for companion animals that includes a quantity of the active preparation of Perna Canaliculus in an effective amount that will provide a pet diet for the maintenance of healthy joints and alleviation of arthritic symptoms in companion animals. The preparation can be in either powder or lipid extract form. The present invention also is embodied in a process for producing the pet food product containing an amount of an active Perna Canaliculus preparation and a process of feeding the companion animals the inventive pet food.

In the following, specific examples of pet foods will be provided, and their efficiency documented.

Example 1: Influence of Green Lipped Mussel on Arthritic Symptoms The effect of a Perna Canaliculus preparation in both powder and lipid extract form in alleviating osteoarthritic symptoms in dogs, was determined wherein forty-seven mixed breed and sex adult dogs, ranging in age from 8-12 years, were fed a base diet consisting of a mix of canned and dry food. The dogs were divided into three groups.

A control group of 15 dogs was given a coloured water placebo; another dogs were given an oil supplement containing generally 80% mussel lipid extract, 20% olive oil and vitamin E; and the other 17 dogs were given GLMP. A lipid extract without the olive oil and vitamin E would provide the same effect. The dosage for the oil supplement group was 216 mg/day for dogs weighing 75 Ibs; 192 mg/day for dogs weighing between 55 to 75 Ibs; and 144 mg/day for dogs weighing 55 Ibs. In the GLMP group, the dosage was 1000 mg/day for dogs weighing 751bs; 750 mg/day for dogs weighing between 55 to 75 Ibs; and 450 mg/day for dogs weighing 55 Ibs.

The control group was dosed at 1 ml for dogs weighing 55 Ibs and 2 ml for dogs weighing 55 Ibs. The GLMP and lipid compounds were provided by ml li 1 -m

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McFarlane Laboratories Pty. Ltd., 410 Canterbury Rd., Surrey Hills, Victoria,3127 Australia.

All dogs were assessed for arthritic symptoms visually and physically by a veterinarian at baseline and again at six weeks. Factors.assessed at each time point included range of motion, mobility, pain swelling and crepitus. These factors were used to calculate total arthritic scores for the dogs. At the end of the six weeks, as shown in Table 1 and Graph 1 below, the data showed that both the lipid and GLMP extract were efficacious in alleviating arthritic symptoms, however, more dogs in theGLMP group improved or had greater reduction in arthritic symptoms as compared to the lipid dosed group of dogs.

TABLE 1 Reduction in total Control Lipid GLMP arthritic scores (n=15) (n=15) (n=17) of dogs with 30% 6.6% 46.7% 82.4% reduction (1/15 dogs) (7/15 dogs) (14/17 dogs) of dogs with 2 50% 0.0% 20.0% 35.5% reduction (0/15 dogs) (3/15 dogs) (6/17 dogs) of dogs with 70% 0.0% 13% 17.6% reduction (0/15 dogs) (2/15 dogs) (3/17 dogs) ou jil illl 14 GRAPH 1: The Influence of Green Lipped Mussel on Arthritic Symptoms S2,* Baseline 20- 6 Weeks 1o -i~5- 0 Control Lipid GLMP *Significantly different from baseline scores (p 0.05) Example 2: The Influence of Different Dosages of GLMP on Total Arthritic Scores A second study was performed to evaluate whether different dose levels of GLMP would alleviate arthritic symptoms in dogs at an earlier time point or at a lower dose level. In this study, forty-seven mixed breed and sex adult dogs, ranging in age from 8-12 years, were fed the same basic diet. The dogs were divided into four groups.

A control group of 12 dogs was given a wheat flour placebo.

A second group of 12 dogs was given a dosage of GLMP in an amount of 1000 mg/day for dogs weighing 751bs; 750 mg/day for dogs weighing between to 751bs; and 450 mg/day for dogs weighing 55 Ibs which was 100% of the dosage given in the initial study.

A third group of11 dogs was given a dosage of GLMP in an amount of 500 mg/day for dogs weighing 751bs; 375 mg/day for dogs weighing between 55 to 75 Ibs; and 225 mg/day for dogs weighing 55 Ibs, which was 50% of the dosage given in the initial study.

A fourth group of 12 dogs was given a dosage of GLMP in the amount of 2000 mg/day for dogs weighing 75 Ibs; 1500 mg/day for dogs weighing between I -liii i 11 to 75 lbs; and 900 mg/day for dogs weighing 55 Ibs, which was 200% of the dosage given in the initial study.

All dogs were assessed for arthritic symptoms visually and physically by a veterinarian at baseline and again at three and seven weeks using the criteria established in the initial study. As illustrated in Table 2 and Graph 2 below, this study revealed that a statistically significant reduction in total arthritic score was found after seven weeks of treatment in the 50%, 100% and 200% dosage groups as compared to their respective baseline time points and to the seven week control group score. Additionally, all the test groups showed statistically significant reductions in total arthritic scores between their respective third week and base line time points. In the control group, three week mean scores were significantly lower than baseline scores, but those differences were not seen at 7 weeks.

TABLE 2 Reduction in total Control GLMP GLMP GLMP arthritic scores (100%) (200%) (n=12) (n=11) (n=15) (n=12) of dogs with t 8.3% 64% 50% reduction (1/12 dogs) (7/11) dogs (6/12 dogs) (6/12 dogs) of dogs with 0.0% 45% 33% 33% reduction (0/12 dogs) (4/11) dogs (4/12 dogs) (4/12 dogs) of dogs with 0.0% 27% 8.3% reduction (0/12 dogs) (3/11) dogs (1/12 dogs) (3/12 dogs) of dogs with 0.0% 18% 0.0% reduction (0/12 dogs) (2/11) dogs (0/12 dogs) (3/12 dogs) O GRAPH 2: The Influence of Different Dosages of GLMP on Total Arthritic Scores 2

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5 Q E Baseline 03 2- n Weeks 3 Basn IN Weeks 7 Control 50% 100% 200% Dosages Represent differences only within each group between the time points at a level of p 0.05. Significant differences were observed between the Baseline, 3 week and 7 week time points in the 50,100 and 200% dosages.

ab Represent after 7 weeks of treatment; differences were observed between the control and the treatment group.

The inventive pet food products, methods for producing the pet. food products, and methods for feeding the pet food products to companion animals for the maintenance of joint health and alleviation of arthritic symptoms in companion animals described herein are presently representative of the preferred embodiments, are exemplary, and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art which are encompassed within the spirit of the invention and are defined by the scope of the claims.

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REFERENCES

All patents and publications mentioned in this specification are indicative of the level of those skilled in the art to which the invention pertains. All patents and publications herein are incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. The following references have been cited in this application: WO 96/05164, Anti-Inflammatory Preparation, published February 22,1996 Cullen, J. Flint, M. H.,and Leider, J. (1975) M. Z. Med. J. 81:260-261.

Miller, T. E. andOrmrod, D. J. (1980), M. Z. Med. J. 92: 187-193.

Winter, C. A.,Risley, A. E.andNuss, G. W. (1962) Prc. Soc. Exp. Biol.

Med.111: 544-547.

Rainsford, K. D. and Whitehouse, M. W. (1980), Arzneim.-forsch./Drug Res. 30 2128-2132.

Korthauer, W. and Delatorre, J.,Kleintierpraxis V. 37, No. 7; (1992) 467- 768.

Whitehouse, M. Macrides, T. Kalafatis, Betts, W. Hayes, D.

and Broadbent, J, (1997) Inflammopharmacology 5: 237-246.

Volker, Garg, M. (1996) J. Clin. Biochem. Nutr. 20:83-97 and Kramer,J. Lawrence, D. Jubiz, DiGiacomo, Rynes, R., Bartholomew, L. and Sherman, M. (1990), Arthritis and Rheumatism 33: 810- 820.

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Claims (22)

1. Commercial-grade, processed cat or dog pet food product, including a basal pet food composition that has been cooked or thermally treated and processed at elevated temperatures to achieve shelf-life stability, the pet food composition being formulated to provide the or part of a daily diet to the dog or cat, and a predetermined amount of an active Perna Canaliculus preparation for assisting in the maintenance of joint health and the alleviation of arthritic symptoms in pet cats and dogs comprising powdered Perna Canaliculus flesh or a lipid extract of Perna Canaliculus, wherein the predetermined amount is selected such that either a dosage range of generally 0.18 to 114 mg of powdered Perna Canaliculus per kg of animal body weight per day is administered to the pet animal with its daily food diet, or the pet food product incorporates about 1.5 to 1000 mg of powdered Perna Canaliculus per 400 kcal of pet food product, or a dosage range of generally 1.0 to 13 mg of Perna Canaliculus lipid extract per kg of animal body weight per day is administered to the pet animal with its daily food diet, or the pet food product incorporates about 10.0 to 100 mg of Perna Canaliculus lipid extract per 400 kcal of pet food product, and wherein the pet food product is processed below a predetermined temperature after incorporation of the Perna Canaliculus preparation at which its arthritis- alleviating and joint-health supporting activity is not substantially degraded.

2. The pet food product of claim 1, wherein the predetermined amount is an amount that provides a dosage range of about 9 to 58 mg of active powdered Perna Canaliculus per kg of animal body weight per day.

3. The pet food product of claim 1, wherein the predetermined amount is an amount that provides about 1.5 to 1000 mg of active powdered Perna Canaliculus per 400 kcal of pet food product.

4. The pet food product of claim 3, wherein the predetermined amount is an amount that provides about 75 to 520 mg of active powdered Perna Canaliculus per 400 kcal of pet food product.

The pet food product of claim 1, wherein the predetermined amount is an amount that provides a dosage range of generally 1.0 to 13 mg of active Perna Canaliculus lipid extract per kg of animal weight per day.

6. The pet food product of claim 5, wherein the predetermined amount is an amount that provides a dosage range of generally 4.6 to 5.1 mg of active Perna Canaliculus lipid extract per kg animal weight per day.

7. The pet food product of claim 1, wherein the predetermined amount is an amount that provides about 10.0 to 100 mg of active Perna Canaliculus lipid extract per 400 kcal of pet food product.

8. The pet food product of claim 7, wherein the predetermined amount is an amount that provides about 33 to 40 mg of active Perna Canaliculus lipid extract per 400 kcal of pet food product.

9. The cat or dog pet food product of any one of claims 1 to 8, wherein basal pet food composition includes ingredient formulations typically used in the manufacture of canned wet pet food, dry pet food kibbles, semi-moist chewy bites, treats or other commercial-grade, industrially manufactured and thermally processed pet foods.

A process for manufacturing a dry cat or dog pet food product as defined in any one of claims 1 to 9, wherein the basal food compoisition is a dry kibble formulation that is extrusion cooked and processed at elevated temperatures to achieve shelf-life stability of the fodd product, and wherein the predetermined amount of the active preparation of Perna Canaliculus is incorporated into a solution which is subsequently coated onto the dry pet food kibble product at temperatures below about 70 0 C

11. A process for manufacturing a semi-moist cat or dog pet food product as defined in any one of claims 1 to 9, wherein the predetermined amount of the active preparation of Perna Canaliculus is admixed into a moist or semi- moist basal food formulation and the mixture obtained is subsequently processed at elevated temperatures but below about 700C to achieve shelf- life stability of the semi-moist pet food product.

12. The manufacturing process of claim 10 or 11, wherein one or more anti- oxidant substances are added to the basal pet food composition, the anti- oxidant substances being of such nature as to stabilize and substantially inhibit oxidative degradation of active compounds contained in the Perna Canaliculus preparation.

13. A process for treating dogs and cats for the maintenance of joint health and alleviation of arthritic symptoms, comprising feeding on a regular, preferably daily basis a pet food diet that consists of or incorporates a pet food product in accordance with any one of claims 1 to 9.

14. The process of claim 13, wherein the feeding regime is such that it administers to a dog 0.18 to 114 mg of powdered Perna Canaliculus per kg of animal body weight per day.

15. The process of claim 14, wherein the feeding regime is such that it administers to a dog 9 to about 58 mg of powdered Perna Canaliculus per kg of animal body weight per day.

16. The process of claim 13, wherein the daily food diet includes a pet food product that has about 1.5 to 1000 mg of powdered Perna Canaliculus per 400 kcal of pet food product.

17. The process of claim 16, wherein the daily food diet includes a pet food product that has about 15 to 750 mg of powdered Perna Canaliculus per 400 kcal of pet food product.

18. The process of claim 17, wherein the daily food diet includes a pet food product that has about 75 to 520 mg of powdered Perna Canaliculus per 400 kcal of pet food product.

19. The process of claim 13, wherein administers to a dog about 1.0 to 13 per kg of animal body weight per day.

The process of claim 19, wherein administers to a dog about 4.6 to 5.1 per kg of animal body weight per day. the feeding regime is such that it mg of Perna Canaliculus lipid extract the feeding regime is such that it mg of Perna Canaliculus lipid extract

21. The process of claim 13, wherein the daily food diet includes a pet food product that has about 10.0 to 100 mg of Perna Canaliculus lipid extract per 400 kcal of pet food product.

22. The process of claim 21, wherein the daily food diet includes a pet food product that has about 33 to 40 mg of Perna Canaliculus lipid extract per 400 kcal of pet food product. DATED this 3rd day of June 2007 MARS, INCORPORATED WATERMARK PATENT TRADE MARK ATTORNEYS 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA P20269AU01