WO2012067641A2 - Methods and compositions for preventing and treating osteoarthritis - Google Patents
Methods and compositions for preventing and treating osteoarthritis Download PDFInfo
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- WO2012067641A2 WO2012067641A2 PCT/US2011/001885 US2011001885W WO2012067641A2 WO 2012067641 A2 WO2012067641 A2 WO 2012067641A2 US 2011001885 W US2011001885 W US 2011001885W WO 2012067641 A2 WO2012067641 A2 WO 2012067641A2
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
- A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/179—Colouring agents, e.g. pigmenting or dyeing agents
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the invention relates generally to methods for preventing and treating osteoarthritis and particularly to methods for using lycopene for preventing and treating osteoarthritis.
- Osteoarthritis also commonly referred to as degenerative joint disease, is characterized by the imbalance between the synthesis and degradation of articular cartilage.
- the breakdown of joint cartilage often results in joint pain and loss of mobility.
- OA commonly affects the hands, feet, spine, and the large weight bearing joints, such as the hips and knees.
- Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion.
- a variety of causes, such as hereditary, developmental, metabolic, and mechanical, may initiate processes leading to loss of cartilage.
- Lycopene is a carotenoid found in red fruits and vegetables, such as tomatoes. Carotenoids are natural pigments that act as antioxidants for the body. Lycopene gets its name from the species classification of the tomato, Lycopersicon esculentum.
- Osteoarthritis is a painful condition and is adverse to the health and wellness of an animal and result in a lower quality of life for an animal. There is, therefore, a need for methods and compositions useful for promoting the health and wellness and improving the quality of life for animals by preventing and treating osteoarthritis.
- lycopene is administered to the animals in amounts of from about 0.005 to about 100 milligrams per kilogram of body weight per day (g/kg/day) for as long as there is a need for such treatment.
- animal means any animal that has a need for preventing or treating osteoarthritis, preventing or treating the degradation of articular cartilage, and promoting and maintaining joint health in an animal, including human, avian, bovine, canine, equine, feline, hicrine, lupine, murine, ovine, or porcine animals.
- the term "companion animal” means domesticated animals such as cats, dogs, rabbits, guinea pigs, ferrets, hamsters, mice, gerbils, horses, cows, goats, sheep, donkeys, pigs, and the like.
- terapéuticaally effective amount means an amount of a compound of the present invention that (i) treats or prevents the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein.
- treating embrace both preventative, i.e., prophylactic, and palliative treatment.
- pharmaceutically acceptable indicates that the substance or composition must be compatible chemically and or toxicologically, with the other ingredients comprising a formulation, and/or the mammal being treated therewith.
- the term "health and or wellness of an animal” means the complete physical, mental, and social well being of the animal, not merely the absence of disease or infirmity.
- extending the prime means extending the number of years an animal lives a healthy life and not just extending the number of years an animal lives, e.g., an animal would be healthy in the prime of its life for a relatively longer time.
- degenerative joint disorder refers to any etiological or pathological symptom affecting a joint. Such symptoms and etiology include swelling, pain and/or stiffness of a joint such that complete or partial loss of function and/or damage to the joint and/or a reduction of the joint mobility.
- the term also includes chronic inflammation, primarily of the synovial tissue, pannus formation, destruction of articular cartilage and release of various enzymes, for example, collagenase and lysosomal enzymes, in an affected joint, osteoarthritis, rheumatic disorders with cartilage breakdown, rheumatoid arthritis, chondrolysis after joint trauma, for example, after meniscus or patella injuries or torn ligaments, or chondrolysis associated with prolonged immobilization of joints.
- various enzymes for example, collagenase and lysosomal enzymes
- degenerative joint disorder includes osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, tendonitis, ankylosing spondilitis, bursitis, spinal disc injuries, and temporomandibular joint disorder.
- conjunction means that lycopene or other compounds or other compositions of the invention are administered to an animal (1) together in a food composition or (2) separately at the same or different frequency using the same or different administration routes at about the same time or periodically.
- Periodically means that lycopene or other compounds or other compositions are administered on a schedule acceptable for specific compounds or compositions.
- “About the same time” generally means that lycopene or other compounds or compositions are administered at the same time or within about 72 hours of each other.
- dietary supplement means a product that is intended to be ingested in addition to a normal animal diet.
- Dietary supplements may be in any form, e.g., solid, liquid, gel, tablet, capsule, powder, and the like. Preferably they are provided in convenient dosage forms, e.g., in sachets. Dietary supplements can be provided in bulk consumer packages such as bulk powders, liquids, gels, or oils. Similarly such supplements can be provided in bulk quantities to be included in other food items such as snacks, treats, supplement bars, beverages, and the like.
- the term “aging” means being of an advanced age such that an animal has reached or exceeded 50% of the average life expectancy for the animal's species and/or breed within such species. For example, if the average life expectancy for a given breed of dog is 12 years, then an "aging animal" within that breed is 6 years old or older.
- the term "food” or “food product” or “food composition” means a product or composition that is intended for ingestion by an animal, including a human, and provides nutrition to the animal.
- the term "regular basis” means at least monthly dosing with lycopene and more preferably weekly dosing. More frequent dosing or consumption, such as twice or three times weekly, is preferred in certain embodiments. Still more preferred are regimens that comprise at least once daily consumption, e.g. , when lycopene is a component of a food composition that is consumed at least once daily.
- single package means that the components of a kit are physically associated in or with one or more containers and considered a unit for manufacture, distribution, sale, or use.
- Containers include, but are not limited to, bags, boxes, cartons, bottles, packages such as shrink-wrap packages, stapled or otherwise affixed components, or combinations thereof.
- a single package may be containers of individual lycopene and food compositions physically associated such that they are considered a unit for manufacture, distribution, sale, or use.
- kits are associated by directions on one or more physical or virtual kit components instructing the user how to obtain the other components, e.g. , in a bag or other container containing one component and directions instructing the user to go to a website, contact a recorded message or a fax-back service, view a visual message, or contact a caregiver or instructor to obtain instructions on how to use the kit or safety or technical information about one or more components of a kit.
- the dosages expressed herein are in milligrams per kilogram of body weight per day (mg/kg/day) unless expressed otherwise.
- dry matter basis means that an ingredient's concentration or percentage in a composition is measured or determined after any free moisture in the composition has been removed.
- ranges are used herein in shorthand, to avoid having to list and describe each and every value within the range. Any appropriate value within the range can be selected, where appropriate, as the upper value, lower value, or the terminus of the range.
- the invention provides methods for preventing and treating osteoarthritis in an animal.
- the methods comprise administering to the animal a therapeutically effective amount of lycopene.
- the invention provides methods for preventing and treating the degradation of articular cartilage in an animal. The methods comprise administering to the animal a therapeutically effective amount of lycopene.
- the invention provides methods for promoting and maintaining joint health in an animal.
- the methods comprise administering to an animal a therapeutically effective amount of lycopene.
- the invention provides methods for promoting the health and wellness of an animal.
- the methods comprise administering to an animal a therapeutically effective amount of lycopene.
- the present invention provides methods for extending the prime years of an animal's life.
- the methods comprise administering lycopene to an animal therapeutically effective amount of lycopene.
- the inventions are based upon the discovery that lycopene is able to positively modulate osteoarthritis markers. Specifically, lycopene is able to decrease the gene expression of Matrix Metalloproteinase 13 (MMP-13, also known as collagenase II) and Tumor Necrosis Factor- Alpha (TNF-alpha). Genes associated with osteoarthritis have been previously identified in WO2005075685. The methods of the present invention may also be useful in the treatment of inflammatory related conditions, cancer metastasis and other degenerative joint disorders.
- MMP-13 Matrix Metalloproteinase 13
- TNF-alpha Tumor Necrosis Factor- Alpha
- lycopene is administered to an animal in amounts of from about 0.005 to about 100 mg/kg/day, preferably from about 0.01 to about 50 mg/kg/day, most preferably from about 0.05 to about 10 mg/kg day. In various embodiments, the lycopene is administered in amounts of from about 0.1 to about 5 mg/kg/day.
- Lycopene can be administered to the animal in any suitable form using any suitable administration route.
- lycopene can be administered in a lycopene composition, in a food composition, in a dietary supplement, in a pharmaceutical composition, in a nutraceutical composition, or as a medicament.
- lycopene can be administered using a variety of administration routes, including oral, intranasal, intravenous, intramuscular, intragastric, transpyloric, subcutaneous, rectal, and the like.
- lycopene is administered to an animal orally.
- lycopene is administered orally to an animal as a dietary supplement or as an ingredient in a food composition.
- lycopene is administered to an animal as an ingredient in a food composition suitable for consumption by an animal, including humans and companion animals such as dogs and cats.
- a food composition suitable for consumption by an animal including humans and companion animals such as dogs and cats.
- Such compositions include complete foods intended to supply the necessary dietary requirements for an animal or food supplements such as animal treats.
- food compositions such as pet food compositions or pet treat compositions comprise from about 5% to about 50% crude protein.
- the crude protein material may comprise vegetable proteins such as soybean meal, soy protein concentrate, corn gluten meal, wheat gluten, cottonseed, and peanut meal, or animal proteins such as casein, albumin, and meat protein.
- meat protein useful herein include beef, pork, lamb, equine, poultry, fish, and mixtures thereof.
- the food compositions may further comprise from about 5% to about 40% fat.
- suitable fats include animal fats and vegetable fats.
- the fat source is an animal fat source such as tallow or grease.
- Vegetable oils such as corn oil, sunflower oil, safflower oil, rapeseed oil, soybean oil, olive oil and other oils rich in monounsaturated and polyunsaturated fatty acids, may also be used.
- the food compositions may further comprise from about 10% to about 60% carbohydrate.
- suitable carbohydrates include grains or cereals such as rice, corn, millet, sorghum, alfalfa, barley, soybeans, canola, oats, wheat, rye, triticale and mixtures thereof.
- the compositions may also optionally comprise other materials such as dried whey and other dairy by-products.
- the moisture content for such food compositions varies depending on the nature of the food composition.
- the food compositions may be dry compositions (e.g., kibble), semi- moist compositions, wet compositions, or any mixture thereof.
- the composition is a complete and nutritionally balanced pet food.
- the pet food may be a "wet food”, “dry food”, or food of "intermediate moisture” content.
- "Wet food” describes pet food that is typically sold in cans or foil bags and has a moisture content typically in the range of about 70% to about 90%.
- “Dry food” describes pet food that is of a similar composition to wet food but contains a limited moisture content typically in the range of about 5% to about 15% or 20% (typically in the form or small biscuit-like kibbles). In one preferred embodiment, the compositions have moisture content from about 5% to about 20%. Dry food products include a variety of foods of various moisture contents, such that they are relatively shelf-stable and resistant to microbial or fungal deterioration or contamination. Also preferred are dry food compositions that are extruded food products such as pet foods or snack foods for either humans or companion animals. [0046] The food compositions may also comprise one or more fiber sources.
- fiber includes all sources of "bulk” in the food whether digestible or indigestible, soluble or insoluble, fermentable or nonfermentable. Preferred fibers are from plant sources such as marine plants but microbial sources of fiber may also be used. A variety of soluble or insoluble fibers may be utilized, as will be known to those of ordinary skill in the art.
- the fiber source can be beet pulp (from sugar beet), gum arabic, gum talha, psyllium, rice bran, carob bean gum, citrus pulp, pectin, fructooligosaccharide, short chain oligofructose, mannanoligofructose, soy fiber, arabinogalactan, galactooligosaccharide, arabinoxylan, or mixtures thereof.
- the fiber source can be a fermentable fiber.
- Fermentable fiber has previously been described to provide a benefit to the immune system of a companion animal.
- Fermentable fiber or other compositions known to skilled artisans that provide a prebiotic to enhance the growth of probiotics within the intestine may also be incorporated into the composition to aid in the enhancement of the benefit provided by the present invention to the immune system of an animal.
- the ash content of the food composition ranges from less than 1% to about 15%, preferably from about 5% to about 10%.
- the composition is a food composition comprising lycopene and from about 15% to about 50% protein, from about 5% to about 40% fat, from about 5% to about 10% ash content, and having a moisture content of about 5% to about 20%.
- the food composition further comprises prebiotics or probiotics as described herein.
- lycopene When administered in a food composition, lycopene comprises from about 0.001 to about 40% of the food composition, preferably from about 0.005 to about 30%, more preferably from about 0.01 to about 20%.
- food compositions comprise about 1%, 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, or 40%.
- lycopene is administered to an animal in a dietary supplement.
- the dietary supplement can have any suitable form such as a gravy, drinking water, beverage, yogurt, powder, granule, paste, suspension, chew, morsel, treat, snack, pellet, pill, capsule, tablet, sachet, or any other suitable delivery form.
- the dietary supplement can comprise lycopene and optional compounds such as vitamins, preservatives, probiotics, prebiotics, and antioxidants. This permits the supplement to be administered to the animal in small amounts, or in the alternative, can be diluted before administration to an animal.
- the dietary supplement may require admixing with a food composition or with water or other diluent prior to administration to the animal.
- lycopene comprises from about 0.001 to about 90% of the supplement, preferably from about 0.005 to about 70%, more preferably from about 0.01 to about 60%.
- lycopene is administered to an animal in a pharmaceutical or nutraceutical composition.
- the pharmaceutical composition comprises lycopene and one or more pharmaceutically or nutraceutically acceptable carriers, diluents, or excipients.
- pharmaceutical compositions are prepared by admixing a compound or composition with excipients, buffers, binders, plasticizers, colorants, diluents, compressing agents, lubricants, flavorants, moistening agents, and the like, including other ingredients known to skilled artisans to be useful for producing pharmaceuticals and formulating compositions that are suitable for administration to an animal as pharmaceuticals.
- lycopene comprises from about 0.001 to about 90% of the composition, preferably from about 0.005 to about 70%, more preferably from about 0.01 to about 60%.
- Lycopene can be administered to the animal on an as needed, on an as-desired basis, or on a regular basis.
- a goal of administration on a regular basis is to provide the animal with a regular and consistent dose of lycopene or the direct or indirect metabolites that result from such ingestion. Such regular and consistent dosing will tend to create constant blood levels of lycopene and its direct or indirect metabolites.
- administration on a regular basis can be once monthly, once weekly, once daily, or more than once daily.
- administration can be every other day, week, or month, every third day, week, or month, every fourth day, week, or month, and the like. Administration can be multiple times per day.
- lycopene When utilized as a supplement to ordinary dietetic requirements, lycopene may be administered directly to the animal, e.g., orally or otherwise. Lycopene can alternatively be contacted with, or admixed with, daily feed or food, including a fluid, such as drinking water, or an intravenous connection for an animal that is receiving such treatment. Administration can also be carried out as part of a dietary regimen for an animal.
- a dietary regimen may comprise causing the regular ingestion by the animal of lycopene in an amount effective to accomplish the methods of the present invention.
- lycopene administration can span a period ranging from parturition through the adult life of the animal.
- the animal is a human or companion animal such as a dog or cat.
- the animal is a young or growing animal.
- the animal is an aging animal.
- administration begins, for example, on a regular or extended regular basis, when the animal has reached more than about 30%, 40%, or 50% of its projected or anticipated lifespan.
- the animal has attained 40, 45, or 50% of its anticipated lifespan.
- the animal is older having reached 60, 66, 70, 75, or 80% of its likely lifespan.
- a determination of lifespan may be based on actuarial tables, calculations, estimates, or the like, and may consider past, present, and future influences or factors that are known to positively or negatively affect lifespan. Consideration of species, gender, size, genetic factors, environmental factors and stressors, present and past health status, past and present nutritional status, stressors, and the like may also influence or be taken into consideration when determining lifespan.
- Lycopene is administered to an animal for a time required to accomplish one or more objectives of the invention, e.g., preventing and treating osteoarthritis in an animal; preventing and treating the degradation of articular cartilage; promoting and maintaining joint health; improving the quality of life; and promoting the health and wellness in an animal.
- lycopene is administered to an animal on a regular basis.
- the invention provides compositions comprising lycopene in a therapeutically effective amount for one or more of preventing and treating osteoarthritis in an animal; preventing and treating the degradation of articular cartilage in an animal; promoting and maintaining joint health in an animal; improving the quality of life in an animal; and promoting the health and wellness in an animal.
- the compositions contain lycopene in amounts sufficient to administer lycopene to an animal in amounts of from about 0.005 to about 100 mg/kg/day, preferably from about 0.01 to about 50 mg/kg/day, most preferably from about 0.05 to about 10 mg/kg/day when the compositions are administered as anticipated or recommended for a particular composition.
- lycopene comprises from about 0.001 to about 90% of a composition, preferably from about 0.005 to about 70%, more preferably from about 0.01 to about 60%.
- food compositions comprise about 1%, 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 45%, 50%, 55%, 60%, 70%, or 80%.
- Lycopene compositions such as food, dietary, pharmaceutical, and other compositions may further comprise one or more substances such as vitamins, minerals, probiotics, prebiotics, salts, and functional additives such as palatants, colorants, emulsifiers, and antimicrobial or other preservatives.
- Minerals that may be useful in such compositions include, for example, calcium, phosphorous, potassium, sodium, iron, chloride, boron, copper, zinc, magnesium, manganese, iodine, selenium, and the like.
- additional vitamins useful herein include such fat soluble vitamins as A, D, E, and K.
- Inulin, amino acids, enzymes, coenzymes, and the like may be useful to include in various embodiments.
- the lycopene compositions contain at least one of (1) one or more probiotics; (2) one or more inactivated probiotics; (3) one or more components of inactivated probiotics that promote health benefits similar to or the same as the probiotics, e.g., proteins, lipids, glycoproteins, and the like; (4) one or more prebiotics; and (5) combinations thereof.
- the probiotics or their components can be integrated into the lycopene compositions (e.g., uniformly or non-uniformly distributed in the compositions) or applied to the lycopene compositions (e.g., topically applied with or without a carrier). Such methods are known to skilled artisans, e.g., US5968569 and related patents.
- Typical probiotics include, but are not limited to, probiotic strains selected from Lactobacilli, Bifidobacteria, or Enterococci, e.g., Lactobacillus reuteii, Lactobacillus acidophilus, Lactobacillus animalis, Lactobacillus ruminis, Lactobacillus johnsonii, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus fermentum, and Bifidobacterium sp., Enterococcus faecium and Enterococcus sp.
- probiotic strains selected from Lactobacilli, Bifidobacteria, or Enterococci, e.g., Lactobacillus reuteii, Lactobacillus acidophilus, Lactobacillus animalis, Lactobacillus ruminis, Lactobacillus johnsonii, Lactobacillus
- the probiotic strain is selected from the group consisting of Lactobacillus reuteri (NCC2581; CNCM 1-2448), Lactobacillus reuteri (NCC2592; CNCM 1-2450), Lactobacillus rhamnosus (NCC2583; CNCM 1-2449), Lactobacillus reuteri (NCC2603; CNCM 1-2451), Lactobacillus reuteri (NCC2613; CNCM 1-2452), Lactobacillus acidophilus (NCC2628; CNCM 1-2453), Bifidobacterium adolescentis (e.g. NCC2627), Bifidobacterium sp.
- Lactobacillus reuteri NCC2581; CNCM 1-2448
- Lactobacillus reuteri NCC2592; CNCM 1-2450
- Lactobacillus rhamnosus NCC2583; CNCM 1-2449
- Lactobacillus reuteri NCC260
- the lycopene compositions contain probiotics in amounts sufficient to supply from about 10 4 to about 10 12 cfu/animal/day, preferably from 10 5 to about lO 11 cfu animal/day, most preferably from 10 7 to 10 10 cfu/animal/day.
- probiotics When the probiotics are killed or inactivated, the amount of killed or inactivated probiotics or their components should produce a similar beneficial effect as the live microorganisms.
- the probiotic is Enterococcus faecium SF68 (NCIMB 10415).
- the probiotics are encapsulated in a carrier using methods and materials known to skilled artisans.
- the lycopene compositions may contain one or more prebiotics, e.g., fructo-oligosaccharides, gluco-oligosaccharides, galacto-oligosaccharides, isomalto- oligosaccharides, xylo-oligosaccharides, soybean oligosaccharides, lactosucrose, lactulose, and isomaltulose.
- the prebiotic is chicory root, chicory root extract, inulin, or combinations thereof.
- prebiotics are administered in amounts sufficient to positively stimulate the healthy microflora in the gut and cause these "good" bacteria to reproduce.
- Typical amounts are from about one to about 10 grams per serving or from about 5% to about 40% of the recommended daily dietary fiber for an animal.
- the probiotics and prebiotics can be made part of the composition by any suitable means.
- the agents are mixed with the composition or applied to the surface of the composition, e.g., by sprinkling or spraying. When the agents are part of a kit, the agents can be admixed with other materials or in their own package.
- the food composition contains from about 0.1 to about 10% prebiotic, preferably from about 0.3 to about 7%, most preferably from about 0.5 to 5%, on a dry matter basis.
- the prebiotics can be integrated into the compositions using methods known to skilled artisans, e.g., US5952033.
- a skilled artisan can determine the appropriate amount of lycopene, food ingredients, vitamins, minerals, probiotics, prebiotics, antioxidants, or other ingredients to be use to make a particular composition to be administered to a particular animal. Such artisan can consider the animal's species, age, size, weight, health, and the like in determining how best to formulate a particular composition comprising lycopene and other ingredients. Other factors that may be considered include the type of composition (e.g., pet food composition versus dietary supplement), the desired dosage of each component, the average consumption of specific types of compositions by different animals (e.g., based on species, body weight, activity/energy demands, and the like), and the manufacturing requirements for the composition.
- type of composition e.g., pet food composition versus dietary supplement
- the desired dosage of each component e.g., the average consumption of specific types of compositions by different animals (e.g., based on species, body weight, activity/energy demands, and the like)
- the manufacturing requirements for the composition e.
- kits suitable for administering lycopene to animals comprise in separate containers in a single package or in separate containers in a virtual package, as appropriate for the kit component, lycopene and one or more of (1) one or more ingredients suitable for consumption by an animal; (2) instructions for how to combine lycopene and other kit components to produce a composition useful for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, promoting and maintaining joint health; (3) instructions for how to use lycopene for preventing and treating osteoarthritis; (4) instructions for how to use lycopene for preventing and treating the degradation of articular cartilage; (5) instructions for how to use lycopene for promoting and maintaining joint health; (6) one or more probiotics; (7) one or more inactivated probiotics; (8) one or more components of inactivated probiotics that promote health benefits similar to or the same as the probiotics, e.g., proteins, lipids,
- the kit comprises lycopene and one or more ingredients suitable for consumption by an animal.
- the kit comprises instructions for how to combine lycopene and the ingredients to produce a composition useful for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, and promoting and maintaining joint health.
- the kit comprises a virtual package
- the kit is limited to instructions in a virtual environment in combination with one or more physical kit components.
- the kit contains lycopene and other components in amounts sufficient for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, and promoting and maintaining joint health.
- lycopene and the other suitable kit components are admixed just prior to consumption by an animal.
- the kits may contain the kit components in any of various combinations and/or mixtures.
- the kit contains a packet containing lycopene and a container of food for consumption by an animal.
- the kit may contain additional items such as a device for mixing lycopene and ingredients or a device for containing the admixture, e.g., a food bowl.
- lycopene is mixed with additional nutritional supplements such as vitamins and minerals that promote good health in an animal.
- the components are each provided in separate containers in a single package or in mixtures of various components in different packages.
- the kits comprise lycopene and one or more other ingredients suitable for consumption by an animal.
- such kits comprise instructions describing how to combine lycopene with the other ingredients to form a food composition for consumption by the animal, generally by mixing lycopene with the other ingredients or by applying lycopene to the other ingredients, e.g.
- the invention provides a means for communicating information about or instructions for one or more of (1) using lycopene for preventing and treating osteoarthritis; (2) using lycopene for preventing and treating degradation of articular cartilage; (3); using lycopene for promoting and maintaining joint health; (4) contact information for consumers to use if they have a question regarding the methods and compositions of the invention; and (5) nutritional information about lycopene.
- the communication means is useful for instructing on the benefits of using the invention and communicating the approved methods for administering lycopene and food compositions containing lycopene to an animal.
- the means comprises one or more of a physical or electronic document, digital storage media, optical storage media, audio presentation, audiovisual display, or visual display containing the information or instructions.
- the means is selected from the group consisting of a displayed website, a visual display kiosk, a brochure, a product label, a package insert, an advertisement, a handout, a public announcement, an audiotape, a videotape, a DVD, a CD-ROM, a computer readable chip, a computer readable card, a computer readable disk, a USB device, a FireWire device, a computer memory, and any combination thereof.
- the invention provides methods for manufacturing a food composition comprising lycopene and one or more other ingredients suitable for consumption by an animal, e.g., one or more of protein, fat, carbohydrate, fiber, vitamins, minerals, probiotics, prebiotics, and the like.
- the methods comprise admixing one or more ingredients suitable for consumption by an animal with lycopene.
- the methods comprise applying lycopene alone or in conjunction or combination with other ingredients onto the food composition, e.g., as a coating or topping. Lycopene can be added at any time during the manufacture and/or processing of the food composition.
- the composition can be made according to any method suitable in the art.
- the invention provides a package useful for containing compositions of the present invention.
- the package comprises at least one material suitable for containing lycopene and a label affixed to the package containing a word or words, picture, design, acronym, slogan, phrase, or other device, or combination thereof that indicates that the contents of the package contains lycopene.
- the label affixed to the package contains a word or words, picture, design, acronym, slogan, phrase, or other device, or combination thereof that indicates that the contents of the package contains lycopene with beneficial properties relating to osteoarthritis.
- such device comprises the words “prevents and treats osteoarthritis”, “prevents and treats the degradation of articular cartilage”, “promotes and maintains joint health", or an equivalent expression printed on the package.
- Any package configuration and packaging material suitable for containing the composition is useful in the invention, e.g., bag, box, bottle, can, pouch, and the like manufactured from paper, plastic, foil, metal, and the like.
- the package further comprises the composition of the present invention.
- the package contains a food composition adapted for a particular animal such as a human, canine, or feline, as appropriate for the label, preferably a companion animal food composition for dogs or cats.
- the package is a can or pouch comprising a food composition of the invention.
- the package further comprises at least one window that permit the package contents to be viewed without opening the package.
- the window is a transparent portion of the packaging material. In others, the window is a missing portion of the packaging material.
- the invention provides for use of lycopene to prepare a medicament for one or more of preventing and treating osteoarthritis; preventing and treating the degradation of articular cartilage; promoting and maintaining joint health; improving the quality of life; and promoting the health and wellness in an animal.
- medicaments are prepared by admixing a compound or composition, i.e., lycopene or a lycopene composition, with excipients, buffers, binders, plasticizers, colorants, diluents, compressing agents, lubricants, flavorants, moistening agents, and other ingredients known to skilled artisans to be useful for producing medicaments and formulating medicaments that are suitable for administration to an animal.
- Canine cartilage was digested in a 37°C shaking water bath using the following enzymes: trypsin (0.25%) for 25 minutes, hyaluronidase (150U/ml) for 1 hour, and collagenase (0.78%) overnight. Digested cartilage was filtered to obtain chondrocytes.
- DMEM Dulbecco's Modified Eagle Medium
- EDTA ethylenediaminetetraacetic acid
- RNAqueousTM lysis binding solution (Ambion, Austin, TX) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at -80°C until RNA isolation could be performed.
- RNAqueousTM filter cartridge 700 uL at a time, and centrifuged for 1 minute at 10,000 rpm.
- the cartridge was washed using 700uL wash solution #1 and 500 uL wash solution #2/3 with centrifugation at 10,000 rpm for 1 minute for each wash.
- the filter cartridge was dried by centrifugation (10,000 rpm) for 1 minute.
- RNA was eluted 3 times by centrifugation (as above) using 30 uL aliquots of 95-100°C elution solution. The resulting RNA was DNAse- treated and quantitated in a Beckman DU 640B spectrophotometer (Beckman Coulter, Inc., Brea, CA) at 260 nm. Additionally, quantity and quality were assessed using a bioanalyzer (Agilent, Santa Clara, CA) according to manufacturer's directions.
- Chondrocytes were enriched with lycopene (10 uM). Tetrahydrofuran (THF) was used as a vehicle. Cells were enriched with lycopene or vehicle (0.1%) for 24 hours in DMEM/HAMS + P/S + 10% FBS and then treated with stimulated monocyte neutrophil conditioned media (SMNCM) for 24 hours in the presence of lycopene.
- IL Interleukin
- MMP Matrix Metalloproteinase
- IGF Insulin-like Growth Factor
- TNF Tumor Necrosis Factor
- PC Procollagen
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Abstract
The invention provides methods for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, and promoting and maintaining joint health in an animal. The methods comprise administering lycopene to the animals, preferably in amounts of from about 0.005 to about 100 mg/kg/day.
Description
METHODS AND COMPOSITIONS FOR PREVENTING AND TREATING
OSTEOARTHRITIS
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application Serial No. 61/458055 filed November 17, 2010, the disclosure of which is incorporated herein by this reference.
BACKGROUND OF THE INVENTION
Field of the Invention
[0002] The invention relates generally to methods for preventing and treating osteoarthritis and particularly to methods for using lycopene for preventing and treating osteoarthritis.
Description of Related Art
[0003] Osteoarthritis (OA), also commonly referred to as degenerative joint disease, is characterized by the imbalance between the synthesis and degradation of articular cartilage. The breakdown of joint cartilage often results in joint pain and loss of mobility. OA commonly affects the hands, feet, spine, and the large weight bearing joints, such as the hips and knees. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion. A variety of causes, such as hereditary, developmental, metabolic, and mechanical, may initiate processes leading to loss of cartilage.
[0004] Lycopene is a carotenoid found in red fruits and vegetables, such as tomatoes. Carotenoids are natural pigments that act as antioxidants for the body. Lycopene gets its name from the species classification of the tomato, Lycopersicon esculentum.
[0005] Osteoarthritis is a painful condition and is adverse to the health and wellness of an animal and result in a lower quality of life for an animal. There is, therefore, a need for methods and compositions useful for promoting the health and wellness and improving the quality of life for animals by preventing and treating osteoarthritis.
SUMMARY OF THE INVENTION
[0006] It is, therefore, an object of the present invention to provide methods and compositions useful for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, and promoting and maintaining joint health.
[0007] It is another object of the invention to provide methods for promoting the health and wellness of animals.
[0008] It is another object of the invention to provide methods for extending the prime years of an animal's life.
[0009] One or more of these or other objects are achieved by administering lycopene to animals in therapeutically effective amounts for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, and promoting and maintaining joint health. In general embodiments, lycopene is administered to the animals in amounts of from about 0.005 to about 100 milligrams per kilogram of body weight per day (g/kg/day) for as long as there is a need for such treatment.
[0010] Other and further objects, features, and advantages of the invention will be readily apparent to those skilled in the art.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
[0011] The term "animal" means any animal that has a need for preventing or treating osteoarthritis, preventing or treating the degradation of articular cartilage, and promoting and maintaining joint health in an animal, including human, avian, bovine, canine, equine, feline, hicrine, lupine, murine, ovine, or porcine animals.
[0012] The term "companion animal" means domesticated animals such as cats, dogs, rabbits, guinea pigs, ferrets, hamsters, mice, gerbils, horses, cows, goats, sheep, donkeys, pigs, and the like.
[0013] The term "therapeutically effective amount" means an amount of a compound of the present invention that (i) treats or prevents the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein.
[0014] The terms "treating", "treat", and "treatment" embrace both preventative, i.e., prophylactic, and palliative treatment.
[0015] The terms "pharmaceutically acceptable" and "nutraceutically acceptable" indicates that the substance or composition must be compatible chemically and or toxicologically, with the other ingredients comprising a formulation, and/or the mammal being treated therewith.
[0016] The term "health and or wellness of an animal" means the complete physical, mental, and social well being of the animal, not merely the absence of disease or infirmity.
[0017] The term "extending the prime" means extending the number of years an animal lives a healthy life and not just extending the number of years an animal lives, e.g., an animal would be healthy in the prime of its life for a relatively longer time.
[0018] The term "degenerative joint disorder" refers to any etiological or pathological symptom affecting a joint. Such symptoms and etiology include swelling, pain and/or stiffness of a joint such that complete or partial loss of function and/or damage to the joint and/or a reduction of the joint mobility. The term also includes chronic inflammation, primarily of the synovial tissue, pannus formation, destruction of articular cartilage and release of various enzymes, for example, collagenase and lysosomal enzymes, in an affected joint, osteoarthritis, rheumatic disorders with cartilage breakdown, rheumatoid arthritis, chondrolysis after joint trauma, for example, after meniscus or patella injuries or torn ligaments, or chondrolysis associated with prolonged immobilization of joints. By way of example, degenerative joint disorder includes osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, tendonitis, ankylosing spondilitis, bursitis, spinal disc injuries, and temporomandibular joint disorder.
[0019] The term "in conjunction" means that lycopene or other compounds or other compositions of the invention are administered to an animal (1) together in a food composition or (2) separately at the same or different frequency using the same or different administration routes at about the same time or periodically. "Periodically" means that lycopene or other compounds or other compositions are administered on a schedule acceptable for specific compounds or compositions. "About the same time" generally means that lycopene or other compounds or compositions are administered at the same time or within about 72 hours of each other.
[0020] The term "dietary supplement" means a product that is intended to be ingested in addition to a normal animal diet. Dietary supplements may be in any form, e.g., solid, liquid, gel, tablet, capsule, powder, and the like. Preferably they are provided in convenient dosage forms, e.g., in sachets. Dietary supplements can be provided in bulk consumer packages such as bulk powders, liquids, gels, or oils. Similarly such supplements can be provided in bulk quantities to be included in other food items such as snacks, treats, supplement bars, beverages, and the like.
[0021] The term "aging" means being of an advanced age such that an animal has reached or exceeded 50% of the average life expectancy for the animal's species and/or breed within such species. For example, if the average life expectancy for a given breed of dog is 12 years, then an "aging animal" within that breed is 6 years old or older.
[0022] The term "food" or "food product" or "food composition" means a product or composition that is intended for ingestion by an animal, including a human, and provides nutrition to the animal.
[0023] The term "regular basis" means at least monthly dosing with lycopene and more preferably weekly dosing. More frequent dosing or consumption, such as twice or three times weekly, is preferred in certain embodiments. Still more preferred are regimens that comprise at least once daily consumption, e.g. , when lycopene is a component of a food composition that is consumed at least once daily.
[0024] The term "single package" means that the components of a kit are physically associated in or with one or more containers and considered a unit for manufacture, distribution, sale, or use. Containers include, but are not limited to, bags, boxes, cartons, bottles, packages such as shrink-wrap packages, stapled or otherwise affixed components, or combinations thereof. A single package may be containers of individual lycopene and food compositions physically associated such that they are considered a unit for manufacture, distribution, sale, or use.
[0025] The term "virtual package" means that the components of a kit are associated by directions on one or more physical or virtual kit components instructing the user how to obtain the other components, e.g. , in a bag or other container containing one component and directions instructing the user to go to a website, contact a recorded message or a fax-back service, view a visual message, or contact a caregiver or instructor to obtain instructions on how to use the kit or safety or technical information about one or more components of a kit.
[0026] The dosages expressed herein are in milligrams per kilogram of body weight per day (mg/kg/day) unless expressed otherwise.
[0027] All percentages expressed herein are by weight of the composition on a dry matter basis unless specifically stated otherwise. The skilled artisan will appreciate that the term "dry matter basis" means that an ingredient's concentration or percentage in a composition is measured or determined after any free moisture in the composition has been removed.
[0028] As used herein, ranges are used herein in shorthand, to avoid having to list and describe each and every value within the range. Any appropriate value within the range can be selected, where appropriate, as the upper value, lower value, or the terminus of the range.
[0029] As used herein, the singular form of a word includes the plural, and vice versa, unless the context clearly dictates otherwise. Thus, the references "a", "an", and "the" are generally inclusive of the plurals of the respective terms. For example, reference to "a
supplement", "a method", or "a food" includes a plurality of such "supplements", "methods", or "foods." Similarly, the words "comprise", "comprises", and "comprising" are to be interpreted inclusively rather than exclusively. Likewise the terms "include", "including" and "or" should all be construed to be inclusive, unless such a construction is clearly prohibited from the context. Similarly, the term "examples," particularly when followed by a listing of terms, is merely exemplary and illustrative and should not be deemed to be exclusive or comprehensive.
[0030] The methods and compositions and other advances disclosed here are not limited to particular methodology, protocols, and reagents described herein because, as the skilled artisan will appreciate, they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to, and does not, limit the scope of that which is disclosed or claimed.
[0031] Unless defined otherwise, all technical and scientific terms, terms of art, and acronyms used herein have the meanings commonly understood by one of ordinary skill in the art in the field(s) of the invention, or in the field(s) where the term is used. Although any compositions, methods, articles of manufacture, or other means or materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred compositions, methods, articles of manufacture, or other means or materials are described herein.
[0032] All patents, patent applications, publications, technical and/or scholarly articles, and other references cited or referred to herein are in their entirety incorporated herein by reference to the extent allowed by law. The discussion of those references is intended merely to summarize the assertions made therein. No admission is made that any such patents, patent applications, publications or references, or any portion thereof, are relevant, material, or prior art. The right to challenge the accuracy and pertinence of any assertion of such patents, patent applications, publications, and other references as relevant, material, or prior art is specifically reserved.
The Invention
[0033] In one aspect, the invention provides methods for preventing and treating osteoarthritis in an animal. The methods comprise administering to the animal a therapeutically effective amount of lycopene.
[0034] In another aspect, the invention provides methods for preventing and treating the degradation of articular cartilage in an animal. The methods comprise administering to the animal a therapeutically effective amount of lycopene.
[0035] In another aspect, the invention provides methods for promoting and maintaining joint health in an animal. The methods comprise administering to an animal a therapeutically effective amount of lycopene.
[0036] In a further aspect, the invention provides methods for promoting the health and wellness of an animal. The methods comprise administering to an animal a therapeutically effective amount of lycopene.
[0037] In another aspect, the present invention provides methods for extending the prime years of an animal's life. The methods comprise administering lycopene to an animal therapeutically effective amount of lycopene.
[0038] The inventions are based upon the discovery that lycopene is able to positively modulate osteoarthritis markers. Specifically, lycopene is able to decrease the gene expression of Matrix Metalloproteinase 13 (MMP-13, also known as collagenase II) and Tumor Necrosis Factor- Alpha (TNF-alpha). Genes associated with osteoarthritis have been previously identified in WO2005075685. The methods of the present invention may also be useful in the treatment of inflammatory related conditions, cancer metastasis and other degenerative joint disorders.
[0039] In the methods of the invention, lycopene is administered to an animal in amounts of from about 0.005 to about 100 mg/kg/day, preferably from about 0.01 to about 50 mg/kg/day, most preferably from about 0.05 to about 10 mg/kg day. In various embodiments, the lycopene is administered in amounts of from about 0.1 to about 5 mg/kg/day.
[0040] Lycopene can be administered to the animal in any suitable form using any suitable administration route. For example, lycopene can be administered in a lycopene composition, in a food composition, in a dietary supplement, in a pharmaceutical composition, in a nutraceutical composition, or as a medicament. Similarly, lycopene can be administered using a variety of administration routes, including oral, intranasal, intravenous, intramuscular, intragastric, transpyloric, subcutaneous, rectal, and the like. Preferably, lycopene is administered to an animal orally. Most preferably, lycopene is administered orally to an animal as a dietary supplement or as an ingredient in a food composition.
[0041] In a preferred embodiment, lycopene is administered to an animal as an ingredient in a food composition suitable for consumption by an animal, including humans and
companion animals such as dogs and cats. Such compositions include complete foods intended to supply the necessary dietary requirements for an animal or food supplements such as animal treats.
[0042] In various embodiments, food compositions such as pet food compositions or pet treat compositions comprise from about 5% to about 50% crude protein. The crude protein material may comprise vegetable proteins such as soybean meal, soy protein concentrate, corn gluten meal, wheat gluten, cottonseed, and peanut meal, or animal proteins such as casein, albumin, and meat protein. Examples of meat protein useful herein include beef, pork, lamb, equine, poultry, fish, and mixtures thereof.
[0043] The food compositions may further comprise from about 5% to about 40% fat. Examples of suitable fats include animal fats and vegetable fats. Preferably, the fat source is an animal fat source such as tallow or grease. Vegetable oils such as corn oil, sunflower oil, safflower oil, rapeseed oil, soybean oil, olive oil and other oils rich in monounsaturated and polyunsaturated fatty acids, may also be used.
[0044] The food compositions may further comprise from about 10% to about 60% carbohydrate. Examples of suitable carbohydrates include grains or cereals such as rice, corn, millet, sorghum, alfalfa, barley, soybeans, canola, oats, wheat, rye, triticale and mixtures thereof. The compositions may also optionally comprise other materials such as dried whey and other dairy by-products.
[0045] The moisture content for such food compositions varies depending on the nature of the food composition. The food compositions may be dry compositions (e.g., kibble), semi- moist compositions, wet compositions, or any mixture thereof. In a preferred embodiment, the composition is a complete and nutritionally balanced pet food. In this embodiment, the pet food may be a "wet food", "dry food", or food of "intermediate moisture" content. "Wet food" describes pet food that is typically sold in cans or foil bags and has a moisture content typically in the range of about 70% to about 90%. "Dry food" describes pet food that is of a similar composition to wet food but contains a limited moisture content typically in the range of about 5% to about 15% or 20% (typically in the form or small biscuit-like kibbles). In one preferred embodiment, the compositions have moisture content from about 5% to about 20%. Dry food products include a variety of foods of various moisture contents, such that they are relatively shelf-stable and resistant to microbial or fungal deterioration or contamination. Also preferred are dry food compositions that are extruded food products such as pet foods or snack foods for either humans or companion animals.
[0046] The food compositions may also comprise one or more fiber sources. The term "fiber" includes all sources of "bulk" in the food whether digestible or indigestible, soluble or insoluble, fermentable or nonfermentable. Preferred fibers are from plant sources such as marine plants but microbial sources of fiber may also be used. A variety of soluble or insoluble fibers may be utilized, as will be known to those of ordinary skill in the art. The fiber source can be beet pulp (from sugar beet), gum arabic, gum talha, psyllium, rice bran, carob bean gum, citrus pulp, pectin, fructooligosaccharide, short chain oligofructose, mannanoligofructose, soy fiber, arabinogalactan, galactooligosaccharide, arabinoxylan, or mixtures thereof.
[0047] Alternatively, the fiber source can be a fermentable fiber. Fermentable fiber has previously been described to provide a benefit to the immune system of a companion animal. Fermentable fiber or other compositions known to skilled artisans that provide a prebiotic to enhance the growth of probiotics within the intestine may also be incorporated into the composition to aid in the enhancement of the benefit provided by the present invention to the immune system of an animal.
[0048] In some embodiments, the ash content of the food composition ranges from less than 1% to about 15%, preferably from about 5% to about 10%.
[0049] In a preferred embodiment, the composition is a food composition comprising lycopene and from about 15% to about 50% protein, from about 5% to about 40% fat, from about 5% to about 10% ash content, and having a moisture content of about 5% to about 20%. In other embodiments, the food composition further comprises prebiotics or probiotics as described herein.
[0050] When administered in a food composition, lycopene comprises from about 0.001 to about 40% of the food composition, preferably from about 0.005 to about 30%, more preferably from about 0.01 to about 20%. In various embodiments, food compositions comprise about 1%, 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, or 40%.
[0051] In another embodiment, lycopene is administered to an animal in a dietary supplement. The dietary supplement can have any suitable form such as a gravy, drinking water, beverage, yogurt, powder, granule, paste, suspension, chew, morsel, treat, snack, pellet, pill, capsule, tablet, sachet, or any other suitable delivery form. The dietary supplement can comprise lycopene and optional compounds such as vitamins, preservatives, probiotics, prebiotics, and antioxidants. This permits the supplement to be administered to the
animal in small amounts, or in the alternative, can be diluted before administration to an animal. The dietary supplement may require admixing with a food composition or with water or other diluent prior to administration to the animal. When administered in a dietary supplement, lycopene comprises from about 0.001 to about 90% of the supplement, preferably from about 0.005 to about 70%, more preferably from about 0.01 to about 60%.
[0052] In another embodiment, lycopene is administered to an animal in a pharmaceutical or nutraceutical composition. The pharmaceutical composition comprises lycopene and one or more pharmaceutically or nutraceutically acceptable carriers, diluents, or excipients. Generally, pharmaceutical compositions are prepared by admixing a compound or composition with excipients, buffers, binders, plasticizers, colorants, diluents, compressing agents, lubricants, flavorants, moistening agents, and the like, including other ingredients known to skilled artisans to be useful for producing pharmaceuticals and formulating compositions that are suitable for administration to an animal as pharmaceuticals. When administered in a pharmaceutical or nutraceutical composition, lycopene comprises from about 0.001 to about 90% of the composition, preferably from about 0.005 to about 70%, more preferably from about 0.01 to about 60%.
[0053] Lycopene can be administered to the animal on an as needed, on an as-desired basis, or on a regular basis. A goal of administration on a regular basis is to provide the animal with a regular and consistent dose of lycopene or the direct or indirect metabolites that result from such ingestion. Such regular and consistent dosing will tend to create constant blood levels of lycopene and its direct or indirect metabolites. Thus, administration on a regular basis can be once monthly, once weekly, once daily, or more than once daily. Similarly, administration can be every other day, week, or month, every third day, week, or month, every fourth day, week, or month, and the like. Administration can be multiple times per day. When utilized as a supplement to ordinary dietetic requirements, lycopene may be administered directly to the animal, e.g., orally or otherwise. Lycopene can alternatively be contacted with, or admixed with, daily feed or food, including a fluid, such as drinking water, or an intravenous connection for an animal that is receiving such treatment. Administration can also be carried out as part of a dietary regimen for an animal. For example, a dietary regimen may comprise causing the regular ingestion by the animal of lycopene in an amount effective to accomplish the methods of the present invention.
[0054] According to the methods of the invention, lycopene administration, including administration as part of a dietary regimen, can span a period ranging from parturition
through the adult life of the animal. In various embodiments, the animal is a human or companion animal such as a dog or cat. In certain embodiments, the animal is a young or growing animal. In more preferred embodiments, the animal is an aging animal. In other embodiments, administration begins, for example, on a regular or extended regular basis, when the animal has reached more than about 30%, 40%, or 50% of its projected or anticipated lifespan. In some embodiments, the animal has attained 40, 45, or 50% of its anticipated lifespan. In yet other embodiments, the animal is older having reached 60, 66, 70, 75, or 80% of its likely lifespan. A determination of lifespan may be based on actuarial tables, calculations, estimates, or the like, and may consider past, present, and future influences or factors that are known to positively or negatively affect lifespan. Consideration of species, gender, size, genetic factors, environmental factors and stressors, present and past health status, past and present nutritional status, stressors, and the like may also influence or be taken into consideration when determining lifespan.
[0055] Lycopene is administered to an animal for a time required to accomplish one or more objectives of the invention, e.g., preventing and treating osteoarthritis in an animal; preventing and treating the degradation of articular cartilage; promoting and maintaining joint health; improving the quality of life; and promoting the health and wellness in an animal. Preferably, lycopene is administered to an animal on a regular basis.
[0056] In another aspect, the invention provides compositions comprising lycopene in a therapeutically effective amount for one or more of preventing and treating osteoarthritis in an animal; preventing and treating the degradation of articular cartilage in an animal; promoting and maintaining joint health in an animal; improving the quality of life in an animal; and promoting the health and wellness in an animal. The compositions contain lycopene in amounts sufficient to administer lycopene to an animal in amounts of from about 0.005 to about 100 mg/kg/day, preferably from about 0.01 to about 50 mg/kg/day, most preferably from about 0.05 to about 10 mg/kg/day when the compositions are administered as anticipated or recommended for a particular composition. Typically, lycopene comprises from about 0.001 to about 90% of a composition, preferably from about 0.005 to about 70%, more preferably from about 0.01 to about 60%. In various embodiments, food compositions comprise about 1%, 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 45%, 50%, 55%, 60%, 70%, or 80%.
[0057] Lycopene compositions such as food, dietary, pharmaceutical, and other compositions may further comprise one or more substances such as vitamins, minerals,
probiotics, prebiotics, salts, and functional additives such as palatants, colorants, emulsifiers, and antimicrobial or other preservatives. Minerals that may be useful in such compositions include, for example, calcium, phosphorous, potassium, sodium, iron, chloride, boron, copper, zinc, magnesium, manganese, iodine, selenium, and the like. Examples of additional vitamins useful herein include such fat soluble vitamins as A, D, E, and K. Inulin, amino acids, enzymes, coenzymes, and the like may be useful to include in various embodiments.
[0058] In various embodiments, the lycopene compositions contain at least one of (1) one or more probiotics; (2) one or more inactivated probiotics; (3) one or more components of inactivated probiotics that promote health benefits similar to or the same as the probiotics, e.g., proteins, lipids, glycoproteins, and the like; (4) one or more prebiotics; and (5) combinations thereof. The probiotics or their components can be integrated into the lycopene compositions (e.g., uniformly or non-uniformly distributed in the compositions) or applied to the lycopene compositions (e.g., topically applied with or without a carrier). Such methods are known to skilled artisans, e.g., US5968569 and related patents.
[0059] Typical probiotics include, but are not limited to, probiotic strains selected from Lactobacilli, Bifidobacteria, or Enterococci, e.g., Lactobacillus reuteii, Lactobacillus acidophilus, Lactobacillus animalis, Lactobacillus ruminis, Lactobacillus johnsonii, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus fermentum, and Bifidobacterium sp., Enterococcus faecium and Enterococcus sp. In some embodiments, the probiotic strain is selected from the group consisting of Lactobacillus reuteri (NCC2581; CNCM 1-2448), Lactobacillus reuteri (NCC2592; CNCM 1-2450), Lactobacillus rhamnosus (NCC2583; CNCM 1-2449), Lactobacillus reuteri (NCC2603; CNCM 1-2451), Lactobacillus reuteri (NCC2613; CNCM 1-2452), Lactobacillus acidophilus (NCC2628; CNCM 1-2453), Bifidobacterium adolescentis (e.g. NCC2627), Bifidobacterium sp. NCC2657 or Enterococcus faecium SF68 (NCIMB 10415). The lycopene compositions contain probiotics in amounts sufficient to supply from about 104 to about 1012 cfu/animal/day, preferably from 105 to about lO11 cfu animal/day, most preferably from 107 to 1010 cfu/animal/day. When the probiotics are killed or inactivated, the amount of killed or inactivated probiotics or their components should produce a similar beneficial effect as the live microorganisms. Many such probiotics and their benefits are known to skilled artisans, e.g., EP1213970B1, EP1143806B1, US7189390, EP1482811B1, EP1296565B1, and US6929793. In a preferred embodiment, the probiotic is Enterococcus faecium SF68
(NCIMB 10415). In one embodiment, the probiotics are encapsulated in a carrier using methods and materials known to skilled artisans.
[0060] As stated, the lycopene compositions may contain one or more prebiotics, e.g., fructo-oligosaccharides, gluco-oligosaccharides, galacto-oligosaccharides, isomalto- oligosaccharides, xylo-oligosaccharides, soybean oligosaccharides, lactosucrose, lactulose, and isomaltulose. In one embodiment, the prebiotic is chicory root, chicory root extract, inulin, or combinations thereof. Generally, prebiotics are administered in amounts sufficient to positively stimulate the healthy microflora in the gut and cause these "good" bacteria to reproduce. Typical amounts are from about one to about 10 grams per serving or from about 5% to about 40% of the recommended daily dietary fiber for an animal. The probiotics and prebiotics can be made part of the composition by any suitable means. Generally, the agents are mixed with the composition or applied to the surface of the composition, e.g., by sprinkling or spraying. When the agents are part of a kit, the agents can be admixed with other materials or in their own package. Typically, the food composition contains from about 0.1 to about 10% prebiotic, preferably from about 0.3 to about 7%, most preferably from about 0.5 to 5%, on a dry matter basis. The prebiotics can be integrated into the compositions using methods known to skilled artisans, e.g., US5952033.
[0061] A skilled artisan can determine the appropriate amount of lycopene, food ingredients, vitamins, minerals, probiotics, prebiotics, antioxidants, or other ingredients to be use to make a particular composition to be administered to a particular animal. Such artisan can consider the animal's species, age, size, weight, health, and the like in determining how best to formulate a particular composition comprising lycopene and other ingredients. Other factors that may be considered include the type of composition (e.g., pet food composition versus dietary supplement), the desired dosage of each component, the average consumption of specific types of compositions by different animals (e.g., based on species, body weight, activity/energy demands, and the like), and the manufacturing requirements for the composition.
[0062] In a further aspect, the invention provides kits suitable for administering lycopene to animals. The kits comprise in separate containers in a single package or in separate containers in a virtual package, as appropriate for the kit component, lycopene and one or more of (1) one or more ingredients suitable for consumption by an animal; (2) instructions for how to combine lycopene and other kit components to produce a composition useful for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage,
promoting and maintaining joint health; (3) instructions for how to use lycopene for preventing and treating osteoarthritis; (4) instructions for how to use lycopene for preventing and treating the degradation of articular cartilage; (5) instructions for how to use lycopene for promoting and maintaining joint health; (6) one or more probiotics; (7) one or more inactivated probiotics; (8) one or more components of inactivated probiotics that promote health benefits similar to or the same as the probiotics, e.g., proteins, lipids, glycoproteins, and the like; (9) one or more prebiotics; (10) a device for preparing or combining the kit components to produce a composition suitable for administration to an animal; and (1 1) a device for administering the combined or prepared kit components to an animal. In one embodiment, the kit comprises lycopene and one or more ingredients suitable for consumption by an animal. In another embodiment, the kit comprises instructions for how to combine lycopene and the ingredients to produce a composition useful for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, and promoting and maintaining joint health.
[0063] When the kit comprises a virtual package, the kit is limited to instructions in a virtual environment in combination with one or more physical kit components. The kit contains lycopene and other components in amounts sufficient for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, and promoting and maintaining joint health. Typically, lycopene and the other suitable kit components are admixed just prior to consumption by an animal. The kits may contain the kit components in any of various combinations and/or mixtures. In one embodiment, the kit contains a packet containing lycopene and a container of food for consumption by an animal. The kit may contain additional items such as a device for mixing lycopene and ingredients or a device for containing the admixture, e.g., a food bowl. In another embodiment, lycopene is mixed with additional nutritional supplements such as vitamins and minerals that promote good health in an animal. The components are each provided in separate containers in a single package or in mixtures of various components in different packages. In preferred embodiments, the kits comprise lycopene and one or more other ingredients suitable for consumption by an animal. Preferably such kits comprise instructions describing how to combine lycopene with the other ingredients to form a food composition for consumption by the animal, generally by mixing lycopene with the other ingredients or by applying lycopene to the other ingredients, e.g. , by sprinkling lycopene on a food composition.
[0064] In a further aspect, the invention provides a means for communicating information about or instructions for one or more of (1) using lycopene for preventing and treating osteoarthritis; (2) using lycopene for preventing and treating degradation of articular cartilage; (3); using lycopene for promoting and maintaining joint health; (4) contact information for consumers to use if they have a question regarding the methods and compositions of the invention; and (5) nutritional information about lycopene. The communication means is useful for instructing on the benefits of using the invention and communicating the approved methods for administering lycopene and food compositions containing lycopene to an animal. The means comprises one or more of a physical or electronic document, digital storage media, optical storage media, audio presentation, audiovisual display, or visual display containing the information or instructions. Preferably, the means is selected from the group consisting of a displayed website, a visual display kiosk, a brochure, a product label, a package insert, an advertisement, a handout, a public announcement, an audiotape, a videotape, a DVD, a CD-ROM, a computer readable chip, a computer readable card, a computer readable disk, a USB device, a FireWire device, a computer memory, and any combination thereof.
[0065] In another aspect, the invention provides methods for manufacturing a food composition comprising lycopene and one or more other ingredients suitable for consumption by an animal, e.g., one or more of protein, fat, carbohydrate, fiber, vitamins, minerals, probiotics, prebiotics, and the like. The methods comprise admixing one or more ingredients suitable for consumption by an animal with lycopene. Alternatively, the methods comprise applying lycopene alone or in conjunction or combination with other ingredients onto the food composition, e.g., as a coating or topping. Lycopene can be added at any time during the manufacture and/or processing of the food composition. The composition can be made according to any method suitable in the art.
[0066] In another aspect, the invention provides a package useful for containing compositions of the present invention. The package comprises at least one material suitable for containing lycopene and a label affixed to the package containing a word or words, picture, design, acronym, slogan, phrase, or other device, or combination thereof that indicates that the contents of the package contains lycopene. In some embodiments, the label affixed to the package contains a word or words, picture, design, acronym, slogan, phrase, or other device, or combination thereof that indicates that the contents of the package contains lycopene with beneficial properties relating to osteoarthritis. Typically, such device
comprises the words "prevents and treats osteoarthritis", "prevents and treats the degradation of articular cartilage", "promotes and maintains joint health", or an equivalent expression printed on the package. Any package configuration and packaging material suitable for containing the composition is useful in the invention, e.g., bag, box, bottle, can, pouch, and the like manufactured from paper, plastic, foil, metal, and the like. In a preferred embodiment, the package further comprises the composition of the present invention. In a preferred embodiment, the package contains a food composition adapted for a particular animal such as a human, canine, or feline, as appropriate for the label, preferably a companion animal food composition for dogs or cats. In a preferred embodiment, the package is a can or pouch comprising a food composition of the invention. In various embodiments, the package further comprises at least one window that permit the package contents to be viewed without opening the package. In some embodiments, the window is a transparent portion of the packaging material. In others, the window is a missing portion of the packaging material.
[0067] In another aspect, the invention provides for use of lycopene to prepare a medicament for one or more of preventing and treating osteoarthritis; preventing and treating the degradation of articular cartilage; promoting and maintaining joint health; improving the quality of life; and promoting the health and wellness in an animal. Generally, medicaments are prepared by admixing a compound or composition, i.e., lycopene or a lycopene composition, with excipients, buffers, binders, plasticizers, colorants, diluents, compressing agents, lubricants, flavorants, moistening agents, and other ingredients known to skilled artisans to be useful for producing medicaments and formulating medicaments that are suitable for administration to an animal.
EXAMPLES
[0068] The invention can be further illustrated by the following example, although it will be understood that this example is included merely for purposes of illustration and is not intended to limit the scope of the invention unless otherwise specifically indicated.
Example 1
[0069] Canine cartilage was digested in a 37°C shaking water bath using the following enzymes: trypsin (0.25%) for 25 minutes, hyaluronidase (150U/ml) for 1 hour, and collagenase (0.78%) overnight. Digested cartilage was filtered to obtain chondrocytes. Dulbecco's Modified Eagle Medium (DMEM) + 2.4% alginate (low melting) + cells were dropped from a lOcc syringe into calcium chloride (102 mM) to form "beads." Chondrocyte
beads were cultured in DMEM F12 + P/S (100 U/mL penicillin and 100 μ^πιΐ, streptomycin) + 10% Fetal Bovine Serum (FBS). Media was changed every other day. At the end of the treatment, the chondrocyte beads were dissolved in sodium citrate (55mM) and ethylenediaminetetraacetic acid (EDTA) (30mM). Suspensions were centrifuged at 1800 rpm for 10 minutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL RNAqueous™ lysis binding solution (Ambion, Austin, TX) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at -80°C until RNA isolation could be performed.
[0070] Samples were vortexed and homogenized using a Quiashredder column (Qiagen, Valencia, CA) according to manufacturer's directions. The homogenized lysate was collected and 1 equal volume of 64% ethanol was added to it. This mixture was then applied to an RNAqueous™ filter cartridge, 700 uL at a time, and centrifuged for 1 minute at 10,000 rpm. The cartridge was washed using 700uL wash solution #1 and 500 uL wash solution #2/3 with centrifugation at 10,000 rpm for 1 minute for each wash. The filter cartridge was dried by centrifugation (10,000 rpm) for 1 minute. RNA was eluted 3 times by centrifugation (as above) using 30 uL aliquots of 95-100°C elution solution. The resulting RNA was DNAse- treated and quantitated in a Beckman DU 640B spectrophotometer (Beckman Coulter, Inc., Brea, CA) at 260 nm. Additionally, quantity and quality were assessed using a bioanalyzer (Agilent, Santa Clara, CA) according to manufacturer's directions.
[0071] Chondrocytes were enriched with lycopene (10 uM). Tetrahydrofuran (THF) was used as a vehicle. Cells were enriched with lycopene or vehicle (0.1%) for 24 hours in DMEM/HAMS + P/S + 10% FBS and then treated with stimulated monocyte neutrophil conditioned media (SMNCM) for 24 hours in the presence of lycopene. SMNCM was made by isolating monocytes and neutrophils from canine whole blood using NycoPrep™ according to the manufacturer's directions. Monocytes and neutrophils were stimulated with lipopolysaccharide (20ng/mL) for 72 hours. The resulting supernatant was used as SMNCM in cell culture experimentation (SMNCM made up 10% of media used during experimentation). N=3 for all treatments (control and lycopene 10 uM).
[0072] All samples were run singularly against each primer/probe set to determine what standard curve should be used. Standard curves were generated using serial dilutions of liver RNA or RNA from experimental samples. Alternately, if the samples did not fall within either of the curve ranges, the sample with the lowest CT (cycle threshold) would be re- reverse transcribed and a 1 : 10 serial dilution would be used as the standard curve for that
primer/probe set. Values were normalized to cyclophilin A levels as determined by quantitative PCR. Inductions were calculated from each of the lowest sample's normalized value.
Table 1
Quantitative PCR expression values
[0073] Values represent relative average induction values. Abbreviations: Interleukin (IL); Matrix Metalloproteinase (MMP); Insulin-like Growth Factor (IGF); Tumor Necrosis Factor (TNF); Procollagen (PC).
[0074] In the specification, there have been disclosed typical preferred embodiments of the invention. Although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation. The scope of the invention is set forth in the claims. Obviously many modifications and variations of the invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described.
Claims
1. A method for preventing and treating osteoarthritis in an animal comprising administering to the animal a therapeutically effective amount of lycopene.
2. The method of claim 1 wherein lycopene is administered in amounts of from about 0.005 to about 100 mg/kg/day.
3. The method of claim 1 wherein lycopene is administered to the animal on a regular basis.
4. The method of claim 1 wherein the animal is suffering from osteoarthritis.
5. The method of claim 1 wherein lycopene is administered as a dietary supplement or a food composition.
6. The method of claim 5 wherein the composition is a food composition and lycopene comprises from about 0.001 to about 40% of the food composition.
7. The method of claim 5 wherein the composition or dietary supplement further comprises one or more probiotics; inactivated probiotics; components of inactivated probiotics that promote health benefits similar to or the same as the probiotics; and one or more prebiotics.
8. The method of claim 1 wherein the animal is a human or a companion animal.
9. The method of claim 8 wherein the companion animal is a canine.
10. The method of claim 8 wherein the companion animal is a feline.
1 1. The method of claim 1 wherein the animal is an aging animal.
12. A method for preventing and treating the degradation of articular cartilage in an animal comprising administering to the animal a therapeutically effective amount of lycopene.
13. The method of claim 12 wherein lycopene is administered in amounts of from about 0.005 to about 100 mg/kg/day.
14. The method of claim 12 wherein lycopene is administered to the animal on a regular basis.
15. The method of claim 12 wherein the animal is suffering from the degradation of articular cartilage.
16. The method of claim 12 wherein lycopene is administered as a dietary supplement or a food composition.
17. The method of claim 16 wherein the composition is a food composition and lycopene comprises from about 0.001 to about 40% of the food composition.
18. The method of claim 16 wherein the composition or dietary supplement further comprises one or more probiotics; inactivated probiotics; components of inactivated probiotics that promote health benefits similar to or the same as the probiotics; and one or more prebiotics.
19. The method of claim 12 wherein the animal is a human or a companion animal.
20. The method of claim 19 wherein the companion animal is a canine.
21. The method of claim 19 wherein the companion animal is a feline.
22. The method of claim 12 wherein the animal is an aging animal.
23. A method for promoting and maintaining joint health in an animal comprising administering to the animal a therapeutically effective amount of lycopene.
24. The method of claim 23 wherein lycopene is administered in amounts of from about 0.005 to about 100 mg/kg/day.
25. The method of claim 23 wherein lycopene is administered to the animal on a regular basis.
26. The method of claim 23 wherein lycopene is administered as a dietary supplement or a food composition.
27. The method of claim 26 wherein the composition is a food composition and lycopene comprises from about 0.001 to about 40% of the food composition.
28. The method of claim 26 wherein the composition or dietary supplement further comprises one or more probiotics; inactivated probiotics; components of inactivated probiotics that promote health benefits similar to or the same as the probiotics; and one or more prebiotics.
29. The method of claim 23 wherein the animal is a human or a companion animal.
30. The method of claim 29 wherein the companion animal is a canine.
31. The method of claim 29 wherein the companion animal is a feline.
32. The method of claim 23 wherein the animal is an aging animal.
33. A method for improving the quality of life in an animal comprising administering to the animal a therapeutically effective amount of lycopene.
34. The method of claim 33 wherein lycopene is administered in amounts of from about 0.005 to about 100 mg/kg/day.
35. The method of claim 33 wherein lycopene is administered to the animal on a regular basis.
36. The method of claim 33 wherein lycopene is administered as a dietary supplement or a food composition.
37. The method of claim 36 wherein the composition is a food composition and lycopene comprises from about 0.001 to about 40% of the food composition.
38. The method of claim 36 wherein the composition or dietary supplement further comprises one or more probiotics; inactivated probiotics; components of inactivated probiotics that promote health benefits similar to or the same as the probiotics; and one or more prebiotics.
39. The method of claim 33 wherein the animal is a human or a companion animal.
40. The method of claim 39 wherein the companion animal is a canine.
41. The method of claim 39 wherein the companion animal is a feline.
42. The method of claim 33 wherein the animal is an aging animal.
43. A method for promoting the health and wellness in an animal comprising administering to the animal a therapeutically effective amount of lycopene.
44. The method of claim 43 wherein lycopene is administered in amounts of from about 0.005 to about 100 mg/kg/day.
45. The method of claim 43 wherein lycopene is administered to the animal on a regular basis.
46. The method of claim 43 wherein lycopene is administered as a dietary supplement or a food composition.
47. The method of claim 46 wherein the composition is a food composition and lycopene comprises from about 0.001 to about 40% of the food composition.
48. The method of claim 46 wherein the composition or dietary supplement further comprises one or more probiotics; inactivated probiotics; components of inactivated probiotics that promote health benefits similar to or the same as the probiotics; and one or more prebiotics.
49. The method of claim 43 wherein the animal is a human or a companion animal.
50. The method of claim 49 wherein the companion animal is a canine.
51. The method of claim 49 wherein the companion animal is a feline.
52. The method of claim 43 wherein the animal is an aging animal.
53. A composition comprising lycopene in a therapeutically effective amount for one or more of preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, and promoting and maintaining joint health.
54. The composition of claim 53 containing lycopene in amounts sufficient to administer lycopene to an animal in amounts to about from about 0.005 to about 100 mg/kg day.
55. A pharmaceutical or nutraceutical composition comprising lycopene and one or more pharmaceutically or nutraceutically acceptable carrier, diluents or excipients
56. A package comprising at least one material suitable for containing lycopene and a label affixed to the package containing a word or words, picture, design, acronym, slogan, phrase, or other device, or combination thereof that indicates that the contents of the package contains lycopene.
57. The package of claim 56 wherein the label affixed to the package contains a word or words, picture, design, acronym, slogan, phrase, or other device, or combination thereof that indicates that the contents of the package contains lycopene with beneficial properties relating to osteoarthritis.
58. The package of claim 57 wherein the beneficial properties are one or more of preventing osteoarthritis, treating osteoarthritis, preventing the degradation of articular cartilage, treating the degradation of articular cartilage, promoting joint health, and maintaining joint health.
59. The package of claim 56 further comprising lycopene.
60. The package of claim 56 further comprising at least one window.
61. A means for communicating information about, or instructions for, one or more of (1) using lycopene for preventing and treating osteoarthritis; (2) using lycopene for preventing and treating the degradation of articular cartilage; (3) using lycopene for promoting and maintaining joint health; (4) contact information for consumers to use if they have a question regarding the methods and compositions of the invention; and (5) nutritional information about lycopene, the means comprising one or more of a physical or electronic document, digital storage media, optical storage media, audio presentation, audiovisual display, or visual display containing the information or instructions.
62. The means of claim 61 selected from the group consisting of a displayed website, a visual display kiosk, a brochure, a product label, a package insert, an advertisement, a handout, a public announcement, an audiotape, a videotape, a DVD, a CD-ROM, a computer readable chip, a computer readable card, a computer readable disk, a USB device, a Fire Wire device, a computer memory, and any combination thereof.
63. A kit suitable for administering lycopene to an animal comprising in separate containers in a single package or in separate containers in a virtual package, as appropriate for the kit component, lycopene and one or more of (1) one or more ingredients suitable for consumption by an animal; (2) instructions for how to combine lycopene and other kit components to produce a composition useful for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, promoting and maintaining joint health; (3) instructions for how to use lycopene for preventing and treating osteoarthritis; (4) instructions for how to use lycopene for preventing and treating the degradation of articular cartilage; (5) instructions for how to use lycopene for promoting and maintaining joint health; (6) one or more probiotics; (7) one or more inactivated probiotics; (8) one or more components of inactivated probiotics that promote health benefits similar to or the same as the probiotics; (9) one or more prebiotics; (10) a device for preparing or combining the kit components to produce a composition suitable for administration to an animal; and (11) a device for administering the combined or prepared kit components to an animal.
64. The kit of claim 63 wherein the lycopene is in a sachet.
65. The kit of claim 63 comprising lycopene and one or more ingredients suitable for consumption by an animal.
66. The kit of claim 65 further comprising instructions for how to combine lycopene and the ingredients to produce a composition useful for preventing and treating osteoarthritis, preventing and treating the degradation of articular cartilage, or promoting and maintaining joint health.
67. The kit of claim 63 comprising lycopene and one or more probiotics.
68. The kit of claim 67 wherein the probiotic is Enterococcus faecium SF68.
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US45805510P | 2010-11-17 | 2010-11-17 | |
US61/458,055 | 2010-11-17 |
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US20060020046A1 (en) * | 2002-02-15 | 2006-01-26 | Dms Ip Assets B.V. | Compositions comprising lycopene for the treatment and prevention of angiogenesis associated pathologies |
US20060281822A1 (en) * | 2005-04-20 | 2006-12-14 | Cardinal Associates, Inc. | Treatment and prevention of elevated homocysteine |
US20100055218A1 (en) * | 2006-07-14 | 2010-03-04 | Daniel Raederstorff | Novel compositions |
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2011
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Publication number | Priority date | Publication date | Assignee | Title |
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US20060020046A1 (en) * | 2002-02-15 | 2006-01-26 | Dms Ip Assets B.V. | Compositions comprising lycopene for the treatment and prevention of angiogenesis associated pathologies |
US20060281822A1 (en) * | 2005-04-20 | 2006-12-14 | Cardinal Associates, Inc. | Treatment and prevention of elevated homocysteine |
US20100055218A1 (en) * | 2006-07-14 | 2010-03-04 | Daniel Raederstorff | Novel compositions |
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