MXPA06008489A - Composition and method for use in cartilage affecting conditions - Google Patents

Abstract

The method for increasing the flexibility of cartilage in an animal in need of such increase which comprises administering to said mammal a cartilage flexibility enhancing effective amount of a sulfur-containing amino acid and manganese.

Description

COMPOSITION AND METHOD TO BE USED IN CONDITIONS AFFECTING CARTILAGE INTRODUCTION Virtually all joints have cartilage. Cartilage is important in the body of animals to provide flexibility, compressibility under pressure, cushioning, resistance to tension, range of motion and smoothness of movement within the joints. Examples of joints that have cartilage include the fingers and feet, neck, knee, hip, shoulder and the like. The animals may suffer from a number of conditions where the cartilage is adversely affected thereby leading to a reduction in the flexibility of the joint, in compressibility and frequent times resulting in a generalized inflammation of the joint and / or surrounding tissue. the joints. Such an animal then has a significant loss of joint function and experiences pain. What is required are new compositions and methods to treat, avoid or improve such conditions.

SYNTHESIS Therefore, the present invention includes compositions and methods for improving the health of the joint. Thus, in several embodiments, the present invention provides methods for decreasing cartilage abnormalities in an animal that comprises administering to the animal an effective amount of at least one amino acid containing sulfur and manganese.

Other embodiments provide methods for preventing degradation of cartilage tissue in an animal that comprises administering to the animal an effective amount of at least one amino acid containing sulfur and manganese.

Other aspects of the invention provide compositions suitable for systemic administration to an animal comprising an effective amount of at least one amino acid containing sulfur and manganese in association with a carrier.

Additional areas of application of the present invention will be apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, even when indicating illustrative embodiments of the invention, are not intended to limit the scope of the invention.

DETAILED DESCRIPTION The following description of the various additions and accompanying examples is merely exemplary. and nature and in no way attempt to limit the invention, its application or its uses.

The present invention provides compositions and methods for improving the health of the joint in animals and in particular in companion animals such as dogs and cats. The following definitions in the non-limiting guides should be considered in the review of the description of the invention set forth herein.

The citations of references given herein do not constitute an admission that those references are prior art or that they have any relief in relation to the patentability of the invention described herein. Any discussion of the content of the references cited in the introduction is merely to provide a general summary of the assertions made by the authors of the references; It does not constitute an admission as to the accuracy of the contents of such references. All references cited in the section and description of the specification are incorporated herein by this statement in its entirety.

The description of the specific examples still indicates embodiments of the invention, is intended for purposes of illustration only and is not intended to limit the scope of the invention. In addition, the recitation of the multiple incorporations of the declared characteristics is not intended to exclude other incorporations that have additional characteristics, or other incorporations that incorporate different combinations of the declared characteristics.

The cartilage is made of living tissue that is continuously broken and replaced. Nevertheless, injuries, tension on the joints and the aging process can damage the cartilage tissue, often without obvious signs until a great damage has been done. Cartilage is a substance that is made up of 65% and 80% water. The remaining part is made up of three other important components, collagen, chondrocytes and proteoglycans. Collagen gives cartilage its shock absorption and elasticity, while proteoglycans are large molecules that give cartilage its ability to stretch and then return in response to movements. However, as with all things, collagen and proteoglycans age. Chondrocytes clean aged proteoglycans and collagen and produce new ones. These four elements work together to ensure that the cartilage is healthy, smooth and free of color in the movement of the joints.

When one of these elements declines, the cartilage may deteriorate and osteoarthritis may begin to develop.

Osteoarthritis predominantly affects the cartilage of the joint, the shiny, smooth surface that covers the bone within the joint. The function of the cartilage is to provide absorbency to the blow and reduce friction as the joint slides. Osteoarthritis causes thinning and damage to the cartilage, which will break and become rough and eroded. Cartilage and bone are also damaged by rubbing the bones together and the deformity results when one side of the joint collapses more than the other side. When the loss of cartilage is large, there may be severe pain in the joint involved with the use or even at rest.

Osteoarthritis is a slow progressive disease of the synovial joints that affects about 20% of the canine population over one year of age (Johnston S.A. Ortearthritis, Veterinary Clinics of North America, Small Animal Practice, 1997 27: 699-720). This joint disorder is characterized by the loss of balance between the synthesis and degradation of the joint cartilage constituents leading to subsequent erosion of the cartilage of the joint, remodeling of the underlying bone, the formation of osteophyte and variable degrees of synovitis. Some of the most common causes of secondary osteoarthritis seen in companion animals are cruciform ligament rupture, osteochondritis dessecans, fragmented coronoid process, and hip dysplasia. (Martínez, - S.A., Coronados M. GX- Acquired conditions that lead to osteoarthritis in a dog, Veterinary Clinics of North America: Small Animal Practice 1997; 27: 759-775). Other examples of affected cartilage conditions include but are not limited to osteochondrosis, synovitis, bacterial purulent arthritis, osteoarthropathy, psoriatic, subchondral cystous lesions, fisitis, angular limb deformities, and cuboidal bone malformation. Most large dogs develop arthritis as they get older. Large dog breeds are more susceptible to arthritis due to their increased mass and / or genetic disposition. Large dogs are not the only animals at risk of arthritis and other cartilage conditions. Arthritis and other degenerative joint diseases have been commonly recognized in dogs and. such conditions have been shown to be prevalent in cats. (Hardie E. U. and others JAVMA 220 (5) 2002, 628-632). Other animals at risk include but are not limited to all dogs, cats, horses, goats, objects, pigs, cattle, humans, birds including turkeys and chickens and the like.

Various substances have been used in attempts to ameliorate such conditions as described above. Such substances have included the use of glucosaline supplements, chondroitin and chondroitin sulfate in the treatment of arthritis. Glucosamine is a component of proteoglycans which maintains fluid in the cartilage. Chondroitin is another component of proteoglycans. The canaliculuss perna is a rich source of glycosaminoglycans (GAGs). Unfortunately, these glycosaminoglycans are poorly absorbed when taken by mouth. Perna may be beneficial for the treatment of arthritis, but the benefits seen may be more of its natural anti-inflammatory effect than of the direct absorption of glycosaminoglycans. Creatine plays an important role in the conversion of glucose into muscle energy and may have value in improving muscle endurance and making older animals feel more energetic. Methylsulfonylmethane (MSM) has an anti-inflammatory effect that slows the progression of arthritis and relieves pain. Of course, other substances typically used by humans can also be used by animals including aspirin, anti-inflammatories such as ibuprofen, COX-2 inhibitors and other medicinal and pharmaceutical compositions.

In various embodiments of the present invention, the compositions and methods can improve, treat, prevent and / or sometimes alleviate the conditions described above including the administration of at least one of glycine and proline. Illustrative examples of such conditions include osteoarthritis, rheumatoid arthritis, osteochondrosis, degenerative joint disease, synovitis, bacterial purulent arthritis, osteoarthropathy, and psoriatic arthritis and the like.

In various embodiments of the present invention, the amino acid containing sulfur and manganese can be administered to the animal, preferably one in need of such administration, in any one of many ways, such as oral, parenteral and the like, even when oral it is preferred. In some embodiments, the amino acid and manganese may be administered in a wet or dry diet, either incorporated thereon or on the surface of the diet component, such as by spraying or precipitation thereon. In certain embodiments, the amino acid and manganese may be present in the nutritional diet by themselves or in a snack, a supplement or a reward or in the liquid part of the diet such as water or another fluid. The amino acid and manganese can be administered as a powder, as a solid or as a liquid including a gel. If desired, the amino acid and manganese can be administered orally in the pharmaceutical dosage form such as a capsule, tablet, capsule and tablet, syringe and the like and with such dosage form of amino acid and manganese can be present as a powder or a liquid such as a gel. Any of the usual pharmaceutical carriers can be employed such as water, glucose, sucrose and the like along with the amino acid and the -manganese. Even when exemplified together, the amino acid and manganese can be administered separately, that is, one in a diet and one in a liquid or a unit dose form, for example. Generally, the amino acid and manganese should be administered at least concomitantly, and preferably in the same carrier. When administered in a food, the sulfur containing the amino acid and manganese can be administered as a compound, within the constituents of normal food or a combination of the two.

Various amino acids containing sulfur and its derivatives are applicable in the invention. These include D-methionine, L-methionine, DL-methionine, D-cysteine, L-cysteine, DL-cysteine, D-cysteine, L-cysteine, DL-cysteine, S-adenosylmethionine, betaine, beta-hydroxy analogue. racemic mixtures of methionine and the described amino acid mixtures as described, and the like. The amino acid containing sulfur can be provided by itself to the animal or it can be naturally present in the diet materials such as fishmeal, corn gluten meal, poultry flour, casein, methionine manganese (a chelate ). and similar.

As mentioned above, in certain embodiments, the amino acid containing sulfur and manganese may be in any food provided to an animal. Examples of such foods are regular diets that provide all the nutrients for the animal, prizes, supplements and the like. In some embodiments, the amino acid and manganese can be provided in liquids or in pharmaceutical dosage forms, such as capsules, tablets, pills, liquids or even through parenteral administration through a syringe. The most important aspect is that the animal is provided with an effective amount of active ingredients to reduce the abnormalities. The preferred route of administration is oral and incorporated, with a food.

The term "diet" as used herein means the food or drink regularly consumed by the animal. The pet's diet can be any suitable pet food formula which provides adequate nutrition for the animal. For example, a typical canine diet for use in the present invention may contain from about 10 to 30% fat, around 22 to 44% by weight of protein and around 10% total of dietary fiber. In another example, a typical feline diet may contain from about 10 to 30% by weight of fat, and from about 30 to 45% by weight of protein. However, no proportions of specific percentages of these or other nutrients are required. A nutrient is any constituent of food that helps support life. The following are examples of nutrients that have important roles in the health of the companion animal. Table 1. Typical components of a pet diet Proteins Main elements of tissues such as muscles, blood, skin, organs, hair and nails. Carbohydrates Provide energy for the body's tissues Fats Fats absorb, store and transport vitamins, the moisture of the skin and the coating, make the taste of healthy pet food and supply energy. Water The most critical nutrient for survival. Vitamins- Help maintain an animal's metabolism. Minerals Necessary for the development of healthy skin and hair, support and development of a suitable skeleton. Minerals are usually abundant in pet food ingredients.

Manganese can be supplied to the animal in various manners including manganese sulfate, manganese oxide, manganese dioxide, manganese carbonate, manganese chloride, manganese proteinate, manganese chelate, manganese monoxide, manganese methionine-like. 1 The amount of amino acid and manganese that can be used to provide the effect or effects of the invention can vary substantially. All percents by weight are calculated on a dry matter basis of a daily diet sufficient to meet the animal's nutrition needs. A minimum amount of the amino acid is above about 1.2% by weight, preferably above 1.5% by weight and more preferably above about 1.8% by weight. The minimum amount of manganese is above 50 parts per million, preferably above about 75 parts per million and more preferably above 100 parts per million. For example, a specific amount can be used in the usual nutrient feed ration on a daily basis or the same amount daily can be provided to the animal in a snack or supplement on a daily basis. Additionally, a combination of these methods or any other means of dosing may be employed provided that the effective amount of sulfur containing and manganese containing amino acid is provided. The maximum amounts are any effective amount to reduce the amount of cartilage abnormalities with very little or (acceptable level) or no toxicity. Examples of such amounts for the amino acid include no more than about 2.6% by weight, 2.3% by weight, and 2.0% by weight over the same as for the minimums,: Examples of such amounts of manganese include no more than about 200 parts per million, preferably about 175 parts per million and more preferably about 150 parts per million on the same basis as the minimums.

Several embodiments of the invention include a method for improving cartilage in the companion animal. In such embodiments, the method comprises feeding the animal a diet comprising manganese in an amount of at least 50 parts per million and an amino acid containing sulfur in an amount of at least 1.2% by weight on a base of dry matter per day. In other embodiments, the method comprises feeding the animal a diet comprising manganese in an amount of at least 100 parts per million and an amino acid containing sulfur in an amount of at least 1.8% by weight based on a material base. dry per day. In still other embodiments, the method comprises feeding the animal a diet comprising manganese in an amount of from about 50 parts per million to about 200 parts per million and an amino acid containing sulfur in an amount of from about 1.2%. by weight to about 2.6% by weight on a dry matter basis per day.

In several embodiments of the invention, a companion animal diet comprises manganese and amino acid containing increased sulfur which improves the health- of the joints of the pet animal. In some embodiments of the invention, manganese and the amino acid containing sulfur are added to the pet food. In such additions, the manganese and the sulfur-containing amino acid can be added during the processing of the pet food that is then packaged and made available to consumers. Such processes may include extrusion, canning, baking and the like or any other method or process for producing animal feeds as is known in the art. In such processes, the manganese and sulfur containing amino acid can be contributed by a natural source as a plant or animal component or manganese and the amino acid containing sulfur can be contributed by a synthetically derived source or the manganese or amino acid containing Sulfur can be contributed by a mixture of natural and synthetic sources. In other embodiments of the invention, the manganese and sulfur-containing amino acid may be in a capsule formula to be fed to the companion animal. In still other embodiments of the invention, the manganese and sulfur-containing amino acid may be in a powder or crystalline form which may be added to the animal feed or fed directly to the animal. In various embodiments of the invention, the diet of the pet animal comprises manganese and amino acid containing sulfur and other necessary nutritional components. In several embodiments of the invention, the companion animal is a dog. In other additions, the pet is a cat. In certain additions, the companion animal is a horse. A measure of cartilage health is the number of abnormalities visually observed on the cartilage. Other ways of observing cartilage abnormalities include MRl, computed tomography and radiography. The higher the abnormalities, the greater the global articulation is weakened which makes it more susceptible to a condition or exacerbation in the existing condition. These conditions include atritis (both osteo and rheumatoid). Osteochondrosis, degenerative joint disease, synovitis, bacterial purulent arthritis, osteoarthropathy and psoriatic among others. The visualized cartilage abnormalities include general injuries, erosions and abnormal growths.

Example 1 Growing pigs (80 experimental units) are used as a test model to determine the effect of methionine and manganese on cartilage abnormalities. The pigs are initially around 35 kilograms. Each pig was individually housed in a 5.2 square foot pigsty with an access at will to food and water. Pigs are foods with test foods for a period of 60 days to a final weight of about 130 kilograms.

At a point of meat manufacture, the distant aspect of the right femur bone is collected and evaluated in total and for histopathology. The distant appearance of the right femur bone is preserved in formaldehyde and stored at room temperature for total observation. Joints are evaluated for the total number of lesions present on the "joint surface (including clinical lesions, cartilage erosions, and abnormal growth patterns.) Large lesions are confirmed by histopathology characterization.

The tissue sections are taken from the aspects except abdominal weight of the middle femoral condyle. The measurements are evaluated on photomicrographs of 2X and 10X to determine the cell counts and to confirm the pathological damage of the cartilage in the subchondral bone.

Table 2. Composition of experimental foods Table 3. Analytical analysis of experimental foods-lot 1 Table 4. Analytical analysis of experimental foods-lot 2 Table 5. Effect of nutrients on cartilage abnormalities Control Sample 1 Sample 2 Sample 3 Injuries 2.38 2.25 1.38 0.88 total As shown by the data, a statistically increased combination of amino acid containing sulfur and manganese reduces the number of visually observed abnormalities (eg, lesions and erosions) of cartilage abnormalities, as shown by sample 3. Neither samples 1 nor 2 show a statistically significant reduction in abnormalities. Sample 1 is high in manganese but approximately the same in amino acid containing sulfur as the control. Sample 2 is high in amino acid containing sulfur but approximately the same in manganese as the control.

Growing pigs (80 experimental units) are used as a test model to determine the effect of methionine and manganese on cartilage abnormalities. The pigs are initially around 35 kilograms. Each pig was individually housed in 5.2-ft2 pigsties with at-will access to water and food. The pigs are fed with test feed for a period of 90 days at a final weight of about 130 kilograms.

Example 2 Table 6 - Effect on synthesis of metalloproteinase and serum matrix collagen Control Sample 4 Sample 5 GAG no yes no Methionine 0.30 0.34 1.43 Manganese 41.0 108.0 128.0 Enzyme MMP- 13 2.29 0.34 0.28 Collagen type 120.43 111.62 89.76 II The serum samples are harvested at the end of the 90 day period to determine the matrix metalloproteinase activity (MMP-13) and the type II collagen synthesis activity. As shown by the above data, an amino acid combination containing increased sulfur and manganese provides an improvement to the cartilage as shown by the improvements in the activity of synthesis of enzyme MMP-13 and collagen type II as shown by the sample 5.

The examples and other embodiments described herein are exemplary and are not intended to be limiting in the description of the full scope of the apparatus, systems, compositions, materials and methods of this invention. The changes, modifications, variations and equivalents in the specific embodiments, apparatus, systems, compositions, materials and methods can be made within the scope of the present invention with essentially similar results. Such changes, modifications or variations should not be seen as a departure from the spirit and scope of the invention. All of the patents cited herein, as well as all publications, articles, pamphlets and product information discussed herein, are hereby incorporated by reference in their entirety.

Claims (28)

R E I V I N D I C A C I O N S

1. A method to improve cartilage abnormalities in an animal, the method comprises: administer to said animal an effective amount of an amino acid containing sulfur and a safe and effective amount of manganese.

2. A method as claimed in clause 1, characterized in that the animal is non-human.

3. A method as claimed in clause 2, characterized in that said animal is a companion animal.

4. A method as claimed in clause 1, characterized in that said animal is a human.

5. A method as claimed in clause 1, characterized in that the amino acid is selected from the group consisting of D-methionine, L-methionine, DL-methionine, D-cysteine, L-cysteine, DL-cysteine, D-cysteine , L-cysteine, DL-cysteine, S-adenosylmethionine, betaine, beta-hydroxy analogue of methionine, manganese methionine and mixtures thereof.

6. A method as claimed in clause 1, characterized in that said effective amount of amino acid containing sulfur is at least 1.2% by weight.

7. A method as claimed in clause 1, characterized in that the effective amount of manganese is at least 50 parts per million on a dry weight basis.

8. A method as claimed in clause 1, characterized in that it comprises administering a food composition comprising amino acid and said manganese.

9. A method as claimed in clause 1, characterized in that said administration is oral.

10. A method as claimed in clause 1, characterized in that it is for the prevention or treatment of an affected cartilage condition.

11. A method as claimed in clause 10, characterized in that said affected cartilage condition is selected from the group consisting of osteoarthritis, rheumatoid arthritis, osteochondrosis, degenerative joint disease, synovitis, bacterial purulent arthritis, osteoarthritis, and psoriatic arthritis.

12. A method as claimed in clause 11, characterized in that it further comprises administering said animal in an effective amount of at least one substance from the group consisting of glucosaline, chondroitin, chondroitin sulfate, MSM, creatine, an antioxidant, canaliculuss, a mega fatty acid and mixtures thereof.

13. A method to prevent the degradation of cartilage in an animal, the method comprises: feeding said animal with a composition comprising amino acid containing sulfur and manganese.

14. A method as claimed in clause 13, characterized in that said animal is a companion animal.

15. A method as claimed in clause 13, characterized in that said amino acid is selected from the group consisting of D-methionine, L-methionine, DL-methionine, D-cysteine, L-cysteine, DL-cysteine, D-cysteine , L-cysteine, DL-cysteine, S-adenosylmethionine, betaine, beta-hydroxy analogue of methionine, manganese methionine and mixtures thereof.

16. A method as claimed in clause 13, characterized in that said effective amount of amino acid containing sulfur is at least 1.2% by weight.

17. A method as claimed in clause 13, characterized in that the effective amount of manganese is at least 50 parts per million on a dry weight basis.

18. A method as claimed in clause 13, characterized in that it comprises feeding an effective amount of at least one substance selected from the group consisting of glucosaline, chondroitin, chondroitin sulfate, MSM, creatine, an antioxidant, canaliculuss perna, a mega fatty acid and mixtures thereof.

19. A method as claimed in clause 13, characterized in that the composition further comprises protein, fat and carbohydrates.

20. A composition for improving cartilage abnormalities in an animal, the composition comprising: an effective amount of at least one amino acid containing sulfur and an effective amount of manganese.

21. A composition as claimed in clause 20, characterized in that said amino acid is selected from D-methionine, L-methionine, DL-methionine, D-cysteine, L-cysteine, DL-cysteine, D-cysteine, L-cysteine , DL-cysteine, S-adenosylmethionine, betaine, beta-hydroxy analogue of methionine, manganese methionine and mixtures thereof.

22. A composition as claimed in clause 20, characterized in that said effective amount of amino acid containing sulfur is at least 1.2% by weight.

23. A composition as claimed in clause 20, characterized in that the effective amount of manganese is at least 50 parts per million on a dry weight basis.

24. A composition as claimed in clause 20, characterized in that it comprises feeding an effective amount of at least one substance selected from the group consisting of glucosaline, chondroitin, chondroitin sulfate, MSM, creatine, an antioxidant, canaliculuss perna, a mega fatty acid and mixtures thereof.

25. A composition as claimed in clause 20, characterized in that it also comprises protein, fat and carbohydrates.

26. A composition as claimed in clause 20, characterized in that said composition is a component of a dog food.

27. A composition as claimed in clause 20, characterized in that said composition is a cat food component.

28. A composition as claimed in clause 20, characterized in that it also comprises an amount of nutrients to sustain life. R E S U E The method for increasing the flexibility of cartilage in an animal in need of such an increase comprising administering said mammal, an effective amount enhancing the cartilage flexibility of an amino acid containing sulfur and manganese.