Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K10/00—Animal feeding-stuffs
  • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K10/00—Animal feeding-stuffs
  • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
  • A23K10/37—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms from waste material
• • 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
  • A23K20/163—Sugars; Polysaccharides
• • 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
  • A23K—FODDER
  • A23K50/00—Feeding-stuffs specially adapted for particular animals
  • A23K50/60—Feeding-stuffs specially adapted for particular animals for weanlings
• • 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
  • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
  • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/04—Anorexiants; Antiobesity agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
  • Y02P60/00—Technologies relating to agriculture, livestock or agroalimentary industries
  • Y02P60/80—Food processing, e.g. use of renewable energies or variable speed drives in handling, conveying or stacking
  • Y02P60/87—Re-use of by-products of food processing for fodder production

Definitions

• the present invention is directed to a method of treating or preventing overweight and obesity in a mammal comprising administering to the mammal a composition comprising an effective amount of a mannoheptulose (mHep). Further, the present invention encompasses a composition comprising a mHep and a process of making the composition.
• mHep mannoheptulose
• fat occurs when the synthesis and deposition of fat (e.g., triglycerides) into adipocytes exceed their breakdown. Over time, this excessive accumulation of body fat leads to overweight then obesity, if left untreated.
• fat e.g., triglycerides
• adipose tissue In addition to adipose tissue's role as a repository of surplus energy (i.e., fat) for the body, it has been recognized as an endocrine organ that produces hormones such as, for example, the sex hormone estrogen. Estrogen is present in both male and female animals. It plays an important role in regulating the function and development of adipocytes that form the adipose tissue and maintenance of normal body fat composition (Cooke, P.S. et al, Exp. Biol. Med., 229: 1127-35, 2004).
• Estrogen may mediate its effects on adipose tissue in different ways. For example, estrogen may affect the number and size of adipocytes; modulate the rate of lipogenesis and lipolysis; and increase appetite or decrease energy expenditure (Pergola, G.D., (2000), supra;
• Hormone replacement therapy and dietary supplementation with estrogen are common approaches that attempt to reverse these effects (Sayegh, R.A., et al, Meopause 6:312-5, 2002).
• the mHep is already incorporated in the pet food composition, then the animal only needs to eat to be treated.
• caloric restriction mimetic As a strategy for delivering against this demand of proper nutrition in pet food. It is believed that caloric restriction leads to an increase in median lifespan (i.e., age at 50% population survival) and maximal lifespan (i.e., age of longest lived individual). Recent studies show that the amount of time the lifespan of an animal is extended will progressively increase as caloric in-take is reduced and the duration of the caloric restricted diet increases.
• mHep mannoheptulose
• mHep mannoheptulose
• mHep a seven- carbon sugar found in a variety of natural sources such as, for example, avocados, figs, and primrose. It is believed that mHep is effective for extending lifespan and life quality in both lower and higher organisms.
• mHep competes with glucose for binding to hexokinase-1, an enzyme in the glycolysis reaction, due to the similarity between their structures. The result is that glucose metabolism is inhibited and fatty acid synthesis is prevented. This leads to decrease levels of fat deposition in adipocytes that may eventually lead to weight loss.
• mHep may function as a glucose anti-metabolite to block the normal metabolism of carbohydrate.
• the resulting physiological changes may include: lower tissue glucose levels, decrease plasma insulin levels and reduction of body weight (see PCT Publication No. WO2012/61446A1). Both effects result from mHep's inhibition of carbohydrate metabolism.
• mHep has not been shown to impact adipocyte expression or activity, and particularly not linked to overweight and obesity.
• the mammals are preferably chosen from sub-groups that have elevated risk of adiposity brought on by, for example, changes in hormonal homeostasis (i.e., menopausal humans and spayed/neutered pets) or arose from normal age-related weight gains (i.e., senior humans or senior pets), particular if the animal is otherwise healthy.
• changes in hormonal homeostasis i.e., menopausal humans and spayed/neutered pets
• normal age-related weight gains i.e., senior humans or senior pets
• the new or improved methods would also benefit growing pets, preferably if the growing pets are overweight or obese or have been spayed/neutered before reaching sexual maturity.
• the animal is exposed to caloric restriction mimetic for a longer duration thereby increasing the chance of extending the lifespan in those animals.
• the present invention is directed to a new use of mHep based on the discovery of different molecular processes and mechanisms by which mHep provides new benefits to the mammal.
• the inventor discovered that mHep inhibits fat stem cells from differentiation into adipocytes, and thereby lessens the body's fat storage capacity due to reduced levels of adipocytes. It has also been discovered that mHep inhibits adipocytes from exhibiting adipogenic or lipogenic effect that may result in the excessive build-up of fatty tissue contributing to body weight increase.
• the inventor have identified new methods of using mHep for treating or preventing overweight and obesity in mammals, wherein the method comprises administering to the mammal a composition comprising an effective amount of a mHep.
• the method relates to a mammal that is a pet, more particularly, wherein the pet is selected from: (a) a growing pet (e.g., puppy, kitten) that may be overweight or obese, reproductively-intact, or spayed/neutered; (b) an adult pet that may be overweight or obese, reproductively-intact, or spayed/neutered; or (c) a senior pet that may be overweight or obese, reproductively-intact, or spayed/neutered.
• a growing pet e.g., puppy, kitten
• an adult pet may be overweight or obese, reproductively-intact, or spayed/neutered
• a senior pet that may be overweight or obese, reproductively-intact, or spayed/neutered.
• the method comprises administering to the mammal a composition comprising an effective amount of an mHep to inhibit or reduce the differentiation process of fat stem cells into adipocytes in the mammal such that the mammal's body fat storage capacity decreases by about at least 5%, about at least 10%, or about at least 20%, relative to an untreated mammal.
• the method wherein the administration comprises feeding to the mammal a composition comprising a daily dosage amount of from about 1 mg/kg to about 50 mg/kg of a mHep, and wherein the composition is selected from the group consisting of a pet food, a supplement, and a liquid, wherein the supplement or the liquid can be taken separately or added to the pet food.
• the composition can be selected from the group consisting of wet composition (i.e., having a total moisture content of greater than 50%, by weight of the product), moist composition (i.e., having a total moisture content of from about 16% to about 50%, by weight of the product), semi-moist composition, dry composition and combinations thereof.
• the composition can be nutrionally balanced pet food composition.
• the present invention is directed to a method of increasing the lifespan of a mammal, preferably a growing pet such as, for example, a puppy or a kitten, by administering to the mammal a composition comprising an effective amount of a mHep to reduce the caloric in-take of the young pet, wherein the administration starts within a window of about one month to 3 years of the birth of the animal.
• the reduction in caloric in-take is preferably anywhere within a range of about 10% to about 50% of the caloric in-take prior to the administration.
• the present invention is directed to a pet food composition
• a pet food composition comprising an effective amount of an mHep for promoting or maintaining a healthy body fat of growing pets, and wherein the mHep is present in the composition at from about 0.0001% to about 10% by weight of the composition.
• the pet food composition is preferably a high fat food composition with a fat content present in the composition from at least about 15% to at least about 45% by weight of the composition. The higher fat content provides more palatability to the pet food composition, while the mHep minimizes and/or counters any negative effects on body weight gain.
• FIG. 1A shows the body condition chart for assessing obesity in dogs.
• FIG. IB shows the body condition chart for assessing obesity in cats.
• FIG. 2 shows the oil staining showing mHep inhibiting MSC differentiation.
• the term "about” is interpreted to mean optionally plus or minus 20%, preferably optionally plus or minus 10%, more preferably optionally plus or minus 5%, even more preferably optionally plus or minus 2%, and most preferably optionally plus or minus 1 %.
• “Obesity”, as used herein refers to an increase in body weight beyond the limitation of skeletal and physical requirement, as a result of excessive body fat accumulation.
• a human subject is “obese” if he has a Body Mass Index (BMI) above 30 kg/m 2 according to the United States CDC guidelines.
• BMI Body Mass Index
• a pet such as, for example, a cat or dog, is identified as being “obese” if the animal possess the physical attributes using the guidelines set out in the Body Condition Chart (BCS) for Assessing Obesity in Cats and Dogs, developed by Greg Sunvold from IAMS ® (1998), and reproduced in FIGS. 1A (dogs) and IB (cats).
• BCS Body Condition Chart
• “Overweight” as used herein means weighing more than is normal or necessary, especially having more body weight than is considered normal or healthy for one's age or build.
• a human subject is “overweight” if he has a Body Mass Index (BMI) between 25.0 kg/m 2 to 29.9 kg/m 2 according to the United States CDC guidelines.
• BMI Body Mass Index
• a pet such as, for example, a cat or dog, is identified as being “overweight” if the animal possess the physical attributes using the guidelines set out in the Body Condition Chart (BCS) for Assessing Obesity in Cats and Dogs, developed by Greg Sunvold from IAMS ® (1998), and reproduced in FIGS. 1A (dogs) and IB (cats).
• BCS Body Condition Chart
• “Mammal” as used herein means a primate, such as a human, ape or monkey, or domesticated animal such as, for example, a pet.
• Pet as used herein means a domesticated animal including, domesticated dogs (canines), cats (felines), horses, cows, ferrets, rabbits, pigs, rats, mice, gerbils, hamsters, horses, and the like. Pet is also referred to as “companion animals” herein.
• “Growing pet” as used herein refers to a subset of "pet” and includes young animals that are still undergoing development and are not yet sexually mature.
• “Kitten” as used herein refers to a type of "growing pet” and includes domesticated cats which are 3 years old or less, or about 2 years old or less, or about 1 year old or less.
• “Puppy” as used herein refers to a type of "growing pet” and includes domesticated dogs which are 3 years old or less, or about 2 years old or less, or about 1 year old or less.
• Adult pet refers to a subset of “pet” and includes, for example, domesticated dogs (canines) and cats (felines) that are between about 3 years old and about 8 years old.
• “Senior pet” as used herein refers to a subset of “pet” and includes, for example, domesticated dogs (canines) and cats (felines) that are about 9 years old and above. "Reproductively-intact” as used herein means that the animal can still reproduce as they have not undergone any procedures to remove or disable the sexual organs (e.g., ovaries, testicles).
• Menopause as used herein means the period of permanent cessation of menstruation in a female human, and typically occurs between the ages of about 45 and about 55. Menopause is marked by dramatic variations in hormone levels such as, for example, decreases in estrogen levels due to the ovaries no longer producing eggs.
• “Spaying” or “neutering” as used herein means surgical procedures performed on animals for population control. “Neutering” is the removal of the testicles from a male animal, and “spaying” is the removal of ovaries from a female animal. “Spaying” or “neutering” can also cover pets that have been altered with respect to their sex organs, for example, through natural causes such as an anatomical defect, biochemical or genetic abnormality, or disease, for example, post-andropausal having reduced circulating estradiol levels relative to a healthy non-obese control animal.
• Treating means the treatment of the conditions of overweight and obesity in a mammal and includes:
• Preventing means to stop the conditions of overweight and obesity from occurring.
• “Ameliorating” as used herein means to make the conditions of overweight and obesity become bearable.
• Body Mass Index based on height and weight. According to the U.S. CDC guidance, the range of BMI for a normal body weight is 18.5 kg/m 2 to 24.9 kg/m 2 .
• Healthy body fat as used herein means age-adjusted percentage of body fat that is considered healthy for a mammal. Healthy body fat comprises: (i) essential body fat, and (ii) storage body fat. Essential body fat is required for maintaining life's necessary functions and reproduction. Storage body fat consists of fat accumulation in adipose tissue. The present invention intends to limit the percentage of the storage body fat to minimize the adverse weight gain.
• Fat stem cells or “adipose stem cells” as used herein means multipotent cells that can differentiate into tissue cells, such as, adipocytes (i.e., fat cells). They are ubiquitously available and are found in adipose tissue. Fat stem cells are also known as “adipose-derived adult stem (ADAS) cells”, “adipose-derived stromal cells (ADSC)”, “adipose stromal cells (ASC)”, “adipose mesenchymal stem cells (AdMSC)”, “preadipocytes”, “processed lipoaspirate (PLA) cells”, and “adipose-derived stromal/stem cells (ASCs)”.
• ADAS adipose-derived adult stem
• ADSC adipose-derived stromal cells
• AdMSC adipose mesenchymal stem cells
• PDA preadipocytes
• PLA processed lipoaspirate
• Adipocytes as used herein means the cells that specialize in storing energy as fat for the body and are the primary cells that compose adipose tissue. “Adipocytes” are also known as “lipocytes” and “fat cells”.
• Adipose Tissue as used herein means the connective tissue comprising adipocytes (i.e., fat cells). Adipose tissue is generally where the body deposits and stores excess fat. Adipose tissue encompasses, without limitation, white, brown, and yellow adipose tissue.
• Body's fat storage capacity as used herein means the body's ability to store energy as fat for the body in adipose tissue. The body fat's storage capacity increases with increasing numbers of adipocytes.
• compositions comprising a Mannoheptulose (mHep)
• the present invention provides for a composition comprising an effective amount of a mHep for treating overweight and obesity in a mammal.
• the compositions of the present invention are food compositions intended for oral ingestion by the mammal, preferably a human or a pet (e.g., cats, dogs).
• the compositions are intended for consumption by a pet, wherein the compositions are selected from the group consisting of a pet food, a supplement, and a liquid.
• Pet food is a composition intended to be ingested by a pet, and preferably a domesticated pet such as, for example, a cat, a kitten, a puppy, or a dog.
• pet food is intended to include things like treats (e.g., biscuits), chews, raw hides, and the like.
• treats e.g., biscuits
• the "pet food” is designed specifically for a growing pet (e.g., puppy food) or
• the "pet food” is a "complete and nutritionally balanced pet food”.
• the pet food composition may be a dry composition (e.g., kibble, and having a total moisture content of from about 0% to about 16%, by weight of the product), a moist or a semi-moist composition (i.e., having a total moisture content of from about 16% to about 50%, by weight of the product), a wet composition (i.e., having a total moisture content of greater than about 50%, by weight of the product), or any mixture thereof.
• a dry composition e.g., kibble, and having a total moisture content of from about 0% to about 16%, by weight of the product
• a moist or a semi-moist composition i.e., having a total moisture content of from about 16% to about 50%, by weight of the product
• a wet composition i.e., having a total moisture content of greater than about 50%, by weight of the product
• the pet food composition may be a "high fat food", preferably a "high fat pet food”, comprising a fat content present in the pet food composition, on a dry matter basis: a) of at least about 15% by weight of the composition; b) of at least about 25% by weight of the composition; c) of at least about 35% by weight of the composition; or d) of at least about 45% by weight of the composition.
• a “high fat food” comprising a fat content present in the pet food composition, on a dry matter basis: a) of at least about 15% by weight of the composition; b) of at least about 25% by weight of the composition; c) of at least about 35% by weight of the composition; or d) of at least about 45% by weight of the composition.
• the mHep interacts with the adipocytes to negate the negative effects of the fat.
• Higher concentrations of mHep can be added to increasing concentrations of fat. to a level where the presence of the high fat content in the pet food composition has minimal or nil impact on the body fat accumulation of the animal consuming the food.
• the mHep is believed to be effective at mitigating the negative effects, even at very high levels of fat content, for example, to at least about 45% by weight of the composition.
• Embodiments related to compositions, preferably pet food compositions, of the present invention may further comprise a source of carbohydrate.
• the compositions may comprise from about 35%, by weight of the composition, up to about 50%, by weight of the composition, carbohydrate source.
• the composition can comprise a source of carbohydrate at from about 35% to about 45%, by weight of the composition, or from about 40% to 50%, by weight of the composition.
• carbohydrate source include, grains or cereals such as rice, corn, milo, sorghum, barley, wheat, and the like are illustrative sources of carbohydrate.
• compositions preferably pet food compositions, of the present invention may also contain other materials such as, but not limited to, dried whey and other dairy by-products, beet pulp, cellulose, fiber, fish oil, flax, vitamins, minerals, flavors, antioxidants, and taurine.
• other materials such as, but not limited to, dried whey and other dairy by-products, beet pulp, cellulose, fiber, fish oil, flax, vitamins, minerals, flavors, antioxidants, and taurine.
• compositions preferably pet food compositions, of the present invention
• beneficial ingredients may be present in the compositions, preferably pet food compositions, of the present invention, for example, crude protein as a percentage of the composition in the range of from about 10% to about 90% by weight of the composition, from about 20% to about 50% by weight of the composition, from about 20% to about 40% by weight of the composition, or from about 20% to about 35%by weight of the composition.
• pet food composition mayinclude: probiotic components (Bifidobacteria and/or Lactobacillus), prebiotic components (e.g., fructoooligosaccharides, PCT Publication No.WO2005/0158294, for example), omega-6 and omega-3 fatty acids, carnitine, hexametaphosphate, glucosamine, chondroitin sulfate, carotenoids including beta carotene, vitamin E, and lutein.
• probiotic components Bacta and/or Lactobacillus
• prebiotic components e.g., fructoooligosaccharides, PCT Publication No.WO2005/0158294, for example
• omega-6 and omega-3 fatty acids e.g., carnitine, hexametaphosphate, glucosamine, chondroitin sulfate, carotenoids including beta carotene, vitamin E, and lutein.
• “Supplement” as used herein is intended to cover both “dietary supplement” and “food supplement” and means a product intended to be ingested separately in addition to the normal diet of the mammal, or added to a food, preferably a pet food, or added to a liquid intended for consumption by the animal.
• Liquid as used herein means fillers, gravies, sauces, beverages, supplemental water, and combinations thereof The liquid is intended to be ingested separately in addition to the normal diet of the mammal, or added to a food, preferably a pet food.
• compositions of the present invention comprises an effective amount of an mHep for treating or preventing overweight and obesity in a mammal to which the composition has been administered.
• the amount of mHep as a percentage of the composition is in the range of from about 0.0001% to about 10% by weight of the composition, from about 0.1% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition, wherein the weight of the composition is on a dry matter basis.
• the amount of mHep is about 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, or 10.0% by weight of the composition.
• the composition When the composition is formulated as a dietary supplement, the composition may be formulated to contain mHep at higher concentrations (i.e., 2X, 3X, 4X, 5X, etc.) to be amenable for administration to a mammal in the form of a tablet, capsule, liquid concentrated, or other similar dosage form, or to be diluted before administrations, such as by dilution in water, spraying or sprinkling onto a composition such as, for example, a pet food, and other similar modes of administration.
• mHep at higher concentrations (i.e., 2X, 3X, 4X, 5X, etc.) to be amenable for administration to a mammal in the form of a tablet, capsule, liquid concentrated, or other similar dosage form, or to be diluted before administrations, such as by dilution in water, spraying or sprinkling onto a composition such as, for example, a pet food, and other similar modes of administration.
• the mHep used in the present invention can be derived from any suitable source.
• Preferred sources of mHep include:
• the mHep may be obtained from a "naturally-derived source", such as, a component of plant matter such as an avocado, avocado extract, avocado meal, avocado concentrate, or other enriched source of mHep.
• a component of plant matter such as an avocado, avocado extract, avocado meal, avocado concentrate, or other enriched source of mHep.
• enriched sources of mHep include alfalfa, fig, or primrose.
• the plant matter may include the fruit, seed (or pit), branches, leaves, or any other portion of the relevant plant or combinations thereof.
• avocado also commonly referred to as alligator pear, aguacate, or palta
• avocado contains unusually enriched sources of mHep, as well as related sugars and other carbohydrates.
• avocado is a sub-tropical evergreen tree fruit, growing most successfully in areas of California, Florida, Hawaii, Guatemala, Mexico, the West Indies, South Africa, and Asia.
• Species of avocado include, for example, Persea Americana and Persea nubigena, including all cultivars within these illustrative species. Cultivars may include 'Anaheim,' 'Bacon,' 'Creamhart,' 'Duke,' 'Fuerte,' 'Ganter,' 'Gwen,' 'Hass,' 'Jim,' 'Lula,' 'Lyon,' 'Mexicola Grande,' 'Murrieta Green,' 'Nabal,' 'Pinkerton,' 'Queen,' 'Puebla,' 'Reed,' 'Rincon,' 'Ryan,' 'Spinks,' opa Topa,' 'Whitsell,' ' Wurtz,' and 'Zutano.' The fruit of the avocado is particularly preferred for use herein, which may contain the pit or wherein
• Fruit from Persea Americana is particularly preferred for use herein, as well as fruit from cultivars which produce larger fruits (e.g., about 12 ounces or more when the fruit is mature), such as Anaheim, Creamhart, Fuerte, Hass, Lula, Lyon, Murrieta Green, Nabal, Queen, Puebla, Reed, Ryan and Spinks.
• Naturally-derived sources of mHep may include plant matter from alfalfa, fig, or primrose, which has been reported to provide relatively high levels of mHep.
• Alfalfa is also referred to as Medicago sativa.
• Fig or Ficus carica including Cluster fig or Sycamore fig, for example) may also be used, as well as primrose or Primula officinalis.
• the mHep may be obtained from a "synthetically-derived source". Synthetic mHep is commercially available (Glycoteam GmbH (Hamburg, DE)) in highly purity forms. However, the highly purified synthetic mHep have the same activity level as the naturally-derived source of mHep, such as avocado extract.
• the mHep may be obtained from a "microbial derived source”.
• compositions of the present invention can be made according to any method suitable in the art such as, for example, that described in Waltham Book of Dog and Cat Nutrition, Ed. ATB Edney, Chapter by A. Rainbird, entitled “A Balanced Diet” on pages 57 to 74, Pergamon Press Oxford.
• the present invention is directed to a pet food composition
• a pet food composition comprising a mHep for promoting or maintaining a healthy body fat of growing pets, and wherein the mHep is present in the composition at from about 0.0001% to about 10% by weight of the composition, from about 0.01% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition.
• health body fat it is intended to mean age-adjusted percentage of body fat that is considered healthy for the mammal.
• WHO World Health Organization
• composition of the present invention can be administered to the mammal by a variety of routes of administration.
• routes of administration include, for example: oral, intranasal, intravenous, intramuscular, intragastric, transpyloric, subcutaneous, rectal, and the like.
• the preferred administration route is "oral" administration of the composition.
• Oral administration means that the mammal ingests the composition or a human feeds the mammal the composition of the present invention, and wherein the "human” that feeds the composition may be, for example, a pet owner, physician, veterinarian or other health professionals (e.g., pharmacists).
• Feeding instructions that which informs and/or directs the human about the use and how to feed the composition to the mammal may include, for example, oral or written direction (e.g., from a physician, veterinarian, other healthy professional); radio, internet or television media (e.g., advertisement); and/or packaging associated with the composition (e.g., label present on the packaging). Additionally, administration in accordance with the present invention may be continuous or intermittent, and will vary depending upon the subject/patient. For example, upon review of the subject's/patient's physiological condition, and whether the purpose of the administration is therapeutic or prophylactic, and others factors that become known to the skilled practitioners.
• mHep inhibits the differentiation process of fat stem cells, specifically, mesenchymal stem cells (MSC), into adipocytes when cultured in the presence of differentiation medium.
• MSC mesenchymal stem cells
• the inventors discovered that the mHep treated fat stem cells have an overall gene expression pattern that is similar to the undifferentiated cells that were not given the differentiation medium.
• mHep effectively inhibit the ability of differentiating fat stem cells to accumulate lipid.
• the present invention is directed to a method of treating or preventing overweight and obesity in a mammal, wherein the method comprises administering to the mammal a composition comprising an effective amount of a mHep.
• the mammal is consuming more than the minimum caloric requirements or is not on a diet regimen.
• the mammal is a human (e.g., woman, man).
• the terms "overweight” and “obesity” may be used to identify states of body weight/ body fatness based on the human subject's Body Mass index (BMI).
• BMI Body Mass index Table 2 below sets out ranges of BMI for each body state according to the guidelines provided by the U.S. CDC. BMI is determined by taking the subject's weight and dividing it by the height.
• the mammal is a pet selected from:
• a growing pet selected from the group consisting of a reproductively-intact puppy, a reproductively-intact kitten, an overweight or obese puppy, an overweight or obese kitten, a spayed or neutered puppy, and a spayed or neutered kitten;
• an adult pet selected from the group consisting of a reproductively-intact adult dog, a reproductively-intact adult cat, an overweight or obese adult dog, an overweight or obese adult cat, a spayed or neutered adult dog, a spayed or neutered adult cat; or c) a senior pet selected from the group consisting of a reproductively-intact senior dog, a reproductively-intact senior cat, an overweight or obese senior dog, an overweight or obese senior cat, a spayed or neutered senior dog, and a spayed or neutered senior cat.
• the terms “overweight” and “obesity” refer to states of body weight/ body fatness based on an assessment of the animal's body using the Body Condition Chart (BCS) for Assessing Obesity in Cats and Dogs, developed by Greg Sunvold from IAMS ® (1998), as reproduced in FIGS. 1A (dogs) and IB (cats).
• the chart provides 5 types of body weight/ fatness status: (1) thin, (2) underweight, (3) ideal, (4) overweight, and (5) obese, with defining physical characteristics for each type to help with the assessment.
• the benefit of the chart approach is that it provides some uniformity to the assessment.
• the degree of the adipocyte's response is dependent on the timing of the mHep administration relative to the stage of adipocyte differentiate, since mHep appears to have limited effect on adipocytes once they have differentiated and are accumulating lipids. Accordingly, the benefit of mHep on adipocyte functionality is dependent on early mHep administration prior to the initiation of adipocyte differentiation. Once fat stem cells have differentiated into adipocytes it is difficult to get rid of them. Therefore, the objective of early on administration of mHep to a mammal is to inhibit the differentiation process and limit your body's reserve of adipocytes.
• the mammal is a growing pet such as, for example, a kitten or a puppy.
• the kitten may be a domesticated cat that is 3 years old or less, 2 years old or less, or 1 year old or less.
• the puppy may be a domesticated dog that is 3 years old or less, 2 years old or less, or 1 year old or less.
• the growing pet is in need thereof such treatment since the animal is overweight or obese, or the method is a prophylactic to prevent the mammal from becoming overweight or obese.
• Non-limiting examples of a growing pet in need of such treatment include an overweight puppy, an obese puppy, an overweight kitten, or an obese kitten.
• the composition comprising mHep is administered to growing pets before they have fully developed to the normal adult weight, so it is not possible or healthy to suppress weight gain altogether.
• the method of the present invention allows for a net weight gain of lean body mass yet at the same time treats or prevents weight gain derived from excessive fat accumulation. Accordingly, for growing pets, the overweight or obesity being targeted by this new method is characterized by a weight gain derived substantially from excessive fat accumulation in adipose tissues. It is desirable that the composition of the present invention has a sparing effect on lean body mass.
• the growing pet may be reproductively-intact or preferably, may have been spayed or neutered. It is possible that after weaning but before reaching sexual maturity. The removal of sex organs results in markedly decreased levels of endogenous sex hormones (e.g., estrogen). Consequently, weight gain is common in mammals following spaying or neutering. Accordingly, the methods of the present invention would benefit growing pets that have been spayed or neutered.
• endogenous sex hormones e.g., estrogen
• the method is for preventing overweight and obesity in a mammal having a body that is characterized as thin, underweight or ideal. It is clear that if the mammal is obese with appreciable levels of body fat storage, due to its mechanism of action, mHep will not be able to treat that animal. However, it is believed that mHep would be beneficial to prevent overweight and obesity in adult/senior pets, if they have not developed appreciable levels of body fat. In this scenario, MH would help to prevent/minimize the "middle-age spread" and "age-related increase in body fat" leading to overweight and obesity in an otherwise lean adult/senior pet, irrespective of whether they are reproductively-intact or neutered.
• the mammal that would be suitable for this preventative method are ones having percentages of total body fat between from about 0.1% to about 20%, or from about 0.5% to about 15%, or from about 1% to about 10%, of the total body weight.
• another way of identifying if a mammal is overweight or obese is by checking if the mammal has (i) a body condition characterized as thin, underweight, or ideal, as determined based on a body condition chart as disclosed herein; or (ii) a body condition score (BCS) of 1 to 3 based on a scale from 1 to 5, wherein the BCS is deteremined according to the Body Condition Score Test as disclosed herein.
• a body condition characterized as thin, underweight, or ideal as determined based on a body condition chart as disclosed herein
• a body condition score BCS
• FIGS. 1A & IB provide the body condition chart for dogs and cats
• the body condition chart lists 5 body conditions (thin, underweight, ideal, overweight and obese) along with physical criteria that may be easily viewed and measurable by anyone such as, for example, non-professionals (e.g., pet owner), and professionals (e.g., veterinarian and animal practiconer).
• non-professionals e.g., pet owner
• professionals e.g., veterinarian and animal practiconer
• the BCS method is the most accessible and commonly used method for estimating obesity in a pet. Under the BCS method, physical examination, visual observation, and palpation may be used to assign a body condition score.
• the method administration to the mammal of a composition comprising an effective amount of an mHep inhibits or reduces the differentiation process of fat stem cells into adipocytes in the mammal.
• an effective amount of a mHep refers to the amount of mHep in a composition of the present invention, when administered to a mammal, preferably a human or a domesticated animal such as, for example, a pet or companion animal (e.g., cats, dogs) sufficient to effect treatment or prevention of overweight and obesity.
• This "effective amount" of a mHep which is a component of the composition of the present invention, will vary depending upon the condition and its severity, the manner/route of administration, the age of the mammal to be treated and its overall health, but can determined routinely by one of ordinary skill in the art having regard to his own knowledge and to this disclosure.
• the dose of the mHep will depend upon the form in which the mHep is delivered to the mammal. The dose will vary depending on the size and condition of the pet to which mHep is to be administered. Dosage in the range of from about 0.0001 or about 0.001 g/kg to about lg/kg can be beneficial in some embodiments. As used herein, when dosage in mg/kg is used, the mg refers to the level of the mHep and kg refers to kilograms of body weight of the mammal, preferably where the mammal is a human or pet such as, for example, a cat or dog.
• the dosage of the component provided to a pet on a daily basis may be from about 0.1, 0.5, 1, 2, or 5 mg/kg to about 15, 20, 50, 100, 150, or 200 mg/kg, and all combinations of these ranges, wherein “mg” refers to the level of the mHep and "kg” refers to kilograms of body weight of the mammal.
• the daily dosage to the pet may be from about 0.1 mg/kg to about 50 mg/kg, from about 1 mg/kg to about 20 mg/kg, 1 mg/kg to about 15 mg/kg, from about 2 mg/kg to about 10 mg/kg, or from about 2 mg/kg to about 5 mg/kg, or about 2mg/kg.
• these amounts may translate to compositions comprising less than about 5%, or less than about 2%, or from about 0.0001% to about 0.5%, or from about 0.1% to about 10%, or from about 5%, of mHep, all by weight of the composition.
• the mHep is present in the compositions in the range of from about 0.0001% to about 10%, or from about 0.01% to about 5%, or from about 0.1% to about 3%, by weight of the compositions. All ranges therebetween are envisioned.
• the level of mHep may be determined by one of ordinary skill in the art based on a variety of factors, for example, the form of the composition.
• composition when the composition is a pet food composition it is selected from a dry composition, a smei-moist composition, wet composition, or supplement, or any other form or mixture thereof.
• a dry composition when the composition is a pet food composition it is selected from a dry composition, a smei-moist composition, wet composition, or supplement, or any other form or mixture thereof.
• the ordinarily skilled artisan will be able to utilize the preferred dosage and determine the optimal level of mHep within a given composition.
• mHep results in the inhibition or reduction of the differentiation process of fat stem cells into adipocytes results in lower levels of adipocytes such that the mammal's body's fat storage capacity decreases by about at least 5%, about at 10%, or about at least 20%, relative to an untreated mammal.
• the present invention is directed to a method to promote or maintain a healthy body weight in a mammal, wherein the method comprises administering to the mammal an effective amount of a composition comprising a mHep to prevent or reduce excessive body fat in the mammal.
• Effective body fat may be any amount that qualifies the mammal to be considered overweight or obese.
• the present invention is directed to a method for preventing or ameliorating overweight and obesity in a mammal comprising feeding to the mammal a composition comprising a mHep present in the composition.
• the mHep is present at from about 0.0001% to about 10% by weight of the composition, from about 0.01% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition.
• the composition is selected from the group consisting of a pet food, a supplement and a liquid, wherein the supplement or the liquid can be taken separately or added to the pet food, and wherein the mammal is an adult pet or a senior pet.
• the present invention is directed to a method for preventing or ameliorating overweight and obesity in a mammal comprising feeding to the mammal a composition comprising a mHep.
• the mHep is present in the composition at from about 0.0001% to about 10% by weight of the composition, from about 0.01% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition.
• the composition is selected from the group consisting of a pet food, a supplement and a liquid, wherein the supplement or the liquid can be taken separately or added to the pet food, and wherein the mammal is an adult pet or a senior pet.
• the present invention is directed to a method for increasing lifespan of a mammal, comprising administering to the mammal a composition comprising a daily dosage amount of 1 mg/kg to about 50 mg/kg, or 1 mg/kg to about 15 mg/kg, or 1 mg/kg to about 5 mg/kg, of a mHep. It is expected that mammals that are exposed to longer duration of the mHep, for example, by starting with the treatment shortly after birth, will reap more benefits in terms of increased lifespan. In an embodiment, the administration starts when the mammal is about 1 month old or less, about 6 months old or less, about 1 year old or less, about 2 years old or less, or about 3 years old or less.
• the reduction of caloric intake by the mammal is at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, or at least about 50%.
• the lifespan increases by about 10% or higher, about 15% or higher, about 20% or higher, about 25%, about 30% or higher, or about 35% or higher.
• the administration of mHep begins when the mammal is about 1 month old and the lifespan increase is about 30% or higher; (ii) the administration of mHep begins when the mammal is about 6 months old and the lifespan increase is about 25% or higher;
• composition comprising an effective amount of mHep or an effective amount of mHep of the present invention may be usefully combined with one or more other therapeutic agent or as any combinations thereof, in the treatment of overweight or obesity.
• the present invention also covers an article of commerce, preferably in form of a package, containing a composition comprising an effective amount of a mHep as described hereinabove together with a feeding manual with instructions for how to orally administer composition to the feline companion animal.
• a composition comprising an effective amount of a mHep as described hereinabove together with a feeding manual with instructions for how to orally administer composition to the feline companion animal.
• Any standard packaging that is suitable for delivery and sale of the compositions as disclosed herein can be used.
• the package can also include specific written benefit statements related to the treatment or prevention of overweight or obesity in a mammal, preferably where the mammal is a pet, and more preferably where the pet is a growing pet such as, for example, kitten or puppy.
• the benefit statements can also relate to the health benefits resulted from such treatment or prevention, such as decrease body weight, healthy body weight, healthy body fat, and prolonged life span.
• Whole avocado fruit (about 900 kg) is provided.
• the fruit is split and the pits are removed, either partially or wholly, providing about 225 kg of pitted avocado halves.
• the raw avocado is charged to a disintegrator, whereupon some agitation, water (about 3000 kg) and CELLUBRIX (commercially available from Novozymes A/S) (about 1 liter) is further charged.
• the mixture is further agitated and concurrently heated to about 66 °C.
• further CELLUBRIX (about 1 L) is added, and the entire mixture is CELLUBRIX held under agitation for about 12 hours at a controlled pH of about 5.5.
• the temperature is then further increased to about 80 °C and then held for at least about 2 hours.
• the resulting digested plant mixture is then filtered at 80 °C to provide the carbohydrate extract as the filtrate.
• the carbohydrate extract is then evaporated in a simplified recirculation system at 80 °C, under vacuum, to provide the carbohydrate extract having from about 10% to about 20% solids and a pH of about 5.5.
• the extract is then further concentrated using a refractance window dryer to provide about 100 kg of the extract as a crystalline or powder (a yield of about 11% carbohydrate extract, based on the starting mass of the whole avocado fruit, which is analyzed as a yield from about 0.25% to about 4.5% mHep, based on the starting mass of the whole avocado fruit).
• the amount of mHep found in avocados varies with the particular strain and state of ripeness of the fruit.
• the extract may be used in the compositions of embodiments of the invention.
• MSC Mesenchymal Stem Cells
• adipocyte differentiating medium Invitrogen
• BP Basal Medium without ADP
• Endpoint measures include: (i) oil red staining as a measure of accumulated fat; (ii) visual inspection of adipocytes; and (iii) an ATP assay to measure cell viability. Assay sensitivity allows for the testing of millimolar levels of mHep on adipocyte differentiation.
• Results indicate the addition of palmitate in the differentiation cocktail increases lipid accumulation over the basal medium.
• MSC cultures with mHep (11 mM and 22 mM) or whole- fruit avocado extract (0.2%) present in the medium reverses lipid accumulation to near basal levels.
• mHep inhibits fat cell differentiation and the ability of differentiated adipocytes to accumulate lipid based on oil red staining (FIG. 2).
• Results are supported by the reduced effectiveness of a lower mHep dose (1.16 mM) or a heat- inactivated source of whole- fruit avocado extract (0.2%) to prevent fat cell differentiation and oil accumulation.
• Every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification includes every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification includes every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

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