WO2007084983A2 - Produits enrichis en morinda citrifolia, destinés à être administrés à un animal - Google Patents

Produits enrichis en morinda citrifolia, destinés à être administrés à un animal Download PDF

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Publication number
WO2007084983A2
WO2007084983A2 PCT/US2007/060768 US2007060768W WO2007084983A2 WO 2007084983 A2 WO2007084983 A2 WO 2007084983A2 US 2007060768 W US2007060768 W US 2007060768W WO 2007084983 A2 WO2007084983 A2 WO 2007084983A2
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WO
WIPO (PCT)
Prior art keywords
citrifolia
plus
roasted
seeds
noni
Prior art date
Application number
PCT/US2007/060768
Other languages
English (en)
Other versions
WO2007084983A3 (fr
Inventor
Richard G. Godbee
Claude Jarake Jensen
J. Xu
A. C. Mcsloy
B. K. Anderson
S. F. Peek
B. J. Darien
Bryant Wadsworth
Original Assignee
Tahitian Noni International, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US11/624,571 external-priority patent/US20070298142A1/en
Application filed by Tahitian Noni International, Inc. filed Critical Tahitian Noni International, Inc.
Priority to BRPI0706675-9A priority Critical patent/BRPI0706675A2/pt
Priority to CA002637673A priority patent/CA2637673A1/fr
Priority to JP2008551546A priority patent/JP2009523453A/ja
Priority to EP07718276A priority patent/EP1988784A4/fr
Publication of WO2007084983A2 publication Critical patent/WO2007084983A2/fr
Publication of WO2007084983A3 publication Critical patent/WO2007084983A3/fr

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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)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/746—Morinda
    • 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
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
    • 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

Definitions

  • the field of the invention relates to products which may be administered to various animals, and more particularly to products enhanced with Morinda citrifolia.
  • Animal food products designed for domestic animals, livestock, or pets are generally and preferably prepared as full-feeding foods, which means that the particular composition contains all the necessary nutrients and supplements needed to maintain the health and vigor of the pet.
  • the food composition is balanced in nutrition so that a diet limited to that particular feed will fulfill all of the animal's nutritional needs.
  • the typical ingredients contained within an animal food formulation are protein, carbohydrates, fat, vitamins and minerals. Each of these is present in varying percentages by weight of the specific formulation or composition, sufficient to meet the complete nutritional requirements of the animal. In addition, other ingredients may be added depending upon the specific needs of the animal for which the food is intended.
  • animal food formulations are commercially available. In the past, the nutrients or ingredients in these formulations were not typically designed to provide specific advantages to an animal if desired or needed. Recently however, animal food formulations have been designed with a specific goal in mind. Many animal food formulations available on the market today are specialized catering to animals of different ages, different breeds, or those with certain needs, such as obesity, bone loss, weight gain, diseases or maladies. Other formulations address different energy requirements among animals. An additional segment of the animal food market incorporates differences in ingredient usage or product form, which tend to lend themselves to more attractive tastes or varieties.
  • animal food may be specifically designed as a selective COX-2 inhibitor.
  • Eicosanoids are continuously synthesized in membranes from 20-carbon fatty acid chains that contain at least three double bonds.
  • the synthesis of all but the leukotrienes involves the enzyme cyclooxygenase (COX), which has two distinct isozymes: the constitutive COX-I and the inducible COX-2.
  • COX cyclooxygenase
  • non-steroidal antiinflammatory drugs such as aspirin, ibuprofen, Celebrex® and Vioxx® reduce inflammation through the inhibition of COX, resulting in blockage of the first oxidation step.
  • NSAIDs non-steroidal antiinflammatory drugs
  • inhibition of COX has been linked to a number of other benefits, such as preventing and treating cancer, preventing pre-term delivery and/or treating Alzheimer's disease.
  • cytokines In addition to COX, the inhibition of cytokines, specifically Interleukin-l ⁇ (IL- l ⁇ ), Interleukin-6 (IL-6), and Tumor Necrosis Factor- ⁇ (TNF- ⁇ ), has proven to have many clinical utilities.
  • cytokines are intercellular regulatory proteins that mediate a multiplicity of immunologic biological functions, and in certain pathological situations, particularly autoimmune diseases, chronic inflammatory diseases, and some leukemias, the production of cytokines are disregulated.
  • the present invention is directed to various formulas and methods of administering various Morinda citrifolia enhanced products to animals to improve physiological condition and to ameliorate and/or prevent various maladies. Therefore, preferred embodiments of the present invention provide a M. citrifolia enhanced product which may be administered to animals. Some embodiments provide an animal product having significant health benefits.
  • Some embodiments of the present invention relate to various methods of using specially processed components of the Indian Mulberry or Morinda citrifolia L. plant to inhibit COX-2, TNF- ⁇ , IL-I ⁇ , IL-8 & IL-6.
  • Some embodiments of the invention include one or more processed Morinda citrifolia components such as: extract from the leaves of Morinda citrifolia, leaf hot water extract, processed Morinda citrifolia leaf ethanol extract, processed Morinda citrifolia leaf steam distillation extract, Morinda citrifolia fruit juice, Morinda citrifolia extract, Morinda citrifolia dietary fiber, Morinda citrifolia puree juice, Morinda citrifolia puree, Morinda citrifolia fruit juice concentrate, Morinda citrifolia puree juice concentrate, freeze concentrated Morinda citrifolia fruit juice, and evaporated concentration of Morinda citrifolia fruit juice, whole Morinda citrifolia fruit in fresh, whole dried Morinda citrifolia fruit, powder or solvent extracted forms as well as enzyme treated Morinda citrifolia seeds, or any other processed Morinda citrifolia seed (i.e.
  • Preferred embodiments of the present invention provide delivery systems, methods, and apparatus for providing to animals food products containing Morinda citrifolia puree and other additives such as seed extracts, fatty acids and minerals.
  • Examples of these delivery systems include pellets, extruded nuggets, extruded flakes, sinking nuggets, delivery in liquid form via a water system or lick tank system, semi- solid and gelatinous forms, low moisture gels, low moisture gel pellets, crumble, mash, loose feed, sweet feed, and liquid drenching.
  • the present invention contemplates administering these various forms of Morinda citrifolia enhanced products by either integrating the products into the feed typically provided for the animal, or as a top dressing.
  • Other administration methods include colostrums administered to newborn calves soon after birth, or dipping with Morinda citrifolia enhanced products to ameliorate mastitis.
  • Figure 3 is a depiction of a delivery system for solid form products such as crumble, pellets, flakes or nuggets.
  • the present invention contemplates administering various forms of M. citrifolia with and without additional nutrients.
  • Non-limiting examples of products which may be administered to animals include: M. citrifolia plus glycosaminoglycans, M. citrifolia plus hyaluronic acid, M. citrifolia plus glucosamine HCl, M. citrifolia plus glucosamine sulfate, and M. citrifolia plus chondroitin sulfate.
  • Other non limiting examples of formulations containing M. citrifolia which may be administered to animals include: M. citrifolia plus essential amino acids, M.
  • citrifolia plus essential fatty acids M. citrifolia plus long chain fatty acids, M. citrifolia plus omega 3 fatty acids, M. citrifolia plus omega 6 fatty acids, M. citrifolia plus macro minerals, M. citrifolia plus micro minerals, M. citrifolia plus peptides chains, M. citrifolia plus branched chain amino acids, M. citrifolia puree plus whole noni seeds, M. citrifolia puree plus whole roasted noni seeds, M. citrifolia puree plus whole roasted defatted noni seeds, M. citrifolia puree plus roasted cracked noni seeds defatted, M.
  • citrifolia puree plus roasted cracked noni seeds M. citrifolia puree plus roasted ground noni seeds, M. citrifolia puree plus roasted ground noni seeds defatted, M. citrifolia puree plus roasted flaked noni defatted seeds, M. citrifolia puree plus roasted flaked noni seeds, M. citrifolia puree plus roasted extruded noni defatted seeds, and M. citrifolia puree plus roasted extruded noni seeds and seed extracts.
  • the Indian Mulberry or Morinda citrifolia plant known scientifically as Morinda citrifolia L. ( u Morinda citrifolia"), is a shrub or small tree up to 10 m in height. The leaves are oppositely arranged with an elliptic to ovate form. The small white flowers are contained in a fleshy, globose, head-like cluster. The fruits are large, fleshy, and ovoid. At maturity, they are creamy-white and edible, but have an unpleasant taste and odor.
  • the plant is native to Southeast Asia and has spread in early times to a vast area from India to eastern Polynesia. It grows randomly in the wild, and it has been cultivated in plantations and small individual growing plots.
  • the Morinda citrifolia flowers are small, white, three to five lobed, tubular, fragrant, and about 1.25 cm long.
  • the flowers develop into compound fruits composed of many small drupes fused into an ovoid, ellipsoid or roundish, lumpy body, with waxy, white, or greenish-white or yellowish, semi-translucent skin.
  • the fruit contains "eyes" on its surface, similar to a potato.
  • the fruit is juicy, bitter, dull-yellow or yellowish-white, and contains numerous red-brown, hard, oblong-triangular, winged 2-celled stones, each containing four seeds. When fully ripe, the fruit has a pronounced odor like rancid cheese.
  • the fruit has been eaten by several nationalities as food, the most common use of the Morinda citrifolia plant has traditionally been as a red and yellow dye source.
  • the leaves of the Morinda citrifolia plant are one possible component of the Morinda citrifolia plant that may be present in some compositions of the present invention.
  • some compositions comprise leaf extract and/or leaf juice as described further herein.
  • Some compositions comprise a leaf serum that is comprised of both leaf extract and fruit juice obtained from the Morinda citrifolia plant.
  • Some compositions of the present invention comprise leaf serum and/or various leaf extracts as incorporated into a nutraceutical product ("nutraceutical” herein referring to any drug or product designed to improve the health of living organisms such as human beings or other animals).
  • the Morinda citrifolia leaf extracts are obtained using the following process. First, relatively dry leaves from the Morinda citrifolia L. plant are collected, cut into small pieces, and placed into a crushing device—preferably a hydraulic press—where the leaf pieces are crushed. In some embodiments, the crushed leaf pieces are then percolated with an alcohol such as ethanol, methanol, ethyl acetate, or other alcohol-based derivatives using methods known in the art. Next, in some embodiments, the alcohol and all alcohol-soluble ingredients are extracted from the crushed leaf pieces, leaving a leaf extract that is then reduced with heat to remove all the liquid therefrom. The resulting dry leaf extract will herein be referred to as the "primary leaf extract.”
  • a crushing device preferably a hydraulic press
  • the primary leaf extract is pasteurized to at least partially sterilize the extract and destroy objectionable organisms.
  • the primary leaf extract is pasteurized preferably at a temperature ranging from 70 to 80 degrees Celsius and for a period of time sufficient to destroy any objectionable organisms without major chemical alteration of the extract. Pasteurization may also be accomplished according to various radiation techniques or methods.
  • the pasteurized primary leaf extract is placed into a centrifuge decanter where it is centrifuged to remove or separate any remaining leaf juice therein from other materials, including chlorophyll. Once the centrifuge cycle is completed, the leaf extract is in a relatively purified state. This purified leaf extract is then pasteurized again in a similar manner as discussed above to obtain a purified primary leaf extract.
  • the primary leaf extract whether pasteurized and/or purified, is further fractionated into two individual fractions: a dry hexane fraction, and an aqueous methanol fraction. This is accomplished preferably via a gas chromatograph containing silicon dioxide and CH 2 Cl 2 -MeOH ingredients using methods well known in the art.
  • the methanol fraction is further fractionated to obtain secondary methanol fractions.
  • the hexane fraction is further fractionated to obtain secondary hexane fractions.
  • leaf extracts including the primary leaf extract, the hexane fraction, methanol fraction, or any of the secondary hexane or methanol fractions may be combined with the fruit juice of the fruit of the Morinda citrifolia plant to obtain a leaf serum (the process of obtaining the fruit juice to be described further herein).
  • the leaf serum is packaged and frozen ready for shipment; in others, it is further incorporated into a nutraceutical product as explained herein. 3. Processing Morinda citrifolia Fruit
  • Some embodiments of the present invention include a composition comprising fruit juice of the Morinda citrifolia plant. Because the Morinda citrifolia fruit is for all practical purposes inedible, the fruit must be processed in order to make it palatable for human consumption and included in the compositions of the present invention.
  • Processed Morinda citrifolia fruit juice can be prepared by separating seeds and peels from the juice and pulp of a ripened Morinda citrifolia fruit; filtering the pulp from the juice; and packaging the juice. Alternatively, rather than packaging the juice, the juice can be immediately included as an ingredient in another product, frozen or pasteurized. In some embodiments of the present invention, the juice and pulp can be pureed into a homogenous blend to be mixed with other ingredients.
  • Other processes include freeze drying the fruit and juice. The fruit and juice can be reconstituted during production of the final juice product. Still other processes may include air drying the fruit and juices prior to being masticated.
  • the fruit is either hand picked or picked by mechanical equipment.
  • the fruit can be harvested when it is at least one inch (2-3 cm) and up to 12 inches (24-36 cm) in diameter.
  • the fruit preferably has a color ranging from a dark green through a yellow-green up to a white color, and gradations of color in between. The fruit is thoroughly cleaned after harvesting and before any processing occurs.
  • the fruit is allowed to ripen or age from 0 to 14 days, but preferably for 2 to 3 days.
  • the fruit is ripened or aged by being placed on equipment so that the fruit does not contact the ground.
  • the fruit is preferably covered with a cloth or netting material during aging, but the fruit can be aged without being covered.
  • the fruit is light in color, such as a light green, light yellow, white or translucent color.
  • the fruit is inspected for spoilage or for excessive green color and firmness. Spoiled and hard green fruit is separated from the acceptable fruit.
  • the ripened and aged fruit is preferably placed in plastic lined containers for further processing and transport.
  • the containers of aged fruit can be held from 0 to 30 days, but preferably the fruit containers are held for 7 to 14 days before processing.
  • the containers can optionally be stored under refrigerated conditions prior to further processing.
  • the fruit is unpacked from the storage containers and is processed through a manual or mechanical separator.
  • the seeds and peel are separated from the juice and pulp.
  • the juice and pulp can be packaged into containers for storage and transport. Alternatively, the juice and pulp can be immediately processed into a finished juice product.
  • the containers can be stored in refrigerated, frozen, or room temperature conditions.
  • the Morinda citrifolia juice and pulp are preferably blended in a homogenous blend, after which they may be mixed with other ingredients, such as flavorings, sweeteners, nutritional ingredients, botanicals, and colorings.
  • the finished juice product is preferably heated- and pasteurized at a minimum temperature of 83° C or higher up to 100° C.
  • Another product manufactured is Morinda citrifolia puree and puree juice, in either concentrate or diluted form. Puree is essentially the pulp separated from the seeds and is different than the fruit juice product described herein.
  • the product is filled and sealed into a final container of plastic, glass, or another suitable material that can withstand the processing temperatures.
  • the containers are maintained at the filling temperature or may be cooled rapidly and then placed in a shipping container.
  • the shipping containers are preferably wrapped with a material and in a manner to maintain or control the temperature of the product in the final containers.
  • the juice and pulp may be further processed by separating the pulp from the juice through filtering equipment.
  • the filtering equipment preferably consists of, but is not limited to, a centrifuge decanter, a screen filter with a size from 1 micron up to 2000 microns, more preferably less than 500 microns, a filter press, a reverse osmosis filtration device, and any other standard commercial filtration devices.
  • the operating filter pressure preferably ranges from 0.1 psig up to about 1000 psig.
  • the flow rate preferably ranges from 0.1 g.p.m. up to 1000 g.p.m., and more preferably between 5 and 50 g.p.m.
  • the wet pulp is washed and filtered at least once and up to 10 times to remove any juice from the pulp.
  • the resulting pulp extract typically has a fiber content of 10 to 40 percent by weight.
  • the resulting pulp extract is preferably pasteurized at a temperature of 83° C minimum and then packed in drums for further processing or made into a high fiber product.
  • Some Morinda citrifolia compositions of the present invention include seeds from the Morinda citrifolia plant.
  • Morinda citrifolia seeds are processed by pulverizing them into a seed powder in a laboratory mill.
  • the seed powder is left untreated.
  • the seed powder is further defatted by soaking and stirring the powder in hexane-preferably for 1 hour at room temperature (Drug : Hexane - Ratio 1 : 10).
  • the residue in some embodiments, is then filtered under vacuum, defatted again (preferably for 30 minutes under the same conditions), and filtered under vacuum again.
  • the powder may be kept overnight in a fume hood in order to remove the residual hexane.
  • the defatted and/or untreated powder is extracted, preferably with ethanol 50% (m/m) for 24 hours at room temperature at a drug solvent ratio of 1 :2.
  • Some embodiments of the present invention may comprise oil extracted from the Morinda citrifolia plant.
  • the method for extracting and processing the oil is described in U.S. Patent Application Serial No. 09/384,785, filed on August 27, 1999 and issued as Patent No. 6,214,351 on April 10, 2001, which is incorporated by reference herein.
  • the Morinda citrifolia oil typically includes a mixture of several different fatty acids as triglycerides, such as palmitic, stearic, oleic, and linoleic fatty acids, and other fatty acids present in lesser quantities.
  • the oil preferably includes an antioxidant to inhibit spoilage of the oil. Conventional food grade antioxidants are preferably used.
  • the present invention contemplates administering various forms of M. citrifolia with additional nutrients.
  • Non-limiting examples of products which may be administered to animals include: M. citrifolia plus glycosaminoglycans, M. citrifolia plus hyaluronic acid, M. citrifolia plus glucosamine HCl, M. citrifolia plus glucosamine sulfate, and M. citrifolia plus chondroitin sulfate.
  • Other non limiting examples of formulations containing M. citrifolia which may be administered to animals include: M. citrifolia plus essential amino acids, M. citrifolia plus essential fatty acids, M. citrifolia plus long chain fatty acids, M.
  • citrifolia plus omega 3 fatty acids M. citrifolia plus omega 6 fatty acids, M. citrifolia plus macro minerals, M. citrifolia plus micro minerals, M. citrifolia plus peptides chains, M. citrifolia plus branched chain amino acids, M. citrifolia puree plus whole noni seeds, M. citrifolia puree plus whole roasted noni seeds, M. citrifolia puree plus whole roasted defatted noni seeds, M. citrifolia puree plus roasted cracked noni seeds defatted, M. citrifolia puree plus roasted cracked noni seeds, M. citrifolia puree plus roasted ground noni seeds, M.
  • citrifolia puree plus roasted ground noni seeds defatted M. citrifolia puree plus roasted flaked noni defatted seeds
  • M. citrifolia puree plus roasted flaked noni seeds M. citrifolia puree plus roasted extruded noni defatted seeds
  • M. citrifolia puree plus roasted extruded noni seeds M. citrifolia puree plus roasted extruded noni seeds.
  • the present invention contemplates administering various forms of M. citrifolia enhanced products.
  • Non-limiting examples of those forms include: pellet, extruded nugget, extruded flake, sinking nugget, liquid via water system, liquid via lick-tank system, semi-solid, gel, low moisture gel, and low moisture gel pellet.
  • Method of delivery of the M. citrifolia enhanced products may be very important.
  • Some non-limiting examples of methods of delivery include top dressing feed with a M. citrifolia product, adding it to the feeding practices used for new calves including adding M. citrifolia product to the colostrums administered to new born calves soon after birth, dipping with M. citrifolia enhanced products to ameliorate mastitis in the dairy industry.
  • M. citrifolia product there are several considerations that may be included in the assessment of what form of administration the M. citrifolia product should take. Some non-limiting examples of consideration include: palatability — will the cows/animals eat the product, suggested intake — what will be the proper dosage, milk flavor — will it taint the flavor of the milk in the dairy industry, incorporation into the feed — can it conveniently be added to the feed without significantly reducing its effectiveness, and uniformity of mixing — can it be mixed into the feed in a uniform and consistent way so that we can be sure that each animal is getting the proper dosage.
  • the present invention features compositions and methods for administering various M. citrifolia enhanced products to animals to improve various physiological conditions.
  • the products of the present invention may be utilized to enhance immunity against gram negative infections.
  • Embodiments of the resent invention also comprise methods for internally and/or externally introducing a Morinda citrifolia composition to the body of an animal.
  • Several embodiments of the Morinda citrifolia compositions comprise various different ingredients, each embodiment comprising one or more forms of a processed Morinda citrifolia component as taught and explained herein.
  • Some embodiments of the invention include one or more processed Morinda citrifolia components such as: extract from the leaves of Morinda citrifolia, leaf hot water extract, processed Morinda citrifolia leaf ethanol extract, processed Morinda citrifolia leaf steam distillation extract, Morinda citrifolia fruit juice, Morinda citrifolia extract, Morinda citrifolia dietary fiber, Morinda citrifolia puree juice, Morinda citrifolia puree, Morinda citrifolia fruit juice concentrate, Morinda citrifolia puree juice concentrate, freeze concentrated Morinda citrifolia fruit juice, and evaporated concentration of Morinda citrifolia fruit juice, whole Morinda citrifolia fruit in fresh, whole dried Morinda citrifolia fruit, powder or solvent extracted forms as well as enzyme treated Morinda citrifolia seeds, or any other processed Morinda citrifolia seed (i.e.
  • compositions of the present invention may also include various other ingredients.
  • other ingredients include, but are not limited to: artificial flavoring, other natural juices or juice concentrates such as a natural grape juice concentrate or a natural blueberry juice concentrate; carrier ingredients; and others as will be further explained herein.
  • the present invention contemplates administering various forms of M. citrifolia with additional nutrients.
  • Non-limiting examples of products which may be administered to animals include: M. citrifolia plus glycosaminoglycans, M. citrifolia plus hyaluronic acid, M. citrifolia plus glucosamine HCl, M. citrifolia plus glucosamine sulfate, and M. citrifolia plus chondroitin sulfate.
  • Other non limiting examples of formulations containing M. citrifolia which may be administered to animals include: M. citrifolia plus essential amino acids, M. citrifolia plus essential fatty acids, M. citrifolia plus long chain fatty acids, M.
  • citrifolia plus omega 3 fatty acids M. citrifolia plus omega 6 fatty acids, M. citrifolia plus macro minerals, M. citrifolia plus micro minerals, M. citrifolia plus peptides chains, M. citrifolia plus branched chain amino acids, M. citrifolia puree plus whole noni seeds, M. citrifolia puree plus whole roasted noni seeds, M. citrifolia puree plus whole roasted defatted noni seeds, M. citrifolia puree plus roasted cracked noni seeds defatted, M. citrifolia puree plus roasted cracked noni seeds, M. citrifolia puree plus roasted ground noni seeds, M.
  • citrifolia puree plus roasted ground noni seeds defatted M. citrifolia puree plus roasted flaked noni defatted seeds
  • M. citrifolia puree plus roasted flaked noni seeds M. citrifolia puree plus roasted extruded noni defatted seeds
  • M. citrifolia puree plus extracts extruded noni seeds M. citrifolia noni puree plus extracts from roasted extruded noni seeds.
  • compositions having the leaf extract from the Morinda citrifolia leaves may comprise one or more of the following: the primary leaf extract, the hexane fraction, methanol fraction, the secondary hexane and methanol fractions, the leaf serum, or the nutraceutical leaf product.
  • active ingredients or compounds of Morinda citrifolia components may be extracted out using various procedures and processes commonly known in the art.
  • the active ingredients may be isolated and extracted using alcohol or alcohol-based solutions, such as methanol, ethanol, and ethyl acetate, and other alcohol-based derivatives using methods known in the art.
  • These active ingredients or compounds may be isolated and further fractioned or separated from one another into their constituent parts.
  • the compounds are separated or fractioned to identify and isolate any active ingredients that might help to prevent disease, enhance health, or perform other similar functions.
  • the compounds may be fractioned or separated into their constituent parts to identify and isolate any critical or dependent interactions that might provide the same health-benefiting functions just mentioned.
  • nutraceutical product any components and compositions of Morinda citrifolia may be further incorporated into a nutraceutical product (again, "nutraceutical” herein referring to any product designed to improve the health of living organisms such as humans or other animals).
  • nutraceutical products may include, but are not limited to: intravenous products, topical dermal products, wound healing products, burn healing and treatment products, first-aid products, antibacterial products, bone healing and treatment products, anti-inflammatory products, eye drops, antifungal products, arthritis treatment products, muscle relaxers, and various nutraceutical and other products as may be further discussed herein.
  • compositions of the present invention may be formulated into any of a variety of embodiments, including oral compositions, topical dermal solutions, intravenous solutions, and other products or compositions.
  • compositions may take the form of, for example, tablets, boluses, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, syrups, or elixirs.
  • Compositions intended for oral use may be prepared according to any method known in the art, and such compositions may contain one or more agents such as sweetening agents, flavoring agents, coloring agents, and preserving agents. They may also contain one or more additional ingredients such as vitamins and minerals, etc. Tablets may be manufactured to contain one or more Morinda citrifolia components in admixture with non-toxic, pharmaceutically acceptable excipients that are suitable for the manufacture of tablets.
  • excipients may be, for example, inert diluents, granulating and disintegrating agents, binding agents, and lubricating agents.
  • the tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide sustained action over a longer period.
  • a time delay material such as glyceryl monostearate or glyceryl distearate may be used.
  • Aqueous suspensions may be manufactured to contain the Morinda citrifolia components in admixture with excipients suitable for the manufacture of aqueous suspensions.
  • excipients include, but are not limited to: suspending agents such as sodium carboxymethyl-cellulose, methylcellulose, hydroxy- propylmethycellulose, sodium alginate, polyvinyl-pyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents such as a naturally-occurring phosphatide like lecithin, or condensation products of an alkylene oxide with fatty acids such as polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols such as heptadecaethylene-oxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitor monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides such as polyethylene sorbitan monooleate.
  • suspending agents such as sodium carboxymethyl-cellulose, methylcellulose, hydroxy- propylmeth
  • Typical sweetening agents may include, but are not limited to: natural sugars derived from corn, sugar beets, sugar cane, potatoes, tapioca, or other starch- containing sources that can be chemically or enzymatically converted to crystalline chunks, powders, and/or syrups.
  • sweeteners can comprise artificial or high- intensity sweeteners, some of which may include aspartame, sucralose, stevia, saccharin, etc.
  • the concentration of sweeteners may be between from 0 to 50 percent by weight of the Morinda citrifolia composition, and more preferably between about 1 and 5 percent by weight.
  • Typical flavoring agents can include, but are not limited to, artificial and/or natural flavoring ingredients that contribute to palatability.
  • concentration of flavors may range, for example, from 0 to 15 percent by weight of the Morinda citrifolia composition.
  • Coloring agents may include food-grade artificial or natural coloring agents having a concentration ranging from 0 to 10 percent by weight of the Morinda citrifolia composition.
  • Typical nutritional ingredients may include vitamins, minerals, trace elements, herbs, botanical extracts, bioactive chemicals, and compounds at concentrations from 0 to 10 percent by weight of the Morinda citrifolia composition.
  • vitamins include, but are not limited to, vitamins A, Bl through B 12, C, D, E, Folic Acid, Pantothenic Acid, Biotin, etc.
  • minerals and trace elements include, but are not limited to, calcium, chromium, copper, cobalt, boron, magnesium, iron, selenium, manganese, molybdenum, potassium, iodine, zinc, phosphorus, etc.
  • Herbs and botanical extracts may include, but are not limited to, alfalfa grass, bee pollen, chlorella powder, Dong Quai powder, Ecchinacea root, Gingko Biloba extract, Horsetail herb, Indian mulberry, Shitake mushroom, spirulina seaweed, grape seed extract, etc.
  • Typical bioactive chemicals may include, but are not limited to, caffeine, ephedrine, L-carnitine, creatine, lycopene, etc.
  • the ingredients to be utilized in a topical dermal product may include any that are safe for internalizing into the body of a mammal and may exist in various forms, such as gels, lotions, creams, ointments, etc., each comprising one or more carrier agents.
  • a Morinda citrifolia composition of the present invention comprises one or more of a processed Morinda citrifolia component present in an amount by weight between about 0.01 and 100 percent by weight, and preferably between 0.01 and 95 percent by weight.
  • a processed Morinda citrifolia component present in an amount by weight between about 0.01 and 100 percent by weight, and preferably between 0.01 and 95 percent by weight.
  • the internal composition comprises the ingredients of: processed Morinda citrifolia fruit juice or puree juice present in an amount by weight between about 0.1-80 percent; processed Morinda citrifolia oil present in an amount by weight between about 0.1-20 percent; and a carrier medium present in an amount by weight between about 20-90 percent.
  • Morinda citrifolia puree juice or fruit juice may also be formulated with a processed Morinda citrifolia dietary fiber product present in similar concentrations.
  • the juice and pulp can be dried using a variety of methods.
  • the juice and pulp mixture can be pasteurized or enzymatically treated prior to drying. The enzymatic process begins with heating the product to a temperature between 32.9°C and 57.2 0 C.
  • the juice and pulp can also be dried with other ingredients, such as those described above in connection with the high fiber product.
  • the typical nutritional profile of the dried juice and pulp is 1 to 20 percent moisture, 0.1 to 15 percent protein, 0.1 to 20 percent fiber, and the vitamin and mineral content.
  • the filtered juice and the water from washing the wet pulp are preferably mixed together.
  • the filtered juice is preferably vacuum evaporated to a brix of 40 to 70 and a moisture of 0.1 to 80 percent, more preferably from 25 to 75 percent.
  • the resulting concentrated Morinda citrifolia juice may or may not be pasteurized. The juice would not be pasteurized in circumstances where the sugar content or water activity was sufficiently low enough to prevent microbial growth. It is packaged for storage, transport and/or further processing.
  • the present invention contemplates administering various forms of M. citrifolia enhanced products.
  • Non-limiting examples of those forms include: pellet, extruded nugget, extruded flake, sinking nugget, liquid via water system, liquid via lick-tank system, semi-solid, gel, low moisture gel, and low moisture gel pellet.
  • Some non-limiting examples of methods of delivery include top dressing feed with a M. citrifolia product, adding it in liquid form to the dry feed normally given that species or drying the M. citrifolia product and adding it in ground, granular or pellet form.
  • Liquid M. citrifolia products are simply mixed in the proper ratio with other liquid feed. Sinking pellets are used for fish or other water dwelling creatures.
  • the M. citrifolia additives whether liquid or dry are mixed into the feed in a uniform and consistent way so that it can be assured that each animal is getting the proper amount for uniform benefits.
  • One method for administering the M. citrifolia enhanced food products is by administering a large liquid dose or "drenching" ("drenching") means giving each cow, horse, sheep and/or other animal about a quart or a liter of product at once down the throat of M. citrifolia enhanced products.
  • drenching means giving each cow, horse, sheep and/or other animal about a quart or a liter of product at once down the throat of M. citrifolia enhanced products.
  • the present invention contemplates administering various forms of M. citrifolia enhanced products.
  • Non-limiting examples of those forms include: pellet, extruded nugget, extruded flake, sinking nugget, liquid via water system, liquid via lick-tank system, semi-solid, gel, low moisture gel, low moisture gel pellet.
  • Method of delivery of the M. citrifolia enhanced products may be very important.
  • Some non-limiting examples of methods of delivery include top dressing feed with a M. citrifolia product, adding it to the feeding practices used for new calves including adding M. citrifolia product to the colostrums administered to new born calves soon after birth, dipping with M. citrifolia enhanced products to ameliorate mastitis in the dairy industry
  • M. citrifolia product there are several considerations that may be included in the assessment of what form of administration the M. citrifolia product should take. Some non-limiting examples of consideration include: palatability — will the cows/animals eat the product, Dosage — what will be the proper dosage, milk flavor — will it taint the flavor of the milk in the dairy industry, incorporation into the feed — can it conveniently be added to the feed without significantly reducing its effectiveness, and uniformity of mixing — can it be mixed into the feed in a uniform and consistent way so that we can be sure that each animal is getting the proper dosage.
  • M. citrifolia enhanced products we contemplate mixing the M. citrifolia enhanced products with the food consumed by the animals. In a non-limiting example we propose mixing the M. ( citrifolia enhanced products with grains or hay. In another non-limiting example we propose missing the M. citrifolia with a water medicator.
  • M. citrifolia enhanced products M. citrifolia puree for example, on mastitis
  • a "drench" with a M. citrifolia enhance product where an afflicted animal is administered a large dose, wherein a non-limiting example of a large dose may include more than two ounces, one quart, two quarts, three quarts, more than three quarts on a periodic basis, wherein a non-limiting example of a periodic basis may include once every other day, once a day, twice a day or more than twice a day. Since the somatic cell count (SCC) of each cow is taken periodically, one could see very soon whether or not the M. citrifolia enhanced products were having the desired effect.
  • SCC somatic cell count
  • M. citrifolia enhanced products Decreasing the use of antibiotics may be achieved by administering various M. citrifolia enhanced products in their place.
  • Several experiments have been conducted which indicate that the taste and smell of M. citrifolia enhanced products does not affect the taste or smell of milk from cattle which have been administered M. citrifolia enhanced products, and that the enhanced products are palatable to the animals. Additionally, experiments have shown that success in treating mastitis by infusing the infected quarter with M. citrifolia enhanced products and rubbing M. citrifolia enhanced products on the udder for relief of pain and inflammation. Further Experiments have shown that administering M. citrifolia enhanced products to new born calves prevents the calves for getting scours. In a non-limiting example new born calves were administered 2 oz. twice a day, decreased the mortality rate of new born calves substantially and substantially improved weight gain. 9. Examples
  • Noni puree in a gel form was fed to baby pigs in three different trials.
  • pigs from 10 litters were identified and divided into four groups in such a way as to minimize differences due to litter and sex. All these pigs were from genetically similar sows and all sired, artificially, by the same boar to minimize genetic differences.
  • the treated pigs gained a total of 297 pounds compared to 202 pounds for the controls, a 47% advantage for the treated pigs. This is especially noteworthy because there was concern that handling the pigs daily would have a negative effect on their rate of gain. Treated pigs were handled individually on a daily basis while untreated pigs were simply weighed on a weekly basis. If these results could be obtained routinely it would mean an advantage of 2.97 pounds per pig.
  • 10 litters of pigs from genetically similar sows and sired by the same boar were divided into two groups of five litters each. Litters in the east side of the farrowing house served as one group and the west side of the farrowing house as the second group. Starting at one week of age, the pigs in one group were force fed noni puree for 10 days while the other group received no treatment. Each group was weighed daily. Here are the results.
  • the treated pigs gained 13.5 % more than the non- treated, not as great an advantage as in trial # 1, but still amounting to 0.86 pounds per pig.
  • the owner noted that the treated pigs were extremely skittish by the end of the trial, having been handled daily for 31 days, pointing out once more that a more efficient means of administering the product needs to be developed. Force feeding by tube is very labor intensive and disadvantageous to the pigs as a stress factor.
  • Example 3 Dairy Calf Stress Test
  • a second group of 135 calves (101 bulls and 34 heifers) received at the farm day two of the trial were fed 15 cc of noni puree gel at the time of pickup and an additional 15 cc at the time of unloading. These 135 calves were subsequently treated morning and evening for two additional days.
  • a third group of 153 calves (116 bulls and 37 heifers) received at the farm day 9 of the trial were given no treatment. All calves, whether on noni puree or not, were also given a 2 cc shot of anti bacteria vaccine upon arrival at the farm.
  • Toxin Blend 0 (0.000) 1 (0.007) 0 (0.000)
  • Numbers in parentheses are percentage based on number of calves, decimals truncated at three places.
  • Toxin Blend 0 (0.000) 0 (0.000) 0 (0.000)
  • Toxin Blend 0 (0.000) 1 (0.029) 0 (0.000)
  • Treatment for seven days proved to be very beneficial compared to treatment for three days, especially considering the high correlation between health problems and time of pickup. There was some visual evidence that calves treated seven days did better overall than any others. There were no readily apparent differences in response due to sex.
  • M. citrifolia puree was administered to a group of four pigs.
  • the pigs were watched for more than one hour, but they never indicated any inclination to try any of the versions of the product. They sniffed it a little but did not try to eat it. The pigs do not like the product and will not eat it on their own.
  • We propose that the solution to this problem is to administer the M. citrifolia product as about one percent of the daily ration of these pigs. One percent should make very little if any difference in the flavor of the total feed mixture.
  • Noni M. citrifolia
  • Noni as a supplement for farm animals under intensive production systems has not previously been explored.
  • a recent limited experiment was conducted with weaned pigs that were drenched with 5 ml liquid Noni supplement twice daily from 5-23 kg live weight. The treatment markedly enhanced pig performance and this prompted interest in Noni as a possible supplement for poultry.
  • Broiler chickens were selected because of their rapid early growth. Broiler chicks average 40-41 g at day-old and the increase is 3.8, 2.6, 1.8, and 1.6 times the previous weeks weight at 1, 2, 3 and 4 weeks of age. Hence a two week experiment represents a period of intense growth and adjustment to the environment. Under praxis conditions a dietary supplement that attenuates the effects of stressors and or improves livability, growth and/or feed efficiency has tremendous market potential. The purpose of the study was to evaluate Noni test material provided by MORINDA, Inc. ® in broiler starter diets.
  • Day-old chicks were wing-banded, weighed and allotted to 24 wire-floored pens in 8 blocks on the basis of initial body weight.
  • the brooder units were maintained in an environment-controlled room with airflow of 60 m 3 , 18 air changes per hour, and 24 hour photoperiod.
  • the chicks were observed twice daily and water vessels cleaned and refilled daily. Feed and water were provided ad libitum.
  • the chicks were fed a standard starter diet (control) and liquid Noni supplement added at 1 and 2% in the basal diet.
  • the starter diet contained 58.25% yellow corn, 35% soybean meal, 3.4% poultry fat, 1.4% dicalcium phosphate, 1.1% calcium carbonate, 0.25% common salt, 0.25% vitamin premix, 0.15% choline chloride premix, 0.15% DL-methionine, and 0.05% trace mineral mix. Due to lack of information on stability of the Noni supplement, 150 kg of the control diet was prepared and experimental diets with Noni puree prepared weekly. Feed consumption, body weight, and livability were measured at 2 weeks of age. Broilers are grown on litter and excreta moisture is important for litter condition, bird health, and quality of poultry meat and hence excreta dry matter was measured on days 13- 14.
  • the experiment consisted of three treatments (0, 1 , and 2% Noni puree) that were randomly assigned to pens in a randomized complete block design with 8 blocks.
  • a pen of 8-9 birds constituted the experimental unit.
  • body weight data the individual values were used to remove the bird to bird variation within each experimental unit and treatment effect tested with the appropriate error term. Means and standard errors are presented in the results section.
  • Example 7 Proposed Milking Cows/Mastitis Trials
  • the present invention contemplates various trials.
  • a non limiting example of a proposed trial includes administering M. citrifolia enhanced products to animals to prevent or ameliorate mastitis.
  • M. citrifolia enhanced products to animals to prevent or ameliorate mastitis.
  • This proposed trial would include administering a large dose or "drenching" ("drenching" means giving each cow about a quart or a liter of product at once down the throat of M. citrifolia enhanced products to one half of the infected cows on daily basis, with subsequent monitoring of the SCC for each cow treated, as compared with those infected cows which are not treated. Additionally, this proposed trial contemplates randomly dividing the infected group into two groups. As mastitis clears up in a cow and that cow moves back onto the list of healthy well cows, new cases coming off the healthy list would be divided at random and one half would be treated with the M. citrifolia enhanced product. The proposed trial contemplates "drenching" the animals not treated with the M. citrifolia enhanced product using only pure water.
  • Example 8 Inhibiting COX-2, TNF- ⁇ , IL-l ⁇ , IL-8 & IL-6.
  • the present invention features compositions and methods for inhibiting COX-
  • Embodiments of the present invention also comprise methods for internally introducing a Morinda citrifolia composition into the body of a mammal.
  • Several embodiments of the Morinda citrifolia compositions comprise various different ingredients, each embodiment comprising one or more forms of a processed Morinda citrifolia component as taught and explained herein.
  • Morinda citrifolia products may modulate endotoxin (lipopolysaccharide, LPS) induced inflammatory responses in equine foal monocytes by regulating cyclo-oxygenase-2 (COX-2) expression, as well as expression of other inflammatory cytokines, specifically TNF- ⁇ , IL- l ⁇ , and IL-6.
  • endotoxin lipopolysaccharide, LPS
  • COX-2 cyclo-oxygenase-2
  • a non-limiting example of a Morinda citrifolia product which may be administered is TAHITIAN NONI® EQUINE ESSENTIALSTM.
  • TAHITIAN NOW® EQUINE ESSENTIALSTM treated foals had a reduction in COX-2, TNF- ⁇ , IL-I ⁇ , IL-8 & IL-6 expression in LPS-stimulated monocytes of 9x,
  • TAHITIAN NONI® EQUINE ESSENTIALSTM may be a promising novel anti-inflammatory therapy, warranting further consideration of its use clinically.

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Abstract

L'invention concerne des produits alimentaires pour animaux enrichis en Morinda citrifolia, sous forme liquide et sèche. Ces produits contiennent de la purée de fruit pasteurisée et d'autres produits végétaux de M. citrifolia.
PCT/US2007/060768 2006-01-20 2007-01-19 Produits enrichis en morinda citrifolia, destinés à être administrés à un animal WO2007084983A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
BRPI0706675-9A BRPI0706675A2 (pt) 2006-01-20 2007-01-19 produtos melhorados de morinda citrifolia para administração a animais
CA002637673A CA2637673A1 (fr) 2006-01-20 2007-01-19 Produits enrichis en morinda citrifolia, destines a etre administres a un animals
JP2008551546A JP2009523453A (ja) 2006-01-20 2007-01-19 動物に対する投与のためのモリンダ・シトリフォリア（ヤエヤマアオキ）強化製品
EP07718276A EP1988784A4 (fr) 2006-01-20 2007-01-19 Produits enrichis en morinda citrifolia, destinés à être administrés à un animal

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US76042806P 2006-01-20 2006-01-20
US76045606P 2006-01-20 2006-01-20
US60/760,428 2006-01-20
US60/760,456 2006-01-20
US80956706P 2006-05-31 2006-05-31
US60/809,567 2006-05-31
US11/624,571 2007-01-18
US11/624,571 US20070298142A1 (en) 2006-01-20 2007-01-18 Morinda Citrifolia Enhanced Products For Administration To Animals

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Cited By (4)

* Cited by examiner, † Cited by third party
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US20090068204A1 (en) * 2007-09-06 2009-03-12 Darien Benjamin J Morinda citrifolia Based Formulations for Regulating T cell Immunomodulation in Neonatal Stock Animals
US8017168B2 (en) 2006-11-02 2011-09-13 The Coca-Cola Company High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith
FR2968171A1 (fr) * 2010-12-07 2012-06-08 Ct De Cooperation Internationale En Rech Agronomique Pour Le Dev Cirad Procede de preparation de jus de noni.
US9101160B2 (en) 2005-11-23 2015-08-11 The Coca-Cola Company Condiments with high-potency sweetener

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* Cited by examiner, † Cited by third party
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KR101778062B1 (ko) * 2016-05-02 2017-09-26 백광성 항산화수를 포함하는 영양제 및 그 영양제로 식물재배용, 동물사육용 또는 어류양식용 급수를 제조하는 방법
KR102609860B1 (ko) * 2022-03-18 2023-12-05 주식회사 커먼피플즈 Gi 수치를 낮춰 소화흡수를 도와주는 반려견 껌 영양제

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US5198216A (en) * 1990-07-30 1993-03-30 Daliff Corporation Performance enhancing compositions of matter, and methods of preparing and utilizing same
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US6737089B2 (en) * 1999-08-27 2004-05-18 Morinda, Inc. Morinda citrifolia (Noni) enhanced animal food product
US7048952B2 (en) * 2002-05-21 2006-05-23 Morinda, Inc. Formulation for inhibiting fungal and microbial growth comprising morinda citrifolia puree juice
US20120237626A9 (en) * 2000-12-05 2012-09-20 Palu Afa Kehaati Profiles of lipid proteins and inhibiting HMG-CoA reductase
US6855345B2 (en) * 2001-11-02 2005-02-15 Morinda, Inc. Preventative and treatment effects of Morinda citrifolia on diabetes and its related conditions

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9101160B2 (en) 2005-11-23 2015-08-11 The Coca-Cola Company Condiments with high-potency sweetener
US8017168B2 (en) 2006-11-02 2011-09-13 The Coca-Cola Company High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith
US20090068204A1 (en) * 2007-09-06 2009-03-12 Darien Benjamin J Morinda citrifolia Based Formulations for Regulating T cell Immunomodulation in Neonatal Stock Animals
WO2009032851A2 (fr) 2007-09-06 2009-03-12 Tahitian Noni International, Inc. Compositions à base de morinda citrifolia utilisables à des fins de régulation de l'immunomodulation des lymphocytes t chez le bétail nouveau-né
EP2182814A2 (fr) * 2007-09-06 2010-05-12 Tahitian Noni International, Inc Compositions à base de<i>morinda citrifolia</i>utilisables à des fins de régulation de l'immunomodulation des lymphocytes t chez le bétail nouveau-né
JP2010537670A (ja) * 2007-09-06 2010-12-09 タヒチアン ノニ インターナショナル インコーポレーテッド 新生家畜においてｔ細胞免疫調節を調整するためのモリンダ・シトリフォリア系製剤
EP2182814A4 (fr) * 2007-09-06 2012-05-16 Tahitian Noni International Inc Compositions à base de<i>morinda citrifolia</i>utilisables à des fins de régulation de l'immunomodulation des lymphocytes t chez le bétail nouveau-né
US8652546B2 (en) * 2007-09-06 2014-02-18 Tahitian Noni International, Inc. Morinda citrifolia based formulations for regulating T cell immunomodulation in neonatal stock animals
FR2968171A1 (fr) * 2010-12-07 2012-06-08 Ct De Cooperation Internationale En Rech Agronomique Pour Le Dev Cirad Procede de preparation de jus de noni.
WO2012077053A1 (fr) * 2010-12-07 2012-06-14 Centre De Cooperation Internationale En Recherche Agronomique Pour Le Developpement (Cirad) Procede de preparation de jus de noni

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CA2637673A1 (fr) 2007-07-26
WO2007084983A3 (fr) 2007-12-06
EP1988784A4 (fr) 2009-03-18
BRPI0706675A2 (pt) 2011-04-05
EP1988784A2 (fr) 2008-11-12
JP2009523453A (ja) 2009-06-25
KR20080088641A (ko) 2008-10-02

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