EP2012598A1 - Concentrés riches en matières bioactives et produits nutritifs et thérapeutiques les contenant - Google Patents

Concentrés riches en matières bioactives et produits nutritifs et thérapeutiques les contenant

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Publication number
EP2012598A1
EP2012598A1 EP06750567A EP06750567A EP2012598A1 EP 2012598 A1 EP2012598 A1 EP 2012598A1 EP 06750567 A EP06750567 A EP 06750567A EP 06750567 A EP06750567 A EP 06750567A EP 2012598 A1 EP2012598 A1 EP 2012598A1
Authority
EP
European Patent Office
Prior art keywords
composition
patient
bioactive
oil
concentrate
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP06750567A
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German (de)
English (en)
Inventor
Reddy Sastry V. Cherukuri
Rukmini C. Cherukuri
Aravind Cherukuri
Kartik Natarajan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
NatuRI LLC
Original Assignee
NatuRI LLC
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Filing date
Publication date
Application filed by NatuRI LLC filed Critical NatuRI LLC
Publication of EP2012598A1 publication Critical patent/EP2012598A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS, COOKING OILS
    • A23D7/00—Edible oil or fat compositions containing an aqueous phase, e.g. margarines
    • A23D7/005—Edible oil or fat compositions containing an aqueous phase, e.g. margarines characterised by ingredients other than fatty acid triglycerides
    • A23D7/0053—Compositions other than spreads
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • This invention relates generally to the field of compositions for use as nutraceuticals, food additives or adjuncts to conventional drug therapies.
  • the invention relates to compositions derived from natural oil sources which can be used for effective and inexpensive prophylaxis of cardiovascular diseases, hypercholesterolemia and/or diabetes, and management of lipid metabolism.
  • bioactives Natural phytonutrients, bioactives and antioxidants
  • bioactives are used in the nutraceutical and pharmaceutical industries for their health benefits.
  • polyphenols from grape seed, pine bark and garlic are used in nutraceutical formulations.
  • bioactives present in rice bran and rice germ oil.
  • the unsaponifiable fraction (i.e., the non-fat portion) of rice oil has a high concentration of useful micronutrients and antioxidants such as tocopherols, tocotrienols, ⁇ -oryzanol, phytosterols, polyphenols and squalene, when compared to other vegetable oils.
  • RBO Rice bran oil
  • Antioxidant defense mechanisms in biological systems play a major role in the prevention of a number of diseases such as cardiovascular, cerebrovascular, carcinogenic, and other metabolic age-related disorders.
  • Free radicals such as singlet oxygen
  • Free radicals are highly reactive, attack cellular components, can damage DNA, and alter normal metabolism, resulting in a disease state.
  • Humans are under constant challenge by free radicals; unless charged with sufficient antioxidants to quench these free radicals, the pace of damage to the body is increased and can result in various disease states.
  • Antioxidants provide a defense mechanism and help in preventing and arresting the progression of diseases. It is a constant battle to maintain the delicate balance between oxidants and antioxidants in the body. Epidemiological evidence is mounting on the significant role of natural antioxidants and their vital role in maintaining health and preventing diseases.
  • Cardiovascular disease is a leading cause of mortality in the United States and in developed countries around the world.
  • the disease is linked with well-defined risk factors, such as lipid anomalies, arterial hypertension, diabetes, obesity and smoking.
  • the estimated breakdown of the CVD patient population is as follows: High blood pressure: 50.0 million; Coronary heart disease: 13.9 million; Congestive heart failure: 4.7 million; Stroke: 4.0 million; Rheumatic heart disease: 1.8 million.
  • Prescription medications alone will not suffice in addressing this need as they have a high direct and indirect cost. Beyond cost, there are also significant side effects associated with prescription drugs and medical practitioners are reluctant to increase dosages unless absolutely needed. For example, statin drugs for lowering cholesterol are effective, but can have undesired side effects.
  • Rice bran oil is obtained from rice bran, i.e., the mesocarp of paddy.
  • RBO is different from other vegetable oils, which are obtained from the seed and/or nuts. Palm oil, coconut oil, olive oil and rice bran oil are obtained from the mesocarp of the fruit. These oils are rich in several natural antioxidants. However, when these oils are processed to an edible grade during normal refining steps, the valuable bioactive micronutrients and antioxidants contained in the unsaponifiable fraction of the oil are degraded or destroyed during normal refining steps, thus reducing both the bioactivity of the micronutrients and antioxidants and their therapeutic benefit.
  • ⁇ -oryzanol is unique to rice bran oil among natural products. It occurs in the highest concentration in the bioactives of the unsaponifiable fraction of rice bran oil.
  • ⁇ -oryzanol is a mixture of at least five components. These five components include ferulic acid esters of cycloartol, 24-methylene cycloartanol, ⁇ -sitosterol, 4-methylsterol and methyl ferulate.
  • ⁇ - oryzanol is a potent antioxidant (Joseph Bruno "The facts on ⁇ -oryzanol” 1987), demonstrated to have UV-quenching properties, and activity on the hypothalamus, relieving stress by increasing DHEA levels and reducing Cortisol levels.
  • U.S. Patent No. 5,660,691 discusses isolating tocopherols and tocotrienols from rice distillate.
  • U.S. Patent No. 5,288,902 discusses isolating ⁇ -oryzanol, another valuable antioxidant, from the soap stock, which is typically discarded as a waste product.
  • the natural matrix is disrupted, and thus the potency and bioavailability of these components is diminished.
  • the present invention provides effective and non-destructive isolation, concentration and use of the bioactive components, in their natural matrix, from the unsaponifiable fraction of rice bran oil or rice germ oil.
  • the importance of the effective isolation and concentration of these bioactives in their natural matrix, has not heretofore been achieved or recognized.
  • Components of the bioactive-rich concentrate acts are believed to act synergistically to produce a more potent and greater hypolipidemic and hypocholesterolemic effect than the art has recognized, e.g., when individual, singly purified bioactives are employed.
  • these natural micronutrients and antioxidants are captured, extracted and concentrated without disrupting or with minimal disruption of the natural matrix within which they exist.
  • One embodiment of the invention features a bioactive-rich concentrate derived from the unsaponifiable fraction of rice germ oil, which includes the unsaponifiable content of rice oil.
  • the concentrate is substantially free of rice bran contaminants and may be substantially free of oil matter such as free fatty acids, fats, and triglycerides, and the unsaponifiable content is present at a concentration 10 to 100 times greater than in raw recovered rice bran oil or rice germ oil.
  • the unsaponifiable contents typically include a 4-dimethyl sterol component, a 4- monomethyl sterol component, a ⁇ -oryzanol component, a polyphenol component, a tocopherol component, and a tocotrienol component.
  • the amount of 4-dimethyl sterol component may be about 10-30%, the amount of 4-monomethyl sterol component may be about 4-14%, the amount of ⁇ -oryzanol component may be about 20-40%, the amount of polyphenol fraction component may be about 5-15%, the amount of tocopherol component may be about 5-20%, and the amount of tocotrienol component may be about 5-20%; by weight (based on total weight of the concentrate.)
  • the bioactive-rich concentrate may be used alone or as part of a formulation, e.g., in combination with a cholesterol lowering drug and/or an HMG CoA reductase inhibitor. Such compositions may be advantageously used for, e.g., lowering serum lipids, cholesterol, blood glucose, triglycerides, and/or HDL-C levels.
  • the bioactive-rich concentrate may be present in an amount from about 250 mg to about 1000 mg; the cholesterol lowering drug is present in amount from about 10 mg to about 50 mg, or from about 10 mg to about 100 mg.
  • the HMG CoA reductase inhibitor e.g., mevastatin, lovastatin, pravastatin, simvastatin, fluvastatin, cerivastatin, atorvastatin, tenivastatin, rosuvastatin, pravastatin and combinations thereof, is generally present in amount from about 1 mg to about 80 mg.
  • Cholesterol lowering drugs may include bile acid sequestrants such as cholestyramine, colesevelam and colestipol; or fibric acid derivatives such as fenofibrate and gemfibrozil.
  • bioactive-rich concentrate for example, orally, to treating a patient in need thereof suffering from hypertension, hyperlipidemia, obesity, inflammatory disease, arthritis, hypercholesterolemia, cardiovascular disease, cerebrovascular disease, arteriosclerosis, diabetes mellitus, immune dysfunction or cancer, wherein the patient is administered a bioactive-rich concentrate derived from the unsaponifiable fraction of rice germ oil, in a effective dosage regime sufficient to treat the patient.
  • the method may comprise treating a patient in need of treatment for total serum cholesterol, LDL-C, apolipoprotein B, triglycerides, improving HDL-C levels, inhibiting platelet aggregation and dissolving aortic streaks, by administering to the patient a bioactive-rich concentrate derived from the unsaponifiable fraction of rice bran oil or rice germ oil, or a composition comprising such a bioactive rich concentrate, in a effective dosage regime sufficient to treat the patient.
  • Especially useful embodiments of the invention include food products containing a bioactive-rich concentrate derived from the unsaponifiable fraction of rice bran oil or rice germ oil, e.g., breakfast cereals, snack or energy bars, butter substitutes, margarines, salad dressings, mayonnaises, or beverages.
  • Food products of the invention generally contain from about 0.1% to 15% of the bioactive-rich concentrate.
  • the invention provides methods for the manufacture of the concentrate disclosed herein comprising thoroughly separating rice germ component solids from remaining solids in rice germ or bran, extracting the oil from the rice germ or bran, and separating the saponifiable from the unsaponifiable components.
  • the latter step may by accomplished by any known method that can produce a micronutrient concentrate in its natural matrix, and preferably is done in the cold immediately after the oil recovery step.
  • the effect is to minimize damage to the micronutrients in the unsaponifiable concentrate otherwise induced by enzymes present in the oil and non germ rice bran components, and greatly to increase the concentration of these micronutrients, while maintaining the microcomponents in their natural chemical state.
  • the concentrate permits the manufacture of convenient dose forms that can be consumed in a pill or capsule to achieve health benefits heretofore obtainable only by consuming much larger quantities of rice bran oil.
  • Figure 1 illustrates the steps in the cholesterol homeostasis pathway.
  • Figure 2 illustrates the performance of a bioactive-rich concentrate of the invention as compared to a placebo high cholesterol diet. The comparison is based on a measure of total cholesterol reduction in hamsters after 9 weeks of administering the treatment.
  • Figure 3 illustrates the performance of a bioactive-rich concentrate of the invention as compared to a placebo high cholesterol diet. The comparison is based on a measure of LDL - cholesterol reduction in hamsters after 9 weeks of administering the treatment.
  • Figure 4 illustrates the performance of a bioactive-rich concentrate of the invention as compared to a placebo high cholesterol diet. The comparison is based on a measure of HDL - cholesterol in mg/dL in hamsters after 9 weeks of administering the treatment.
  • Figure 5 illustrates the performance of a bioactive-rich concentrate of the invention as compared to a placebo high cholesterol diet. The comparison is based on a measure of blood glucose levels in hamsters after 9 weeks of administering the treatment.
  • Plant as used herein is includes nonnutritive bioactive plant substance, such as a flavonoids or carotenoids, considered to have a beneficial effect on human health.
  • Micronutrients include phytonutrients, vitamins and minerals which are essential for healthy body function, as well components present in, for example, rice germ oil in very small concentrations that have not been fully characterized but contribute to the known health effects of rice oil preparations..
  • Bioactives collectively include phytonutrients, micronutrients and antioxidants.
  • Root bran contaminants include all components of rice bran excepting the rice germ component.
  • (Natural) matrix refers to the proportion of naturally-occurring components and the form in which the components are present in rice germ oil.
  • rice oil includes phytosterols that are present naturally as a range of phytosterols of specific chemical structures, and particular esters thereof.
  • “Matrix,”in this case, refers to the phytosterol fraction as just described.
  • the natural matrix represents the bioactives occurring in their native form in their natural lipid environment.
  • a key concept of the present invention is that the bioactives, e.g., the micronutrients, in their natural matrix are biologically more potent than their isolated (purified or separately extracted) forms. Conventional techniques used by others to isolate these micronutrients separate them from their lipid substrate and degrade their molecular structure.
  • phytosterols that are present in RBO exist as free sterols as well as sterol esters. They occur in a dissolved state in the natural lipids of RBO. Together, the micronutrient (in its original form) and the lipid in which it exists are termed as the natural matrix.
  • the present invention ensures that the bioactives, e.g., micronutrients, are maintained as they are in their natural lipid environment.
  • Combination therapy includes the administration of a bioactive-rich concentrate of the invention and at least a second agent as part of a specific treatment regimen intended to provide the beneficial effect from the co-action of these therapeutic agents.
  • the beneficial effect of the combination includes, but is not limited to, pharmacokinetic or pharmacodynamic co-action resulting from the combination of therapeutic agents.
  • Combination therapy may, but generally is not, intended to encompass the administration of two or more of these therapeutic agents as part of separate monotherapy regimens that incidentally and arbitrarily result in the combinations of the present invention.
  • Combination therapy is intended to embrace administration of these therapeutic agents in a sequential manner, that is, wherein each therapeutic agent is administered at a different time, as well as administration of these therapeutic agents, or at least two of the therapeutic agents, in a substantially simultaneous manner. Substantially simultaneous administration can be accomplished, for example, by administering to the subject a single capsule having a fixed ratio of each therapeutic agent or in multiple, single capsules for each of the therapeutic agents.
  • each therapeutic agent can be effected by any appropriate route including, but not limited to, oral routes, intravenous routes, intramuscular routes, and direct absorption through mucous membrane tissues.
  • the therapeutic agents can be administered by the same route or by different routes.
  • a first therapeutic agent of the combination selected may be administered by intravenous injection while the other therapeutic agents of the combination may be administered orally.
  • all therapeutic agents may be administered orally or all therapeutic agents may be administered by intravenous injection.
  • the sequence in which the therapeutic agents are administered is not narrowly critical.
  • Combination therapy also can embrace the administration of the therapeutic agents as described above in further combination with other biologically active ingredients and non-drug therapies (e.g., surgery or radiation treatment.)
  • the combination therapy further comprises a non-drug treatment
  • the non-drug treatment may be conducted at any suitable time so long as a beneficial effect from the co-action of the combination of the therapeutic agents and non-drug treatment is achieved. For example, in appropriate cases, the beneficial effect is still achieved when the non-drug treatment is temporally removed from the administration of the therapeutic agents, perhaps by days or even weeks.
  • One embodiment of the invention features a bioactive-rich concentrate derived from the unsaponifiable fraction of rice bran oil or rice germ oil, which includes the unsaponifiable content of rice oil; the concentrate is substantially free of rice bran contaminants; and the unsaponifiable content is present at a concentration 10 to 100 times greater than in rice bran oil or rice germ oil.
  • the unsaponifiable contents include a 4-dimethyl sterol component, a 4- monomethyl sterol component, a ⁇ -oryzanol component, a polyphenol component, a tocopherol component, and a tocotrienol component.
  • the amount of 4-dimethyl sterol component may be 10-30%, the amount of 4-monomethyl sterol component may be 4-14%, the amount of ⁇ -oryzanol component may be 20-40%, the amount of polyphenol component may be 5-15%, the amount of tocopherol component may be 5-20%, and the amount of tocotrienol component may be 5-20%; by weight (based on total weight of the concentrate.)
  • the bioactive-rich concentrate may be used alone or as part of a formulation, e.g., in combination with a cholesterol lowering drug and/or an HMG CoA reductase inhibitor.
  • compositions may be advantageously used for, e.g., lowering serum lipids, cholesterol, blood glucose, triglycerides, and/or HDL-C levels.
  • the bioactive-rich concentrate may be present in an amount from about 250 mg to about 1000 mg; the cholesterol lowering drug is present in amount from about 250 mg to about 1000 mg.
  • the HMG CoA reductase inhibitor e.g., mevastatin, lovastatin, pravastatin, simvastatin, fluvastatin, cerivastatin, atorvastatin, tenivastatin, rosuvastatin, pravastatin and combinations thereof, is generally present in amount from about 1 mg to about 80 mg.
  • Cholesterol lowering drugs may include bile acid sequestrants such as cholestyramine, colesevelam and colestipol; or fibric acid derivatives such as fenofibrate and gemfibrozil.
  • Other combination compositions contemplated herein include a composition that includes a bioactive-rich concentrate and natural components such as herbs and/or herbal ingredients.
  • Such herbs and/or herbal ingredients may include those used to lower cholesterol levels, such as guggul gum resin derived from or in the form of gum from Commiphora mukul, policosanol that may be derived from sugar cane wax, curcumin that may be derived from turmeric, garlic, psyllium, green tea and/or green tea extracts, and licorice and/or licorice extracts.
  • Other combination compositions can include such ingredients as DHA, EPA, CoQlO, fish oil, olive oil, vitamin E and vitamin C.
  • Especially useful embodiments of the invention include food products containing a bioactive-rich concentrate derived from the unsaponifiable fraction of rice bran oil or rice germ oil.
  • Such food products may include, for example, breakfast cereals, snack or energy bars, butter substitutes, margarines, salad dressings, mayonnaises, or beverages.
  • Food products of the invention generally contain from about 0.1% to about 15% of the bioactive-rich concentrate.
  • Rice germ may be used as one preferred source of oil from which the bioactive-rich concentrates of the invention may be obtained.
  • Rice germ is a by-product of the rice milling industry and may comprise a portion of rice bran.
  • the lipases present in the germ come into contact with the oil during milling, they can hydrolyze the triglycerides into free fatty acids, which damage the micronutrients.
  • the rice germ is polished repeatedly, for example polished with three or four passes or more, and delicately. Hullers should be avoided, and the mills should separate the bran generated from the polishes as well as stringently separate stone and grit from the paddy. Raw rice milling may be more desirable.
  • Rice bran should be separated from the germ after the initial polishing by sieving and air classification, or other density based separation technique, more desirably within 24 hours after polishing, followed by cold storage, e.g., 3-5°C, to stabilize the germ and halt any residual lipase activity.
  • the germ should be processed as soon as possible after cold storage is initiated.
  • the rice germ oil may be extracted from the germ by cold pressing; solvent extraction, e.g., with non- polar solvents such as hexane, or polar solvents such ethanol or isopropanol; or supercritical fluid extraction techniques, e.g., super critical fluid fractionation, CO 2 , fluorohydrocarbons, or propane.
  • solvent extraction e.g., with non- polar solvents such as hexane, or polar solvents such ethanol or isopropanol
  • supercritical fluid extraction techniques e.g., super critical fluid fractionation, CO 2 , fluorohydrocarbons, or propane.
  • the bioactive-rich concentrates of the invention may be obtained from rice bran oil deodorizer distillate (DOD).
  • DOD is obtained as a by-product of the rice bran oil refining industry.
  • Deodorization is the final step of the rice oil refining process; the deodorization step removes the unwanted impurities in crude rice bran oil, such as aldehydes, ketones and sulfur compounds. This process consists of heating the degummed, deacidified, and bleached rice bran oil to about 250 0 C under high vacuum and steam injection. During this process, several key micronutrients in rice bran oil such as tocotrienols and tocopherols can be distilled away with the impurities.
  • rice bran oil DOD is less desirable than rice germ oil, but may be used in the invention under controlled conditions.
  • DOD for use in the invention should employ minimal alkali treatment during de-acidification, so that the micronutrients in the oil are preserved. Further, it should be used within a short time, e.g., one week, of its creation, to minimize FFA micronutrient degradation.
  • the bioactive-rich concentrates of the invention may be produced from crude rice germ oil by, for example any method that would yield the heretofore unobtained high concentration of the components from the unsaponifiable fraction components.
  • Such methods include preferential concentration (selective solubility) using polar solvents such as ethyl alcohol, isopropyl alcohol, etc.; fractionation of the bioactives of the germ oil after converting the FFAs present in the germ oil to methyl esters followed by SCF treatment; and/or FFA conversion to the ethyl or methyl esters using conventional techniques, followed by short path distillation.
  • DOD is used as a raw material
  • the following techniques may be used to obtain a product with a high concentration of unsaponifiable fraction components: neutralization of FFAs present in the germ oil with sodium bicarbonate, sodium carbonate, sodium hydroxide or calcium hydroxide, followed by filtration of the FFA salts; or converting the FFAs into its (m)ethyl ester, followed by short path distillation or super critical fluid treatment such as super critical fluid fractionation.
  • compositions of the invention are characterized as follows:
  • the bioactive-rich concentrates of the present invention may be produced at an estimated cost of $0.02 to $0.03 per serving, which is several times lower than the individual pharmaceutical compounds targeted at the same ailments.
  • tocotrienols retail for around $200/kg
  • ⁇ -oryzanol retails for around $75/kg.
  • compositions containing the compositions of matter of the invention will be known to those of skill in the art in light of the present disclosure.
  • such compositions may be prepared as orally ingestible preparations such as tablets or other solids for oral administration.
  • they may be formulated as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid prior to injection; as time release capsules; or in any other form currently used, including creams, lotions, mouthwashes, inhalants and the like.
  • compositions of the invention may take many forms, such as capsules, pills and gelcaps, for personal daily or other intermittent use, they also are especially useful when formulated as food additives, e.g. ,in spreads, frozen desserts, beverages and nutritional bars.
  • Examples of food products comprising the compositions of the invention include margarines or other spreads of oil based products, bakery products, dairy products, e.g., yogurt, cheese and milk-based drinks, beverages, e.g., soft drinks, fruit juices and tea- and coffee-based drinks, sauces, dressings and mayonnaise and confectionery products, e.g., frozen confectionery products such as water-ice or ice-cream, and dietary supplements such as health bars.
  • dairy products e.g., yogurt, cheese and milk-based drinks
  • beverages e.g., soft drinks, fruit juices and tea- and coffee-based drinks
  • sauces, dressings and mayonnaise and confectionery products e.g., frozen confectionery products such as water-ice or ice-cream
  • dietary supplements such as health bars.
  • compositions comprising fat and non-fat components to provide general health benefits, including cardiovascular benefits, such as lowering cholesterol in the consumer, treating, preventing, and/or inhibiting heart disease (e.g., atherosclerosis, restenosis, thrombosis) and treating other conditions such as hypertension, poor circulation, complications associated with diabetes, cerebrovascular disease, neurological disorders, and liver abnormalities.
  • cardiovascular benefits such as lowering cholesterol in the consumer
  • heart disease e.g., atherosclerosis, restenosis, thrombosis
  • other conditions such as hypertension, poor circulation, complications associated with diabetes, cerebrovascular disease, neurological disorders, and liver abnormalities.
  • the compounds can be used in the production of baked goods in any form, such as mixes, shelf-stable baked goods (including health bars), and frozen baked goods.
  • Applications include cakes, brownies, muffins, bar cookies, health bars, wafers, biscuits, pastries, pies, pie crusts, and cookies, including sandwich cookies and chocolate chip cookies.
  • the baked goods can contain fruit, cream, or other fillings.
  • Other baked good uses include breads and rolls, crackers, pretzels, pancakes, waffles, ice cream cones and cups, yeast-raised baked goods, pizzas and pizza crusts, and other baked salted snacks.
  • the compositions herein can be used alone or in combination with fats to make shortening and oil products.
  • the fats can be synthetic or derived from animal or vegetable sources, or combinations of these.
  • Shortening and oil products include shortenings, margarines, spreads, butter blends, lards, cooking and frying oils, salad oils, popcorn oils, salad dressings, mayonnaise, and other edible oil products.
  • the compositions include margarines, butter, dressings and spreads.
  • compositions of the present invention include partial or complete replacement fats and/or oils present in peanut butter, frozen desserts such as ice cream and ice cream coatings, whipped toppings, frosting products, processed meat products such as vegetable protein-based meat analog products, sauces, gravies, and dairy products such as milkshakes, milk products, coffee whiteners, and cheese products.
  • the compounds described herein may also be used in beverage compositions, e.g., dilute water beverages (also called “near- water” beverages), milks, coffees, teas, colas, and fruit juices.
  • dilute water beverages also called “near- water” beverages
  • milks e.g., milks, coffees, teas, colas, and fruit juices.
  • compositions of the invention may be used as the pharmaceutical, nutraceutical, cosmeceutical and health food dietary supplements for treating health disorders including high blood pressure, hypercholesterolemia, hyperlipidemia, cardiovascular disease, cerebrovascular disease, diabetes, cancer, obesity, inflammatory diseases, arthritis, improve immune function; as a sports and weight loss formulations in improving lean body mass and liver disorders; and other uses including skin care, hair growth, UV protection, antidandruff agents, and cosmeceuticals.
  • Composition A is derived from two starting materials: rice germ and deodorizer distillate. Purified and stabilized rice germ from the bran is obtained from the first two polishes of rice using 2 successive steps. First, size based separation or sieving is conducted. Density based separation (air classification) is then performed. These operations are carried out within 24 Hrs of polishing operation at the mill. These successive steps yield pure rice germ (over 90% purity). This rice germ is maintained in a cold storage facility at 3 to 5 degrees Celsius to arrest the lipase activity and keep it stable. A crude rice germ oil is extracted from this pure rice germ by solvent extraction with hexane. Hexane is then removed to leave behind crude rice germ oil. This crude rice germ oil is then subject to a degumming process, a dewaxing process, and then esterified. This esterified oil is subject to short path distillation and a concentrated fraction of the rich germ oil is collected.
  • Rice bran oil deodorizer distillate (DOD) is obtained as a by-product of the rice bran oil refining industry. This distillate is subjected to short path distillation and a concentrated fraction is collected. [0063] The two collected fractions from rice germ and DOD are analyzed for their micronutrient content and on the basis of the analysis are combined in proportions to yield Composition A.
  • Composition A is characterized by HPLC and GC. Within each class of nutrient, the relative concentration of individual isomers and components is the same as the original source (rice bran/germ). [0065] The table below describes a sample preparation of a composition (“Composition A”) made in accordance with the invention, and which was tested in an animal study described below:
  • Table 3 shows results of the Watson clinical study, investigating the effects of RBO performed using a RBO unsaponifiable fraction, using rice bran oil as a whole. This study was conducted on 50 human subjects over a 12 month period showed that administering 3.1 g/day of RBO unsaponifiables resulted in a 14.1% reduction in total cholesterol and a 20.5% reduction in LDL-C in addition to an increase in HDL-C levels and significant decrease in triglycerides levels
  • composition A The results indicated significant hypocholesterolemic, hypolipidemic and hypoglycemic effect of Composition A compared to two groups: 1) phytosterols, which is the positive control or "gold standard", and are currently the only natural products in the market with a FDA health claim for cardiovascular health (at least 800 mg of phytosterols or 1300 mg of phytosterol esters in two meals per day); and 2) a placebo control (no treatment) group.
  • phytosterols may compete with cholesterol uptake releasing cholesterol for excretion. The average decline in LDL-c levels through the use of phytosterols is thought to be between 8%-15% in humans.
  • 0.1% Composition A ( ⁇ 10mg dosage): [0073] In the 0.1% Composition A group, total cholesterol levels were 16 % lower (242 mg/dl) and statistically significant (P ⁇ 0.008) when compared to placebo group (287 mg/dl) and more than 6 % greater reduction than the 0.1% phytosterols group (260 mg/dl). The significance of this result is further underscored because the 0.1% Composition A group contains less than 1/lOth the concentration of phytosterols as compared to the 0.1% phytosterol group.
  • Figure 2 shows a comparative performance of Composition A as measured by total cholesterol reduction.
  • Triglycerides also showed an excellent reduction of 21 % (242 mg/dl) when compared with placebo (306 mg/dl) and this was 12 % greater to reduction shown by the 0.1% phytosterol group (279 mg/dl).
  • composition A ( ⁇ 50mg dosage):
  • Composition A showed good animal growth performance and health maintenance at very high doses. It did not show any adverse effects or any physical signs and symptoms of toxicity. Further, the AST and ALT measurement made by increasing the Composition A dosage by 10 times (1% Composition A) were not different from the control group and indicated its safety.
  • Composition A at 0.1 % contains 1.1 mg Tocos (Tocopherol and Tocotrienols), 3.0 mg Gamma Oryzanol and less than 1.0 mg of phytosterols.
  • Tocos Tocopherol and Tocotrienols
  • Gamma Oryzanol 3.0 mg
  • the observed significant hypolipidemic effect in 0.1% Composition A group is significant. It shows the synergistic effect of RBO bioactives acting in concert at very low concentration in their natural matrix. Previous studies on individually purified RBO bioactives have never shown any hypocholesterolemic or hypolipidemic at such low concentrations.
  • Composition A at 5 times the concentration (0.5%) demonstrated a significant increase in HDL-C, which is a positive factor to reduce the risk of CVD.
  • Composition A at 5 times the concentration (0.5%) demonstrated a significant hypoglycemic effect, which is again risk factor of cardiovascular disease.
  • composition A is safe and superior to plant phytosterols (the gold standard) for the reduction of CVD risk factors.
  • These results indicate significant hypocholesterolemic, hypolipidemic and hypoglycemic effect of 0.1 % Composition A compared with 0.1% phytosterols which may be a "gold" standard, as well as compared with placebos.
  • Total cholesterol levels were lower and statistically significant (P value between groups is 0.010). It has shown a reduction of 16% compared to placebo; and more than 6 % reduction compared to phytosterols @ 1/1 Oth the sterol concentration, which is statistically significant (P value between groups less than 0.001).
  • Composition A group also showed significant hypoglycemic effects by lowering blood glucose levels by 23% over the placebo group.
  • Composition A showed good growth performance and did not show any adverse effects by any signs and symptoms or by the AST and ALT measurement which were not different from the control group indicating its safety.
  • Composition A (I Omg of Composition A in the diet) includes 1.1 mg Tocos, 3.0 mg Gamma Oryzanol and less than 1.0 mg of phytosterols. The observed results show a significant synergistic effect of RBO bioactives acting in concert at very low concentration in their natural matrix. [0091] 2. Composition A at 5 times the concentration (of 0.1%,), demonstrate significant raise in HDL-C, which is a positive factor to reduce the risk of CVD.
  • composition A at 5 times the concentration (of 0.1%) demonstrated significant hypoglycemic effect, which is a factor to reduce the risk of cardiovascular disease.
  • Composition A at 5 times the concentration (of 0.1%) demonstrate significant raise in HDL-C, which is a positive factor to reduce the risk of CVD.
  • Composition A at 5 times the concentration (of 0.1%) demonstrated significant hypoglycemic effect, which is again a factor to reduce the risk of cardiovascular disease.
  • composition A demonstrated to be safe without any adverse effects and more efficacious than a "gold" standard, phytosterol.

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Abstract

Cette invention concerne d'une manière générale des compositions destinées à être utilisées comme nutraceutiques, additifs alimentaires ou appoints à des thérapies médicamenteuses classiques. En particulier, l'invention porte sur des compositions dérivées d'huiles naturelles, le contenu insaponifiable d'une huile de son de riz ou de germe de riz qui peut être utilisée pour un traitement efficace et bon marché des maladies cardiovasculaires, de l'hypercholestérolémie, du diabète, des maladies cérébrovasculaires, des troubles neurologiques ou d'anomalies du foie.
EP06750567A 2006-04-13 2006-04-13 Concentrés riches en matières bioactives et produits nutritifs et thérapeutiques les contenant Withdrawn EP2012598A1 (fr)

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JPH04320645A (ja) * 1991-04-19 1992-11-11 Tokyo Yushi Kogyo Kk 強化米ぬか油の製法
ATE531381T1 (de) * 1997-08-29 2011-11-15 Ricex Company Inc Stabilisierte reiskleiederivate zur behandlung von diabetes
AU9209898A (en) * 1997-09-02 1999-03-22 Ricex Company, Inc., The A method for treating hypercholesterolemia, hyperlipidemia, and atherosclerosis
US6197357B1 (en) * 1998-05-28 2001-03-06 University Of Massachusetts Refined vegetable oils and extracts thereof
WO2002060272A1 (fr) * 2001-01-29 2002-08-08 Redeem, Inc. Huile comestible anticholesterol
JP2005255563A (ja) * 2004-03-10 2005-09-22 Chikuno Shokuhin Kogyo Kk 機能性米糠油不ケン化物濃縮物
JP4913330B2 (ja) * 2004-03-10 2012-04-11 築野食品工業株式会社 米糠油脱臭スカム不ケン化物濃縮物製造法

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