[go: up one dir, main page]

WO2001032031A2 - Compositions de sterols reduisant le cholesterol, preparation et procede d'utilisation - Google Patents

Compositions de sterols reduisant le cholesterol, preparation et procede d'utilisation Download PDF

Info

Publication number
WO2001032031A2
WO2001032031A2 PCT/US2000/030350 US0030350W WO0132031A2 WO 2001032031 A2 WO2001032031 A2 WO 2001032031A2 US 0030350 W US0030350 W US 0030350W WO 0132031 A2 WO0132031 A2 WO 0132031A2
Authority
WO
WIPO (PCT)
Prior art keywords
phytosterol
weight percent
group
surfactant
mixtures
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.)
Ceased
Application number
PCT/US2000/030350
Other languages
English (en)
Other versions
WO2001032031A3 (fr
Inventor
Vinod P. Menon
Patrick J. Kinlen
Pichai Pirakitikulr
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.)
Monsanto Technology LLC
Monsanto Co
Original Assignee
Monsanto Technology LLC
Monsanto Co
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
Application filed by Monsanto Technology LLC, Monsanto Co filed Critical Monsanto Technology LLC
Priority to JP2001534247A priority Critical patent/JP2004525856A/ja
Priority to BR0015331-1A priority patent/BR0015331A/pt
Priority to CA002388339A priority patent/CA2388339A1/fr
Priority to AU14608/01A priority patent/AU1460801A/en
Priority to EP00976899A priority patent/EP1225812A2/fr
Priority to CN00818085A priority patent/CN1450863A/zh
Priority to MXPA02004504A priority patent/MXPA02004504A/es
Publication of WO2001032031A2 publication Critical patent/WO2001032031A2/fr
Publication of WO2001032031A3 publication Critical patent/WO2001032031A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/10—Foods or foodstuffs containing additives; Preparation or treatment thereof containing emulsifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • This invention relates to plant sterol compositions and its derivatives for reduction of cholesterol absorption. More particularly, the invention provides compositions containing a phytosterol and/or a phytosterol ester and surfactant(s) that are useful for reducing cholesterol absorption. The invention also relates to methods of preparing such compositions for reducing cholesterol absorption.
  • Cholesterol while an essential nutrient for humans, is well known to be a leading cause of death in the United States and most countries around the world. Many foods consumed today have high cholesterol content. Once the cholesterol reaches the small intestine it can be absorbed which results in an increase in serum cholesterol levels .
  • the serum cholesterol is well-known to be deposited in various parts of the circulatory system, for example, in soft tissues. The long-term accumulation or build-up of cholesterol deposits leads to atherosclerotic disease. By reducing cholesterol content of food, as well as inhibiting the absorption of cholesterol, it has been possible to reduce serum levels of cholesterol.
  • Plant sterols have been found to be particularly effective at reducing serum cholesterol levels.
  • studies conducted employing beta-sitosterol were found to produce significant reductions (17%) in the amounts of cholesterol in the blood (Farquhar, J. . et al., Circulation, 14, 77-82 (1956)).
  • large doses of beta-sitosterol were required, 12-18 grams per day. This is a major impediment to the use of beta- sitosterol for cholesterol reduction.
  • a related class of compounds, plant stanols (saturated plant sterols) have also been found to be effective for reducing cholesterol absorption.
  • Plant stanols and sterols have represented particularly attractive classes of compounds for use in lowering serum cholesterol levels, since they are natural components of vegetable fats and oils. Additionally, plant stanols and sterols are absorbed in very small quantities compared to the absorption of bile and dietary cholesterol. In fact, sitostanol is considered to be practically unabsorable, i.e., less than 5%. Although, plant sterols and stanols are attractive as cholesterol absorption inhibitors, they have proven to be difficult to formulate. A major factor in these difficulties has been the fact that plant sterols are virtually insoluble in water. Considerable efforts have been made to develop plant sterol or stanol preparations that can easily be formulated with consumer food products .
  • U.S. Patent No. 5,244,887 is directed to plant stanol food additives for reducing the absorption of cholesterol in the gastro-intestinal tract.
  • the greatest effectiveness was obtained when the stanols were evenly distributed in finely divided form throughout the food product or beverage to which it is added. This was accomplished by dissolution of the stanols or by suspension of the stanols in an emulsion.
  • Solubilizing agents listed for the stanols include vegetable oil, monoglycerides , diglycerides , triglycerides, tocopherols, and the like and mixtures thereof.
  • Suspensions or emulsions of stanols include water, alchohols, polyols, and other edible compounds.
  • Dispersing agents may be used to aid in the formation of suspensions, such as lecithin, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 85, sodium lauryl sulfate, and the like.
  • the stanol food additives are used with cholesterol containing foods, such as meats, eggs and dairy products .
  • EP 0 897 671 discloses aqueous dispersions of high melting lipids, such as plant sterols, with non-sterol emulsifiers.
  • Emulsifiers used to disperse the high melting lipids include polyglycerol esters and tweens, especially polysorbate 60. Mono- and diglycerides are also mentioned as suitable emulsifiers .
  • the dispersions have reduced size on the order of 15 microns or lower. The dispersions are said to be useful in spreads and other food products. Additionally, the dispersions provide structure to the food products and their use can apparently permit minimization or elimination of saturated fats and trans fatty acids.
  • formulations which lower serum cholesterol levels by preventing or significantly reducing the absorption of cholesterol.
  • Such formulations would desirably be able to be delivered in a variety of ways to individuals, e.g., as an additive to food products or as a pill for oral administration.
  • formulations comprising a plant sterol or a plant sterol ester and a surfactant(s) are effective at inhibiting the absorption of cholesterol.
  • compositions for inhibiting the absorption of cholesterol comprise a plant sterol and/or a plant sterol ester and a surfactant(s) .
  • the surfactant(s ) is selected from the group consisting of anionic, cationic, nonionic and zwitterionic surfactants.
  • plant sterols examples include sitosterol, campesterol, brassicasterol, stigmasterol, clionasterol and mixtures thereof.
  • the compositions of the present invention provide an effective method of reducing cholesterol without any adverse side-effects.
  • compositions of the present invention can be used as food additive compositions for reducing cholesterol absorption from foods .
  • the food additive composition may be employed in small quantities making it convenient for use and also an inexpensive method to reduce cholesterol absorption.
  • the food additive compositions of the present invention are storage-stable for extended periods of time.
  • the food additive compositions may be added before, during or after cooking with foods.
  • the food additive compositions may be added to food products during production prior to sale to the consumer.
  • the compositions of the present invention can be used in non-fat containing foods .
  • the present invention also contemplates various combinations of the foregoing surfactant(s) and a phytosterol and/or a phytosterol ester being administered orally in any of the usual solid forms such as pills, tablets, capsules or powders, including sustained release preparations .
  • the present invention relates to the use of plant sterol and/or plant sterol ester compositions that inhibit the absorption of cholesterol. More particularly, the invention relates to the formation of water soluble/dispersible sterol and/or sterol ester systems comprising a plant sterol and/or a plant sterol ester and anionic, cationic, nonionic, or zwitterionic surfactant systems, which reduce cholesterol absorption.
  • the terms “phytosterols” and “sterols” are used herein interchangeably.
  • the phytosterols used in the present invention typically may include sitosterol, campesterol, brassicasterol, stigmasterol, clionasterol and mixtures thereof.
  • the phytosterols in the present invention will be a mixture of two or more of such phytosterols .
  • the phytosterols are preferably present in the free form. However, in some instances, the phytosterols may be in the naturally occurring ester form. It will also be appreciated that modifications of the plant sterols are also well within the scope of the present invention, for example, small side chains.
  • sterol ester refers to plant sterols that has been modified to form a plant sterol ester derivative.
  • Sterols and their ester derivatives are well known in the art and are described "Analysis of Sterols" by L.J. Goad and T. Akihisa, (published by Blackie Academic & Professional, in imprint of Chapman and Hall, United Kingdom, 1997) hereby incorporated by reference.
  • a larger number of inexpensive sources of plant sterols are known. These include, vegetable oils, vegetable oil sludge, vegetable oil distillates, and other plant oil sources such as tall oils.
  • vegetable oils include, vegetable oils, vegetable oil sludge, vegetable oil distillates, and other plant oil sources such as tall oils.
  • a preparation of sterols from vegetable oil sludge by using solvents such as methanol is taught in U.S. Pat. No. 4,420,427.
  • Sterols isolated from plant sources are usually mixtures of several different sterols.
  • Sitosterol may be obtained from cold pressed wheat germ oil, soy extract, or rice extract. (It will be appreciated that natural sitosterol contains about 40% alpha-sitosterol and about 60% beta-sitosterol.)
  • plant stanols and/or plant stanol esters and mixtures may be used in the disclosed formulations of the present invention.
  • Applicants hereby incorporate by reference the entire disclosure of attorney docket 775.4800, U.S. Serial No. 60/163,382, filed November 4, 1999, and the entire disclosure of attorney docket 775.5100, U.S. Serial No. 60/198,326, filed April 19, 2000, both entitled "Cholesterol Reducing Stanol Compositions, Preparation and Method of Use".
  • the surfactants to be employed according to the invention can be anionic, cationic, nonionic, zwitterionic and mixtures thereof.
  • Suitable anionic surfactants include AOT, also known as sodium dioctylsulfosuccinate or sodium docusate, ammoniated glycyrrhizin, and sodium stearoyl lactylate.
  • Nonionic surfactants include, polyoxyethylene castor oil (cremophor EL polyoxyl 35 castor oil), polyethylene glycol "PEG” (low molecular weight 1000 to 4000), diacetyl lactic acid of esters of mono- and diglycerides, diacetyl tartaric acid esters of mono- and diglycerides, monosodium phosphate derivatives of mono- and diglycerides, ethoxylated mono- and diglycerides, polyethylene glycol (8) stearate, polyethylene glycol (40) stearate, sorbitan esters of fatty acids, quillaja saponin, ethylene oxide propylene oxide block copolymers, vitamin E TPGS (d-alpha tocopheryl poy
  • Preferred fatty alcohols include but are not limited to the following, 1-decanol (CH 3 (CH 2 ) 8 CH 2 OH) also known as n- decyl alcohol, 1-dodecanol (CH 3 (CH 2 ) 10 CH 2 OH) also known as dodecyl or lauryl alcohol, 1-tetradecanol (CH 3 (CH 2 ) 12 CH 2 OH) also known as myristyl alcohol, 1-hexadecanol
  • Zwitterionic surfactants include, hydroxylated lecithin and the like.
  • anionic surfactants such as sodium stearate, sodium palmitate, sodium laurate, sodium myristate, sodium linoleate, and potassium oleate may also be employed.
  • Additional nonionic surfactants that may be included in the compositions of the present invention include polyglycerol esters and tweens, polysorbate 20 (tween 20), polysorbate 40 (tween 40), polysorbate 60 (tween 60), polysorbate 80 (tween 80), polysorbate 85 (tween 85), fatty acids such as oleic acid (C 17 H 33 COOH) , stearic acid (C 17 H 36 COOH) , and palmitic acid (C 15 H 31 COOH) , triglycerides CH 3 (CH 2 ) 6 COOH and CH 3 (CH 2 ) 8 COOH and mixtures thereof (e.g., MCT oil).
  • Naturally occurring polymers such as guar gum, karaya gum, gum arabic, carrageenan, xanthan gum, dextran, maltodextrin, chondroitin sulfate, polyglycerol esters of fatty acids commercially known as Polyaldo, succinoglucan and hyaluronic acid may also be employed in the compositions of the present invention.
  • Synthetic polymers such as poly(vinyl alcohol), poly(vinyl pyrrolidone) , hydroxypropyl methyl cellulose, and sodium carboxymethyl cellulose may also be employed in the compositions of the present invention.
  • fatty acids that may be employed in the present invention, include caprylic, capric, lauric, myristic, myristoleic, palmitoleic, oleic, ricinoleic, linoleic, linolenic, eleostearic, arachidic, arachidonic, behenic and erucic acid.
  • the fatty acids of the present invention can be derived from naturally occurring or synthetic fatty acids; they can be saturated or unsaturated, including positional and geometric isomers, depending on the desired physical properties, for example liquid or solid.
  • the composition of the present invention comprises a mixture of a phytosterol and a surfactant selected from the group consisting of sodium docusate, ammoniated glycyrrhizin, polyoxyethylene castor oil, polyethylene glycol, diacetyl lactic acid esters of mono- and diglycerides, diacetyl tartaric acid esters of mono- and diglycerides, monosodium phosphate derivatives of mono- and diglycerides, ethoxylated mono- and diglycerides, quillaja saponin, ethylene oxide propylene oxide block copolymers, vitamin E TPGS, hydroxylated lecithin and mixtures thereof.
  • a surfactant selected from the group consisting of sodium docusate, ammoniated glycyrrhizin, polyoxyethylene castor oil, polyethylene glycol, diacetyl lactic acid esters of mono- and diglycerides, diacetyl tartaric acid esters of mono- and digly
  • composition of the present invention may further comprise a surfactant selected from the group consisting of sodium salts of fatty acids, fatty alcohols, polyethylene glycol (8) stearate, polyethylene glycol (40) stearate, sucrose fatty acid esters, tween and mixtures thereof.
  • a surfactant selected from the group consisting of sodium salts of fatty acids, fatty alcohols, polyethylene glycol (8) stearate, polyethylene glycol (40) stearate, sucrose fatty acid esters, tween and mixtures thereof.
  • One preferred embodiment of the present invention comprises a mixture of a phytosterol and/or a phytosterol ester and fatty acid alcohol, preferably, octadecanol.
  • Another preferred embodiment of the present invention comprises a mixture a phytosterol and/or a phytosterol ester, Tween 60 and PEG.
  • Other preferred embodiments include a phytosterol and/or a phytosterol ester, fatty acid alcohol and sucrose fatty acid ester, such as Crodesta.
  • One preferred embodiment of the present invention provides a method of reducing cholesterol absorption in humans which comprises orally administering an effective amount of a composition of the present invention.
  • the invention also provides for a method for reducing serum cholesterol levels comprising administering a mixture of a phytosterol and/or a phytosterol ester and a surfactant(s) .
  • emulsifiers may be used in the formulation of dispersible sterol and/or sterol ester systems.
  • Preferred emulsifiers include a variety of phospholipids, phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), N-acylphosphatidyl ethanolamine (NAPE), phosphatidyl serine (PS), phosphatidyl inositol (PI), phosphatidyl glycerol (PG), diphosphatidyl glycerol (DPG), phosphatidic acid (PA) and plasmalogen.
  • PC phosphatidyl choline
  • PE phosphatidyl ethanolamine
  • NAPE N-acylphosphatidyl ethanolamine
  • PS phosphatidyl serine
  • PS phosphatidyl inositol
  • PG phosphatidyl glycerol
  • DPG diphosphatidyl glycerol
  • the phospholipids may be used individually or in various combinations, and may be obtained from "natural" sources (e.g., soybean lecithin) or from chemical synthesis.
  • the phospholipids may be in the form of relatively unpurified mixtures of phospholipids and other constituents (e.g., crude commercial lecithins obtained from the refining of soybean oil and other vegetable oils such as sunflower and canola), or may be purified to various degrees.
  • phospholipids including those found in crude soybean lecithins or other crude commercial lecithins may be chemically modified.
  • Lecithins, other phospholipid preparations, or individual phospholipids purified from natural sources or obtained by chemical synthesis contain one or more functional groups susceptible to chemical modification, e.g., carbon-carbon double bonds, esters, phosphonate esters, amines and hydroxyl groups. Chemical modification of phospholipids can be compatible with the present methods. Thus, phospholipids that have been acetylated, hydroxylated, hydrolyzed (e.g., to produce lysophospholipids ) , hydrogenated, halogenated, phosphorylated, sulfated epoxidated, ethoxylated, or otherwise modified are potentially useful in the present methods and are included within the meaning of the term "phospholipid" as used herein.
  • Various natural and synthetic phospholipids including various types of lecithins, may be obtained commercially, for example Ultralec from ADM Corp., and other lecithins may be obtained from CALBIOCHEM®, La Jolla, Calif., USA and from SIGMA® Chemical Company, St. Louis, Mo., USA.
  • lecithin refers to the entire phospholipid fraction obtained from natural sources such as soybean, cotton seed, corn, wheat germ, oat, barley, sunflower, rapeseed, canola, linseed, peanut, palm kernel, egg yolk, milk and brain. Generally these fractions include a mixture of polar and neutral lipids with a polar lipid content (as defined by insolubility in acetone) of at least 50%.
  • the art has also used the term “lecithin” as the common name for phosphatidyl choline.
  • lecithin refers to the first usage, i.e., the entire phospholipid fraction obtained from selected vegetable oils or other appropriate sources. See, Chapter 2 of Szuhaj and List. It is to be noted, however, that phosphatidyl choline is an appropriate phospholipid for use in the present methods, either alone or in combination with other phospholipids .
  • soybean lecithin a preferred source of phospholipids
  • Crude soybean oil generally contains about 1.0 to 3.0 weight percent phospholipids.
  • the first step generally is to remove the phospholipids. This step, often called “degumming,” is accomplished by first adding water to the crude oil. The water hydrates the phospholipids and makes them less soluble in the oil. The denser phospholipids and water are then separated from the less-dense oil, typically by centrifugation. Removal of the water from the dense phase results in a product having approximately equal amounts of phosphatidyl choline, phosphatidyl ethanolamine, and inositol phosphatides .
  • Partially refined soybean oil is commonly added back to produce a liquid product that is flowable at room temperature (sometimes called "fluidized lecithin").
  • Commercial fluid soybean lecithin contains about 50 to about 65 weight percent phospholipids and a small amount ( generally less than about 5 weight percent) of various carbohydrates, mineral salts, protein materials, free fatty acids, sterols, and water. The remainder of commercial soybean lecithin is soybean oil.
  • lecithin powders enriched for phospholipid content are available commercially and may also be used in the present methods. Such lecithin powders are also within the scope of the term "lecithin” as used herein.
  • the powders are typically derived by fractionation, for example acetone fractionation, of crude lecithins such as commercial soybean lecithin, and may contain from about 60% to over 95% phospholipid.
  • soybean lecithin may be chemically or ezymatically modified, e.g., via reaction with maleic anhydride. Certain components may be removed from commercial soybean lecithin.
  • another approach is to add various components, for example nonionic emulsifiers, to the commercial soybean lecithin.
  • emulsifiers include, without limitation, polyoxyalkylene monoglyceride, polyoxyalkylene diglycerides, and the polyoxyethylene derivatives of partial fatty acid esters .
  • Hydroxylated lecithin is a preferred embodiment of the phospholipids used in the invention.
  • Hydroxylated lecithin is prepared by hydroxylating the double bonds in the fatty acids attached to the phospholipids and glycolipids of lecithin, which can be carried out by reaction with hydrogen peroxide and a weak acid such as lactic acid.
  • hydrogen peroxide and a weak acid such as lactic acid.
  • hydroxylation is not specific and can occur at any double bond within any of the lipids.
  • the degree of hydroxylation is typically about 10% but can be varied by methods known to those of ordinary skill in the art.
  • compositions of the present invention are preferably formed into a fine dispersion using melt processing.
  • melt processing comprises dry-mixing a phytosterol and/or a phytosterol ester and a surfactant(s ) together with a stirring device such as a mechanical stirrer, shear mixer, vibrational mixer or sonicator. The mixture is then heated to a temperature sufficient to melt same, but not so high as to degrade the phytosterol, phytosterol ester or surfactant(s) . The resulting mixture is then rapidly cooled, e.g., liquid nitrogen, to form a salt like material.
  • the step of melt blending the phytosterol and/or phytosterol ester and surfactant(s) prior to rapid cooling facilitates the formation of a composition that is in a finely dispersed state that is able to reach the small intestine thereby being able to inhibit the absorption of cholesterol.
  • An alternative variation on the melt processing described above comprises the addition of a surfactant(s) to a phytosterol and/or phytosterol ester melt. This may be desirable in cases where the surfactant(s) is thermally unstable and would not survive prolonged heating at high temperatures, i.e., thus the residence time for the surfactant(s) is reduced by its later addition to a melt. Once the surfactant(s) has been added to the melt, the mixture can be treated in a fashion similar to that described previously.
  • a further alternative procedure to melt blending for forming the compositions of the present invention is high pressure melting. This procedure is also desirable for blending heat sensitive surfactant(s) and phytosterol and/or phytosterol esters. It has been discovered that by using a mixing or compression means allowing for increasing the pressure on the ingredients, the surfactant(s) , phytosterol and/or phytosterol esters will melt blend at ambient temperatures . Homogenous mixtures of heat sensitive surfactant(s) and phytosterol and/or phytosterol esters can therefore be formed while avoiding temperatures at which thermal decomposition of ingredients will occur.
  • high pressure melting is roller compaction.
  • the surfactant(s ) and phytosterol and/or phytosterol ester are mixed together as described previously, the mixture is then compressed together under high pressure using a roller.
  • the pressure exerted on the mixture is high enough to result in the flow of the ingredients and surface sintering of the mixture results.
  • An additional embodiment of high pressure melting is extrusion.
  • a loosely packed powder mixture of surfactant(s) and phytosterol and/or phytosterol ester is propelled continuously along a screw through regions of high pressure and controlled temperature. Shear forces from the screw melt and mix the material into a continuous stream of molten material, which is then forced through a die.
  • the mixture resulting from the high pressure melting process is typically a soft, pliable solid material that can be further processed by cooling to solidify followed by breaking into chips or milling to form a uniform powder for use in the formation of products as described herein.
  • Mixtures of a phytosterol and/or a phytosterol ester and surfactant(s) may also be processed using solution processing or steric stabilization. Use of solution processing is particularly effective for use with surfactant(s) that are thermally stable.
  • the phytosterol and/or phytosterol ester and surfactant(s) are generally dry mixed together, although this is not always necessary, the resulting solid mixture is then dissolved in an organic solvent, such as methylene chloride. The solvent is then removed to provide an amorphous/dispersible solid form.
  • Steric stabilization provides an effective method to form a dispersible solid form of a phytosterol and/or phytosterol ester and surfactant(s) .
  • a fine dispersion of a phytosterol and/or phytosterol ester is added to water containing the surfactant(s) .
  • the surfactant(s) in the water help to keep the sterol(s) in suspension. Once a finely divided suspension has formed the water is evaporated off leaving a more readily dispersible solid form.
  • Preferred embodiments of the present invention include a mixture of from about 10 to about 99.99 weight percent of a phytosterol and/or phytosterol ester and from about 0.01 to about 90 weight percent of a surfactant(s) , preferably from about 40 to about 95 weight percent of a phytosterol and/or phytosterol ester and from about 5 to about 60 weight percent of a surfactant(s ) , and more preferably about 95 weight percent of a phytosterol and/or phytosterol ester and about 5 percent by weight percent of a surfactant(s) .
  • the compositions of the present invention comprise a phytosterol and/or phytosterol ester and at least two surfactants.
  • a mixture comprises from about 10 to about 99.99 weight percent of a phytosterol and/or phytosterol ester and the sum of the at least two surfactants is from about 0.01 to about 90 weight percent, preferably such a mixture comprises from about 40 to about 95 weight percent of a phytosterol and/or phytosterol ester and the sum of at least two surfactants is from about 5 to about 60 weight percent, and more preferably about 95 weight percent of a phytosterol and/or phytosterol ester and the sum of at least two surfactants is about 5 weight percent. Desirable characteristics of food additive compositions for reducing cholesterol absorption include absence of side effects, efficacy without absorption of the compound, stability at cooking temperatures, stability in storage and in oxidizing environments, low cost, availability, and small dose requirements.
  • compositions of the present invention may be orally administered in a variety of forms: uncoated tablets, coated tablets such as film, sugar or gelatin coated, chewable tablets, swallowable tablets (capsules), effervescent tablets, immediate release tablets, sustained (controlled or modified) release tablets; soft gelatin capsules either liquid (non-aqueous) or paste (slurry); hard gelatin capsules in powder (granulation), bead, tablet, liquid, semi-solid, sprinkle (immediate or controlled release) forms; oral liquids such as aqueous, emulsions or suspension; sachets (packages) in powder, granule or sprinkle (immediate or controlled release) forms.
  • Other forms for administering the compositions of the present invention include syrup, fruit beverages, or fruit gelatines.
  • compositions of the invention may be used in various embodiments it may be said, one preferred embodiment is when the compositions of the present invention are evenly distributed in finely divided form throughout the food product or beverage to which it is added.
  • the compositions of the present invention may be added to food products or beverages prior to purchase by the consumer for consumption.
  • the compositions of the present invention may be purchased in bulk form or individually wrapped packages, e.g., 8 oz. servings.
  • a serving from the bulk form, e.g., 8 oz., or the contents of a package may be added to a glass of cold or hot water or other beverage, stirred to dissolve the contents, prior to consumption.
  • Typical beverages include the following, instant ice tea in Orange Pekoe, English Breakfast, Passion Fruit and Hisbiscus Flavors, powdered soft drinks such as Crystal Light and Contry Time Lemonade, Instant Iced Coffee in flavors such as Mocchacchino, Hazelnut, French Vanilla, and Hot Chocolate and Fruit Smoothies .
  • compositions of the present invention may also be included in mini-sweets.
  • the mini-sweets will typically be consumed after any and all meals of each day.
  • the mini-sweets will typically contain between 25 and 60 calories and 1 to 3 grams of fat.
  • Mini-sweets include the following varieties: chocolate chews; caramel chews; hard candies such as cinnamon, butterscotch, coffee and fruit flavors; chocolate truffles such as hard dark chocolate on the outside filled with hazelnut creme, irish creme or cappucinno creme; brown bites; cookie chews in peanut butter, chocolate chip or ginger snaps; granola/nutrition bar miniatures such as chocolate covered oat and peanut butter; and chewy breath mints.
  • Mini-sweets may be prepared in individually wrapped packages or in larger containers for multiple uses.
  • the method by which the novel food additive composition, i.e., the sterol and/or sterol ester and surfactant(s) , is used to reduce cholesterol absorption from foods and beverages includes the step of commingling the food additive composition with foods and beverages, mixing until uniformly blended.
  • the food additive is added such that the amount of sterols in the food additive is in the ratio of about 1:1 by weight to the cholesterol contained in the foods and beverages.
  • the ratio of food additive to food product is about 1:250 by weight.
  • the food additive composition of the invention can be commingled with foods by a step selected from the group of infusion, injection, mixing, kneading, blending, immersion, spraying, surface application (for example, brushing and basting), cooking in oils which contain the food additive-invention, and combinations thereof.
  • Preferred steps for commingling the food additive-invention with ground meat are kneading and mixing; for meat pieces such as steaks, chicken breasts, and chopped, diced or sliced meat, the preferred steps are injection, infusion, spraying, immersion, and surface applications such as basting and marinating.
  • Two preferred steps for commingling the food additive-invention with beverages are mixing and blending.
  • compositions of the present invention will be used as food additives to foods such as meats, eggs and dairy products. Generally, when used as food additives, the compositions of the present invention will not contribute substantially to the taste of the food product. Accordingly, the compositions of the present invention can be used in food products without compromising the food products taste and flavor.
  • compositions of the present invention may also be formulated into fine particles which may be sprinkled on to other food products, i.e., dairy products such as ice cream or candy.
  • compositions of the invention may be administered to any animal.
  • animals are mammals, e.g., humans, although the invention is not intended to be so limited.
  • the dosage administered will be dependent upon the age, health, and weight of the recipient, kind of concurrent treatment, if any, frequency of treatment, and the nature of the effect desired.
  • compositions of the present invention may be administered orally in any of the usual solid forms such as pills, tablets, capsules or powders, including sustained release preparations .
  • unit dosage form as used in this specification and the claims refer to physically discrete units to be administered in single or multiple dosage to animals, each unit containing a predetermined quantity of active material, i.e., phytosterol and/or phytosterol ester, in association with a surfactant(s) and a carrier.
  • the quantity of active material is that calculated to produce the desired therapeutic effect upon administration of one or more of such units.
  • active material i.e., phytosterol and/or phytosterol ester
  • the quantity of active material is that calculated to produce the desired therapeutic effect upon administration of one or more of such units.
  • the exact treatment level will depend upon the case history of the animal, e.g., human being, that is treated. The precise treatment level can be determined by one of ordinary skill in the art without undue experimentation.
  • the require dosage of the phytosterol and/or phytosterol ester will vary with the severity of the condition and the duration of the treatment.
  • Unit dosages can range from about 0.01 mg/kg to about 500 mg/kg (the unit designated "mg/kg” as used herein refers to mg of phytosterol and/or phytosterol ester per kilogram of body weight), preferably from about 0.1 mg/kg to about 125 mg/kg with up to six doses daily, preferably four dosages daily. Most preferably, the doses are administered at meal times .
  • the dosages may be administered orally in any suitable unit dosage form such as pills, tablets, and capsules. Preferred are capsules made from gelatin.
  • carrier denotes a solid or liquid filler, diluent, or encapsulating substance.
  • substances that can act as carriers are sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, cellulose acetate; powdered tragacanth; malt; gelatin; talc; stearic acid; magnesium stearate; calcium sulfate; vegetable oils, such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and of the broma; polyols such as propylene glycol, glcerin, sorbitol, mannitol, and polyethylene glycol; agar, alginic acid; pyrogen-free water; isotonic saline; ethyl alcohol and phosphate buffer solutions, as well as other non-toxic compatible substances used in
  • wetting agents and lubricants such as sodium lauryl sulfate, as well as coloring agents, flavoring agents, and preservatives can also be present.
  • Dye stuffs or pigments may be added to the tablets, for example, for identification or in order to characterize combinations of active doses
  • compositions that can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer such as glycerol or sorbitol.
  • the push-fit capsules can contain the active compounds in the form of granules, which may be mixed with fillers such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers.
  • the active compounds are preferably dissolved or suspended in suitable liquids, such as fatty oils, or liquid paraffin.
  • stabilizers may be added.
  • Powders are prepared by comminuting the compositions of the present invention to a suitable fine size and mixing with a similarly comminuted diluent pharmaceutical carrier such as an edible carbohydrate material as for example, starch. Sweetening, flavoring, preservative, dispersing and coloring agents can also be present.
  • a similarly comminuted diluent pharmaceutical carrier such as an edible carbohydrate material as for example, starch.
  • Sweetening, flavoring, preservative, dispersing and coloring agents can also be present.
  • Capsules are made by preparing a powder mixture as described above and filling formed gelatin sheaths.
  • a lubricant such as talc, magnesium stearate and calcium stearate can be added to the powder mixture as an adjuvant before the filling operation;
  • a glidant such as colloidal silica may be added to improve flow properties;
  • a disintegrating or solubilizing agent may be added improve the availability of the medicament when the capsule is ingested.
  • Tablets are made by preparing a powder mixture, granulating or slugging, adding a lubricant and disintegrant and pressing into tablets.
  • a powder mixture is prepared by mixing the compositions of the present invention, suitable comminuted, with a diluent or base such as starch, sucrose, kaolin, dicalcium phosphate and the like.
  • the powder mixture can be granulated by wetting with a binder such as syrup, starch paste, acacia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen.
  • a binder such as syrup, starch paste, acacia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen.
  • the powder mixture can be run through the tablet machine and the resulting imperfectly formed slugs broken into granules.
  • the granules can be lubricated to prevent sticking to the tablet forming dies by means of the addition of stearic acid, a stearate salt, talc or mineral oil.
  • the lubricated mixture is then compressed into tablets.
  • the medicaments can also be combined with free flowing inert carriers and compressed into tablets directly without going through the granulating or slugging steps.
  • a protective coating consisting of a sealing coat of shellac, a coating of sugar or polymeric material and a polish coating of wax can be provided.
  • Dye stuffs or pigments may be added to the tablets, for example, for identification or in order to characterize combinations of active doses.
  • the carrier comprises from about 0.1% to 99% by weight of the total composition.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Botany (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Obesity (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Mycology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

Cette invention se rapporte à une composition comprenant un mélange d'un phytostérol et/ou d'un ester de phytostérol et d'un ou de plusieurs tensioactifs. Les tensioactifs sont choisis dans le groupe constitué par des tensioactifs anioniques, cationiques, non ioniques et zwittérioniques. Le phytostérol est sélectionné dans le groupe constitué de sitostérol, campestérol, brassicastérol, stigmastérol, clionastérol et de mélanges de ceux-ci. Les esters de phytostérols sont des dérivés des phytostérols mentionnés. Cette invention concerne également un procédé de production de ces compositions, et des produits alimentaires sans matières grasses contenant ces compositions.
PCT/US2000/030350 1999-11-04 2000-11-03 Compositions de sterols reduisant le cholesterol, preparation et procede d'utilisation Ceased WO2001032031A2 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP2001534247A JP2004525856A (ja) 1999-11-04 2000-11-03 コレステロールを低下させるステロール組成物、調製及び使用方法
BR0015331-1A BR0015331A (pt) 1999-11-04 2000-11-03 Composições de esterol para a redução de colesterol, preparação e método de utilização
CA002388339A CA2388339A1 (fr) 1999-11-04 2000-11-03 Compositions de sterols reduisant le cholesterol, preparation et procede d'utilisation
AU14608/01A AU1460801A (en) 1999-11-04 2000-11-03 Cholesterol reducing sterol compositions, preparation and method of use
EP00976899A EP1225812A2 (fr) 1999-11-04 2000-11-03 Compositions de sterols reduisant le cholesterol, preparation et procede d'utilisation
CN00818085A CN1450863A (zh) 2000-11-03 2000-11-03 降低胆固醇的甾醇组合物、制备和使用方法
MXPA02004504A MXPA02004504A (es) 1999-11-04 2000-11-03 Composiciones de esterol que reducen colesterol, preparacion y metodo de uso.

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US16338399P 1999-11-04 1999-11-04
US60/163,383 1999-11-04
US19844900P 2000-04-19 2000-04-19
US60/198,449 2000-04-19

Publications (2)

Publication Number Publication Date
WO2001032031A2 true WO2001032031A2 (fr) 2001-05-10
WO2001032031A3 WO2001032031A3 (fr) 2001-12-06

Family

ID=26859603

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/030350 Ceased WO2001032031A2 (fr) 1999-11-04 2000-11-03 Compositions de sterols reduisant le cholesterol, preparation et procede d'utilisation

Country Status (7)

Country Link
EP (1) EP1225812A2 (fr)
JP (1) JP2004525856A (fr)
AU (1) AU1460801A (fr)
BR (1) BR0015331A (fr)
CA (1) CA2388339A1 (fr)
MX (1) MXPA02004504A (fr)
WO (1) WO2001032031A2 (fr)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1108365A3 (fr) * 1999-12-15 2002-04-17 McNEIL-PPC, INC. Alcools à chaine longue encapsulés
EP1108364A3 (fr) * 1999-12-15 2002-05-29 McNEIL-PPC, INC. Alcools à chaine longue en mélange dans des composés stéroliques
EP1177729A3 (fr) * 2000-08-03 2002-09-25 Härting, Thomas Francis Compositions pharmaceutiques et alimentaires contenant des "alcools de bois" et "stérols de bois" pour diminuer le cholesterol sérique
US6623780B1 (en) 2002-03-26 2003-09-23 Cargill, Inc. Aqueous dispersible sterol product
JP2004532272A (ja) * 2001-06-06 2004-10-21 エフ．ホフマン−ラ　ロシュ　アーゲー 新規医薬組成物
JP2006051030A (ja) * 2004-08-10 2006-02-23 Kraft Foods Holdings Inc 水分散性の植物ステロールおよび植物スタノールを目的とした組成物および方法
JP2006524047A (ja) * 2003-04-22 2006-10-26 ライシオ ベネコール オサケユイチア 苦味、酸味及び／又は渋味をマスクした食用製品
CN1293882C (zh) * 2003-01-15 2007-01-10 李安国 具有降低血清胆固醇作用的复方植物甾醇及其制备工艺
EP2042180A1 (fr) * 2007-09-28 2009-04-01 Swiss Caps Rechte und Lizenzen AG Préparations contenant du phytostérol
US20110236364A1 (en) * 2010-03-23 2011-09-29 Bromley Philip J Compositions containing non-polar compounds
US9078464B2 (en) 2008-02-06 2015-07-14 Edio Healthcare Ab Compositions of phytosterols with enhanced bioavailability
US9610276B2 (en) 2013-06-17 2017-04-04 Kgk Synergize, Inc. Compositions and methods for glycemic control of subjects with impaired fasting glucose
US9788564B2 (en) 2008-03-20 2017-10-17 Virun, Inc. Compositions containing non-polar compounds
US9861611B2 (en) 2014-09-18 2018-01-09 Virun, Inc. Formulations of water-soluble derivatives of vitamin E and soft gel compositions, concentrates and powders containing same
US10220007B2 (en) 2008-03-20 2019-03-05 Virun, Inc. Compositions containing non-polar compounds
US10335385B2 (en) 2010-06-21 2019-07-02 Virun, Inc. Composition containing non-polar compounds
CN110236196A (zh) * 2019-07-19 2019-09-17 陕西益恺生物科技有限公司 一种水分散性植物甾醇混合物粉剂及其制备方法
WO2020144439A1 (fr) * 2019-01-10 2020-07-16 Arkema France Composition d'huile végétale pour l'enrobage de particules
US11925665B2 (en) * 2016-09-27 2024-03-12 Guangxi Jiufu Biotechnology Co., Ltd Extract effective in treating drug addiction

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007097464A (ja) * 2005-10-04 2007-04-19 Tama Seikagaku Kk 丸剤製造に好適な組成物
KR101505064B1 (ko) 2013-05-07 2015-03-30 한국과학기술연구원 혈흔을 활용한 시토스테롤 대사이상증 판별 기술
CN107594506A (zh) * 2016-09-20 2018-01-19 福建奥正投资发展有限公司 亲水性脂类组合物与水基液体的组合，其制备及调配方法和应用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62186936A (ja) * 1986-02-13 1987-08-15 Asahi Denka Kogyo Kk ステリン乳化乃至可溶化組成物
US5244887A (en) * 1992-02-14 1993-09-14 Straub Carl D Stanols to reduce cholesterol absorption from foods and methods of preparation and use thereof
US6423363B1 (en) * 1997-08-22 2002-07-23 Lipton, Division Of Conopco, Inc. Aqueous dispersion
US6063776A (en) * 1998-05-26 2000-05-16 Washington University Sitostanol formulation with emulsifier to reduce cholesterol absorption and method for preparing and use of same
US6123978A (en) * 1998-08-31 2000-09-26 Mcneil-Ppc, Inc. Stable salad dressings
AU2426500A (en) * 1999-02-03 2000-08-25 Forbes Medi-Tech Inc. Method of preparing microparticles of phytosterols or phytostanols

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1108364A3 (fr) * 1999-12-15 2002-05-29 McNEIL-PPC, INC. Alcools à chaine longue en mélange dans des composés stéroliques
US6875443B2 (en) 1999-12-15 2005-04-05 Mcneil-Ppc, Inc. Encapsulated long chain alcohols
EP1108365A3 (fr) * 1999-12-15 2002-04-17 McNEIL-PPC, INC. Alcools à chaine longue encapsulés
EP1177729A3 (fr) * 2000-08-03 2002-09-25 Härting, Thomas Francis Compositions pharmaceutiques et alimentaires contenant des "alcools de bois" et "stérols de bois" pour diminuer le cholesterol sérique
JP2004532272A (ja) * 2001-06-06 2004-10-21 エフ．ホフマン−ラ　ロシュ　アーゲー 新規医薬組成物
US6623780B1 (en) 2002-03-26 2003-09-23 Cargill, Inc. Aqueous dispersible sterol product
CN1293882C (zh) * 2003-01-15 2007-01-10 李安国 具有降低血清胆固醇作用的复方植物甾醇及其制备工艺
JP2006524047A (ja) * 2003-04-22 2006-10-26 ライシオ ベネコール オサケユイチア 苦味、酸味及び／又は渋味をマスクした食用製品
JP2012191944A (ja) * 2003-04-22 2012-10-11 Raisio Benecol Oy 苦味、酸味及び／又は渋味をマスクした食用製品
JP2006051030A (ja) * 2004-08-10 2006-02-23 Kraft Foods Holdings Inc 水分散性の植物ステロールおよび植物スタノールを目的とした組成物および方法
EP2042180A1 (fr) * 2007-09-28 2009-04-01 Swiss Caps Rechte und Lizenzen AG Préparations contenant du phytostérol
US9078464B2 (en) 2008-02-06 2015-07-14 Edio Healthcare Ab Compositions of phytosterols with enhanced bioavailability
US10668029B2 (en) 2008-03-20 2020-06-02 Virun, Inc. Compositions containing non-polar compounds
US9788564B2 (en) 2008-03-20 2017-10-17 Virun, Inc. Compositions containing non-polar compounds
US10220007B2 (en) 2008-03-20 2019-03-05 Virun, Inc. Compositions containing non-polar compounds
US9320295B2 (en) * 2010-03-23 2016-04-26 Virun, Inc. Compositions containing non-polar compounds
US20110236364A1 (en) * 2010-03-23 2011-09-29 Bromley Philip J Compositions containing non-polar compounds
US10335385B2 (en) 2010-06-21 2019-07-02 Virun, Inc. Composition containing non-polar compounds
US9610276B2 (en) 2013-06-17 2017-04-04 Kgk Synergize, Inc. Compositions and methods for glycemic control of subjects with impaired fasting glucose
US9861611B2 (en) 2014-09-18 2018-01-09 Virun, Inc. Formulations of water-soluble derivatives of vitamin E and soft gel compositions, concentrates and powders containing same
US10285971B2 (en) 2014-09-18 2019-05-14 Virun, Inc. Formulations of water-soluble derivatives of vitamin E and soft gel compositions, concentrates and powders containing same
US11925665B2 (en) * 2016-09-27 2024-03-12 Guangxi Jiufu Biotechnology Co., Ltd Extract effective in treating drug addiction
DE112017004827B4 (de) 2016-09-27 2025-10-30 Guangxi Jiufu Biotechnology Co.,Ltd Extrakt mit pharmazeutischer Entgiftungswirkung und Herstellungsverfahren dafür
WO2020144439A1 (fr) * 2019-01-10 2020-07-16 Arkema France Composition d'huile végétale pour l'enrobage de particules
FR3091706A1 (fr) * 2019-01-10 2020-07-17 Arkema France Composition d’huile végétale pour l’enrobage de particules
CN113301986A (zh) * 2019-01-10 2021-08-24 阿科玛法国公司 用于包覆粒子的植物油组合物
CN113301986B (zh) * 2019-01-10 2023-10-20 阿科玛法国公司 用于包覆粒子的植物油组合物
CN110236196A (zh) * 2019-07-19 2019-09-17 陕西益恺生物科技有限公司 一种水分散性植物甾醇混合物粉剂及其制备方法

Also Published As

Publication number Publication date
AU1460801A (en) 2001-05-14
CA2388339A1 (fr) 2001-05-10
WO2001032031A3 (fr) 2001-12-06
MXPA02004504A (es) 2002-09-02
BR0015331A (pt) 2002-07-09
EP1225812A2 (fr) 2002-07-31
JP2004525856A (ja) 2004-08-26

Similar Documents

Publication Publication Date Title
WO2001032031A2 (fr) Compositions de sterols reduisant le cholesterol, preparation et procede d'utilisation
HUP0300878A2 (hu) Vízben diszpergálható kapszulázott szterinek
CA2332450A1 (fr) Compositions de phytosterol esterifie et hydrogene et leur utilisation dans des denrees alimentaires, des boissons, des produits pharmaceutiques, des aliments fonctionnels et analogue
WO2021119844A1 (fr) Formulations émulsifiantes de cannabinoïdes et/ou d'extraits de cannabinoïdes
RU2501328C2 (ru) Дисперсии фитостеролов
WO2000045770A2 (fr) Preparations de lecithine comprimees
EP1729595B1 (fr) Fruit artificiel
US20040156887A1 (en) Stabilized dispersion of phytosterol in oil
CA2808710A1 (fr) Compositions alimentaires fonctionnelles et procedes associes
WO2001032036A1 (fr) Compositions de stanol reduisant le cholesterol, preparation et procede d'utilisation
WO2004064805A1 (fr) Preparations cochleaires de nutriants fragiles
WO2007024770A2 (fr) Procedes permettant de fabriquer une poudre de cacao fortifiee au phytosterols et produit ainsi obtenu
EP3258789B1 (fr) Mélanges d'huiles et leur utilisation dans des compositions
CN1450863A (zh) 降低胆固醇的甾醇组合物、制备和使用方法
JP2000026283A (ja) 油性組成物を含有した粉末組成物
CA2451146A1 (fr) Procede de fabrication de poudre a ecoulement libre renfermant des sterols dispersibles dans l'eau
AU2006263577B2 (en) Compositions to improve the bioavailability of polymethoxyflavones and tocotrienols for treatment of cardiovascular disease
EP0972513B1 (fr) Procede de preparation de poudre emulsionnee
CN101991127B (zh) 一种包含植物甾醇和谷维素的粉状混合物及其制备方法
CN1479581A (zh) 降低胆固醇的甾烷醇组合物、制备和使用方法
WO2005074720A1 (fr) Composition et utilisation d'une poudre de corps gras a point de fusion eleve afin d'induire une sensation de satiete prolongee
AU2002317786A1 (en) Stabilized dispersion of phytosterol in oil
MXPA06010015A (en) Artificial fruit

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

WWE Wipo information: entry into national phase

Ref document number: 2388339

Country of ref document: CA

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2001 534247

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: PA/a/2002/004504

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 2000976899

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 008180857

Country of ref document: CN

WWP Wipo information: published in national office

Ref document number: 2000976899

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 2000976899

Country of ref document: EP