MXPA02004511A - Cholesterol reducing stanol compositions, preparation and method of use. - Google Patents

Abstract

A composition comprising a mixture of a phytostanol and or phytostanol ester and a surfactant(s). The surfactants are selected from the group consisting of anionic, cationic, nonionic, and zwitterionic surfactants. The phytostanol is selected from the group consisting of sitostanol, campestanol, 22,23 dihydrobrassicastanol, and mixtures thereof. The phytostanol esters are derivatives of the aforementioned phytostanols. The invention is also directed to a method of making the disclosed compositions, and to non fat containing food products including the disclosed compositions.

Description

CHOLESTEROL REDUCING STENOL COMPOSITIONS, PREPARATION AND METHOD OF USE FIELD OF THE INVENTION This invention relates to vegetative sienol compositions and their derivatives for the reduction of cholesterol absorption. More particularly, the invention provides compositions comprising a phytostanol and / or an ester of phytostanol and surfactants, which are useful for reducing the absorption of cholesterol. The invention also relates to methods for preparing said compositions to reduce the absorption of choleslerol.

BACKGROUND OF THE INVENTION Although cholesferol is a nuírienle essential for humans, it is well known that it is a leading cause of death in the U.S.A. and most of the countries in the world. Many foods eaten in the year are also known as coleserol. Cholesterol can be absorbed once it reaches the thin intestine, which produces an increase in the level of cholesterol in the serum. It is well known that cholesterol in serum is deposited in various parts of the circulatory system, for example, in soft tissues. Prolonged accumulation or development of cholesterol deposits leads to alerosclerotic disease.

The reduction of the cholesterol content in the food and also the inhibition of the absorption of cholesferol have made possible the reduction of serum cholesterol levels. One of the areas that has been explored to control serum cholesterol level is the use of dietary supplements such as chloresphiramine resin, probucol, co-sodium HCl, nicoinic acid, mevinolin, pecphine, guar gum and oat bran. Another area that has received considerable attention has been the development of food additives that reduce the absorption of cholesterol in the small intestine. The prevention of cholesterol absorption results in lower blood cholesterol levels and thus helps prevent the formation of atherosclerotic plaques. It has been found that vegetale eserols are particularly effective in reducing serum cholesterol levels. In particular, in studies conducted using befa-siiosferol, it was found that it produces significant reductions (17%) in the amount of cholesterol in the blood (Farguhar J.W. et al., Circulation, 14, 77-82 (1956)). However, large doses of beta-siioserol, 12-18 grams per day, are required. This is a major impediment to the use of bela-siioserol to reduce cholesterol. It has also been found that a related class of compounds, vegetale silanols (vegetative saíred vegetables), is effective in reducing the absorption of cholesterol. It has been posited that the vegetable spheres block the absorption of choleslerol by compiling with it for the formation of bile acid micelles. It is believed that, as a result of this competition, it spreads vegetative spheres and cholesterol, the vegetal spheres displace the cholesterol of the micellar phase and thus prevent its absorption in the small intestine. Estanols and plant sterols have represented particularly cross-sectional classes of compounds for use in reducing the level of serum cholesterol, as they are natural components of vegetable fats and oils. In addition, plant stanols and sterols are absorbed in very small amounts compared to the absorption of bile and cholesterol from the diet. In fact, sitosanol is considered practically non-absorbable, that is, in less than 5%. Although plant sterols and steels are attractive as inhibitors of choleslerol absorption, they have been found difficult to formulate. A major factor in this difficulty has been the fact that the vegetable stanols are virtually insoluble in water. Considerable efforts have been made to develop vegetative sterol or stanol preparations that can be easily formulated with food products for the consumer. The patent of E.U.A. No. 5,244,887 is directed to vegetable stanol food additives to reduce the absorption of cholesterol in the gastrointestinal tract. The highest effectiveness was obtained when the stanols were uniformly distributed in a finely divided form throughout the product or food beverage to which they were added. This was done by dissolving the silanols or by suspension of the silanols in an emulsion. The solubilization agents mentioned for tin cans include vegetable oil, monoglycerides, diglycerides, triglycerides, tocopherols and the like, and mixtures thereof. Tin suspension or emulsions include water, alcohols, polyols and other edible compounds. Dispersing agents can be used to aid in the formation of suspensions, such as lecithin, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 85, sodium laurisulfate and the like. Stanol food additives are used with foods that contain cholesterol such as meats, eggs and dairy products. EP 0 897 671 discloses aqueous dispersions of high melting lipids such as plant sterols, with emulsifiers which are not sterile. Emulsifiers used to disperse the high melting point lipids include polyglycerol and Tweens esters, especially polysorbate 60. Mono- and diglycerides are also mentioned as suitable emulsifiers. The dispersions have a reduced size in the order of 15 microns or less. It is said that dispersions are useful in spreads and other food products. Additionally, dispersions provide structure to food products and their use can apparently allow the reduction or elimination of saturated fats and trans fatty acids. There is a continuing need for formulations that reduce serum cholesterol levels, preventing or significantly reducing cholesterol absorption. Said formulations may conveniently be delivered in a variety of ways to individuals, for example as an additive for food products or as a pill for oral administration. In addition, for the formulations to be more effective in reducing cholesterol absorption, they must reach the gastrointestinal tract so that they can be rapidly and efficiently solubilized in the micellar phase thus preventing the absorption of cholesterol. It has now been discovered that formulations comprising a vegetable stanol or a vegetable eslanol ester and one or more surfactant agents are effective in inhibiting the absorption of cholesterol.

BRIEF DESCRIPTION OF THE INVENTION Compositions are described for inhibiting the absorption of cholesterol. The compositions comprise a plant stanol and / or a plant stanol ester and one or more surfactants. The surfactants are selected from the group consisting of anionic, cationic, nonionic and zwitterionic surfactants. Examples of plant silanols that may be employed include sitosanol, campestanol, 22,23-dihydrobenicasinol and clionasinol. The compositions of the present invention provide an effective method for reducing cholesterol without any adverse side effects. The compositions of the present invention can be used as food additive compositions to reduce the absorption of * cholesterol from food. The food additive composition can be used in small amounts making it convenient to use and also a cheap method to reduce the absorption of cholesterol. The food additive compositions of the present invention are stable in storage for extended periods. Food additive compositions can be added with food before, during, or after cooking. The food additive compositions can be added to food products during their production before they came to the consumer. Inadvertently, the compositions of the present invention can be used in foods that do not contain fat. The present invention also contemplates various combinations of the above surfactant agents and a phytostanol and / or a phytosanol ester, administered orally in any usual solid form such as in pills, tablets, capsules or powders, including sustained release preparations.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the use of plant stanol and / or plant stanol ester compositions, which inhibit the absorption of cholesterol. More particularly, the invention relates to the formation of water-soluble or dispersible systems of stanol and / or ester of sienol, comprising a vegetable spherol and / or a vegetal spherol ester and anionic, cationic, nonionic or zwitterionic surfactant systems , which reduce the absorption of cholesterol.

The terms "phytosanols" and "silanols" are used interchangeably herein. The term "silanols", as used herein, refers to plant sterol derivatives in which all the carbon-carbon bonds of the rings are saturated. The main steels of the present invention are those which are composed of 28 to 29 carbon atoms. Four main plant stanols are beta-siiostanol, campestanol, 22,23-dihydrobasicastanol and clionastanol, "The Lipids", Vol. 1, Deuel, H.J., Jr., Iníerscience Publishers, 1951, N.Y., pp. 348-361. These four esanols have the following structure: wherein R is CH3 for campestanol and its epimer, 22,23-dihydrobrasicasfanol, and wherein R is C2Hs for chitosanol and its epimer, clionaslanol. The silanols of C28 campesíanol and 22,23-dihydrobasicasfanol differ only by their steric configuration at C24. Likewise, the C29 stanols differ only because of the steric configuration in C24. Alkalimative nomenclature for clionastanol is (3-beta, 5-alpha, 24S) -sigmasf-5-an-3-ol; for sitosanol is (3-befa, 5-alpha, 24R) -stigmasi-5-an-3-ol; for campestanol is (3-beta, -5alpha, 24R) -ergosf-5-an-3-ol; for 22,23-dihydrobasicastanol is (3-beta, 5-alpha, 24S) -ergost-5-an-3-ol. It will also be appreciated that modifications of the vegetable steels will also be within the scope of the present invention, for example small side chains. The terms "fifosanol ester" and "esfanol esters" are used interchangeably herein. The term "stanol ester", as used herein, refers to vegetable silanols that have been modified to form a plant stanol ester derivative. These derivatives are well known in the art and are described in the U.S.A. Nos. 4, 588,717, 5,270,041, and 5,958,913, in International applications WO 98/06405, and WO 99/25362, European application EP 911385, and in H.Gylling et al., Journal of Lipid Research, 40, 593-600 (1999) , whose descriptions are incorporated herein by reference. Tinnels are found in small amounts in nature in many fields, for example wheat, barley and corn. As a result, this is not a particularly good source of large amounts of stanols due to the high cost associated with extricating sufficient quantities of spheres. A more cost-effective method to obtain spheres in great quantities is through hydrogenation of the much more abundant plant sterols. Many methods of hydrogenation of plant sterols are well known to those of ordinary skill in the art. For example, plant sterols can be converted to sphenoles by means of hydrogenation techniques employing Pd / C cacifier in organic solvents (Augustine, RL et al., Org. Prep. And Proc. 1: 107-109, (1969) ). A large number of inexpensive sources of vegetative eserols are known. Esias include vegetable oils, vegetable oil pellets, vegetable oil distillates, and other sources of vegetable oils such as wood pulp byproducts. For example, in the patent of the U.S.A. No. 4,420,427 a preparation of steels is taught from vegetable oil sediment using solvents such as methanol. Steles isolated from plant sources are usually mixtures of several different stellar; the hydrogenation leads to a mixture of the corresponding stenoles. Stereos, which differ only by the degree of unsaturation in the carbon bonds of the ring or side chains, after hydrogenation usually produce silanols that differ only in epimeric centers such as carbon C24. A preferred plant stanol, sitostanol, can be obtained by hydrogenation of sitoserol. Sifoslerol can be obtained from cold compressed wheat germ oil, soy extract or rice extract (it will be appreciated that natural sitosterol contains approximately 40% alpha-sitoserol and approximately 60% beta-sipholsterol; as sitosterol bela can be used to form sitostanol for use in the present invention). The particularly preferred stanol comprises a minimum of 63% by weight of sitostanol, a maximum of 35% by weight of peasantol and a minimum of 93% by weight of sitostanol and campestanol. It should also be noted that the hydrogenation of vegetable starrals can leave a certain amount of unreacted sterals. However, hydrogenation produces mostly eslanol. For the purposes of the present invention, it is acceptable to have small residual amounts of unreacted sterals, generally less than about 10%. It will be very clear to the person with average knowledge in the matter that the presence of residual spherical presence can be reduced substantially (< 1.5%) depending on the solvents and the reaction conditions used. However, if it is desired to have a stanol free of unreacted stearates, then a pure sterol preparation can be employed. The surfactant agents to be employed according to the invention can be anionic, cationic, nonionic, zwitterionic and mixtures thereof. Suitable anionic lens agents include AOT, also known as sodium diocylylsulphosuccinate or sodium docusate, ammoniacal glycyrrhizin and sodium eslearoyl lactylate. Nonionic surfactants include polyoxyethylene castor oil (cremophor castor oil Polyoxyl 35), polyethylene glycol "PEG" (low molecular weight 1000 to 4000), diacetyl-lacphic acid of mono- and diglyceride esters, diacetyl diacetic acid esters of mono- and diglycerides, monosodium phosphate derivatives of mono- and diglycerides, ethoxylated mono- and diglycerides, polyethylene glycol stearate (8), polyethylene glycol stearate (40), sorbitan esters of fatty acids, quillaja saponin, copolymers of block of ethylene oxide and propylene oxide, violin E TPGS (polyethylene glycol 10OO-d-alpha-tocopheryl succinate), fatty alcohols and sucrose fatty acid esters such as sucrose stearam, sucrose distearate, saccharose palmitate. Preferred fatty alcohols include, without limitation, the following: 1-decanol (CH3 (CH2) 8CH2OH), also known as n-decyl alcohol, 1 -dodecanol (CH3 (CH2)? Or CH2OH), also known as dodecyl or lauryl alcohol , 1-ephradecanol (CH3 (CH2) i2CH2OH), also known as myristyl alcohol, 1-hexadecanol (CH3 (CH2) i4CH2? H), also known as cetyl or palmityl alcohol, 1-okadecanol (CH3 (CH2) i6CH2OH) , also known as stearyl alcohol, 9-ociadecen-1-ol (CH3 (CH2) 7CH = CH (CH2) 7CH2OH), also known as oleyl alcohol, 1-eicosanol (CH3 (CH2) i8CH2OH), also known as arachidyl alcohol , 1-docosanol (CH3 (CH2) 20CH2OH), also known as behenyl alcohol, 1-hexacosanol (CH3 (CH2) 24CH2? H), 1-ocfacosanol (CH3 (CH2) 26CH2? H), also known as octacosyl alcohol ( wheat leaf wax), 1-triaconanol (CH3 (CH2) 28CH2OH), also known as melisyl alcohol (beeswax as stearol). A particularly preferred fatty alcohol is 1-octadecanol. Zwitterionic agents include hydroxylated lecithin and the like. Other anionic surfactants such as sodium stearate can also be used, sodium palmilafo, sodium laurate, sodium myristate, sodium linoleap and pofasium oleander. Additional non-ionic surfactants which may be included in the compositions of the present invention, include polyglycerol and Tweens esters, polysorbamide 20 (Tween 20), polysorbate 40 (Tween 40), polysorbate 60 (Tween 60), polysorbamide 80 (Tween 80 ), polysorba 85 (Tween 85), fatty acids such as oleic acid (C-? H33COOH), stearic acid (C-? 7H36COOH) and palmitic acid (C15H3? COOH); triglycerides CH3 (CH2) 6COOH and CH3 (CH2) 8COOH and mixtures thereof (e.g., MCT oil). Also, nalural 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 can be employed in the compositions of the present invention.; succinoglucan and hyaluronic acid. Synthetic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, may also be employed in these compositions. Other fatty acids which may be employed in the present invention include caprylic, capric, lauric, myristic, myristic, palmifollic, oleic, ricinoleic, linoleic, linolenic, eleosleary, arachidic, arachidonic, behenic, and erucic acid. The fatty acids of the present invention can be derived from natural or synthetic fatty acids; they may be unsaturated or unsaturated, including positional and geometric isomers, depending on the desired physical properties, for example liquid or solid.

In a preferred embodiment, the composition of the present invention comprises a mixture of phytosanol and / or an ester of phyllostanol and a surfactant selected from the group consisting of docusa sodium, ammonia glycyrrhizin, polyoxyethylene castor oil, polyalkylene glycol, esters of mono- and diglycerides of diacetyl-lactic acid, mono-and diglyceride esters of acetyl artaric acid, monosodium phosphate derivatives of mono- and diglycerides, mono- and diglycerides ethoxylated, saponin quillaja, block copolymers of ethylene oxide and oxide of propylene, vitamin E TPGS, hydroxylated lecithin, and mixtures thereof. The 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 stearate (8), polyethylene glycol stearate (40), fatty acid esters of sucrose, Tween, and mixtures thereof. A preferred embodiment of the present invention comprises a mixture of a phytosanol and / or an ester of phytostanol and fatty acid alcohol, preferably octadecanol. Another preferred embodiment of the present invention comprises a mixture of phytostanol and / or an ester of phytosanol, Tween 60 and PEG. Preferred embodiments will include a phytosanol and / or a phytospnane ester, fatty acid alcohol and sucrose fatty acid ester such as Crodesia. A preferred embodiment of the present invention provides a method for reducing the absorption of cholesterol in humans, which comprises orally administering an effective amount of the composition of the present invention. The invention also provides a method for reducing serum cholesterol levels, which comprises administering a mixture of phytostanol and / or a phytostanol ester and one or more surfactants. In another embodiment of the present invention, emulsifiers may be used in the formulation of stanol and / or stanol ester dispersible systems. Preferred emulsifiers include a variety of phospholipids, phosphatidylcholine (PC), phosphatidylenealamine (PE), N-acylphosphatidyl-ethanolamine (NAPE), phosphatidylserine (PS), phosphatidylinositol (Pl), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidic acid (PA), and plasmalogen. These and other phospholipids are described, for example, in Szuhaj and List (eds.), "Lecithins", American Oil Chemisls Society (1985) ("Szuhaj and List"), incorporated herein by reference in their language. The phospholipids can be used individually or in various combinations, and can be obtained from "natural" sources (for example soy lecithin) or from chemical synthesis. The phospholipids may be in the form of relatively purified mixtures of phospholipids and other particles (for example, raw commercial lecifins obtained from the refining of soybean oil and other vegetable oils such as sunflower and canola), or they may be purified in several grades. In addition, phospholipids, which include those found in raw soy lecithins or you will hear raw commercial lecithins, can be chemically modified. Lecithins, other preparations of phospholipids or individual phospholipids purified from natural sources or obtained by chemical synthesis, contain one or more functional groups susceptible to chemical modification, for example, carbon-carbon double bond groups, esters, phosphonate esters, amines and hydroxyl The chemical modification of phospholipids may be compatible with the methods herein. In this manner, phospholipids that have been acetylated, hydroxylated, hydrolyzed (for example to produce lysophospholipids), hydrogenated, halogenated, phosphorylated, sulphatized, epoxidized, ethoxylated, or otherwise modified, are potentially useful in the methods of the present and are included within the meaning of the term "phospholipids" as used herein. Several natural and syngeneic phospholipids that include several types of leciiins can be obfener commercially, for example, Ullralec from ADM Corp., and other lecithins can be obtained from CALBIOCHEM®, La Jolla, California, E.U.A. and from SIGMA® Chemical Company, St. Louis, Missouri, E.U.A. In common use, the term "lecithin" refers to the complete fraction of phospholipids obtained from natural sources such as soybean, cottonseed, corn, wheat germ, oats, barley, sunflower, rapeseed, canola, flaxseed, peanut, almond of palm, egg yolk, milk and brain. Generally, such fractions include a mixture of polar and neutral lipids with a polar lipid content (defined by insolubility in acetone) of at least 50%. The technique has also used the term "lecithin" as the common name for phosphatidylcholine. As used herein, the term "lecithin" refers to the first use, ie, the entire fraction of phospholipids obtained from selected vegetable oils, or other appropriate sources. See chapter 2 of Szuhaj and List. However, it is also to be noted that phosphatidylcholine is a suitable phospholipid for use in the methods herein, either alone or in combination with other phospholipids. Commercial soy lecithin, a preferred source of phospholipids, is obtained from the refining of soybean oil. Crude soybean oil generally contains 1.0 to 3.0 weight percent phospholipids, approximately. When raw oil is refined, the first step is usually to remove the phospholipids. This step, often called "degumming", is done by first adding water to the crude oil. Water hydrates phospholipids and makes them less soluble in the oil. Then the denser phospholipids and water are separated from the less dense oil, typically by means of centrifugation. The removal of water from the dense phase results in a product having approximately equal amounts of phosphatidylcholine, phosphatidylethanolamine, and inositol phosphatides. Partially refined soybean oil is commonly added back to produce a liquid product that is fluid at ambient temperature (sometimes called "fluidized lecifin"). The commercial fluid soy lecithin contains from 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, starches and water. The rest of the commercial soy lecithin is soybean oil. Various lecithin powders enriched in phospholipid content are commercially available and can also be used in the present methods. These lecithin powders are also within the scope of the term "lecithin" as used herein. The powders are typically derived by fractionation, for example fractionation with acetone, from crude lecithins such as commercial soy lecithin, and may contain from about 60% to over 95% phospholipid. Another commercial source of phospholipids is the class of products resulting from the modification of soy lecithin to improve its hydrophilic properties. Several approaches have been used to effect such modifications. For example, soy lecithin can be modified chemically or enzymatically, for example by reaction with maleic anhydride. Certain components can be removed from commercial soy lecithin. Alternatively, another approach is to add several components to commercial soy lecifin, for example nonionic emulsifiers. Such emulsifiers include, without limitation, polyoxyalkylene monoglyceride, polyoxyalkylene diglycerides, and polyoxyethylene derivatives of partial fatty acid esters. These modified lectins are also included in the term "lecithin" as used herein. 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 bound to the phospholipids and lecithin glycolipids, which can be carried out by reaction with hydrogen peroxide and a weak acid such as lactic acid. Although not wishing to be bound by theory, it is believed that the hydroxylation is not specific and can occur at any double bond within any of the lipids. The degree of hydroxylation is usually about 10%, but it can be varied by methods known to the person of ordinary skill in the art. The compositions of the present invention are preferably formed in a fine dispersion using melt processing. A particular preferred method of processing in molten state comprises dry mixing a phytosanol and / or a phytostanol ester and one or more surface active agents in a stirring device such as a mechanical stirrer, cutting mixer, vibrating mixer or sonicator. The mixture is then heated to a temperature sufficient to melt it, but not so high as to degrade phytosolol, phytostanol ester or surfactants. Then, the resulting mixture is rapidly cooled, for example by liquid nitrogen, to form a salt-like material. Although not wishing to be bound by theory, it is believed that the step of melt mixing the phytostanol and / or phytostanol ester and one or more surfactants before rapid cooling facilitates the formation of a composition that is in a finely dispersed state. which is able to reach the thin intestine, thus being able to inhibit the absorption of cholesterol. An aliemative variation of the melt processing described above comprises the addition of one or more surfactants to a molten mixture of phytostanol and / or ester of fiiosanol. This may be convenient in cases in which the surface-active agents are thermally unstable and do not resist prolonged heating at high temperatures.; that is, the residence time of the surfactants is reduced by their addition to the melted mixture of fifosphanol. Once the surfactants have been added to the melt, the mixture can be treated in a manner similar to that described above. An additional altemative process for mixing in the molten state for the formation of the compositions of the present invention is high pressure fusion. This process is also convenient for mixing surfactants and phytosanol and / or heat-sensitive phyllostanol esters. It has been discovered that by using a mixing or compression medium that allows to increase the pressure on the ingredients, the surfactant agents, the phytosanol and / or the phytostanol esters, will be mixed in the molten state at room temperature. Therefore, homogeneous mixtures of surfactants and phytostanol and / or heat-sensitive phyllostanol esters can be formed, avoiding temperatures in which the thermal decomposition of the ingredients could occur. One mode of high-pressure melting is roll compaction, where the heat-sensitive agents and the phytostanol and / or the phytostanol ester are mixed as described above. The mixture is then compressed using a roller, in such a way that the pressure exerted on the mixture is sufficiently high to cause the flow of the ingredients and produce surface sintering of the mixture. An additional mode of high pressure fusion is extrusion. For example, in an extrusion process, a powder mixture of loosely compacted surfactants and phytosanol and / or phyllosanol ester is continuously driven along a helix through regions of high pressure and controlled temperature. The shearing forces of the propeller melt and mix the material in a continuous stream of molten material which is then forced through a matrix. The mixture resulting from the high pressure melting process is typically a soft ductile solid material which can be further processed by cooling to solidify it, followed by chip breaking or grinding to form a uniform powder for use in the formation of products such as those described at the moment. Mixtures of a phytosolol and / or phytostanol ester and one or more surfactants can also be processed using solution processing or steric stabilization. The use of solution processing is particularly effective for use with surfactants that are thermally stable. In general, the phytostanol and / or phytosolol ester and one or more surfactants are mixed dry, 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 a dispersible amorphous solid form. The spherical bil tation provides an effective method for forming a dispersible solid of a phytostanol and / or phytostanol ester and one or more surfactants. A fine dispersion of a phytosanol and / or phytosanol ester is added to the water containing the resistive agents. Agents active in water help keep the splanol or silanols in suspension. Once a finely divided suspension is formed, the water is removed by evaporation leaving a more easily dispersible solid form. Preferred embodiments of the present invention include a mixture of about 10 to about 99.99 weight percent of a phytosanol and / or phyllostanol ester, and about 0.01 to about 90 weight percent of one or more surfactants, preferably from about 40 to about 95 weight percent of a phytosanol and / or phytostanol ester, and from about 5 to about 60 weight percent of one or more surfactants, and about 95 weight percent of a Phostanol and / or phytostanol ester, and about 5 weight percent of one or more tensio-active agents. In a preferred embodiment of the present invention, the compositions herein comprise a phytosanol and / or phyllosanol ester and at least two surfactant agents. Said mixture comprises from about 10 to about 99.99 percent by weight of a phytostanol and / or phytostanol ester, and the sum of at least two surfactants is from about 0.01 to about 90 percent by weight; preferably said mixture comprises from about 40 to about 95 weight percent of a phytosolol and / or phytosanol ester, and the sum of at least two surfactants is from about 5 to about 60 weight percent; and about 95 weight percent of a phyllosanol and / or phytostanol ester is most preferred and the sum of at least two surfactants is about 5 weight percent. The desirable characteristics for food additive compositions for reducing cholesterol absorption include the absence of side effects, efficacy without compound absorption, stability to cooking temperatures, stability in storage and in oxidizing media, low cost, availability and requirements. of small doses. The compositions of the present invention can be administered orally in a variety of forms: uncoated tablets, tablets coated for example with film, sugar or gelatin; chewable tablets, swallowable tablets (capsules), effervescent lablettes, immediate-release tablets, sustained-release tablets (controlled or modified); soft gelatin capsules, whether liquid (non-aqueous) or paste (suspension); hard capsules of gelatin powder (granulation), globule, tablet, liquid, semisolid, sprayed (immediate or controlled release); oral liquids such as aqueous suspensions or emulsions; bags (packages) in powder, granule or spray (immediate or controlled release). Other forms for administering the compositions of the present invention include syrup, fruity drinks or fruit gelainas. It can be said that although the composition of the invention can be used in various embodiments, a preferred embodiment is when the compositions herein are evenly distributed in finely divided form throughout the product or food beverage to which they are added. The compositions of the present invention can be added to produce or food beverages before being purchased by the consumer for consumption. Alfematively, the compositions of the present invention can be purchased in bulk or in individually wrapped packages, for example 250 gram portions. A portion of the bulk form, for example 250 grams, or the contents of a package, can be added to a glass of hot or cold water or another beverage, and stirred to dissolve the contents before consumption. Typical beverages include the following, instant iced tea at Orange Pekoe, English Breakfast, Passion Fruií and Hisbiscus Flavors, powdered beverages such as Crystal Light and Contry Time Lemonade, Insíant leed Coffee in flavors such as Mocchacchino, Hazelnut, French Vanilla, and Hot Chocolate and Fruif Smooíhies. The compositions of the present invention can also be included in minidulces. The minidulces will typically be consumed after any of the meals of the day. The minidulces will typically contain between 25 and 60 calories and 1 to 3 grams of fat. The minidulces include the following varieties: chewable chocolates; chewy candies; solid candies for example of cinnamon flavor, butter, coffee and fruit; chocolate truffles teles like dark solid chocolate on the outside, filled with hazelnut cream, Irish cream or cappuccino cream; toasted sandwiches; cookies in peanut butter, chocolate chips or gingerbread cookies; miniafurs in granola / nutrient bars such as oatmeal and peanut butter covered with chocolate; chewable breath mints; meltable mint products; and minibudin. Mini-candies can be prepared in individually wrapped packages or in larger containers for multiple uses. The method by which the novel feed additive composition, ie, the sienol and / or ester of sienol and one or more skin sensitizing agents, is used to reduce the absorption of cholesterol from food and beverages includes the step of mixing uniformly the composition of food additive with food and beverages. In a preferred method of mixing the indicated food additive with foods and beverages containing cholesterol, the food additive is added in such a way that the amount of silanols in the food additive is in a ratio of about 1: 1 by weight to cholesterol contained in food and beverages. Thus, for a food additive composition comprising 25% of tin cans and a food containing approximately 0.1% cholesterol (for example a hamburger), the ratio of food additive to food prodrug is about 1: 250 in weight. The food additive composition of the invention can be mixed with food by a step selected from the group consisting of infusion, injection, mixing, kneading, dipping, spraying, surface application (for example by brushing and pringing), cooked in oil which contain the food additive of the invention, and combinations thereof. The preferred steps for mixing the food additive of the invention with ground meat are kneaded and mixed; for pieces of meat such as steak, chicken breast and shredded meat, cut or sliced, the preferred steps are injection, infusion, spraying, immersion and surface applications such as pringing and marinating. Two preferred steps for incorporating the food additive of the invention with beverages are combined and mixed. The compositions of the present invention will be used as food additives in foods such as meats, eggs and dairy products. Generally, when used as food additives, the compositions of the present invention do not substantially contribute to the flavor of the food product. Therefore, the compositions of the present invention can be used in food products without compromising the taste of the food products. The compositions of the present invention can also be formulated into fine particles that can be dusted onto other food products, for example dairy products such as ice cream or candy. The compositions of the invention can be administered to any animal. First among such animals are mammals, for example humans, although the invention is not considered limited in this regard. The dose administered will depend on the age, health and weight of the recipient, the type of concurrent delivery, if applicable, the frequency of irradiation and the nature of the desired effect. The compositions of the present invention can be administered orally in any of the usual solid forms such as pills, tablets, capsules or powders, including sustained release preparations. The term "unilary dosage form" as used in this specification and the claims, refers to physically discrete units for administering in individual or multiple doses to animals, each unit containing a predetermined amount of active material, esius, fifosphanol and / or phytostanol ester, together with one or more surfactants and a vehicle. The amount of active material is calculated to produce the desired therapeutic effect by administering one or more of said units. Of course, it is understood that the exact level of tracking will depend on the history of the case of the animal being raped, for example human. The precise level of treatment can be determined by a person with average knowledge in the field without excessive experimentation. The required dosage of phytoslanol and / or phytostanol ester varies with the severity of the condition and the duration of the treatment. Unit doses may range from about 0.01 mg / kg to about 500 mg / kg (the unit designated "mg / kg" as used herein, refers to mg of phytostanol and / or phyllosanol ester per kilogram of body weight) , preferably from about 0.1 mg / kg to about 125 mg / kg, with six daily doses, preferably four doses per day. Preferably, the doses are administered at mealtime. The doses may be administered orally in any suitable unit dosage form such as pill, tablet and capsule. I know they prefer gelatin capsules. As used herein, the term "carrier" denotes a solid or liquid encapsulant filler, diluent or substance. Some examples of the substances that can be used as vehicles are sugars such as lactose, glucose and sucrose.; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate; powdered tragacanth; malt; jelly; talcum powder; stearic acid; magnesium stearate; calcium sulfate; vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and cocoa oil; polyols such as propylene glycol, glycerin, sorbiol, mannitol and polyethylene glycol; agar, alginic acid; pyrogen-free water; isotonic saline solution; ethyl alcohol and phosphate buffer solutions, as well as other non-toxic compatible substances used in the preparation of formulations. Wetting agents and lubricants may also be present such as sodium lauryl sulfate and coloring agents, flavoring agents and preservatives. Dyes or pigments can be added to the tablets, for example, to identify or characterize combinations of active doses. Other preparations that can be used orally include snap-fit capsules made of gelatin, and also sealed soft capsules made of gelatin and a plasticizer such as glycerol or sorbitol. Pressure-adjusting capsules can contain the active compounds in the form of granules which can be mixed with fillers such as lactose, binders and starches, and / or lubricants such as talc or magnesium stearate and optionally stabilizers. In soft capsules, the active compounds are preferably dissolved or suspended in suitable liquids such as fatty acids or liquid paraffin. In addition, stabilizers can be added. The powders are prepared by mixing the compositions of the present invention to a suitable fine size and mixing them with a similarly milled diluting pharmaceutical carrier, such as a comixible carbohydrate material, for example starch. Sweetening, flavoring, preservative, dispersing and coloring agents may also be present. The capsules are made by preparing a powder mixture as described above and emptying it into the gelatin-shaped covers. A lubricant such as falco, magnesium stearate and calcium stearate may be added to the powder mixture prior to the filling operation; A slider can be added as colloidal silica to improve flow properties; A disintegrating or solubilizing agent can be added to improve the availability of the drug when the capsule is ingested. The tablets are made by preparing a powder mix, granulating or kneading, adding a lubricant and disintegrating and compressing into tablets. A mixture of powder is prepared by mixing the compositions of the present invention, is suitably trilized 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 cellulose or polymeric materials, and forcing it through a screen. As an alímafive to granulation, the powder mixture can be passed through the fablefeadora machine and the imperfectly formed masses are broken into granules. The granules can be lubricated to prevent adhesion to the tablet forming dies by the addition of stearic acid, a stearic salt, secular or mineral oil. The lubricated mixture is then compressed to form the tablets. The drugs can also be combined with free flowing inert vehicles and can be compressed directly into tablets, without going through the steps of granulation or kneading. The tablet can be provided with a protective coating consisting of a shellac sealing coating, a sugar coating or a polymeric material, and a polishing or wax coating. Dyes or pigments may be added, for example, to identify or characterize combinations of active doses. In tablet form, the vehicle comprises approximately 0.1% to 99% by weight of the total composition. This invention will be better understood from the examples that follow. However, the person skilled in the art will readily appreciate that the specific methods and the results described are only illustrative of the invention and do not imply limitation thereof.

EXAMPLE 1 Soy sitostanol (AC Humko, NF00114) (1g) was physically mixed with an equal amount of sodium dioctylsulfosuccinate (Aldrich Chemicals). The mixture was melted at 170 ° C to form a clear solution. The clear solution was rapidly cooled by emptying it in liquid nitrogen. A crystalline fransparenle salt was obtained. The salt (2g) was added to water (8g) to give a milky white emulsion with no visible particles. The solubility of the crystals was found to be 1200 micrograms per ml using the dissolution test described below (it was found that the maximum solubility of cold-milled beta-siloslanol in the dissolution test was 300 micrograms per ml) .

Dissolution test A solution of supply solution (5X) was prepared comprising taurocholic acid Na2 + (500 mM, Sigma, Cai # T400), 2-monoolein (10 mM, Un-Check Prep, cat # M-239), acid Free oleic acid (10 mM, Sigma cat # 01008) in chloroform: MeOH (1: 1). A buffer solution comprising 0.01 M of sodium phosphate buffer with 3 mM sodium azide, pH 7.4, was prepared. To prepare the solution solution for use in the dissolution test, 1 ml of the 5X supply solution solution was dried in a 20 ml flask under a stream of N2 at 50 ° C. The dried solution solution was then re-dried twice of 2 ml efill ether with vortex formation of the flask after each addition. The excess ether was removed by drying the flask for 1 hour at 100 ° C in an oven. The bottle with the dry solution solution was rehydrated with 5 ml of the sodium phosphate buffer. Nitrogen was bubbled through the solution for 5 minutes to ensure complete removal of ether. The final concentrations of the dissolution constituents were faurocholic acid (100 mM), 2-monoolein (2mM), oleic acid (2mM), in sodium phosphate (0.01 M, pH 7.4) with 3mM NaN3. To determine the solubility of the mixture of the present example, a sample of the mixture having an equivalent of 100 mg sitosanol was added to the bottle with the 5 ml of the rehydrated solution solution. The contents of the bottle were shaken gently and then placed in the rotary incubator. A 100 mg sample of cholesterol was prepared for analysis, in the same manner as the sample mixture, as well as a sample of cold-milled 100 mg esianol. At 4 hours a 1.0 ml aliquot was taken from each bottle. The aliquots were filtered immediately through a 0.2 μm syringe filter. Using an enzymatic cholesterol Cll team (Wako Puré Chemical industries, Ltd.), the amount of stanol dissolved in the solution solution filtered was determined according to the following protocol. It should be noted that the concentration of espanol is given as the amount of unesterified stanol. 1. A 2X color reagent was prepared by adding only half of the recommended buffer solution to the lyophilized reagent provided. 2. A sitosianol standard of 0.2 mg / ml was prepared by taking an aliquot of siioslanol from a 1: 1 CHCI3 / MeOH supply solution and adding triton-X 100 for a final rehydrated concentration of Triton 2.0%, sitosanol 0.2 mg / ml. This solution was stirred to form a vortex and dried under a stream of N2 at 50 ° C, followed by drying twice with ethyl ether. The sample was rehydrated in a 0.01 M sodium phosphate buffer with 3mM NaN3, pH 7.4. The mixture was then stirred with vortex formation. 4. A 96-well plate was prepared. The first two columns were used for the standard. Each sample was run in quadruplicate. 5. Samples were formed for a standard curve by adding water to the well followed by the standard, according to the proportions described in the following table: 6. Samples (5 microliters) were added to wells containing water to make a final volume of 100 ml. 7. The 2X color reagent was added to each of the wells using a Multi-pipetitor. Care must be taken to avoid contact with the solutions by touching the tips of the pipettes on the upper edges of the well wall. 8. Then, the reactants were mixed by shaking on a plate shaker (cover with plastic plate seal). Plates were incubated at 37 ° C for 15 minutes. 9. The plate was removed from the incubator and a reader was used.

ELISA at 500 nm (in the course of 1 hour of the removal of the plates from the incubator) to read the plate and thus determine the solubility of the sample in the solution solution.

EXAMPLE 2 The formulation (20 g) of example 1 was dispersed in water (100 ml) in a high speed mixer before mixing with hamster meal containing 10% by weight corn oil (0.24% cholesterol). The dispersion was added to the hamster feed to give 2 wt% stanol equivalent. The hamsters were fed for 7 days and fecal cholesterol levels were determined in the samples collected during the last 48 hours. The ratio of fecal cholesterol ("FC ratio") for each sample, stanol formulated and stanol not formulated (control), is determined by dividing its amount of cholesterol by the amount of cholesterol in the hamster meal administered with 10% by weight of oil of corn and 0.24% cholesterol (containing only food). The comparison of the FC ratios with respect to the control, 2% by weight of non-formulated stanol equivalent, showed that the hamsters fed with food with the formulation of example 1, absorbed less cholesterol, that is, a higher FC ratio. The results are shown in table 1.

TABLE 1 Further studies were conducted using dispersions of the formulation prepared in Example 1 having 1 wt% stanol equivalent in hamster feed, as described above. The results indicated that with the feed with 1% equivalent weight of esfanol there were increases in the ratio of fecal cholesterol with respect to the control. It should be noted that there is some variability between FC ratios due to the use of different hamsters in the studies. The results are shown in table 2.

TABLE 2 EXAMPLE 3 An evaluation of the efficacy of the formulations of the present invention was carried out to inhibit the absorption of cholesterol in the intestine using male beagle dogs. The dogs had an approximate weight of 8 to 12 kg at the beginning of the study and were approximately 11 to 13 months of age at the time of purchase. The dogs were housed in individual stainless steel cages. The cages were modified for the separation of urine and faeces, and the collection of faeces during the fecal collection periods. During the acclimation and washing periods, the dogs were fed a certified canine diet # 5007 (PMl Feeds, Inc.). During the trial period, on days 1-4, the dogs were fed a certified canine diet # 5007, supplemented with 0.25% cholesterol made by Ed Uhlman at Research Dieis, Inc. New Brunswick, New Jersey. All diets were offered daily from 2 to 4 hours, approximately at the same time of day. They were supplied with water freely. The environment of the animal in the cage was maintained at a temperature of 18 to 29 ° C, a relative humidity of 50% ± 20%, and a cycle of 12 hours of light / 12 hours of darkness. The following formulations were tested: a stanol control sample in a snap-fit gelatin capsule and a 50% by weight cremophor / 50% by weight mixture of soy stanol which was prepared by melting together the cremophor and the stanol at 180 ° C and rapidly inactivating the molten mixture in liquid nitrogen to produce a clear crystalline salt. The salt was milled into a fine powder using a cryo-mill and placed in a pressure-adjusted gelatin capsule for administration. A mixture formulation of 9% AOT / 9% PEG / 72% soybean siphostanol by mixing in chloroform solution. The chloroform was then evaporated to give an amorphous material which was milled cold to form a fine powder. The powder was placed in a snap-fit gelatin capsule for administration. The animals were dosed at 63 mg / kg stanol equivalents. Each animal received the diet supplemented with cholesterol and the formulations of the present invention in the form of a gelatin capsule, daily for 4 days. The gelatin capsules and controls were offered at approximately the same time of day, before feeding the animals each day. Faecal samples were collected prior to the test for 72 hours before administration of the test formulation and test days 3, 4 and 5. Samples were collected before feeding each day (and before administration of the samples). and control); they were transferred to plastic containers and concentrated at 3-day intervals. The fecal cholesterol level was then determined in each of the collected samples using mass spectrometry and liquid chromatography ("LC-MS").

TABLE 3 EXAMPLE 4 TABLE 4 Stanol, 1-octadecanol (Aldrich, Milwaukee, Wl), and half of Ac-Di-Sol (croscarmellose sodium NF type A, FMS Corp., Newark, were mixed.

Delaware) in a V-type mixer (Twin Shell Dry Blender mixer model # 4QT, Patterson-Kelly Co., East Stroudsbourgh, PA) for 5 minutes to form a powder mix. The resulting mixture was compacted in a TF-Miniroller compactor (Model No. TF-Mini, Vector Corp., Marion, Iowa, 180 kg / cm2 of pressure, feed speed of 10 RPM and roller speed of 7 RPM) giving as The sintering and melting of the mixture result. Afterwards, the compacted material is passed through a Cornil (Model No. 197.5, Quadro Engineering Inc., Waterloo, Canada). The powder is then mixed with the remainder of Ac-Di-Sol and Crodesta F-160 (sucrose sucrose, Croda, Inc., Mili Hall, PA), followed by mixing with the V-mixer for 5 minutes. Stearic acid (triple compressed, Mallinckrodt Baker, Inc., Phillipsbury, NJ), which was first passed through a 40 mesh screen, added to the mix in mixer V and mixed for 3 minutes. The resulting mixture was compressed into tablets in a standard tablet press. The ratio of fecal cholesterol for this formulation to Benecol was compared as a control. The results are shown in the following table: Pressure adjusting capsules were prepared comprising a unit dose form of a stanol as described in example 4, which has the following composition, Avicel PH-102 is microcrystalline cellulose and is available from FMC Corp., Newark, Delaware. The fecal cholesterol ratio for this formulation was compared with Benecol as a control. Benecol is a spreads product that incorporates vegetable stanol esters, as a method to promote healthy cholesterol levels, and is available from McNeil Consumer Healthcare, Ft. Washington PA. The results are shown in the following table: TABLE 5 EXAMPLE 6 Pressure adjusting capsules were prepared comprising a unit dose form of a slanol as described in example 4, having the following composition, The fecal cholesterol ratio for this formulation was compared with Benecol as a control. The results are shown in the following table: TABLE 6 EXAMPLE 7 Pressure adjusting capsules were prepared comprising a unit dose form of a stanol as described in example 4, having the following composition, The ratio of fecal cholesterol to this formulation was compared with Benecol as a control. The results are shown in the following table: TABLE 7 EXAMPLE 8 Defatted hydroxylated lecithin (10 g, Central Soya) was dispersed in water (30 g) using a high speed mixer. Sodium (20 g) ground in a hammer mill was added to the dispersion and the product was mixed once more under a cut. The resulting mixture was dried at 70 ° C under reduced pressure (15.2 mm Hg) overnight in a vacuum oven. The resulting mixture was milled in a hammer mill to obtain a fine powder. The solubility of the powder was found to be 750 mg per ml using the dissolution test described in Example 1. A pressurized gelatin capsule was prepared using the powder with a dosage of 63 mg of stanol per kg. dog's weight The effectiveness of the prepared gelatin capsule containing the powder was compared to one of benecol at the same dosage level as the stanol. The benecol was administered to the dog in liquid form using a syringe. The FC ratio for the dosed dog was determined with the powder prepared in this example and compared with the FC ratio of a control dog dosed with benecol. The results are shown in table 8.

TABLE 8 EXAMPLE 9 A formulation containing lecithin was prepared in place of hydroxylated leciin as in example 8. The following table shows the FC ratios determined for the formulation compared to Benecol from a dog study treated in the same manner as in example 8 TABLE 9 EXAMPLE 10 Compressed tablets comprising a unit dose form of a stanol were prepared as described in Example 4, having the following composition, TABLE 10 The fecal cholesterol ratio for this formulation was compared with Benecol as a control. The results are shown in the following table.

TABLE 11 EXAMPLE 11 33.47 grams of stanol octadecanoic acid ester were dissolved in 250 ml of chloroform. 1.05 grams of octadecanol added to chloroform solution was dissolved with heating at 51 ° C to facilitate dissolution. The chloroform was removed by evaporation under nitrogen producing a solid mixture containing 3.04% of ocladecanol. The mixture was milled cold to form hamster food that was given to hamsters as 1 percent stanol equivalent in their diet. It was found that the hamsters that consumed the food with eshenol ester absorbed less cholesterol than a conirol group of hamsters that ate hamster feed without stanol ester.

EXAMPLE 12 Hydroxylated lecithin powder was combined (Precepí 8120, Cenlral Soy) with espanolol powder (AC Humko NF00114) to give a mixture containing 70% w / w of esfanol and 30% w / w of hydroxylated lecithin. The mixture was extruded using a double prism worm that allows temperature control over four zones and the end of the die. For this example, the temperatures of zones 1 to 4 were set at 65 ° C. The temperature of the worm was set at 90 ° C and the speed of the worm at 200 r.p.m. Approximately 100 grams of this material was exluded in long strips such as spaghetti that were too soft and brittle to be processed through a chopper. The liras were milled under liquid nihinogen in a hammer mill to form a free-flowing powder. Hard gelatin capsules were filled with the lecithin / stanol powder product and the inhibition of choleslerol uptake was analyzed in the spherical dog model described above in example 3. Table 12 shows dose-response results indicating a statistically higher performance than the control at 30, 120 and 360 mg / kg. TABLE 12 EXAMPLE 13 Sodium stearate (Witco) was added to a 70:30 mixture of stanol powder: hydroxylated lecithin prepared as in example 12, to give 16.7% w / w of stearate. The powders were loaded in a double-worm Prism extruder using a vibratory feeder. The temperatures of zones 1 to 4 were set at 50, 57, 68 and 91 ° C, respectively (the actual temperatures measured in zones 2-4 were 57, 69 and 99 ° C, respectively). The iris temperature was set at 110 ° C (actual temperature 102 ° C). The speed of the worm was set to 100 r.p.m. As in example 12, lyres were extruded as spaghetti and ground in a hammer mill to produce a free flowing powder. The powder was incorporated into gelatin capsules and analyzed in the dog model for cholesterol absorption described in example 3.

EXAMPLE 14 A mixture of stanol 62% (w / w) (AC Humko), hydroxylated lecithin 30% (w / w) (Precep 8120, Cenlral Soy) and Ac-Di-Sol 8% (w / w) (croscarmellose sodium NF type A, FMS Corp., Newark, Delaware) was compressed using roll compaction and then co-milled. The resulting powder had sufficient mass density to allow filling a gel capsule with at least 400 mg of stanol. The material was analyzed in the dog model for cholesterol absorption described in example 3.

TABLE 13 EXAMPLE 15 The following tablet formulations were prepared. Formulation A Formulation B Equivalent to 27.8 mg of ociadecanol and 27.8 mg of Tween 60 per tablet.

Formulation C Formulation D Other objects, advantages, characteristics and modifications of this invention will be evident to those with average knowledge in this matter. This invention is not limited but as indicated in the following claims.

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1. - A composition characterized in that it comprises a mixture of a phytosolol and a surfactant selected from the group consisting of sodium docusate, ammonia glycyrrhizin, polyoxyethylene castor oil, polyethylene glycol, diacetyl-lactic acid esters of mono- and diglycerides, acid esters diacetyl-aartic acid mono- and diglycerides, monosodium phosphate derivatives of mono- and diglycerides, ethoxylated mono- and diglycerides, saponin quillaja, block copolymers of ethylene oxide and propylene oxide, vitamin E TPGS, hydroxylated lecithin, and mixtures thereof same. 2 - The composition according to claim 1, further characterized in that it additionally comprises a surfactant selected from the group consisting of sodium salts of fatty acids, fatty alcohols, polyethylene glycol stearate (8), polyethylene glycol stearate (40), esters of sucrose fatty acid, Tween, and mixtures thereof. 3. The composition according to claim 1, further characterized in that the phytostanol is selected from the group consisting of sitostanol, campestanol, 22,23-dihydrobrasicastanol, clionaslanol and mixtures thereof. 4. The composition according to claim 3, further characterized in that sitoslanol is alpha-sifoslanol or beta-sitostanol. 5. The composition according to claim 2, further characterized in that said fatty alcohol is selected from the group consisting of 1-decanol, 1-dodecanol, 1-tetradecanol, 1-hexadecanol, 1-octadecanol, 9-octadecen-1 -ol, 1-eicosanol, 1-docosanoI, 1-hexacosanol, 1-octacosanol, 1 -triacontanol and mixtures thereof. 6. The composition according to claim 5, further characterized in that said fatty alcohol is 1-octadecanol. 7. The composition according to claim 2, further characterized in that said sucrose fatty acid ester is selected from the group consisting of sucrose stearate, sucrose distearate, sucrose palmitate and mixtures thereof. 8. The composition according to claim 2, further characterized in that said Tween is selected from the group consisting of poiisorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 and polysorbate 85. 9. The composition according to claim 1 , further characterized in that it comprises from about 10 to about 99.99 weight percent of said phyllostanol, and from about 0.01 to about 90 weight percent of said surfactant. 10. The composition according to claim 9, further characterized in that it comprises from about 40 to about 95 weight percent of said phytostanol, and from about 5 to about 60 weight percent of said surfactant. 11. The composition according to claim 10, further characterized in that it comprises about 95 weight percent of said phytosanol and about 5 weight percent of said surfactant. 12. A method for reducing the absorption of cholesterol in humans, characterized in that it comprises orally administering an effective amount of a mixture of a phytostanol and a surfactant selected from the group consisting of sodium docusate, ammonia glycyrrhizin, polyoxyethylene castor oil, polyethylene glycol, diacetyl-lactic acid esters of mono- and diglycerides, diacetyltartaric acid esters of mono- and diglycerides, monosodium phosphate derivatives of mono- and diglycerides, ethoxylated mono- and diglycerides, saponin quillaja, oxide block copolymers ethylene and propylene oxide, vitamin E TPGS, hydroxylated lecithin, and mixtures thereof. 13. The method according to claim 12, further characterized in that the mixture additionally comprises a surfactant agent selected from the group consisting of sodium salts of fatty acids, fatty alcohols, polyethylene glycol stearate (8), polyethylene glycol stearate (40). ), fatty acid esters of sucrose, Tween, and mixtures thereof. 14. - The method according to claim 12, further characterized in that the phytostanol is selected from the group consisting of sitostanol, campestanol, 22,23-dihydrobrasicastanol, clionastanol and mixtures thereof. 15. The method according to claim 14, further characterized in that sitoslanol is alpha-sitostanol or beta-sitostanol. 16. The method according to claim 13, further characterized in that said fatty alcohol is selected from the group consisting of 1-decanol, 1-dodecanol, 1-tetradecanol, 1-hexadecanoI, 1-octadecanol, 9-octadecen-1 -ol, 1-eicosanol, 1-docosanol, 1-hexacosanol, 1-octacosanol, 1 -triacontanol and mixtures thereof. 17. The method according to claim 16, further characterized in that said fatty alcohol is 1-octadecanol. 18. The method according to claim 13, further characterized in that said sucrose fatty acid ester is selected from the group consisting of sucrose stearate, sucrose distearate, sucrose palmitate and mixtures thereof. 19. The method according to claim 13, further characterized in that said Tween is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 and polysorbate 85. 20. The method according to claim 12 , further characterized in that said mixture comprises from about 10 to about 99.99 weight percent of said phytostanol, and from about 0.01 to about 90 weight percent of said surfactant. 21. The method according to claim 20, further characterized in that said mixture comprises approximately 40 to about 95 weight percent of said phytostanol, and from about 5 to about 60 weight percent of said surfactant. 22. The method according to claim 21, further characterized in that said mixture comprises about 95 percent by weight of said phytostanol and about 5 percent by weight of said surfactant. 23. The method according to claim 12, further characterized in that said mixture is administered orally in the form of tablets, chewable, effervescent, swallowable or coated; capsules; soft gelatin capsules; syrup; fruit drink; bags of granules, fruit jelly, mini-sweet or sweet. 24. A method for reducing serum cholesterol levels, characterized in that it comprises administering a mixture of a phytostanol and a surfactant selected from the group consisting of sodium docusate, ammonia glycyrrhizin, polyoxyethylene castor oil, polyethylene glycol, diacetyl acid esters -lactic mono- and diglycerides, diacetyltartaric acid esters of mono- and diglycerides, monosodium phosphate derivatives of mono- and d-glycerides, mono- and diglycerides eryoxylates, saponin quillaja, block copolymers of ethylene oxide and propylene oxide , vitamin E TPGS, hydroxylated lecithin, and mixtures thereof. 25. The method according to claim 24, 5 further characterized in that said mixture additionally comprises a surfactant selected from the group consisting of sodium salts of fatty acids, fatty alcohols, polyethylene glycol stearate (8), polyethylene glycol stearate (40), sucrose fatty acid esters, Tween, and mixtures thereof. 10 26.- The method according to claim 24 or 25, , further characterized in that the mixture is administered orally. 27. The method according to claim 24, f. further characterized in that the phytoslanol is selected from the group consisting of sitosanol, peasanol, 22,23-dihydrobrasicaslanol, clionamphenol and mixtures thereof. 28. The method according to claim 27, further characterized in that the sitostanol is alpha-sitostanol or beta-silostanol. 29-- The method according to claim 25, further characterized in that said fatty alcohol is selected from the group that 20 consists of 1-decanol, 1 -dodecanol, 1-tetradecanol, 1-hexadecanol, 1-octadecanol, 9-octadecen-1 -ol, 1-eicosanol, 1-docosanol, 1-hexacosanol, 1- octacosanol, 1 -triacontanol and mixtures thereof. 30. The method according to claim 29, further characterized in that said fatty alcohol is 1-octadecanol. 31. The method according to claim 25, further characterized in that said sucrose fatty acid ester is selected from the group consisting of sucrose stearate, sucrose distearate, sucrose palmitate and mixtures thereof. 32. The method according to claim 25, further characterized in that said Tween is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 and polysorbate 85. 33.- The method according to claim 24 , further characterized in that said mixture comprises approximately 10 to about 99.99 weight percent of said phytostanol, and from about 0.01 to about 90 weight percent of said surfactant. 34.- The method according to claim 33, further characterized in that said mixture comprises from about 40 to about 95 weight percent of said phyllostanol, and from about 5 to about 60 weight percent of said surfactant. The method according to claim 34, further characterized in that said mixture comprises approximately 95 weight percent of said phylloslanol and approximately 5 weight percent of said surface active agent. 36. - A method for preparing a composition for reducing cholesterol absorption, characterized in that it comprises the step of mixing a phytostanol and a surfactant selected from the group consisting of sodium docusate, ammonia glycyrrhizin, polyoxyethylene castor oil, polyethylene glycol, esters of diacetyl-lactic acid of mono- and diglycerides, diacetyltartaric acid esters of mono- and diglycerides, monosodium phosphate derivatives of mono- and digiicerides, ethoxylated mono- and diglycerides, saponin quillaja, block copolymers of ethylene oxide and propylene, vitamin E TPGS, hydroxylated lecithin, and mixtures thereof. 37.- The method according to claim 36, further characterized in that the mixing is carried out under high pressure. 38.- The method according to claim 37, further characterized in that the mixing is performed by roll compaction. 39.- The method according to claim 37, further characterized in that the mixing is carried out in an extruder. The method according to claim 36, further characterized in that said composition further comprises a surfactant selected from the group consisting of sodium salts of fatty acids, fatty alcohols, polyethylene glycol stearate (8), polyethylene glycol stearate (40). ), fatty acid esters of sucrose, Tween, and mixtures thereof. 41. - The method according to claim 40, further characterized in that it comprises the step of heating said mixture of said phytostanol and said surfactants to a temperature that causes the formation of a molten mixture. The method according to claim 41, further characterized in that it comprises the step of rapidly cooling said molten mixture. 43. The method according to claim 42, further characterized in that liquid nitrogen is used to cool. 44.- A food product characterized in that it comprises a mixture of a phytostanol and a surfactant selected from the group consisting of sodium docusate, ammonia glycyrrhizin, polyoxyethylene castor oil, polyethylene glycol, diacetyl lactic acid esters of mono- and diglycerides, esters of diacetyltartaric acid of mono- and diglycerides, monosodium phosphate derivatives of mono- and diglycerides, mono- and diglycerides ethoxylated, quillaja saponin, block copolymers of ethylene oxide and propylene oxide, vitamin E TPGS, hydroxylated lecithin, and mixtures thereof. 45.- The food product according to claim 44, further characterized in that it comprises a surfactant selected from the group consisting of sodium salts of fatty acids, fatty alcohols, polyethylene glycol stearate (8), polyethylene glycol stearate (40), fatty acid esters of sucrose, Tween, and mixtures thereof. 46. - The food product in accordance with the claim 44, further characterized in that the phytostanol is selected from the group consisting of sitostanol, campestanol, 22,23-dihydrobrasicastanol, clionastanol and mixtures thereof. 47.- The food product in accordance with the claim 46, further characterized in that the sitostanol is alpha-sitostanol or beía-sitostanol. 48.- The food product in accordance with the claim 45, further characterized in that said fatty alcohol is selected from the group% consisting of 1-decanol, 1-dodecanoi, 1-tetradecanol, 1-hexadecanol, 1-octadecanol, 9-octadecen-1-ol, 1-eicosanol, 1- docosanol, 1-hexacosanol, 1-octacosarol, 1 -triacontanol and mixtures thereof. 49.- The food product according to claim 48, further characterized in that said fatty alcohol is 1-octadecanol. 50.- The food product in accordance with the claim 45, further characterized in that said sucrose fatty acid ester is selected from the group consisting of sucrose stearate, sucrose distearate, sucrose palmitate and mixtures thereof. 51.- The food product according to claim 45, further characterized in that said Tween is selected from the group consisting of polysorbate 20, polysorbate 40, poisorbate 60, polysorbate 80 and poisorbate 85. 52.- The food product according to claim 44, further characterized in that it comprises from about 10 to about 99.99 weight percent of said phyllostanol, and from about 0.01 to about 90 weight percent of said surfactant. 53.- The food product in accordance with the claim 52, further characterized in that it comprises from about 40 to about 95 weight percent of said phyllostanol, and from about 5 to about 60 weight percent of said surfactant. 54.- The food product in accordance with the claim 53, further characterized in that it comprises about 95 weight percent of said phytostanol and about 5 weight percent of said surfactant. 55.- A composition comprising a mixture of a phytostanol ester and a surfactant selected from the group consisting of sodium docusate, ammonia glycyrrhizin, polyoxyethylene castor oil, polyethylene glycol, diacetyl lactic acid esters of mono- and diglycerides, esters of diacetyltartaric acid of mono- and diglycerides, monosodium phosphate derivatives of mono- and diglycerides, ethoxylated mono- and diglycerides, saponin quillaja, block copolymers of ethylene oxide and propylene oxide, vitamin E TPGS, hydroxylated lecithin, and mixtures thereof. 56.- The composition according to claim 55, further characterized in that it comprises a surfactant selected from the group consisting of sodium salts of fatty acids, fatty alcohols, polyethylene glycol stearate (8), polyethylene glycol stearate (40), esters of sucrose fatty acid, Tween, and mixtures thereof. 57.- The composition according to claim 55, further characterized in that said fatty alcohol is selected from the group consisting of 1 -decano !, 1 -dodecanol, 1-tetradecanol, 1-hexadecanol, 1-ocíadecanol, 9-octadecenol- 1-ol, 1-eicosanol, 1-docosanol, 1-hexacosanol, 1-octacosanol, 1-triacontanol and mixtures thereof. 58.- The composition according to claim 57, further characterized in that said fatty alcohol is 1-octadecanol. 59. The composition according to claim 56, further characterized in that said sucrose fatty acid ester is selected from the group consisting of sucrose stearate, sucrose distearate, sucrose palmitate and mixtures thereof. 60.- The composition according to claim 56, further characterized in that said Tween is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 and polysorbate 85. 61.- The composition according to claim 55 , further characterized in that it comprises from about 10 to about 99.99 weight percent of said phytostanol ester, and from about 0.01 to about 90 weight percent of said surfactant. 62. - The composition according to claim 61, further characterized in that it comprises from about 40 to about 95 weight percent of said phytostanol ester, and from about 5 to about 60 weight percent of said surfactant. 63. The composition according to claim 62, further characterized in that it comprises about 95 weight percent of said phytostanol ester and about 5 weight percent of said surfactant.