JPS6339568B2 - - Google Patents

Description

[Detailed description of the invention]

BACKGROUND OF THE INVENTION This invention relates to certain edible but non-absorbable and non-digestible liquid polyesters that can be used as low calorie fat substitutes in foods and as pharmaceutical compositions. The polyesters according to the invention prevent the absorption of cholesterol in the body and thus provide a means of treating hypercholesterolemia. Polyester is undesirable because it can harm fat-soluble vitamin sources in the body;
However, in a preferred embodiment, this problem is overcome by fortification with vitamins. The liquid polyester of the present invention can be used to prevent unwanted anal leakage (anal leakage).
It has been newly discovered that it may cause a diarrheal effect (leakage) or diarrhea. According to the present invention, certain reagents are added to the polyester composition to avoid this undesirable effect. Preferred compositions for the treatment of hypercholesterolemia and/or hyperlipidemia are provided that include a polyester and an anal leakage or antidiarrheal agent. A highly preferred composition for treating cholesterolemia and/or hyperlipidemia is provided that includes a polyester, an antidiarrheal agent, and one or more fat-soluble vitamins. High blood cholesterol (hypercholesterolemia) is recognized as a risk factor for cardiovascular disease, which today constitutes a major health care problem. Epidemiological studies have demonstrated that, with few exceptions, populations that consume large amounts of saturated fat and cholesterol have relatively high serum cholesterol concentrations and higher mortality rates from coronary heart disease. Although it is recognized that other factors exist as a cause of the development of cardiovascular disease, the concentration of serum cholesterol [hypercholesterolemia
There is a causal relationship between the accumulation of undesirable amounts of cholesterol in various parts of the circulatory system (atherosclerosis) or in the soft tissues (xanthomatosis) and coronary artery disease and mortality from the disease. seems to exist. Various dietary and pharmaceutical treatments have been suggested to reduce or prevent hypercholesterolemia. By providing fat substitutes that are non-absorbable and non-digestible, the cholesterol content in the body can be lowered. Mineral oil is a well-known laxative and has been suggested for use as a fat substitute and as a type of "enteric agent" to dissolve cholesterol and remove it as body waste. However, mineral oil has never been acceptable for these applications. Additionally, mineral oil is undesirable because it is partially absorbed into the body and deposited in the liver. In the present invention, liquid, non-absorbable, non-digestible polyesters of sugars (or sugar alcohols) are used as fat substitutes in foods and therapeutic compositions, conveniently in unit dosage form. The polyesters of the present invention are fat-like in physical properties and are excellent fat substitutes suitable for use in low calorie foods and diets.
Moreover, the polyester of the present invention effectively prevents the absorption of cholesterol by the body and is absorbed into the liver during use in the treatment/prevention treatment of hypercholesterolemic patients or people likely to suffer from the above-mentioned diseases compared to mineral oil. and/or not deposited. The diarrheal effects of liquid polyesters of the type described herein can be overcome by adding antidiarrheal agents of the type described below to the liquid polyesters or foods containing them. The following documents are relevant to the present invention. U.S. Pat. Its use as a cholesterolemic and antihyperlipidemic agent and its stool-softening laxative effect are disclosed. U.S. Pat. No. 3,600,186 (1971) discloses low calorie food compositions containing polyol polyesters of the general type used in the present invention and their use in combination with hardstock, a source of fatty acids. . The antidiarrheal effect of fatty acids has not been described. US Pat. A variety of sugar polyesters are disclosed. A variety of optional carriers are described, including fatty acids, stearic acid. The antidiarrheal effect of stearic acid has not been described. US Pat. No. 1,656,474 (1928) discloses edible fat compositions consisting of ethyl and glycerol esters of odd-chain fatty acids in combination with fat-soluble vitamins. Mattson and Nolen, The Journal of Nutrition, Vol. 102, No. 9, 9.
1972, pp. 1171-1175, it is reported that sugar polyesters of the general type used in the present invention are not absorbed by mice. "Clinical Research" No.
3, page 319A (1975), it is reported that serum cholesterol and vitamin A and E levels are reduced in subjects receiving sugar polyesters of the type of the present invention. US Pat. No. 2,962,419 (1960) discloses neopentyl fatty esters and their use as fat substitutes. US Pat. No. 3,160,565 (1964) relates to sugar mono-, di- and tri-esters and their use as carriers for various orally administered pharmaceuticals. US Pat. No. 3,849,554 (1974) discloses a means of lowering serum cholesterol by consuming a low sucrose diet containing a source of fatty acids. US Pat. No. 2,893,990 (1959) discloses fatty acid mono- and di-esters of sucrose that aid absorption from the digestive system. US Pat. No. 3,158,490 (1964) includes 5
A clear salad oil is disclosed that contains two types of esters in which less than or equal to 1,000 unesterified hydroxyl groups are present. See also US Pat. No. 3,059,009 (1962) and US Pat. No. 3,059,010 (1962). US Pat. No. 2,997,492 (1961) relates to a method for producing partial fatty acid esters of hexitol. US Pat. No. 2,997,491 (1961) relates to the synthesis of partially fatty esters of inositol.
The general synthetic methods disclosed in these patents can be used to prepare the liquid polyesters of the present invention. Preferred synthetic methods are detailed below. In addition to the foregoing, there are other patent specifications directed to the use of fat-soluble vitamins in various natural oils that are not contemplated by the present invention. for example,
See US Pat. No. 2,685,517 (published August 3, 1954). SUMMARY OF THE INVENTION The administration of an anti-hypercholesterolaemic amount of a composition comprising a polyester of the type described herein to an animal (particularly a human) suffering from or susceptible to hypercholesterolemia can reduce cholesterol in the body. It is an effective means of controlling levels. Unfortunately, administration of cholesterol-controlled amounts of liquid polyester can cause an undesirable "laxative" effect, ie, liquid polyester leakage from the anal sphincter. By combining the polyester composition with anti-laxative agents, particularly C ₁₂ or higher saturated fatty acids or edible sources that provide such fatty acids in the gastrointestinal tract, this undesirable laxative effect is prevented.
("Antidiarrheal agent" or "AAL" refers to a substance that prevents the free leakage of liquid polyester. The natural stool-softening effect of polyester is not substantially affected, and its effectiveness is not in question.) The present invention provides a liquid, non-absorbable, non-digestible polyol fatty acid polyester of the type described below, and an anti-laxative or "curing" amount of an anti-laxative agent, particularly
Compositions containing C ₁₂ or higher fatty acid sources are included. This composition can be used as a fat substitute in cooking or can be administered itself to lower cholesterol levels in the body. Such compositions are also used as dietary supplements for hyperlipidemic solids. According to a preferred embodiment of the invention, the composition contains a sufficient amount of a fat-soluble vitamin selected from the group consisting of vitamins A, D, E, K, and mixtures thereof, such that any of these vitamins This prevents abnormally low levels in the tissues of animals that consume the composition. The invention also encompasses effective unit doses of non-laxative pharmaceutical compositions for inhibiting cholesterol absorption.
However, the lever composition contains from about 1 to about 5 g of the liquid polyester of the present invention and sufficient AAL agent, particularly _C12 , to prevent diarrhea in humans ingesting the composition.
or higher saturated fatty acids or edible sources thereof. Preferably, the composition also includes fat-soluble vitamins. The polyester materials of the present invention are non-absorbable and non-digestible fat-like materials suitable for use as fat substitutes in low calorie fat-containing food compositions. Accordingly, the present invention also provides low calorie fats comprising a non-fat component and a fat component in which about 10 to about 100% of the total fat component is a liquid, non-absorbable, non-digestible polyester of the type described below. This includes food compositions containing food products. The composition comprises an effective amount of an AAL agent that prevents undesirable diarrheal effects;
It also contains saturated fatty acids or edible sources of fatty acids, especially C ₁₂ or higher. According to a preferred embodiment of the low calorie fat-containing food composition of the present invention, more than the amount naturally present in the food composition is provided to prevent very low levels of the fat-soluble vitamins in humans consuming the composition. of fat-soluble vitamins or mixtures thereof. The present invention also includes methods for inhibiting cholesterol absorption without causing diarrheal effects.
The method thus comprises systematically (generally orally) administering to an animal susceptible to or suffering from hypercholesterolemia continuous therapeutically effective doses of a composition of the type described above. It is. The present invention also provides for the systematic (generally orally) administration to animals susceptible to or suffering from hypercholesterolemia of continuous therapeutically effective doses of compositions of the above type fortified with fat-soluble vitamins. The invention encompasses a method of inhibiting cholesterol absorption without reducing tissue supply of fat-soluble vitamins or causing diarrheal effects. Of course, the edible, non-absorbable, non-digestible polyester materials of the present invention are liquid at body temperature, ie, have a melting point of about 37°C or less. (Non-absorbable, non-digestible polyester materials that are solid at body temperature do not exhibit the undesirable diarrheal effects seen with liquid polyesters. In fact, such solid polyesters can be used as one type of AAL agent of the present invention. ) Generally, liquid polyesters are materials made from unsaturated fatty acids, while solid polyesters are substantially saturated. DETAILED DESCRIPTION OF THE INVENTION Consumption of foods containing sucrose polyester (SPE) has been shown to result in a desirable reduction in the absorption of dietary cholesterol in animals. See Matusson, Zyandasek and Gruetsk: Clinical Research 23 445A (1975). The same results have been observed in humans. About 300 to about 3000 per day for the above type of research
Mice who ingested mg of total liquid polyester and human volunteers who ingested from about 10 to about 50 g of total liquid polyester per day exhibited undesirable polyester diarrhea. Further research has indicated that this diarrheal effect is a direct result of the polyester passing through the anal sphincter. Simply stated, this undesirable effect is different from the effect that can be caused by ingesting excessive amounts of mineral oil. It has now been found that this undesirable effect can be eliminated by combining liquid polyester compositions with certain AAL agents. Below, we briefly discuss the animal studies that first determined the effect of ingestion of the non-absorbable, non-digestible sutucarose polyester of the present invention on vitamin A (an oil-soluble vitamin) absorption in rats. Generally, in this animal study, groups of mice were deprived of vitamin A-free food for 7 days.
During this period, animals were fed cottonseed oil (CSO) or SPE or a mixture of both as the sole fat source in their diet. (SPE is detailed below.) After the first 7 days, the animals' diets were supplemented with vitamin A. After 7 days on a diet containing vitamin A,
The animals were sacrificed and their livers removed and analyzed for vitamin A by the Carl Price method using the method of Amis, Wrisley and Harris. In this study, significant differences in animal response to the type of dietary fat ingested were evident. Therefore, if the dietary fat is CSO,
More than 70% of the vitamin A consumed is stored in the liver. When normal dietary fat was completely replaced with SPE, less than 10% of the consumed vitamin A was stored. According to said studies, it is possible to delineate the effect of SPE on fat-soluble vitamin (and cholesterol) absorption by individuals. Under normal dietary conditions (ie when ingesting normally absorbable, digestible oils or fats such as CSO), vitamin A, like cholesterol, is initially dissolved in the triglyceride oil phase in the intestinal lumen. A portion of the triglycerides is hydrolyzed to monoglycerides and free fatty acids, which together with bile salts form the micellar phase. Vitamin A is then partitioned between the oil phase of undegraded triglycerides and the micellar phase. The proportion of vitamin A in each phase will be a function of the volume of each phase and the vitamin's partition coefficient. Eventually, almost all of the triglycerides are hydrolyzed and most of the vitamins are absorbed. In contrast, SPE and triglycerides are miscible. When both are present, a single oil phase is formed. The triglyceride digestion products enter the micellar phase, but the SPE is not hydrolyzed and remains as an oil phase. A significant portion of the ingested vitamin A (and cholesterol) remains in this SPE oil phase, again depending on the volumes of the SPE oil and micellar phase and the partition coefficient of the vitamin.
If SPE is released into the stool and remains unchanged, SPE
Oil-soluble vitamin A dissolved in water is also lost. The same sequence of events probably occurs with vitamin E and with the other fat-soluble vitamins D and K. As can be seen from the foregoing, the physicochemical properties that make SPE so effective in interfering with the absorption of cholesterol by the body are the very same properties that undesirably impede the absorption of fat-soluble vitamins. This type of interference with the absorption of vitamins A and E
Proven in human volunteers who consumed SPE.
The result of SPE intake was a decrease in serum (plasma) levels of these vitamins. According to the invention, the SPE polyester is enriched with fat-soluble vitamins, in particular vitamin A, vitamin E and vitamin D, and mixtures thereof. (Polyester can also be fortified with vitamin K. However, since the body can synthesize vitamin K, polyester may be supplemented with vitamin K for proper nutrition in normal patients (or diseased animals). (Probably not critical.) Vitamin-enriched polyesters may be used as dietary fat substitutes, as pharmaceutical compositions in unit dosage form, or given in bulk for self-administration in therapeutic diets or dietetics. It will be done. The types of AAL agents that can be used in the present invention to overcome the aforementioned diarrhea problems without interfering with the beneficial effects of the compositions of the present invention are listed below. Antidiarrheal Agents One class of substances that provide an antidiarrheal effect in the present invention include fatty acids having a melting point of about 37° C. or higher and ingestible, digestible sources of such fatty acids. Fatty acid AAL agents include, for example, C ₁₂ -
Included are _C24 saturated fatty acids and ingestible, digestible sources thereof. Without wishing to be limited by theory, the above types of
AAL agents appear to function in the gastrointestinal tract through the production of calcium or magnesium fatty acid soaps. These soaps apparently interact with the liquid polyester of the present invention to impart a "setting" effect to the polyester. Solidifies in the gastrointestinal tract
or partially coagulated, the polyester does not leak through the anal sphincter. The antihypercholesterolemic effect of liquid polyester is not reduced. Specific examples of saturated fatty acids and their sources that can be used as AAL agents in the present invention include, but are not limited to, free saturated fatty acids themselves, compounds that yield such saturated fatty acids when hydrolyzed in the gastrointestinal tract; For example, esters (e.g. triglycerides, fatty acid soaps e.g. sodium,
There are potassium water-soluble soaps and calcium and magnesium water-insoluble soaps. Highly preferred in the present invention for diarrheal effects are C ₁₆ -C ₂₂ saturated fatty acids or edible sources thereof, most preferred are C ₁₆ -C ₁₈ saturated fatty acids or edible sources thereof. Specific examples of substances useful as AAL agents of the above type include natural or processed fats that yield _C12 - _C24 saturated fatty acids in the gastrointestinal tract, such as cocoa butter, palm oil, palm kernel oil, coconut oil, tallow, and lard. There are enriched concentrates of triglycerides with a high saturated fatty acid content that can be obtained from these sources and sources such as highly saturated cottonseed oil (this highly saturated cottonseed oil fraction is the "hard stock" fraction obtained). (obtained by methods such as crystallization or direct rearrangement resulting in the desired higher concentration of more saturated fatty acids in minutes). Such substances are
All are available by known methods. Partially hydrogenated oils, including all of the foregoing, as well as partially hydrogenated soybean oil, safflower seed oil, rapeseed oil or oils which, when hydrogenated and concentrated (e.g. by crystallization), are enriched in sources of long-chain substantially saturated fatty acids. All substances that produce the AAL of the present invention
(here, ``substantial hydrogenation'')
means oils with an iodine value of approximately 50 or less). Of course, any unsaturated oil mentioned above can be substantially fully hydrogenated to form unsaturated fatty acids (esters).
Effective in the present invention after the group has been converted to the corresponding saturated fatty acid. Synthetic substances, especially _C12 - _C24 , more preferably _C16
-C22 , most preferably _C16 - _C18 , fatty acid esters made from saturated fatty acids are useful in the present invention. Such materials include esters of tetrahydric alcohols such as erythritol, esters of pentahydric alcohols such as xylitol, and esters of hexahydric alcohols such as sorbitol. C ₁₂ -C ₂₄ saturated fatty acid esters of monohydric alcohols such as methyl, ethyl and propyl alcohol (preferably ethyl alcohol) are also useful. Esters of dihydric alcohols such as 1,2-propanediol and 1,3-butanediol can also be used. Highly preferred AAL agents, which yield the aforementioned fatty acids upon hydrolysis in the gastrointestinal tract, together with the liquid polyester provide compositions with organoleptically pleasing organoleptic properties, i.e., better "mouthfeel."
It is an AAL agent. Such sensory pleasing materials include natural cocoa butter and various synthetic cocoa and confectionery butters. These preferred AAL agents include, for example, the so-called "positionspecific" triglycerides, e.g.
-stearoyldiolein (SOO), 2-oleoyl-1,3-distearin (SOS), or corresponding compounds in which the stearoyl group is replaced by a palmitoyl, arachidoyl or behenoyl group. Other types of sensory preferred antilaxatives are 1-oleoyl distearin (OSS), 1-palmitoyl distearin (PSS),
1-arachidoyl distearin (ASS) and 1-behenoyl distearin (BSS). These highly preferred regiospecific triglycerides that can be used as fatty acid source types for AAL agents are
It can be produced by the method described in US Pat. No. 3,809,711 (published on May 7, 1974).
The description of this patent specification is hereby incorporated by reference. As mentioned above, AAL agents of the type described above appear to work by providing saturated fatty acids in the gastrointestinal tract, which then presumably form insoluble calcium or magnesium soaps in situ. This soap then appears to have a "solidifying" effect on the liquid polyester, thereby preventing undesirable diarrheal effects. As previously mentioned, solid polyester materials of the type of the present invention (ie, solid edible, non-digestible, non-absorbable polyesters) do not cause undesirable diarrheal effects. These solid polyester materials can also be used as AAL agents, and they are
It was found that it represents a second class of agents. Because these solid polyester materials do not hydrolyze in the gastrointestinal tract to form free fatty acids or calcium or magnesium fatty acid soaps, their antidiarrheal effect may be by a different mechanism than that which operates in the case of the hydrolyzable ester and fatty acid sources described above. It must be the result of a mechanism. Presumably, the solidification effect occurs when a solid polyester is combined with a liquid polyester simply due to some type of crystallization or phase change within the gastrointestinal tract. The combination of liquid and solid non-absorbable, non-digestible polyesters to provide the desired antidiarrheal effect ensures a completely edible but non-digestible, non-absorbable, non-caloric composition. will be understood. These compositions are highly effective in the treatment of hypercholesterolemia and low calorie diets. Typical examples of solid non-absorbable, non-digestible polyester AAL agents include sucrose octastearate, sucrose octapalmitate, sucrose heptaseate, xylitol pentastearate, galactose pentapalmitate, C ₁₀ - C ₂₂ There are saturated polyol polyesters having at least four -OH groups esterified with saturated fatty acids. Other types of AAL agents include fatty acid esters, which are branched at the α-carbon atom of the fatty acid moiety and are therefore nondigestible. Such substances, which are well known in the chemical arts, include, for example, lower alcohols such as ethanol and polyols such as glycerol, α-methyl and α,α-dimethyl C ₁₀ -C ₁₈
There are fatty acid esters. Liquid polyester The liquid polyol polyester (sometimes simply referred to as polyester) used in the present invention includes:
There are certain polyols, especially sugars or sugar alcohols, that are esterified with at least four fatty acid groups. It is therefore necessary that the polyol starting material has at least 4 esterifiable hydroxyl groups. Examples of preferred polyols include sugars and sugar alcohols, including monosaccharides and disaccharides. Examples of monosaccharides containing four hydroxyl groups include xylose and arabinose and the sugar alcohol derived from xylose, which has five hydroxyl groups, or xylitol (the monosaccharide erythrose has only three hydroxyl groups). However, since it does not, it is inappropriate for implementing the present invention.
However, the sugar alcohol derived from erythrose, erythritol, contains four hydroxyl groups and can therefore be used).
Suitable monosaccharides containing five hydroxyl groups are galactose, fructose and sorbose. 6 derived from sucrose and the hydrolysis products of glucose and sorbose
Sugar alcohols containing OH groups, such as sorbitol, are also suitable. Examples of disaccharide polyols that can be used include maltose, lactose and sucrose, all of which contain eight hydroxyl groups. Preferred polyols for the preparation of polyesters for use in the present invention are selected from the group consisting of erythritol, xylitol, sorbitol, glucose and sucrose. Sucrose is particularly preferred. A polyol starting material having at least four hydroxyl groups requires that at least four --OH groups be esterified with a fatty acid having from about 8 to about 22 carbon atoms. Examples of such fatty acids include caprylic, capric, lauryl, myristyl, myristolein, palmitin, palmitoolein, stearin, olein, ricinol, linole, linolenic, eleostearin, arachine, arachidon, behene and erucic acid. There is.
Fatty acids can be derived from natural or synthetic fatty acids, and they can be saturated or unsaturated, including positional and geometric isomers. However, to provide liquid polyesters of the type used in this invention, it is necessary that at least about half of the fatty acids incorporated into the polyester molecules be unsaturated. Particularly preferred are oleic acid and linoleic acid, and mixtures thereof. Liquid polyol fatty acid polyesters useful in the present invention must contain at least four fatty acid ester groups. Polyol fatty acid polyester compounds containing 3 or fewer fatty acid ester groups are digested and the digestion products are absorbed from the intestinal tract in much the same way as ordinary triglyceride fats, whereas polyols containing 4 or more fatty acid ester groups The polyol fatty acid polyester compounds are substantially indigestible and therefore not absorbed by the human body. It is not necessary that all of the hydroxyl groups of the polyol be esterified with fatty acids, but it is preferred that the polyester contain no more than two non-esterified hydroxyl groups. Most preferably, substantially all of the hydroxyl groups of the polyol are esterified with fatty acids (ie, the compound is substantially completely esterified). The fatty acids esterified with the polyol molecule can be the same or mixed fatty acids (although, as mentioned above, the presence of a substantial amount of unsaturated acid ester groups is necessary to provide fluidity). . To illustrate the point, sucrose fatty triesters are not suitable for use in the present invention because they do not contain the required four fatty acid ester groups. Sucrose tetrafatty acid esters are suitable, but are not preferred because they have more than one unesterified hydroxyl group. Sucrose hexafatty acid esters are preferred because they have two or fewer non-esterified hydroxyl groups. A highly preferred compound in which all hydroxyl groups are esterified with fatty acids is liquid sucrose octafatty acid ester. Below are specific non-limiting examples of specific liquid polyol fatty acid polyesters containing at least four fatty acid ester groups suitable for use in the present invention. Glucose tetraoleate, glucose tetraester of soybean oil fatty acids (unsaturated), mannose tetraester of mixed soybean oil fatty acids, galactose tetraester of oleic acid, arabinose tetraester of linoleic acid, xylose tetralinoleate, galactose pentaoleate , sorbitol tetraoleate, sorbitol hexaesters of unsaturated soybean oil fatty acids, xylitol pentaoleate, sucrose tetraoleate, sucrose pentaoleate, sucrose hexaoleate, sucrose heptaoleate, sucrose octaoleate and mixtures thereof. As mentioned above, highly preferred polyol fatty acid esters are those in which the fatty acid contains about 14 to about 18 carbon atoms. Polyol fatty acid polyesters suitable for use in the present invention can be made by a variety of methods well known to those skilled in the art. These methods include transesterification of polyols with methyl, ethyl or glycerol fatty acid esters using various catalysts, acylation of polyols with fatty acid chlorides,
There are acylations of polyols with fatty acid anhydrides and acylations of polyols with fatty acids themselves. As an example, the preparation of polyol fatty acid esters is described in US Pat. No. 2,831,854 (herein incorporated by reference). A non-limiting example of the preparation of a polyol fatty acid ester suitable for use in the examples of the present invention is as follows: Erythritol tetraoleate is prepared by combining erythritol and a 5-fold molar excess of methyl oleate. It is heated at 180° C. with stirring under vacuum in the presence of sodium methoxide catalyst for two reaction times of several hours each. The reaction product (mainly erythritol tetraoleate) is purified with petroleum ether and crystallized three times from several volumes of acetone at 1°C. Xylitol pentaoleate is prepared by preparing a solution of xylitol and a 5-fold molar excess of methyl oleate in dimethylacetamide (DMAC) in the presence of sodium methoxide catalyst under vacuum at 180°C.
Heat for 5 hours. During this time DMAC is removed by distillation. The product (mainly xylitol pentaoleate) is purified in petroleum ether solution and, after removal of petroleum ether, separated as a liquid phase four times from acetone at about 1°C and twice from alcohol at about 10°C. Sorbitol hexaoleate is made by essentially the same method of preparing xylitol pentaoleate, except that sorbitol is used in place of xylitol. Sucrose octaoleate is prepared in substantially the same manner as erythritol tetraoleate, except that sucrose is used in place of erythritol. Vitamins The vitamins used to fortify the aforementioned polyesters in the preferred practice of the invention are detailed below. It will be appreciated that commercial preparations of suitable vitamins and/or suitable vitamin mixtures providing vitamins A, D, E and K can be used in the present invention. Generally, vitamins are classified as "fat-soluble" or "water-soluble." Fat-soluble vitamins are used to fortify the polyester materials of this invention. Fat-soluble vitamins include vitamin A, vitamin D, vitamin E, and vitamin K. Vitamin A (retinol) can be used in the present invention to strengthen polyesters. Vitamin A
is a fat-soluble alcohol with the general formula C ₂₀ H ₂₉ OH.
Natural vitamin A is commonly esterified with fatty acids, and the metabolically active forms of vitamin A also include the corresponding aldehydes and acids. All such fat-soluble forms of vitamin A (including carotenoids)
are intended for use in the present invention and are considered to be encompassed by the term "vitamin A" of the present invention. Vitamin A in normal human metabolism
Although the role of
However, this vitamin is known to be essential for proper vision. Vitamin D (calciferol) can be used in the present invention to strengthen polyesters.
Vitamin D is a fat-soluble vitamin well known for its use in the treatment and prevention of rickets and other skeletal diseases. "Vitamin D" includes sterols, and there are at least 11 types of sterols that have vitamin D-type activity. In this, D ₂ and
Only the one known as D ₃ is of practical importance. Ergosterol, a plant sterol that is structurally similar to cholesterol, is known as "provitamin _D2 " and 7-dehydrocholesterol is known as "provitamin _D3 ." Each of these provitamins is converted to the corresponding active form by irradiation with ultraviolet light. Ergocalciferol ( _D2 ) is commercially prepared for use as a vitamin supplement. Cholecalciferol (D ₃ ) is a form that is synthesized in animal tissues and is primarily found in natural fish oil. The present invention contemplates the use of any of the vitamins and provitamins that have "vitamin D-type" activity, where "vitamin D" is intended to include all such fat-soluble substances. . Vitamin E (tocopherol) is a third fat-soluble vitamin that can be used in the present invention. Four different tocopherols have been identified (α, β,
γ and δ), all of which are oily yellow liquids, insoluble in water but soluble in fats and oils. Among the four tocopherols, the alpha form is the most biologically active, a factor that may be associated with better absorption from the intestine. The δ type is the most potent antioxidant of the four types. It has been suggested that vitamin E deficiency can cause a variety of symptoms such as fetal malformations and death, myocardial degeneration and liver necrosis, but the role of this vitamin in human nutrition is not yet well established. Here, "vitamin E" includes all fat-soluble tocopherols having vitamin E-type activity. Vitamin K exists in at least three forms:
All belong to a group of chemical compounds known as quinones. Natural fat-soluble vitamins are _K1 (phylloquinone),
K ₂ (menaquinone), and K ₃ (menadione). Vitamin K deficiency usually results in poor blood clotting, among other symptoms. Here, "vitamin K" includes all of the above-mentioned fat-soluble quinones having vitamin K type activity. From the above, vitamin A in animals, especially humans,
D, E and K, vitamins A, D, E or corresponding provitamins with K-type activity and their derivatives such as esters are well contemplated for use in the present invention and are included in the term "vitamin" herein. It should be understood that this is included. The amount of individual fat-soluble vitamins used to fortify the compositions of the present invention may vary depending on the age of the recipient, the dosage used, and the amount of vitamins ingested from other dietary sources. For example, it has been recognized that younger growing children (juveniles) or pregnant women (females) must receive greater amounts of certain vitamins than adult males (adult males) for optimal nutritional benefit. It is being If the user of the composition of the invention happens to consume food that is very rich in a certain fat-soluble vitamin, that vitamin is required in the composition of the invention to ensure proper intestinal absorption for good nutrition. The amount may be smaller. In any case, your doctor can measure the amount of fat-soluble vitamins in your plasma if you so desire. Based on these data, the appropriate type and amount of fat-soluble vitamins to be used in polyester fortification can be determined on an individual basis. More simply, the formulator of the compositions of the present invention provides a Recommended Daily Allowance (RDA) of the fat-soluble vitamin, such that the user of the composition maintains nutritionally adequate absorption of the vitamin.
Alternatively, the polyester can be strengthened by increasing or multiplying the RDA. For example, vitamin A ranges from 20 to about 57 international units (I.
U.) amount can be used every day. In the case of vitamin D, the total amount is about 400 I.U. per day.
It is sufficient to fortify the composition so as to give
When supplementing with vitamin E, the optimal amount of vitamin E in the diet is 3 total per day for infants (young children).
-6 I.U., and 25-30 I.U. for adults (adults).
When supplementing with vitamin K, it is more difficult to estimate the amount that should be taken to provide adequate nutrition since microorganisms living in the intestines can synthesize this vitamin. However, it is known that intake of 0.5-1 mg of vitamin K per day prevents deficiency. As can be seen from the foregoing, the amount of fat-soluble vitamins used in the present invention to fortify the polyester can vary. Generally, polyester has an average RDA
Fortified with enough fat-soluble vitamins to provide about 0.08 to about 150% of In dietary therapy, the dosage of the compositions of the invention may vary depending on the severity of the hypercholesterolemic condition and the duration of treatment. Individual dosages range from about 0.01 to about 500 mg/Kg and more (unless otherwise specified, "mg/Kg" refers to mg of polyester per Kg of body weight), preferably about 0.1
It can range from about 125 mg/Kg, up to 6 doses, preferably 3 doses, each day, most preferably at mealtimes. Because of AAL agents, such high doses can be given without fear of anal leakage effects. about
At doses below 0.1 mg/Kg, cholesterol absorption is not actually suppressed in most patients (receptors). The dosage may be in a suitable unit dosage form, e.g.
It can be administered orally in tablets and capsules. Capsules made of gelatin are preferred. The dosage can also be administered as part of a controlled diet, such as synthetic salad oils or cooking oils or fats. The pharmaceutical composition of the present invention comprises polyester/AAL
The agents can be fortified with fat-soluble vitamins alone or not, or in combination with any desired non-interfering carrier. "Pharmaceutical carrier" herein refers to a solid or liquid filler, diluent or capsule-forming substance. Examples of substances that can be used as pharmaceutical carriers include sugars such as lactose, glucose and sutucarose;
Starches such as corn starch and potato starch, cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate, powdered tragacanth, malt, gelatin, talf, oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and soybean oil , polyols such as propylene glycol, glycerin, sorbitol, mannitol, and polyester glycols, agar, alginic acid, pyrogen-free water, isotonic salts,
Ethyl alcohol and phosphate buffer solutions and other non-toxic compatible substances used in pharmaceutical formulations,
There is. Wetting agents and lubricants, such as sodium lauryl sulfate, and coloring agents, flavoring agents, and preservatives can also be present in the compositions at the desire of the formulator. Pharmaceutical carriers of the type described above are optionally used in combination with liquid polyesters to provide practical dimensions relevant to administration, the form of an easily ingestible composition, and a means to provide precise unit dosages in a convenient manner. I can do it. The pharmaceutical carrier will normally represent from about 5 to about 50% by weight of the total pharmaceutical composition. Since the liquid polyesters of the compositions of the invention do not differ in physical properties from cooking and salad oils and fats, the compositions of the invention can be used to partially or completely replace common triglyceride fats in any fat-containing food composition. , can provide antihypercholesterolemic and hypocaloric effects. To achieve these effects in a reasonable amount of time, it is necessary that at least about 10% of the fat in the food composition be the polyester of the present invention. A highly desirable food composition is one in which the fat content is up to approx.
It is a 100% polyester/antidiarrheal composition. Accordingly, the compositions of the present invention can be used to partially or completely replace common triglyceride fats in salad oils or cooking oils or plastic coatings used in frying, confectionery, baking, etc. The compositions of the invention can also be used to partially or completely replace common triglyceride fats in fat-containing food products such as mayonnaise, margarine and dairy products. Preferred fat-containing food compositions of the type of the invention include a non-fat component and a fat component in which about 10 to about 95% of the total fat consists essentially of a liquid sugar fatty acid polyester having at least 4 fatty acid ester groups; Each fatty acid has about 8 to about 22 carbon atoms;
The sugar fatty acid polyesters and/or food compositions made from the polyesters contain AAL agents of the type described herein and are preferably fortified with fat-soluble vitamins. Such food compositions most often contain at least about 10%, and generally 15 to 25%, source of fatty acids that provide anti-diarrheal effects.
(based on the weight of liquid polyester). Food compositions in which the sugar fatty acid ester contains no more than two non-esterified hydroxyl groups are highly preferred. Liquid sucrose polyesters, especially those in which the ester groups are predominantly unsaturated and 14 to
Those containing 18 carbon atoms are particularly preferred for use in such antihypercholesterolemic and low calorie food compositions when used in the methods of the invention. The total AAL agent used in any composition and method of the invention will depend somewhat on the total amount of liquid polyester ingested per day. Antidiarrheal agent is at least 10% of liquid polyester
It should be present in an amount equal to % by weight. AAL agents contain at least about 20% of liquid polyester to prevent diarrhea even at high intake rates.
% by weight is more preferable. Compositions in which the weight of the AAL agent is about 20 to about 50% of the weight of the liquid polyester provide excellent control of serum cholesterol without the diarrhea of the polyester. Compositions containing edible fatty acids, edible salts thereof, or edible digestible esters thereof as AAL agents contain approximately
Contains 10 to about 50% by weight. Compositions using palatable regiospecific triglycerides as AAL agents preferably contain from about 20 to about 40% (based on the weight of the liquid polyester) of these AAL agents.
When using an edible, non-absorbable, non-digestible solid polyester as an AAL agent, approximately
Preferably, a proportion of 20 to about 50% by weight is used. The following examples illustrate some of the compositions and methods of the invention. It will be understood that sugars and sugar alcohols (suitably esterified) are encompassed by the term "sugar" and that such materials can be interconverted in the composition. EXAMPLE Gelatin capsules for use in hypercholesterolemic patients are prepared in the usual manner as follows. Ingredients Quantity per Capsule Sucrose Polyester ^* 2000mg Stearic Acid 250mg ^* Liquid mixed hexer, heptare, and octase sucrose esters, primarily octaesters, esterified with mixed soybean oil fatty acids of primarily C ₁₆ - C ₁₈ chain lengths. Capsules of the above type are prepared by simply mixing the ingredients and filling standard gelatin capsules. The capsules are administered orally three times a day (three times with each meal). With this therapy, cholesterol absorption is significantly suppressed and serum cholesterol levels in the circulation of people who have or are at risk of hypercholesterolemia are reduced. Patients do not suffer from unwanted diarrhea with this therapy. In the example capsules, instead of sucrose polyester, we use glucose tetraoleate, glucose tetraoleate, mixed glucose tetraesters of unsaturated soybean oil, mixed mannose tetraesters of oleic acid, mixed galactose tetraesters of linoleic acid, arabinose of oleic acid. selected from the group consisting of tetraester, xylosetetralinoleate, galactose pentaoleate, sorbitol tetraoleate, sucrose tetraoleate, sucrose pentaoleate, sucrose hexaoleate, sucrose heptaoleate, and sucrose octaoleate Similar results are obtained using each equivalent amount of fatty acid polyester. In the example composition, in place of the stearic acid anti-diarrheal agent, equivalent amounts of each of methyl stearate, propyl stearate, methyl behenate, ethyl behenate, substantially fully hydrogenated palm oil, hydrogenated rapeseed oil, etc. , and mixed hydrogenated tallow triglycerides, the same results are obtained. Preferred pharmaceutical compositions of the type, particularly for inhibiting the absorption of cholesterol in the human body, preferably contain from about 0.1 to about 5 grams of a liquid polyester and an effective amount (as described above) of an AAL agent. EXAMPLE Gelatin capsules for use in hypercholesterolemic patients are prepared in the usual manner as follows. Ingredients Amount Per Capsule Sucrose Polyester ^* 2000mg Retinol 0.3RDA Stearic Acid 750mg ^* Liquid mixed hexer, heptare and octase sucrose esters, primarily octaesters, esterified with mixed soybean oil fatty acids of primarily C ₁₆ - C ₁₈ chain lengths. Capsules of the aforementioned types, simply mix the ingredients,
Prepared by filling standard gelatin capsules. Take this capsule 3 times daily (3 times with each meal)
Administer orally. With this therapy, cholesterol absorption is significantly suppressed and serum cholesterol levels in the circulatory system of people who have or are about to suffer from hypercholesterolemia are reduced. The patient's vitamin A level is normal to moderately low. Patients do not suffer from unwanted diarrhea with this therapy. In the example capsules, instead of sucrose polyester, we use glycose tetraoleate, glucose tetrastearate, mixed glucose tetraesters of soybean oil fatty acids, mixed mannose tetraesters of tallow fatty acids, mixed galactose tetraesters of olive oil fatty acids, mixed arabinose of cottonseed oil fatty acids. Tetraester, xylose tetralinoleate, galactose pentastearate,
The same results are obtained using equivalent amounts of each fatty acid polyester selected from the group consisting of sorbitol tetraoleate, sucrose tetrastearate, sucrose pentastearate, sucrose hexaoleate, sucrose heptaoleate and sucrose octaoleate. . If retinol is replaced in the example composition with an equivalent level of commercially available vitamin A ester concentrate,
I get the same result. In the composition of the example, instead of the stearic acid antidiarrheal ingredient, equivalent amounts of methyl stearate, ethyl stearate, propyl stearate, methyl behenate, behenate ester, hydrogenated palm oil, hydrogenated rapeseed oil, and mixed hydrogen are used. The same results are obtained using added tallow triglycerides. Particularly preferred compositions of the type for inhibiting the absorption of cholesterol in the human body include from about 0.1 to about 5 g
liquid polyester, an effective amount (as previously described)
of an AAL agent and at least about 0.1 RDA of one or more fat-soluble vitamins. EXAMPLE Gelatin capsules containing unit doses of AAL agent and liquid polyester are prepared in conventional manner as follows. Ingredients Amount per capsule Sucrose octaoleate 3500mg Hydrogenated palm oil 750mg The above capsules are orally administered three times a day (3 times per meal/70Kg/person). This therapy substantially inhibits cholesterol absorption in the patient and reduces serum levels of cholesterol. No diarrhea has been observed with the use of capsules. Substituting an equivalent amount of tristearin for the example hydrogenated palm oil provides the same antidiarrheal effect. When oleic acid is used instead of hydrogenated palm oil, no substantial antidiarrheal effect is observed. The capsules are fortified with vitamin E consisting of mixed alpha, beta, gamma and delta tocopherols using 0.2 RDA of vitamin E per capsule. The capsules are further fortified with enough beta-carotene to provide 0.25 RDA of vitamin A per capsule. Example A gelatin capsule containing an AAL agent and a liquid polyester is as follows. Ingredients mg per capsule Sucrose octaoleate 2000 Ethyl stearate 250 3 capsules of the type prepared in the example 5 times a day
Orally administered twice (3 capsules each time),
Inhibits cholesterol absorption, suppresses sterolemia, and lowers cholesterol levels in the circulatory system of a 70 kg patient suffering from hypercholesterolemia. No diarrhea is observed at these dose levels.
The same dosage of the aforementioned capsules without ethyl stearate causes unwanted leakage of satucalose octaoleate from the anal sphincter. Example A gelatin capsule containing an AAL agent, liquid polyester and fat-soluble vitamins is as follows. Ingredients mg sucrose octaoleate per capsule 2000 Vitamin A 0.1 Vitamin D 0.01 Vitamin E 0.1 Vitamin K 0.1 Ethyl stearate 750 The vitamin A used in the capsules was retinol, and the vitamin D was irradiated ergosterol and irradiated 7-dehydrochloride. It is a 1:1 mixture of cholesterol, vitamin E contains a commercial mixture of alpha, beta, gamma and delta tocopherols, and vitamin K contains fat-soluble phylloquinones. 3 capsules of the type prepared in the example 5 times a day
Administered orally twice (3 at each meal), it inhibits cholesterol absorption and lowers cholesterol levels in the circulatory system of a 70 kg patient with hypercholesterolemia. Body levels of fat-soluble vitamins A, D, E and K do not fall below normal levels. The same capsules in this dosage range without ethyl stearate cause an undesirable laxative effect, ie leakage of polyester from the anal sphincter. EXAMPLE A highly palatable, lower calorie composition suitable for use by patients in antihypercholesterolemic treatment and/or as a cooking fat substitute in an antihyperlipidemic diet is as follows: It is. Ingredients wt% Liquid Sucrose Polyester ^* 50 Cocoa Butter 50 ^* Average 7.5 esters of sucrose and oleic acid. Compositions of the above type are suitable for use in standard procedures as low calorie cooking fats. Liquid polyester diarrhea is not observed. The example composition taken at a rate of 50 g/day (150 lb patient) reduces serum cholesterol without liquid polyester diarrhea. In place of natural cocoa butter in the example composition, an equivalent amount of each regiospecific triglyceride SOO,
With SOS, OSS, PSS, ASS and BSS,
The same composition is obtained. In the example composition, about 1000 I.U. per 1 oz. of the composition instead of liquid sucrose polyester.
A vitamin-fortified liquid sucrose polyester containing an average of 7.5 esters of sucrose and unsaturated mixed soybean oil fatty acids fortified to provide vitamin A is used. Similar results are obtained and no vitamin A deficiency occurs in the tissues. Example: Prepare a plastic shotening from the following ingredients: Ingredients Weight % Cocoa Butter 40 Liquid Xylitol Pentaoleate 50 OSS 10 Example compositions are prepared by thoroughly mixing these ingredients. This composition is suitable for use in frying and other types of cooking using plastic fats. The example fat compositions can also be used in bread making suitable for use by hypercholesterolemic patients. Continuous ingestion of the plastic shavings or foods made therefrom lowers the body's serum cholesterol levels without xylitol pentaoleate diarrhea. For example, shortening can be used by normal people or hyperlipidemic patients to control body weight. Approximately 56 g (2 oz) of example composition per use
Fortify with enough irradiated ergosterol to provide 40.0 IU of vitamin D. The same result is obtained,
Vitamin D deficiency does not occur. EXAMPLE A non-diarrheal, low-calorie, anti-hypercholesterolaemic composition prepared using an edible, non-absorbable, non-digestible, solid polyester AAL agent is as follows. Ingredients Weight % Sucrose Octoleate 70 Sucrose Octastearate 30 Example compositions are prepared by simply mixing the ingredients. This composition is suitable for use by hypercholesterolemic patients to lower serum cholesterol levels, and no diarrhea is observed. Example compositions can be used by normal humans or hyperlipidemic patients to control serum cholesterol without increasing caloric intake. The same results are obtained by substituting equivalent amounts of each of sucrose heptasteate and sucrose octapalmitate for sucrose octastearate as AAL agents in the example compositions. Enough vitamins A, D, and E to provide the RDA of each of the example compositions per 84 g (3 oz.) use.
and vitamin-fortified with a commercial mixture of K. and K. The same results are obtained while maintaining normal levels of fat-soluble vitamins. Comparative Example Sucrose Polyester (SPE) Prevention of Diarrhea The following is a comparison between foods containing SPE and foods containing fully hydrogenated palm oil
This is a comparison between diarrhea.

[Table] Sucrose polyester is in liquid form and has the following fatty acid composition. Palmitic Acid 6.7% Stearic Acid 2.6% Oleic Acid 12.3% Linoleic Acid 77.1% All of the lipid-soluble test substances were heated and mixed with soybean oil plus
Dissolved in SPE. Test method: Male Sprague-Dawley weighing between 250g and 350g.
Mice were fed an unlimited amount of semi-refined food containing 20% soybean oil (Food A in the table above) for 3 days to become accustomed to this type of food. The mice were weighed and divided into groups of 10 each. One group received Food B and the second group received Food C. Test and control foods were given for 10 days. The rats were examined for signs of diarrhea after 10 days. Evaluation of Diarrhea Greasy fur was evidence of diarrhea. Three independent assessments were obtained for each of the 10 mice, grading the severity on a 5-point scale: 0 no trace, 0.5 trace, 1 slight, 2 moderate, 3
Expressed as equivalent. The maximum score would be 30 if all 10 rats were rated as "fair".
A control food containing SPE but no curing agent was used as the standard in each test. The sum of the scores of the 10 mice in the test group was used to calculate the efficacy rate for each compound as follows. Validity rate (%) = 100 - [total observed scores / 30]

【table】

Claims (1)

[Scope of Claims] 1. A composition for ingestion by animals, characterized by containing the following ingredients: (a) an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups; (b) sufficient to prevent leakage of said liquid polyester from the anal sphincter; and (i) an edible C ₁₂
and higher saturated fatty acids and their edible salts; (ii) sources of edible digestible _C12 and higher saturated fatty acids; (iii) edible, non-absorbable, non-digestible solids having at least 4 fatty acid groups. polyol fatty acid polyesters, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups, each fatty acid group having from about 8 to about 22 carbon atoms;
and (iv) an anti-diarrheal agent selected from the group consisting of edible, non-digestible esters of C ₁₀ to _{C 18} fatty acids having α-branched chains. 2 The liquid polyol fatty acid polyester is about 2
2. A composition according to claim 1, containing no more than 3 free hydroxyl groups. 3. The composition of claim 2, wherein the fatty acid ester group contains about 14 to about 18 carbon atoms. 4. The composition according to claim 3, wherein the polyol is selected from the group consisting of erythritol, xylitol, sorbitol, glucose and sucrose. 5. The composition of claim 4, wherein the polyol is sucrose. 6. The composition of claim 5, wherein the sucrose fatty acid polyester is selected from the group consisting of hexaoleate, heptaoleate and octaoleate of sucrose and mixtures thereof. 7. Contains at least about 10% by weight antidiarrheal agent;
A composition according to claim 1. 8. Contains at least about 20% by weight antidiarrheal agent;
A diarrhea composition according to claim 1. 9. The composition of claim 1, comprising about 20 to about 50% by weight of an antidiarrheal agent. 10. The composition according to claim 1, comprising about 10 to about 50% by weight of an antidiarrheal agent selected from the group consisting of edible _{C12 -} C24 saturated fatty acids and edible salts of _C12 - _C24 saturated fatty acids. thing. Claim 1 comprising about 10 to about 50% by weight of an antidiarrheal agent selected from the group consisting of: 11 sources of edible, digestible _C12 - _C24 saturated fatty acids and mixtures thereof;
The composition described in Section. 12. The composition according to claim 11, wherein the antidiarrheal agent is a lower alkyl ester of a _C12 - _C24 saturated fatty acid or a mixture thereof. 13. The composition of claim 11, wherein the antidiarrheal agent comprises substantially saturated triglyceride esters of _C12 - _C24 fatty acids or mixtures thereof. 14. The composition according to claim 13, wherein the antidiarrheal agent is hydrogenated palm oil. 15. The composition of claim 13, wherein the antidiarrheal agent is natural or synthetic cocoa butter. 16 Antidiarrheal agents include 1-stearoyl, 1-palmitoyl, 1-arachidoyl, 1-behenoyl 2,3-diolein, 2-oleoyl 1,3
-Distearin, 1,3-dipalmitin, 1,3
-Dialachidin and 1,3-dibehenin, 1-
Claim 13, which is an edible regiospecific triglyceride selected from the group consisting of oleoyl distearin, 1-palmitoyl distearin, 1-arachidoyl distearin, and 1-behenoyl distearin, and mixtures thereof. Composition of. 17. The composition of claim 16, comprising about 20 to about 40% by weight regiospecific triglycerides. 18 Edible, non-absorbable, non-digestible solid polyol fatty acid polyester having at least 4 fatty acid ester groups (where polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups, each The composition of claim 1, comprising from about 20 to about 50% by weight of an antidiarrheal agent selected from fatty acid groups having from about 8 to about 22 carbon atoms. 19. The composition according to claim 18, wherein the antidiarrheal agent is selected from the group consisting of _C10 - _C22 saturated fatty acid polyol esters. 20. The composition according to claim 1, which contains non-fat components and fat components, with about 10 to 100% of the total fat component consisting of the following components, and is used as a low-calorie fat food. (a) an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups; (b) sufficient to prevent leakage of said liquid polyester from the anal sphincter; and (i) an edible C ₁₂
and higher saturated fatty acids and their edible salts; (ii) sources of edible digestible _C12 and higher saturated fatty acids; (iii) edible, non-absorbable, non-digestible solids having at least 4 fatty acid groups. polyol fatty acid polyesters, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups, each fatty acid group having from about 8 to about 22 carbon atoms;
and (iv) an anti-diarrheal agent selected from the group consisting of edible, non-digestible esters of C ₁₀ to _{C 18} fatty acids having α-branched chains. 21. The composition of claim 20, wherein the liquid polyol fatty acid polyester contains no more than about 2 free hydroxyl groups. 22. The composition of claim 21, wherein the fatty acid ester group contains about 14 to about 18 carbon atoms. 23. Claim 2, wherein the polyol is selected from the group consisting of erythritol, xylitol, sorbitol, glucose and sucrose.
Composition according to item 2. 24. The composition of claim 23, wherein the polyol is sucrose. 25. The composition of claim 24, wherein the sucrose fatty acid polyester is selected from the group consisting of hexaoleate, heptaoleate and octaoleate of sucrose and mixtures thereof. 26. The composition of claim 20, wherein the liquid polyester portion of the fat component comprises at least about 10% by weight antidiarrheal agent. 27. The diarrhea composition of claim 20, wherein the liquid polyester portion of the fat component comprises at least about 20% by weight antidiarrheal agent. 28. The composition of claim 20, wherein the liquid polyester portion of the fat component comprises from about 20 to about 50% by weight antidiarrheal agent. 29 The liquid polyester part of the fat component is edible.
About 10 antidiarrheal agents selected from the group consisting of C ₁₂ - C ₂₄ saturated fatty acids and edible salts of C ₁₂ - _{C 24} saturated fatty acids.
21. The composition of claim 20, comprising from about 50% by weight. 30 The liquid polyester part of the fat component is edible,
an antidiarrheal agent selected from the group consisting of sources of digestible _C12 - _C24 saturated fatty acids and mixtures thereof;
21. A composition according to claim 20, comprising 50% by weight. 31. The composition according to claim 30, wherein the anti-diarrheal agent is a lower alkyl ester of a _C12 - _C24 saturated fatty acid or a mixture thereof. 32. The composition of claim 30, wherein the anti-diarrheal agent comprises substantially saturated triglyceride esters of _C12 - _C24 fatty acids or mixtures thereof. 33. The composition of claim 13, wherein the antidiarrheal agent is hydrogenated palm oil. 34. The composition of claim 32, wherein the antidiarrheal agent is natural or synthetic cocoa butter. 35 Antidiarrheal agents include 1-stearoyl, 1-palmitoyl, 1-arachidoyl, 1-behenoyl 2,3-diolein, 2-oleoyl 1,3
-Distearin, 1,3-dipalmitin, 1,3
-Dialachidin and 1,3-dibehenin, 1-
Claim 32, which is an edible regiospecific triglyceride selected from the group consisting of oleoyl distearin, 1-palmitoyl distearin, 1-arachidoyl distearin, and 1-behenoyl distearin, and mixtures thereof. Composition of. 36. The composition of claim 35, wherein the liquid polyester portion of the fat component comprises from about 20 to about 40% by weight regiospecific triglycerides. 37. Edible, non-absorbable, non-digestible solid polyol fatty acid polyesters in which the liquid polyester portion of the liquid component has at least 4 fatty acid ester groups (where the polyol is composed of sugars and sugar alcohols containing 4 to 8 hydroxyl groups) 21. The composition of claim 20, comprising from about 20 to about 50% by weight of an anti-diarrheal agent selected from the group consisting of: 20 to 50% by weight of an anti-diarrheal agent selected from the group consisting of: 1, 2, 3, 3, 3 and 4, each fatty acid group having from about 8 to about 22 carbon atoms. 38. The composition according to claim 37, wherein the antidiarrheal agent is selected from the group consisting of _C10 - _C22 saturated fatty acid polyol esters. 39. The composition according to claim 1, which comprises the following ingredients and is used as a unit dose of a pharmaceutical composition effective for inhibiting cholesterol absorption without causing diarrheal effects. (a) an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups; (b) sufficient to prevent leakage of said liquid polyester from the anal sphincter; and (i) an edible C ₁₂
and higher saturated fatty acids and their edible salts; (ii) sources of edible digestible _C12 and higher saturated fatty acids; (iii) edible, non-absorbable, non-digestible solids having at least 4 fatty acid groups. polyol fatty acid polyesters, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups, each fatty acid group having from about 8 to about 22 carbon atoms;
and (iv) an anti-diarrheal agent selected from the group consisting of edible, non-digestible esters of C ₁₀ to _{C 18} fatty acids having α-branched chains. 40. The composition of claim 39, wherein the liquid polyol fatty acid polyester contains no more than about 2 free hydroxyl groups. 41. The composition of claim 40, wherein the fatty acid ester group contains about 14 to about 18 carbon atoms. 42 Claim 4, wherein the polyol is selected from the group consisting of erythritol, xylitol, sorbitol, glucose and sucrose.
Composition according to item 1. 43. The composition of claim 42, wherein the polyol is sucrose. 44. The composition of claim 43, wherein the sucrose fatty acid polyester is selected from the group consisting of hexaoleate, heptaoleate and octaoleate of sucrose and mixtures thereof. 45. The composition of claim 39, comprising at least about 10% by weight antidiarrheal agent. 46. The diarrhea composition of claim 39, comprising at least about 20% by weight antidiarrheal agent. 47 Contains about 20 to about 50% by weight of an antidiarrheal agent,
A composition according to claim 39. 48. The composition of claim 39, comprising about 10 to about 50% by weight of an antidiarrheal agent selected from the group consisting of edible _C12 - _C24 saturated fatty acids and edible salts of _C12 - _C24 saturated fatty acids. thing. 49. Claim 3 comprising from about 10 to about 50% by weight of an antidiarrheal agent selected from the group consisting of edible, digestible sources of _C12 - _C24 saturated fatty acids and mixtures thereof.
Composition according to item 9. 50. The composition according to claim 49, wherein the antidiarrheal agent is a lower alkyl ester of a _C12 - _C24 saturated fatty acid or a mixture thereof. 51. The composition of claim 49, wherein the antidiarrheal agent comprises substantially saturated triglyceride esters of _C12 - _C24 fatty acids or mixtures thereof. 52. The composition of claim 51, wherein the antidiarrheal agent is hydrogenated palm oil. 53. The composition of claim 51, wherein the antidiarrheal agent is natural or synthetic cocoa butter. 54 Antidiarrheal agents include 1-stearoyl, 1-palmitoyl, 1-arachidoyl, 1-behenoyl 2,3-diolein, 2-oleoyl 1,3
-Distearin, 1,3-dipalmitin, 1,3
- dialachidin and 1,3-dibehenin is an edible regiospecific triglyceride selected from the group consisting of 1-oleoyl distearin, 1-palmitoyl distearin, 1-arachidoyl distearin, and 1-behenoyl distearin, and mixtures thereof. , the composition according to claim 51. 55. The composition of claim 54, comprising about 20 to about 40% by weight regiospecific triglycerides. 56 Edible, non-absorbable, non-digestible solid polyols having at least 4 fatty acid ester groups Fatty acid polyesters (where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups; each 40. The composition of claim 39, comprising from about 20 to about 50% by weight of an antidiarrheal agent selected from fatty acid groups having from about 8 to about 22 carbon atoms. 57. The composition according to claim 56, wherein the antidiarrheal agent is selected from the group consisting of _C10 - _C22 saturated fatty acid polyol esters. 58 A composition for ingestion by animals, characterized in that it contains the following ingredients: (a) Edible, non-absorbable, non-digestible liquid polyol fatty acid polyesters having at least 4 fatty acid ester groups (wherein polyols are selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups); (b) sufficient to prevent the liquid polyester from leaking out of the anal sphincter; and (i) an edible C ₁₂
and higher saturated fatty acids and their edible salts; (ii) sources of edible, digestible _C12 and higher saturated fatty acids; (iii) edible, nonabsorbable, nonabsorbable, digestible solid polyol fatty acid polyesters, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups, each fatty acid group having from about 8 to about 22 carbon atoms; and (iv) α-branched C ₁₀ —
An anti-diarrheal agent selected from the group consisting of edible, non-digestible esters of _C18 fatty acids. (c) from enough of the above vitamins to prevent very low levels of any of the fat-soluble vitamins vitamin A, vitamin D, vitamin E and vitamin K in animals (including humans) consuming this composition; A fat-soluble vitamin selected from the group consisting of: 59. The composition of claim 58, wherein the liquid polyol fatty acid polyester contains no more than about 2 free hydroxyl groups. 60. The composition of claim 59, wherein the fatty acid ester group contains about 14 to about 18 carbon atoms. 61 Claim 6, wherein the polyol is selected from the group consisting of erythritol, xylitol, sorbitol, glucose and sucrose.
The composition according to item 0. 62. The composition of claim 61, wherein the polyol is sucrose. 63. The composition of claim 62, wherein the sucrose fatty acid polyester is selected from the group consisting of hexaoleate, heptaoleate and octaoleate of sucrose and mixtures thereof. 64. The composition of claim 58, comprising at least about 10% by weight antidiarrheal agent. 65. The composition of claim 58, comprising at least about 20% by weight of an antidiarrheal agent. 66 Contains about 20 to about 50% by weight of an antidiarrheal agent,
A composition according to claim 58. 67. The antidiarrheal agent according to claim 58, comprising about 10 to about 50% by weight of an antidiarrheal agent selected from the group consisting of edible C ₁₂ - C ₂₄ saturated fatty acids and edible salts of C ₁₂ - _{C 24} saturated fatty acids. Composition. 68 Antidiarrheal agents selected from the group consisting of edible, digestible _C12 - _C24 saturated fatty acid sources and mixtures thereof.
Claim 58 containing from 10 to about 50% by weight
The composition described in Section. 69. The composition of claim 68, wherein the anti-diarrheal agent is a lower alkyl ester of a _C12 - _C24 saturated fatty acid or a mixture thereof. 70. The composition of claim 68, wherein the antidiarrheal agent comprises substantially saturated triglyceride esters of _C12 - _C24 fatty acids or mixtures thereof. 71. The composition of claim 70, wherein the antidiarrheal agent is hydrogenated palm oil. 72. The composition of claim 70, wherein the antidiarrheal agent is natural or synthetic cocoa butter. 73 Antidiarrheal agents include 1-stearoyl, 1-palmitoyl, 1-arachidoyl and 1-behenoyl 2,3-diokirein, 2-oleoyl 1,
3-distearin, 1,3-dipalmitin, 1,
3-Diarachidin and 1,3-dibehenine, 1
- an edible regiospecific triglyceride selected from the group consisting of oleoyl distearin, 1-palmitoyl distearin, 1-arachidoyl distearin, and 1-behenoyl distearin, and mixtures thereof. Compositions as described. 74. The composition of claim 73, comprising about 20 to about 40% by weight regiospecific triglycerides. 75 Edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups (wherein the polyol is 4 to 8
from about 20 to about 50% by weight of an antidiarrheal agent selected from the group consisting of sugars and sugar alcohols containing hydroxyl groups, each fatty acid group having from about 8 to about 22 carbon atoms. , the composition of claim 58. 76. The composition according to claim 75, wherein the antidiarrheal agent is selected from the group consisting of _C10 - _C22 saturated fatty acid polyol esters. 77 About 50 to about 90% by weight non-absorbable, non-digestible liquid polyol fatty acid polyester, at least about 10% by weight antidiarrheal agent and 0.001 to 2% by weight vitamin A, vitamin D, vitamin E, vitamin K and 59. The composition of claim 58, comprising a vitamin selected from the group consisting of mixtures thereof. 78 Contains non-fat components and fat components, with about 10 to 100% of the total fat component consisting of (a) edible, non-absorbable, non-digestible liquid polyols having at least 4 fatty acid ester groups; (b) the liquid polyester is is sufficient to prevent leakage from the anal sphincter and contains (i) edible C ₁₂
and higher saturated fatty acids and their edible salts; (ii) sources of edible, digestible _C12 and higher saturated fatty acids; (iii) edible, non-absorbable, non-digestible sources having at least 4 fatty acid groups; solid polyol fatty acid polyester (in which case the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups;
each fatty acid group having about 8 to about 22 carbon atoms), and (iv) C ₁₀ -C ₁₈ having α-branched chains.
Contains an anti-diarrheal agent selected from the group consisting of edible, non-digestible esters of fatty acids; and any of the fat-soluble vitamins vitamin A, vitamin D, vitamin E, and vitamin K, in animals (including humans) ingesting this composition. Enriched with fat-soluble vitamins selected from the group consisting of more of the above vitamins than are naturally present in this composition to prevent very low levels of the vitamins in
59. The composition according to claim 58, which is used as a low-calorie fat-containing food. 79. The composition of claim 78, wherein the liquid polyol fatty acid polyester contains no more than about 2 free hydroxyl groups. 80. The composition of claim 79, wherein the fatty acid ester group contains about 14 to about 18 carbon atoms. 81. Claim 8, wherein the polyol is selected from the group consisting of erythritol, xylitol, sorbitol, glucose and sucrose.
The composition according to item 0. 82. The composition of claim 81, wherein the polyol is sucrose. 83. The composition of claim 82, wherein the sucrose fatty acid polyester is selected from the group consisting of hexaoleate, heptaoleate and octaoleate of sucrose and mixtures thereof. 84. The composition of claim 78, wherein the liquid polyester portion of the fat component comprises at least about 10% by weight antidiarrheal agent. 85. The composition of claim 78, wherein the liquid polyester portion of the fat component comprises at least about 20% by weight antidiarrheal agent. 86. The composition of claim 78, wherein the liquid polyester portion of the fat component comprises from about 20 to about 50% by weight antidiarrheal agent. 87 The polyester part of the fat component is edible C ₁₂ -
79. The composition of claim 78, comprising from about 10 to about 50% by weight of an antidiarrheal agent selected from the group consisting of _C24 saturated fatty acids and edible salts of _C12 - _C24 saturated fatty acids. 88 The liquid polyester part of the fat component is edible.
from about 10 to about 50 of an antidiarrheal agent selected from the group consisting of digestible _C12 - _C24 saturated fatty acid sources and mixtures thereof;
79. The composition of claim 78, comprising % by weight. 89. The composition of claim 88, wherein the antidiarrheal agent is a lower alkyl ester of a _C12 - _C24 saturated fatty acid or a mixture thereof. 90. The composition of claim 88, wherein the anti-diarrheal agent comprises substantially saturated triglyceride esters of _C12 - _C24 fatty acids or mixtures thereof. 91. The composition of claim 90, wherein the antidiarrheal agent is hydrogenated palm oil. 92. The composition of claim 70, wherein the antidiarrheal agent is natural or synthetic cocoa butter. 93 Antidiarrheal agents include 1-stearoyl, 1-palmitoyl, 1-arachidoyl, and 1-behenoyl 2,3-diokirein, 2-oleoyl 1,
3-distearin, 1,3-dipalmitin, 1,
3-Diarachidin and 1,3-dibehenine, 1
- an edible regiospecific triglyceride selected from the group consisting of oleoyl distearin, 1-palmitoyl distearin, 1-arachidoyl distearin, and 1-behenoyl distearin, and mixtures thereof. Compositions as described. 94. The composition of claim 93, wherein the liquid polyester portion of the fat component comprises from about 20 to about 40% by weight regiospecific triglycerides. 95 Edible, non-absorbable, non-digestible liquid polyol fatty acid polyesters in which the liquid polyester portion of the fat component has at least 4 fatty acid ester groups (where polyols are sugars and sugars containing 4 to 8 hydroxyl groups) about 20 antidiarrheal agents selected from the group consisting of alcohols, each fatty acid group having about 8 to about 22 carbon atoms;
79. The composition of claim 78, comprising from about 50% by weight. 96. The composition according to claim 95, wherein the antidiarrheal agent is selected from the group consisting of _C10 - _C22 saturated fatty acid polyol esters. 97 Claims for use as a unit dose of a pharmaceutical composition containing the following ingredients and effective in inhibiting the absorption of cholesterol without causing diarrheal effects or interfering with the body's stores of fat-soluble vitamins: Composition according to paragraph 58. (a) an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups; (b) sufficient to prevent leakage of said liquid polyester from the anal sphincter; and (i) an edible C ₁₂
and higher saturated fatty acids and their edible salts; (ii) sources of edible digestible _C12 and higher saturated fatty acids; (iii) edible, non-absorbable, non-digestible solids having at least 4 fatty acid groups. polyol fatty acid polyesters, where the polyol is selected from the group consisting of sugars and sugar alcohols containing 4 to 8 hydroxyl groups, each fatty acid group having from about 8 to about 22 carbon atoms;
and (iv) an anti-diarrheal agent selected from the group consisting of edible, non-digestible esters of C ₁₀ to _{C 18} fatty acids having α-branched chains. (c) from enough of the above vitamins to prevent very low levels of any of the fat-soluble vitamins vitamin A, vitamin D, vitamin E and vitamin K in animals (including humans) consuming this composition; A fat-soluble vitamin selected from the group consisting of: 98. The composition of claim 97, wherein the liquid polyol fatty acid polyester contains about 2 or less free hydroxyl groups. 99. The composition of claim 98, wherein the fatty acid ester group contains about 14 to about 18 carbon atoms. 100. The composition of claim 99, wherein the polyol is selected from the group consisting of erythritol, xylitol, sorbitol, glycose and sucrose. 101. The composition of claim 100, wherein the polyol is sucrose. 102. The composition of claim 101, wherein the sucrose fatty acid polyester is selected from the group consisting of hexaoleate, heptaoleate and octaoleate of sucrose and mixtures thereof. 103. The composition of claim 97, comprising at least about 10% by weight antidiarrheal agent. 104. The composition of claim 97, comprising at least about 20% by weight antidiarrheal agent. 105. The composition of claim 97, comprising from about 20 to about 50% by weight of an antidiarrheal agent. 106 Edible _C12 - _C24 Saturated Fatty Acids and _C12 - _C24
98. The composition of claim 97, comprising from about 10 to about 50% by weight of an antidiarrheal agent selected from the group consisting of edible salts of saturated fatty acids. 107. The composition of claim 97, comprising from about 10 to about 50% by weight of an antidiarrheal agent selected from the group consisting of sources of edible, digestible _C12 - _C24 saturated fatty acids and mixtures thereof. 108. The composition of claim 107, wherein the antidiarrheal agent is a lower alkyl ester of a _C12 - _C24 saturated fatty acid or a mixture thereof. 109. The composition of claim 107, wherein the antidiarrheal agent comprises substantially saturated triglyceride esters of _C12 - _C24 fatty acids or mixtures thereof. 110 The antidiarrheal agent is hydrogenated palm oil,
A composition according to claim 109. 111. The composition of claim 109, wherein the antidiarrheal agent is natural or synthetic cocoa butter. 112 The antidiarrheal agent is 1-stearoyl, 1-
palmitoyl, 1-arachidoyl and 1-behenoyl 2,3-diolein, 2-oleoyl 1,
3-distearin, 1,3-dipalmitin, 1,
3-Diarachidin and 1,3-dibehenin 1-
Claim 109, which is an edible regiospecific triglyceride selected from the group consisting of oleoyl distearin, 1-palmitoyl distearin, 1-arachidoyl distearin, and 1-behenoyl distearin, and mixtures thereof. Composition of. 113. The composition of claim 112, comprising about 20 to about 40% by weight of regiospecific triglycerides. 114 Edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups (where polyols range from 4 to 8
from about 20 to about 50% by weight of an antidiarrheal agent selected from the group consisting of sugars and sugar alcohols containing hydroxyl groups, each fatty acid group having from about 8 to about 22 carbon atoms; A composition according to claim 97. 115. The composition of claim 114, wherein the antidiarrheal agent is selected from the group consisting of _C10 - _C22 saturated fatty acid polyol esters. 116 Vitamin A, vitamin D, vitamin E,
98. The composition of claim 97, containing at least about 0.1 RDA of a vitamin selected from the group consisting of vitamin K and mixtures thereof.