Compositions for treating hypercholesterolemia

Abstract

Anti-anal leakage agents are used in combination with liquid polyol fatty acid polyesters to provide pharmaceutical and food compositions for treating and/or preventing hypercholesterolemia while avoiding undesired anal leakage of the liquid polyesters.

What is claimed is: 
     
       1. A composition of matter, comprising: (a) an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and   (b) sufficient anti-anal leakage agent to prevent leakage of said liquid polyester through the anal sphincter.Iadd., wherein the anti-anal leakage agent is a member selected from the group consisting of: edible C 12  and higher saturated fatty acids, and their edible salts; edible, digestible sources of C 12  and higher saturated fatty acids, other than tristearin or C 18  saturated fatty acid esters of 1,3-propanediol; edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group is a saturated fatty acid group having from about 8 to about 22 carbon atoms; and edible, non-digestible esters of alpha-branched chain C 10  -C 18  fatty acids.Iaddend..   
     
     
       2. A composition according to claim 1 wherein the liquid polyol fatty acid polyester contains no more than about 2 free hydroxyl groups. 
     
     
       3. A composition according to claim 2 wherein the fatty acid ester groups contain from about 14 to about 18 carbon atoms. 
     
     
       4. A composition according to claim 3 wherein the polyol is a member selected from the group consisting of erythritol, xylitol, sorbitol, glucose and sucrose. .[. 
     
     
       5.  A composition according to claim 4 wherein the polyol is sucrose..]. .[.6. A composition according to claim 5 wherein the sucrose fatty acid polyester is a member selected from the group consisting of the hexaoleate, heptaoleate and octaoleate of sucrose, and mixtures thereof..]. .[.7. A composition according to claim 1 wherein the anti-anal leakage agent is a member selected from the group consisting of: edible C 12  and higher saturated fatty acids, and their edible salts; edible, digestible sources of C 12  and higher saturated fatty acids; edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and edible, non-digestible esters of alpha-branched 
     
     
        chain C 10  -C 18  fatty acids..]. 8. A composition according to claim .[.7.]. .Iadd.1 .Iaddend.which comprises at least about 10% by 
     
     
        weight of the anti-anal leakage agent. 9. A composition according to claim .[.7.]. .Iadd.1 .Iaddend.which comprises at least about 20% by weight of 
     
     
        the anti-anal leakage agent. 10. A composition according to claim .[.7.]. .Iadd.1 .Iaddend.which comprises from about 20% to about 50% by weight of 
     
     
        the anti-anal leakage agent. 11. A composition according to claim .[.7.]. .Iadd.1 .Iaddend.which comprises from about 10% to about 50% by weight of an anti-anal leakage 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. 12. A composition according to claim .[.7.]. .Iadd.1 .Iaddend.which comprises from about 10% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible, digestible sources of C 12  -C 24  saturated fatty acids, and mixtures thereof.Iadd., other than tristearin or C 18  saturated 
     
     
        fatty acid esters of 1,3-propanediol.Iaddend.. 13. A composition according to claim 12 wherein the anti-anal leakage agent is a lower alkyl ester of 
     
     
        C 12  -C 24  saturated fatty acids, or mixtures thereof. 14. A composition according to claim 12 wherein the anti-anal leakage agent comprises substantially saturated triglyceride esters of C 12  -C 24  fatty acids, or mixtures thereof.Iadd., other than 
     
     
        tristearin.Iaddend.. 15. A composition according to claim 14 wherein the 
     
     
        anti-anal leakage agent is hydrogenated palm oil. 16. A composition according to claim 14 wherein the anti-anal leakage agent is natural or 
     
     
        synthetic cocoa butter. 17. A composition according to claim 14 wherein the anti-anal leakage agent is an edible position-specific triglyceride selected from the group consisting of: the 1-stearoyl, 1-palmitoyl, 1-arachidoyl and 1-behenoyl 2,3-dioleins; the 2-oleoyl 1,3-distearins, 1,3-dipalmitins, 1,3-diarachidins and 1,3-dibehenins; 1-oleoyl distearin; 1-palmitoyl distearin; 1-arachidoyl distearin; and 1-behenoyl distearin; 
     
     
        and mixtures thereof. 18. A composition according to claim 17 which comprises from about 20% to about 40% by weight of the position-specific 
     
     
        triglyceride. 19. A composition according to claim .[.7.]. .Iadd.1 .Iaddend.which comprises from about 20% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group .[.has.]. .Iadd.is a saturated fatty acid group having .Iaddend.from about .[.8.]. .Iadd.10 
     
     
        .Iaddend.to about 22 carbon atoms. 20. A composition according to claim 19 wherein the anti-anal leakage agent is selected from the group consisting of .[.C 10  -C 22  saturated fatty acid polyol esters.]. .Iadd.sucrose octastearate, sucrose octapalmitate, sucrose heptastearate, 
     
     
        xylitol pentastearate and galactose pentapalmitate.Iaddend.. 21. A method for inhibiting the absorption of cholesterol in animals without causing an anal leakage effect comprising systemically administering to an animal susceptible to or afflicted with hypercholesterolemia successive therapeutically effective doses of a composition comprising: a non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms and sufficient anti-anal leakage agent to prevent 
     
     
        leakage of said liquid polyester through the anal sphincter. 22. A method according to claim 21 wherein the anti-anal leakage agent is a member selected from the group consisting of: edible C 12  -C 24  saturated fatty acids, and their edible salts; edible, digestible sources of C 12  -C 24  saturated fatty acids; edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and edible, non-digestible esters of alpha-branched chain 
     
     
        C 10  -C 18  fatty acids. 23. A method according to claim 22 wherein the composition comprises at least about 10% by weight of the anti-anal 
     
     
        leakage agent. 24. A method according to claim 23 wherein the composition comprises at least about 20% by weight of the anti-anal leakage agent. 
     
     
            A low calorie fat-containing food composition comprising non-fat ingredients and fat ingredients, wherein from about 10% to about 100% of the total fat ingredients comprise: (a) a portion comprising an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and   (b) sufficient anti-anal leakage agent, .Iadd.other than tristearin or C 18  saturated fatty acid esters of 1,3-propanediol, .Iaddend.to   
     
     
        prevent leakage of said liquid polyester through the anal sphincter. 26. A composition according to claim 25 wherein the liquid polyol fatty acid 
     
     
        polyester contains no more than about 2 free hydroxyl groups. 27. A composition according to claim 26 wherein the fatty acid ester groups 
     
     
        contain from about 14 to about 18 carbon atoms. 28. A composition according to claim 27 wherein the polyol is a member selected from the group consisting of erythritol, xylitol, sorbitol, glucose and sucrose. 
     
     
        .[.9.  A composition according to claim 28 wherein the polyol is sucrose..]. .[.30. A composition according to claim 29 wherein the sucrose fatty acid polyester is a member selected from the group consisting of the hexaoleate, heptaoleate and octaoleate of sucrose, and mixtures 
     
     
        thereof..]. 31. A composition according to claim 25 wherein the anti-anal leakage agent is a member selected from the group consisting of: edible C 12  and higher saturated fatty acids, and their edible salts; edible, digestible sources of C 12  and higher saturated fatty acids.Iadd., other than tristearin or C 18  saturated fatty acid esters of 1,3-propanediol.Iaddend.; edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and edible, non-digestible esters of alpha-branched chain C 10  -C 18  fatty 
     
     
        acids. 32. A composition according to claim 31 wherein the liquid polyester portion of the fat ingredients comprises at least about 10% by 
     
     
        weight of the anti-anal leakage agent. 33. A composition according to claim 32 wherein the liquid polyester portion of the fat ingredients comprises at least about 20% by weight of the anti-anal leakage agent. 
     
     
            A composition according to claim 33 wherein the liquid polyester portion of the fat ingredients comprises from about 20% to about 50% by 
     
     
        weight of the anti-anal leakage agent. 35. A composition according to claim 31 wherein the liquid polyester portion of the fat ingredients comprises from about 10% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible C 12  -C 24  saturated fatty acids and edible salts of C 12  -C 24  fatty acids. 
     
     
         6. A composition according to claim 31 wherein the liquid polyester portion of the fat ingredients comprises from about 10% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible, digestible sources of C 12  -C 24  saturated fatty acids, and mixtures thereof.Iadd., other than tristearin or C 18  saturated 
     
     
        fatty acid esters of 1,3-propanediol.Iaddend.. 37. A composition according to claim 36 wherein the anti-anal leakage agent is a lower alkyl ester of 
     
     
        C 12  -C 24  saturated fatty acids, or mixtures thereof. 38. A composition according to claim 36 wherein the anti-anal leakage agent comprises substantially saturated triglyceride esters of C 12  -C 24  fatty acids, or mixtures thereof.Iadd., other than 
     
     
        tristearin.Iaddend.. 39. A composition according to claim 38 wherein the 
     
     
        anti-anal leakage agent is hydrogenated palm oil. 40. A composition according to claim 38 wherein the anti-anal leakage agent is natural or 
     
     
        synthetic cocoa butter. 41. A composition according to claim 38 wherein the anti-anal leakage agent is an edible position-specific triglyceride selected from the group consisting of: the 1-stearoyl, 1-palmitoyl, 1-arachidoyl and 1-behenoyl 2,3-dioleins; the 2-oleoyl 1,3-distearins, 1,3-dipalmitins, 1,3-diarachidins and 1,3-dibehenins; 1-oleoyl distearin; 1-palmitoyl distearin; 1-arachidoyl distearin; and 1-behenoyl distearin; 
     
     
        and mixtures thereof. 42. A composition according to claim 41 wherein the liquid polyester portion of the fat ingredients comprises from about 20% 
     
     
        to about 40% by weight of the position-specific triglyceride. 43. A composition according to claim 31 wherein the liquid polyester portion of the fat ingredients comprises from about 20% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to 
     
     
        about 22 carbon atoms. 44. A composition according to claim 43 wherein the anti-anal leakage agent is selected from the group consisting of C 10   
     
     
        -C 22  saturated fatty acid polyol esters. 45. A pharmaceutical composition in effective unit dosage amounts for inhibiting the absorption of cholesterol without causing an anal leakage effect, comprising: a. from about 0.1 gram to about 5 grams of an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and   b. sufficient anti-anal leakage agent to prevent leakage of said liquid   
     
     
        polyester through the anal sphincter. 46. A composition according to claim 45 wherein the liquid polyol fatty acid polyester contains no more than 
     
     
        about 2 free hydroxyl groups. 47. A composition according to claim 46 wherein the fatty acid ester groups contain from about 14 to about 18 
     
     
        carbon atoms. 48. A composition according to claim 47 wherein the polyol is a member selected from the group consisting of erythritol, xylitol, 
     
     
        sorbitol, glucose and sucrose. 49. A composition according to claim 48 
     
     
        wherein the polyol is sucrose. 50. A composition according to claim 49 wherein the sucrose fatty acid polyester is a member selected from the group consisting of the hexaoleate, heptaoleate and octaoleate of sucrose, 
     
     
        and mixtures thereof. 51. A composition according to claim 45 wherein the anti-anal leakage agent is a member selected from the group consisting of: edible C 12  and higher saturated fatty acids, and their edible salts; edible, digestible sources of C 12  and higher saturated fatty acids; edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and edible, non-digestible esters of alpha-branched 
     
     
        chain C 10  -C 18  fatty acids. 52. A composition according to claim 51 which comprises at least about 10% by weight of the anti-anal leakage 
     
     
        agent. 53. A composition according to claim 51 which comprises at least 
     
     
        about 20% by weight of the anti-anal leakage agent. 54. A composition according to claim 51 which comprises from about 20% to about 50% by 
     
     
        weight of the anti-anal leakage agent. 55. A composition according to claim 51 which comprises from about 10% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible C 12  -C 24  saturated fatty acids and edible salts of C 12   
     
     
        -C 24  fatty acids. 56. A composition according to claim 51 which comprises from about 10% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible, digestible sources of 
     
     
        C 12  -C 24  saturated fatty acids, and mixtures thereof. 57. A composition according to claim 56 wherein the anti-anal leakage agent is a lower alkyl ester of C 12  -C 24  saturated fatty acids, or mixtures 
     
     
        thereof. 58. A composition according to claim 56 wherein the anti-anal leakage agent comprises substantially saturated triglyceride esters of 
     
     
        C 12  -C 24  fatty acids, or mixtures thereof. 59. A composition according to claim 58 wherein the anti-anal leakage agent is hydrogenated 
     
     
        palm oil. 60. A composition according to claim 58 wherein the anti-anal 
     
     
        leakage agent is natural or synthetic cocoa butter. 61. A composition according to claim 58 wherein the anti-anal leakage agent is an edible position-specific triglyceride selected from the group consisting of: the 1-stearoyl, 1-palmitoyl, 1-arachidoyl and 1-behenoyl 2,3-dioleins; the 2-oleoyl 1,3-distearins, 1,3-dipalmitins, 1,3-diarachidins and 1,3-dibehenins; 1-oleoyl distearin; 1-palmitoyl distearin; 1-arachidoyl 
     
     
        distearin; and 1-behenoyl distearin; and mixtures thereof. 62. A composition according to claim 61 which comprises from about 20% to about 
     
     
        40% by weight of the position-specific triglyceride. 63. A composition according to claim 51 which comprises from about 20% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to 
     
     
        about 22 carbon atoms. 64. A composition according to claim 63 wherein the anti-anal leakage agent is selected from the group consisting of C 10   
     
     
        -C 22  saturated fatty acid polyol esters. .Iadd.65.  A composition according to claim 12 wherein said edible sources of saturated fatty acids have an iodine value of from about 9.8 to about 50. .Iaddend. .Iadd.66. A composition according to claim 36 wherein said edible sources of saturated fatty acids have an iodine value of from about 9.8 to about 50. .Iaddend. 
     
     
        .Iadd.67.  A composition of matter, comprising: (a) an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, wherein the polyol is sucrose and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and   (b) sufficient anti-anal leakage agent to prevent leakage of said liquid polyester through the anal sphincter, wherein the anti-anal leakage agent is a member selected from the group consisting of: edible C 12  and higher saturated fatty acids, and their edible salts; edible, digestible sources of C 12  and higher saturated fatty acids; edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group is a saturated fatty acid group having from about 8 to about 22 carbon atoms; and edible, non-digestible esters of alpha-branched chain C 10  -C 18  fatty acids. .Iaddend. .Iadd.68. A composition according to claim 67 wherein the sucrose fatty acid polyester is a member selected from the group consisting of the hexaoleate, heptaoleate and octaoleate of sucrose, and   
     
     
        mixtures thereof. .Iaddend. .Iadd.69.  A composition according to claim 67 which comprises from about 20% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is sucrose and wherein each fatty acid group is a saturated fatty acid group having from about 10 to about 22 carbon atoms. .Iaddend. .Iadd.70. A composition according to claim 69 wherein the anti-anal leakage agent is selected from the group consisting of sucrose octastearate, sucrose octapalmitate, and sucrose heptastearate. .Iaddend. .Iadd.71. A low calorie fat-containing food composition comprising non-fat ingredients and fat ingredients, wherein from about 10% to about 100% of the total fat ingredients comprise: (a) a portion comprising an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, wherein the polyol is sucrose and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and   (b) sufficient anti-anal leakage agent to prevent leakage of said liquid polyester through the anal sphincter. .Iaddend. .Iadd.72. A composition according to claim 71 wherein the sucrose fatty acid polyester is a member selected from the group consisting of the hexaoleate, heptaoleate and   
     
     
        octaoleate of sucrose, and mixtures thereof. .Iaddend. .Iadd.73.  A composition according to claim 71 wherein the liquid polyester portion of the fat ingredients comprises from about 20% to about 50% by weight of an anti-anal leakage agent selected from the group consisting of edible, non-absorbable, non-digestible solid polyol fatty acid polyesters having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms. .Iaddend. .Iadd.74. A composition according to claim 73 wherein the anti-anal leakage agent is selected from the group consisting of C 10  -C 22  saturated fatty acid polyol esters of sucrose. .Iaddend. .Iadd.75. A composition according to claim 74 wherein the anti-anal leakage agent is selected from the group consisting of sucrose octastearate, sucrose octapalmitate and sucrose heptastearate. .Iaddend. .Iadd.76. A composition of matter, comprising fat ingredients and nonfat ingredients in which at least a portion of the fat ingredients comprise: (a) an edible, non-absorbable, non-digestible liquid polyol fatty acid polyester having at least 4 fatty acid ester groups, wherein the polyol is selected from the group consisting of sugars and sugar alcohols containing from 4 to 8 hydroxyl groups and wherein each fatty acid group has from about 8 to about 22 carbon atoms; and   (b) sufficient anti-anal leakage agent, other than tristearin or C 18  saturated fatty acid esters of 1,3-propanediol, to prevent leakage of said liquid polyester through the anal sphincter. .Iaddend.