Patent Application: US-81541404-A

Abstract:
novel preparations of phytochemical ingredients that are serviceable as health supplements for the body , particularly tissues susceptible to cancer , including , e . g . prostate tissue and breast tissue and , including , e . g ., female breast tissue ; for example , all possible combinations and permutations of member from each of the following 5 groups : 1 ) plant indoles , including sources of plant indoles ; 2 ) plant flavonoids , polyphenols , stilbenes and related substances , including sources of plant flavonoids , polyphenols , stilbenes , and related substances ; 3 ) d - glucaric acid and derivatives thereof and sources thereof ; 4 ) medium chain triglycerides and sources thereof ; and 5 ) phospholipids and sources thereof .

Description:
this invention provides novel preparations of encapsulated bioavailable chelating agents ( poebaca ), wherein in each of different preferred embodiments a poebaca is comprised of the following ingredients ( or peobacai ), for which non - limiting examples are listed in table 1 : a ) one or more members selected from group a ( e . g . alpha lipoic acid ); b ) one or more members selected from group b ( e . g . edta ); c ) one or more members selected from group c ( e . g . lecithin ); d ) optionally , in separate embodiments , one or more members selected from group d ( e . g . magnesium chloride ); e ) optionally , in separate embodiments , one or more members selected from group e ( glutathione ); f ) optionally , in separate embodiments , one or more members selected from group f ( e . g . vinpocetine ); g ) optionally , in separate embodiments , one or more members selected from group g ( e . g . nitrogen gas ); wherein the ingredients are prepared in a manner that provides the encapsulation of a significant fraction of one or more ingredient ( s ) into liposomes or micropsheres . this invention also provides novel preparations comprised of the following ( optionally encapsulated ) edible ingredients , for which non - limiting examples are listed in table 3 : a ) one or more members selected from group 1 ( e . g . dim ); b ) one or more members selected from group 2 ( e . g . grape skin extract , resveratrol , and piceatannol ); c ) one or more members selected from group 3 ( e . g . calcium d - glucarate ); d ) one or more members selected from group 4 ( e . g . medium chain triglycerides ); e ) optionally , in separate embodiments , one or more members selected from group 5 ( e . g . lecithin ); in one embodiments , this invention provides that a serviceable ingredient that is a member of group 4 , can be a preparation in which at least half of the content by weight is mcts , said at least half of the content by weight of mcts comprising at least about 40 % mcts having lengths between c 5 and c 11 . in separate embodiments , said at least half of the content by weight of mcts can range from at least about 40 % to at least about 95 % ( also including every integer value in this range ) mcts having lengths between c 5 and c 11 . thus , for example , this invention provides that a serviceable ingredient that is a member of group 4 , can be a preparation in which at least half of the content by weight is mcts , said at least half of the content by weight of mcts comprising at least about 90 % mcts having lengths between c 5 and c 11 . according to this invention , separate preferred embodiments of “ preparations of encapsulated bioavailable chelating agents ” ( i . e . poebaca ) are provided herein , each of which is comprised of at least a minimum number of members , i . e . “ n ” member ( s ), selected from group a , where n = 1 , 2 , 3 ,. . . 100 , including every integer value within the range of 1 to 100 . thus , there are at least 100 embodiments of poebaca , differing in that the minimum number of members selected from group a that is contained in each embodiment ranges from one to one hundred ( including every integer value in between ), i . e . at least one , at least two , at least three , at least four , . . . , and up to at least 100 . thus , one preferred embodiment of this invention provides a poebaca comprised of at least one member selected from group a ; another preferred embodiment of this invention provides a poebaca comprised of at least two members selected from group a ; another preferred embodiment of this invention provides a poebaca comprised of at least three members selected from group a ; etc . ; another preferred embodiment of this invention provides a poebaca comprised of at least one hundred members selected from group a ; for convenience these are referred to as preferred embodiments a1 to a100 , and these separate embodiments are intended to be the subject matter of separate claims according to this invention . according to this invention , separate preferred embodiments of “ preparations of encapsulated bioavailable chelating agents ” ( i . e . poebaca ) are provided herein , each of which is comprised of at least a minimum number of members , i . e . “ n ” member ( s ), selected from group b , where n = 1 , 2 , 3 , . . . , 100 , including every integer value within the range of 1 to 100 . thus , there are at least 100 embodiments of poebaca , differing in that the minimum number of members selected from group b that is contained in each embodiment ranges from one to one hundred ( including every integer value in between ), i . e . at least one , at least two , at least three , at least four , . . . , and up to at least 100 . thus , one preferred embodiment of this invention provides a poebaca comprised of at least one member selected from group b ; another preferred embodiment of this invention provides a poebaca comprised of at least two members selected from group b ; another preferred embodiment of this invention provides a poebaca comprised of at least three members selected from group b ; etc . ; another preferred embodiment of this invention provides a poebaca comprised of at least one hundred members selected from group b ; for convenience these are referred to as preferred embodiments b1 to b100 , and these separate embodiments are intended to be the subject matter of separate claims according to this invention . according to this invention , separate preferred embodiments of “ preparations of encapsulated bioavailable chelating agents ” ( i . e . poebaca ) are provided herein , each of which is comprised of at least a minimum number of members , i . e . “ n ” member ( s ), selected from group c , where n = 1 , 2 , 3 , . . . , 100 , including every integer value within the range of 1 to 100 . thus , there are at least 100 embodiments of poebaca , differing in that the minimum number of members selected from group c that is contained in each embodiment ranges from one to one hundred ( with every integer value in between ), i . e . at least one , at least two , at least three , at least four , . . . , and up to at least 100 . thus , one preferred embodiment of this invention provides a poebaca comprised of at least one member selected from group c ; another preferred embodiment of this invention provides a poebaca comprised of at least two members selected from group c ; another preferred embodiment of this invention provides a poebaca comprised of at least three members selected from group c ; etc . ; another preferred embodiment of this invention provides a poebaca comprised of at least one hundred members selected from group c ; for convenience these are referred to as preferred embodiments c1 to 100 , and these separate embodiments are intended to be the subject matter of separate claims according to this invention . according to this invention , separate preferred embodiments of “ preparations of encapsulated bioavailable chelating agents ” ( i . e . poebaca ) are provided herein , each of which is comprised of at least a minimum number of members , i . e . “ n ” member ( s ), selected from group d , where n = 1 , 2 , 3 , . . . , 20 , including every integer value within the range of 1 to 20 . thus , there are at least 20 embodiments of poebaca , differing in that the minimum number of members selected from group d that is contained in each embodiment ranges from one to twenty ( including every integer value in between ), i . e . at least one , at least two , at least three , at least four , . . . , and up to at least 20 . thus , one preferred embodiment of this invention provides a poebaca comprised of at least one member selected from group d ; another preferred embodiment of this invention provides a poebaca comprised of at least two members selected from group d ; another preferred embodiment of this invention provides a poebaca comprised of at least three members selected from group d ; etc . ; another preferred embodiment of this invention provides a poebaca comprised of at least twenty members selected from group d ; for convenience these are referred to as preferred embodiments d1 to d20 , and these separate embodiments are intended to be the subject matter of separate claims according to this invention . according to this invention , separate preferred embodiments of “ preparations of encapsulated bioavailable chelating agents ” ( i . e . poebaca ) are provided herein , each of which is comprised of at least a minimum number of members , i . e . “ n ” member ( s ), selected from group e , where n = 1 , 2 , 3 ,. . . , 20 , including every integer value within the range of 1 to 20 . thus , there are at least 20 embodiments of poebaca , differing in that the minimum number of members selected from group e that is contained in each embodiment ranges from one to twenty ( including every integer value in between ), i . e . at least one , at least two , at least three , at least four , . . . , and up to at least 20 . thus , one preferred embodiment of this invention provides a poebaca comprised of at least one member selected from group e ; another preferred embodiment of this invention provides a poebaca comprised of at least two members selected from group e ; another preferred embodiment of this invention provides a poebaca comprised of at least three members selected from group e ; etc . ; another preferred embodiment of this invention provides a poebaca comprised of at least twenty members selected from group e ; for convenience these are referred to as preferred embodiments e1 to e20 , and are intended to be claimed subject matter according to this invention . according to this invention , separate preferred embodiments of “ preparations of encapsulated bioavailable chelating agents ” ( i . e . poebaca ) are provided herein , each of which is comprised of at least a minimum number of members , i . e . “ n ” member ( s ), selected from group f , where n = 1 , 2 , 3 ,. . . , 20 , including every integer value within the range of 1 to 20 . thus , there are at least 20 embodiments of poebaca , differing in that the minimum number of members selected from group f that is contained in each embodiment ranges from one to twenty ( including every integer value in between ), i . e . at least one , at least two , at least three , at least four , . . . , and up to at least 20 . thus , one preferred embodiment of this invention provides a poebaca comprised of at least one member selected from group f ; another preferred embodiment of this invention provides a poebaca comprised of at least two members selected from group f ; another preferred embodiment of this invention provides a poebaca comprised of at least three members selected from group f ; etc . ; another preferred embodiment of this invention provides a poebaca comprised of at least twenty members selected from group f ; for convenience these are referred to as preferred embodiments f1 to f20 , and these separate embodiments are intended to be the subject matter of separate claims according to this invention . according to this invention , separate preferred embodiments of “ preparations of encapsulated bioavailable chelating agents ” ( i . e . poebaca ) are provided herein , each of which is comprised of at least a minimum number of members , i . e . “ n ” member ( s ), selected from group g , where n = 1 , 2 , 3 ,. . . , 20 , including every integer value within the range of 1 to 20 . thus , there are at least 20 embodiments of poebaca , differing in that the minimum number of members selected from group g that is contained in each embodiment ranges from one to twenty ( including every integer value in between ), i . e . at least one , at least two , at least three , at least four , . . . , and up to at least 20 . thus , one preferred embodiment of this invention provides a poebaca comprised of at least one member selected from group g ; another preferred embodiment of this invention provides a poebaca comprised of at least two members selected from group g ; another preferred embodiment of this invention provides a poebaca comprised of at least three members selected from group g ; etc . ; another preferred embodiment of this invention provides a poebaca comprised of at least twenty members selected from group g ; for convenience these are referred to as preferred embodiments g1 to g20 , and these separate embodiments are intended to be the subject matter of separate claims according to this invention . this invention further provides the additional preferred aspects that result from all the possible combinations and permutations of the preferred embodiments of a1 to a100 , b1 to b100 , c1 to c100 , d1 to d20 , e1 to e20 , f1 to f20 , and g1 to g20 . by way of illustration , ( 100 preferred embodiments corresponding to a1 to a100 )×( 100 preferred embodiments corresponding to b1 to b100 )×( 100 preferred embodiments corresponding to c1 to c100 )×( 20 preferred embodiments corresponding to d1 to d20 )×( 20 preferred embodiments corresponding to e1 to e20 )×( 20 preferred embodiments corresponding to f1 to f100 )×( 100 preferred embodiments corresponding to g1 to g20 )= 160 , 000 , 000 , 000 or one hundred and sixty billion preferred aspects , and these separate aspects are intended to be the subject matter of separate claims according to this invention . furthermore , the relative amounts of each ingredient that can comprise a poebaca according to this invention are illustrated in table 2 . in separate embodiments , this invention provides all the physically possible combinations and permutations of ingredient amounts that listed in table 2 . thus , this invention provides that the relative amounts of these ingredients can vary ( as illustrated in table 2 ), yielding additional aspects . therefore , when considering the claim limitations regarding the relative amount of ingredients , the number of preferred embodiments is greater , by orders of magnitude , than 160 , 000 , 000 , 000 or one hundred and sixty billion preferred embodiments that don &# 39 ; t specify amounts of ingredients , and all these preferred embodiments are intended to be the subject matter of separate claims according to this invention . this invention provides that the instant preparations comprising ingredients exemplified in table 1 are preferably orally ingestible . in a non - limiting exemplification these preparations can be liquids ( e . g . that can be orally ingested with the help of a spoon ), or capsules , tablets , and pills . in non - limiting exemplifications , they can also be formed into flavored bars ( e . g . similar to what bars that are marketed as “ power bars ”, “ diet bars ”, “ energy bars ”, and “ nutritional bars ”). this invention provides that the instant preparations comprising ingredients exemplified in table 3 are preferably orally ingestible . in a non - limiting exemplification these preparations can be liquids ( e . g . that can be orally ingested with the help of a spoon ), or capsules , tablets , and pills . in non - limiting exemplifications , they can also be formed into flavored bars ( e . g . similar to what bars that are marketed as “ power bars ”, “ diet bars ”, “ energy bars ”, and “ nutritional bars ”). this invention provides that the ingredients required herein , such as the ingredients exemplified in table 1 and in table 3 ( for making the instant preparations ) are ingredients that are commercially available from numerous commercial sources . in table 2 the relative amounts of each ingredient ( poebacai ) have been expressed in the context of a 2 ounce dose . this is for convenience and consistency , but in separate embodiments this invention provides that that dosages or other sizes can be prepared and administered , particularly ranging , by way of non - limiting exemplification , from about 0 . 1 ounce to about 128 ounces ( or one gallon ), including every 0 . 1 ounce increment in between . this invention provides separate embodiments wherein per 2 ounces the total amount of ingredient ( s ) from group a ( e . g . alpha lipoic acid ) collectively is preferably from about 0 . 01 mg to about 20 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . furthermore , this invention provides separate embodiments wherein per 2 ounces the total amount of each specific group a ingredient ( s ) individually is preferably from about 0 . 01 mg to about 20 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . 1 ) in one embodiment , this invention provides preparations of encapsulated bioavailable chelating agents ( i . e . poebaca ) wherein the total amount of group a members ( e . g . alpha lipoic acid ) is preferably 0 . 01 mg ; 2 ) in another embodiment , this invention provides preparations of encapsulated bioavailable chelating agents ( i . e . poebaca ) wherein the total amount of group a members ( e . g . alpha lipoic acid ) is preferably 0 . 02 mg ; 3 ) in another embodiment , this invention provides preparations of encapsulated bioavailable chelating agents ( i . e . poebaca ) wherein the total amount of group a members ( e . g . alpha lipoic acid ) is preferably 0 . 03 mg ; etc . ; and 2 , 000 , 000 ) in another embodiment , this invention provides preparations of encapsulated bioavailable chelating agents ( i . e . poebaca ) wherein the total amount of group a members ( e . g . alpha lipoic acid ) is preferably 20 , 000 mg . thus , there are at least 2 , 000 , 000 preferred embodiments . this is illustrated in table 2 . this invention provides separate embodiments wherein per 2 ounces the total amount of ingredient ( s ) from group b ( e . g . edta ) collectively is preferably from about 0 . 01 mg to about 30 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . furthermore , this invention provides separate embodiments wherein per 2 ounces the total amount of each specific group b ingredient ( s ) individually is preferably from about 0 . 01 mg to about 30 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . this invention provides separate embodiments wherein per 2 ounces the total amount of ingredient ( s ) from group c ( e . g . lecithin ) collectively is preferably from about 0 . 01 mg to about 40 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . furthermore , this invention provides separate embodiments wherein per 2 fluid ounces the total amount of each specific group c ingredient ( s ) individually is preferably from about 0 . 01 mg to about 40 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . this invention provides separate embodiments wherein per 2 ounces the total amount of ingredient ( s ) from group d ( e . g . magnesium chloride ) collectively is preferably from about 0 . 01 mg to about 10 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . furthermore , this invention provides separate embodiments wherein per 2 ounces the total amount of each specific group d ingredient ( s ) individually is preferably from about 0 . 01 mg to about 10 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . this invention provides separate embodiments wherein per 2 ounces the total amount of ingredient ( s ) from group e ( e . g . glutathione ) collectively is preferably from about 0 . 01 mg to about 10 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . furthermore , this invention provides separate embodiments wherein per 2 fluid ounces the total amount of each specific group e ingredient ( s ) individually is preferably from about 0 . 01 mg to about 10 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . this invention provides separate embodiments wherein per 2 ounces the total amount of ingredient ( s ) from group f ( e . g . vinpocetine ) collectively is preferably from about 0 . 01 mg to about 10 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . furthermore , this invention provides separate embodiments wherein per 2 ounces the total amount of each specific group f ingredient ( s ) individually is preferably from about 0 . 01 mg to about 10 , 000 mg inclusive , including specifically each increment of about 0 . 01 mg within this range . this invention provides separate embodiments wherein one or more gases may be contained in a percentage of the liposomes or micropsheres in a poebaca . in separate embodiments , the percent of liposomes or micropsheres that contains a gas is from about 1 % to about 100 %, including every integer value in between . this invention provides poebaca that can be administered by several routes , including intravenous , topical , and oral . furthermore , in separate embodiments , this invention provides forms of poebaca that can be administered by inoculation or injection , ( e . g ., intraperitoneal , intramuscular , subcutaneous , intra - aural , intra - articular , intra - mammary , etc . ), topical application ( e . g ., on areas , such as eyes , ears , skin or on afflictions such as wounds , burns , etc . ), and by absorption through epithelial or mucocutaneous linings ( e . g . vaginal and other epithelial linings , gastrointestinal mucosa , etc .). methods are known for making poebaca containing liposomes that are suitable for each of these methods of administration as well as other methods of administration that are know in the art . for example , in preferred embodiments , this invention provides poebaca in liquid forms that can be administered orally . the poebaca can be also prepared as capsules , tablets , pellets ( e . g . for animal consumption ), suppositories , or creams and ointments . the poebaca can be also prepared as physiological solutions suitable for i . v . administration or other parenteral administration . in as many separate aspects , this invention also provides all the possible combinations of ingredient quantities that are possible ( e . g . the total of all the ingredients or poebacai does not surpass 100 % of the relevant total dosage of the poebaca , and admixing or solubility limitations are not exceeded ). preferred percentages of ingredients that are contained in liposomes or micropsheres in separate aspects , this invention also provides that a poebaca may include ingredients ( or poebacai ) that are not contained in micropsheres or liposomes in addition to ingredients that are contained in liposomes , and that these ingredients may be the same or different substances . in separate aspects , this invention also provides that for each ingredient ( or poebacai ) the percent that is contained in micropsheres or liposomes ( in contrast to the percentage that is not contained in micropsheres or liposomes , but rather is in solution ) may be from about 0 . 1 % to about 100 . 0 %, including every 0 . 1 % increment within this range . this provides at least about 1000 separate aspects that are intended for protection according to this invention . in separate aspects , this invention also provides that in a single poebaca , the micropsheres or liposomes may be fairly homogeneous in size or in content ; alternatively they may be fairly heterogeneous in size or in content . group a members include : antioxidants , particularly hydrophobic antioxidants and other hydrophobic ingredients . r -(+)-. alpha .- lipoic acid ( substantially enantiomerically pure ), s -(−)-. alpha .- lipoic acid ( substantially enantiomerically pure ), r / s -. alpha .- lipoic acid ( racemic mixture ), r / s -. gamma .- lipoic acid ( racemic micture ), other isomers of alpha lipoic acid , derivatives of alpha lipoic acid ( such as the dihydro version of these alpha lipoic acid isomers , also known as dihydrolipoic acid or dhla ), animal and vegetable oils , hydrocarbon oils , ester oils , silicone oils , higher fatty acids , higher alcohols , sunscreening agents , vitamins , ferulic acid . fatty acids , lysolipids , dipalmitoylphosphatidylcholine , distearoylphosphatidylcholine , phosphatidylcholine , phosphatidic acid , sphingomyelin , cholesterol , cholesterol sulfate , cholesterol hemisuccinate , tocopherol hemisuccinate , phosphatidylethanolamine , phosphatidylinositol , glycosphingolipids , glucolipids , glycolipids , sulphatides , lipids bearing sulfonated mono -, di -, oligo - or polysaccharides , lipids with ether and ester - linked fatty acids , and polymerized lipids . edta , egta , dpta , ttha , hedha , nota , dota , hedta , other polyaminopolycarboxylic acids , iminodiacetic acid ( ida ), cyclam , penicillamine , dimercaptosuccinic acid , tartrate , thiomalic acid , crown ethers , nitrilotriacetatic acid ( nta ), 3 , 6 - dioxaoctanedithioamide , 3 , 6 - dioxaoctanediamide , salicyladoximine , dithio - oxamide , 8 - hydroxyquinoline , cupferron , 2 , 2 ′- thiobis ( ethyl acetoacetate ), 2 , 2 ′- dipyridyl , and derivatives thereof . according to this invention , other chelators that are members of group b are provided herein or are otherwise known in the art and can serve as ingredients for this invention . lecithin , phophatidylcholine , phosphatidylserine , phosphatidylethanolamine , dilinoleylphosphatidylcholine , lysolipids , dipalmitoylphosphatidylcholine , distearoylphosphatidylcholine , phosphatidylcholine , phosphatidic acid , sphingomyelin , cholesterol , cholesterol sulfate , cholesterol hemisuccinate , tocopherol hemisuccinate , phosphatidylethanolamine , phosphatidylinositol , fatty acids ( e . g . palmitic acid , stearic acid , oleic acid , linolenic acid , limoleic acid , etc . ), glycosphingolipids , glucolipids , glycolipids , sulphatides , lipids bearing sulfonated mono -, di -, oligo - or polysaccharides , lipids with ether and ester - linked fatty acids , triglycerides , lipoproteins ( high or low density ), cholesterol , and other lipids and polymerized lipids . magnesium chloride , magnesium gluconate , magnesium carbonate , calcium magnesium citrate , magnesium sulfate , other salts of magnesium , and other forms of magnesium . group e embers include : sulfur - contaning amino acids , sulfur - containing peptides , sulfur - containing proteins , and other sulfur - containing substances . magnesium chloride , magnesium gluconate , magnesium carbonate , calcium magnesium citrate , magnesium sulfate , other salts of magnesium , and other forms of magnesium group g members include : nitrogen gas , atmospheric air , and other mixtures of gases that contain nitrogen , oxygen , mixtures of gases that contain oxygen , argon , and mixtures of gases that contain argon , etc . alpha - lipoic acid , in addition to its non - toxicity and lipophilicity , has the advantage of being rapidly converted in tissues into its reduced form , dihydrolipoic acid ( dhla ). dhla also has potent antioxidant effects . further , both . alpha .- lipoic acid and dhla have been shown to disarm oxidants through a variety of mechanisms including free radical quenching , metal chelation , and regeneration of other common natural antioxidants . in one embodiment , the present invention provides a lipophilic antioxidant in an aqueous physiological fluid , such as a resuscitation fluid by lipid encapsulation , e . g . by providing liposomal formation methods to form stable micellular solutions of . alpha .- lipoic acid or other lipophilic antioxidant ( s ). the present invention seeks to overcome previous limitations by solubilizing . alpha .- lipoic acid in aqueous solution without the use of solvents such as harsh organic solvents . . alpha .- lipoic acid and other antioxidants are rendered soluble in aqueous solutions by the use of liposomal formation processes , such as ultrasonication . because the . alpha .- lipoic molecule contains a polar ( water soluble ) carboxy - acid group and a non - polar , lipid soluble chain of carbon and sulfur atoms , the molecule is amphipathic , i . e ., it has the ability to form micelles . micelles may be formed in aqueous solution if a molecule possesses both polar and non - polar groups . after ultrasonication the polar , a number of the water soluble ends of the . alpha .- lipoic acid molecule are on the outside of aggregations of . alpha .- lipoic acid . a number of the non - polar , lipid soluble tails are directed inward forming a tiny droplet , a micelle , which is water soluble . ultrasonication of amphipathic molecules into micelles such as can be done with . alpha .- lipoic acid also has the possibility of creating mixed micelles . in this manner a mixture of . alpha .- lipoic acid with other antioxidants , which may not have the ability to form micelles alone for lack of any polar group , can be contained within a micelle of . alpha .- lipoic acid . in this way , mixed micelles containing . alpha .- lipoic acid and purely non - polar but highly lipid soluble antioxidants can be used to convey antioxidants to the tissues . there are numerous other clinical conditions besides hemorrhagic shock which have as their final common pathway oxidant - inducing injury to tissues which can be treated and / or prevented with the inventive solutions . according to this invention , the polyaminopolycarboxylic acid , edta ( ethylene - diaminetetraacetic acid ) is provided as a chelating agent for removing toxins such as heavy metals . additionally , a related polyaminopolycarboxylic acid , diethylenetriaminepentaacetic acid ( dtpa ) is also provided as a chelating agent that has been shown to have an ability to remove various heavy metals . according to this invention , egta ( ethyleneglycol - bis [. beta .- aminoethyl ether ]- n , n ′- tetra - acetic acid ) is also provided as chelating agent . egta is more specific for particular substances such as calcium when compared to other substances such as magnesium , and thus may be used as a preferred ingredient when it is desirable to chelate calcium ( e . g . as is found in arterial plaques , and thus for diminishing arterial plaques ) more than for chelating magnesium . dmsa ( dimercaptosuccinic acid ) is one effective oral chelating agent that is absorbed orally , and is more effective at chelating particular substances such as mercury , lead , and arsenic in comparison to other substances ; and thus dmsa may be used as a preferred ingredient when it is desirable to chelate mercury lead and arsenic ( such for the detoxification of poisoning from lead or mercury r arsenic ) more than for chelating other substances . according to this invention , other useful chelating agents are also provided , including diethylenetriamine - pentaacetic acid ( dtpa ), triethylenetetraminehexaacetic acid ( ttha ), n - hydroxyethylenediaminehexaacetic - acid ( hedha ), 1 , 4 , 7 - triazacyclononane - n , n ′, n ″- triacetic acid ( nota ), 1 , 4 , 7 , 10 - tetrazacyclododecane - n , n ′, n ″, n ′″- tetraacetic acid ( dota ), and n ′ hydroxyethylenediamine - n , n , n ′- triacetic acid ( hedta ). according to this invention , preferred chelating agents also include iminodiacetic acid ( ida ), cyclam , penicillamine , dimercaptosuccinic acid , tartrate , thiomalic acid , crown ethers , nitrilotriacetatic acid ( nta ), 3 , 6 - dioxaoctanedithioamide , 3 , 6 - dioxaoctanediamide , salicyladoximine , dithio - oxamide , 8 - hydroxyquinoline , cupferron , 2 , 2 ′- thiobis ( ethyl acetoacetate ), 2 , 2 ′- dipyridyl . ida is a preferred chelating headgroup which is selective for copper ions . preferable chelators for use in the present invention include , but are not limited to , ethylenediamine - n , n , n ′, n ′- tetraacetic acid ( edta ); the disodium , trisodium , tetrasodium , dipotassium , tripotassium , dilithium and diammonium salts of edta ; the barium , calcium , cobalt , copper , dysprosium , europium , iron , indium , lanthanum , magnesium , manganese , nickel , samarium , strontium , and zinc chelates of edta ; trans - 1 , 2 - diaminocyclohexane - n , n , n ′, n ′- tetraaceticacid monohydrate ; n , n - bis ( 2 - hydroxyethyl ) glycine ; 1 , 3 - diamino - 2 - hydroxypropane - n , n , n ′, n ′- tetraacetic acid ; 1 , 3 - diaminopropane - n , n , n ′, n ′- tetraacetic acid ; ethylenediamine - n , n ′- diacetic acid ; ethylenediamine - n , n ′- dipropionic acid dihydrochloride ; ethylenediamine - n , n ′- bis ( methylenephosphonic acid ) hemihydrate ; n -( 2 - hydroxyethyl ) ethylenediamine - n , n ′, n ′- triacetic acid ; ethylenediamine - n , n , n ′, n ′- tetrakis ( methylenephosponic acid ); o , o ′- bis ( 2 - aminoethyl ) ethyleneglycol - n , n , n ′, n ′- tetraacetic acid ; n , n - bis ( 2 - hydroxybenzyl ) ethylenediamine - n , n - diacetic acid ; 1 , 6 - hexamethylenediamine - n , n , n ′, n ′- tetraacetic acid ; n - 2 - hydroxyethyl ) iminodiacetic acid ; iminodiacetic acid ; 1 , 2 - diaminopropane - n , n , n ′, n ′- tetraacetic acid ; nitrilotriacetic acid ; nitrilotripropionic acid ; the trisodium salt of nitrilotris ( methylenephosphoric acid ); 7 , 19 , 30 - trioxa - 1 , 4 , 10 , 13 , 16 , 22 , 27 , 33 - octaazabicyclo [ 11 , 11 , 11 ] pentatriacontane hexahydrobromide ; and triethylenetetramine - n , n , n ′, n ″, n ′″, n ′″- hexaacetic acid . it is contemplated that any chelator which binds barium , calcium , cerium , cobalt , copper , iron , magnesium , manganese , nickel , strontium , or zinc will be acceptable for use in the present invention . more preferably , the chelators for use in conjunction with the present invention may include ethylenediamine - n , n , n ′, n ′- tetraacetic acid ( edta ); the disodium , trisodium , tetrasodium , dipotassium , tripotassium , dilithium and diammonium salts of edta ; 1 , 3 - diamino - 2 - hydroxypropane - n , n , n ′, n ′- tetraacetic acid ; 1 , 3 - diaminopropane - n , n , n ′, n ′- tetraacetic acid ; o , o ′- bis ( 2 - aminoethyl ) ethyleneglycol - n , n , n ′, n ′- tetraacetic acid ; and 7 , 19 , 30 - trioxa - 1 , 4 , 10 , 13 , 16 , 22 , 27 , 33 - octaazabicyclo [ 11 , 11 , 11 ] pentatriacontane hexahydrobromide . most preferably , the chelators for use in the present invention may include ethylenediamine - n , n , n ′, n ′- tetraacetic acid ( edta ); the disodium salt of edta ; 1 , 3 - diaminopropane - n , n , n ′, n ′- tetraacetic acid ; and o , o ′- bis ( 2 - aminoethyl ) ethyleneglycol - n , n , n ′, n ′- tetraacetic acid . in a preferred embodiment this invention provides a preparation ( or poebaca ), wherein said chelator in said poebaca may be selected from the group of chelators consisting of edta free acid , edta 2na , edta 3na , edta 4na , edta 2k , edta 2li , edta 2nh . sub . 4 , edta 3k , ba ( ii )- edta , ca ( ii )- edta , co ( ii )- edta , cu ( ii )- edta , dy ( iii )- edta , eu ( iii )- edta , fe ( iii )- edta , in ( iii )- edta , la ( iii )- edta , mg ( ii )- edta , mn ( ii )- edta , ni ( ii )- edta , sm ( iii )- edta , sr ( ii )- edta , zn ( ii )- edta , cydta , dheg , dtpa - oh , dtpa , edda , eddp , eddpo , edta - oh , edtpo , egta , hbed , hdta , hida , ida , methyl - edta , nta , ntp , ntpo , o - bistren , and ttha . preferred chelating agents may also be selected from ethylenebis ( oxyethylene nitrilio ) tetraacetic acid ( egta ) and ethylene diamine tetracetic acid ( edta ), sodium citrate , or oxalate salts such as sodium , potassium , ammonnium or lithium oxalte . preferred chelating groups include those derived from polyamino - polycarboxylic groups , e . g . those derived from edta , dtpa , dota , teta , tetra , titra or 3 , 3 , 9 , 9 - tetramethyl - 4 , 8 - diazaundecane - 2 , 10 - dione dioxime ( hmpao ) or from such groups substituted , e . g . by a p - isothiocyanato - phenylc . sub . 1 - 3 alkyl , preferably p - isothiocyanatobenzyl . chelating groups derived from dtpa are also preferred . in a preferred embodiment this invention provides a preparation ( or poebaca ), wherein the chelating group is derived from ethylene diaminetetraacetic acid ( edta ), diethylene triamine pentaacetic acid ( dtpa ), ethylene glycol - 0 , 0 ′- bis ( 2 - aminoethyl )- n , n , n ′, n ′- tetraacetic acid ( egta ), n , n ′- bis ( hydroxybenzyl ) ethylenediamine - n , n ′- diacetic acid ( hbed ), triethylenetetramine hexaacetic acid ( ttha ), substituted edta or - dtpa 1 , 4 , 7 , 10 - tetra - azacyclododecane - n , n ′, n ″, n ′″- tetraacetic acid ( dota ) and 1 , 4 , 8 , 11 - tetraazacyclotetradecane - n , n ′, n ″, n ′″- tetraacetic acid ( teta ), in free form or in pharmaceutically accepted salt form . in a preferred embodiment this invention provides a preparation ( or poebaca ), wherein the chelating group is derived from 1 , 4 , 7 , 10 - tetraa acyclotridecane - 1 , 4 , 7 , 10 - tetraacetic acid ( titra ), 1 , 4 , 8 , 11 - tetraazacyclotetradecane ( tetra ); edta , dtpa , dota , teta , titra , tetra or 3 , 3 , 9 , 9 - tetramethyl - 4 , 8 - diazaundecane - 2 , 10 - dione dioxime ( hmpao ) substituted by p - isothiocyanato - phenyl - c . sub . 1 - 3 alkyl , in free form or in pharmaceutically accepted salt form . in a preferred embodiment this invention provides a preparation ( or poebaca ), comprising r / s -. gamma .- lipoic acid ( 6 , 8 - dimercaptooctanoic acid ) or r / s -. alpha .- lipoic acid ( d , l - thioctic acid ). according to separate but non - limiting embodiments of this invention , “ substantially enantiomerically pure ” 1 , 2 - dithiolane - 3 - pentanoic acid ( thioctic acid , . alpha .- lipoic acid ) is within the range from at least about 80 % pure to at least about 99 % pure inclusive as well as every 1 % increment within this range ( i . e . at least about 80 % pure , at least about 81 % pure , at least about 82 % pure , etc .). according to another embodiment of this invention , d , l - thioctic acid can used in the form of the racemic mixture . according to this invention , a racemic mixture can be comprised of two isomers that are found at a ratio within the range from about 20 %: 80 % to about 80 %: 20 % inclusive as well as every 1 % increment within this range ( i . e . about 20 %: 80 %, about 21 %: 79 %, about 22 %: 78 %, etc .). according to another embodiment of this invention , optically active r -(+)-. alpha .- lipoic acid is used . r -(+)-. alpha .- lipoic acid is a natural substance that is found in animals and humans , and it acts as coenzyme in the oxidative decarboxylation of . alpha .- keto acids . specific , but non - limiting , examples of microspheres according to this invention are provided herein . specific , but non - limiting , examples of ways of making , administering , and using microspheres according to this invention are provided herein . in separate non - limiting embodiments , this invention provides that the micropsheres can be made using lecithin ( and / or alternative ingredients as per table 1 and 2 ) in amounts in the range from about 0 . 1 gram to about 40 grams inclusive , including specifically each increment of about 0 . 1 gram within this range , in a total of 2 ounces of final poebaca product . in one embodiment , this invention provides poebaca comprising gas - filled microspheres . the invention further relates to methods for employing such microspheres as delivery systems to deliver the poebacai . in one embodiment , this invention provides poebaca comprising at least one member selected from the group consisting of animal and vegetable oils , hydrocarbon oils , ester oils , silicone oils , higher fatty acids , higher alcohols , sunscreening agents , vitamins , alpha lipoic acid , ferulic acid , and flavors and said solid or semi - solid oil component is at least one member selected from the group consisting of animal and vegetable oils , hydrocarbon oils , ester oils , higher fatty acids , higher alcohols , waxes , sunscreening agents and flavors 1 ) dissolve alpha lipoic acid and edta in half the amount of alcohol . 2 ) disperse lecithin in half the amount of alcohol and equal amount of water heat to 50c , mix with high shear mixing or sonication ( sufficient to form micropsheres or liposomes ) for 20 minutes , cool to 40c . 3 ) add magnesium chloride and gum arabic to the remaining amount of water , stir for 30 minutes at room temperature 4 ) add step number 3 to step number 2 . mix for 20 minutes 5 ) add step 4 to step 1 , stir gently for 20 minutes . 6 ) take a random samples and test for the presence of liposomes . 1 ) dissolve alpha lipoic acid in half the amount of alcohol . 2 ) disperse lecithin in half the amount of alcohol and equal amount of water heat to 50c , mix with high shear mixing or sonication ( sufficient to form micropsheres or liposomes ) for 20 minutes , cool to 40c . 3 ) add edta , magnesium chloride and gum arabic to the remaining amount of water , stir for 30 minutes at room temperature 4 ) add step number 3 to step number 2 . mix for 20 minutes 5 ) add step 4 to step 1 , stir gently for 20 minutes . 6 ) take a random samples and test for the presence of liposomes . per about 760 mg % ingredients : di - indolemethane 100 mg 13 . 15 grape ( skin ) extract 200 mg 26 . 3 calcium d - glucarate 200 mg 26 . 3 medium chain triglycerides ( mcts ) 50 mg 6 . 58 lecithin ( phosphatidyl choline 20 - 30 %) 50 mg 6 . 58 other ingredients : cellulose powder ( 13 . 52 %), magnesium silicate ( 5 . 65 %), magnesium stearate ( 0 . 52 %), silicon dioxide ( 1 . 34 %) capsule size : “ 00 ” vcaps capsule fill : 760 mg 1 . sift calcium - d - glucarate into a planetary mixer ( e . g . hobart ) or v - blender tumbler through # 18 mesh screen . 2 . sift grape skin extract into a planetary mixer ( e . g . hobart ) or v - blender tumbler through # 18 mesh screen . mix for 8 + minutes 3 . sift dim into a planetary mixer ( e . g . hobart ) or v - blender tumbler through # 18 mesh screen . mix for 8 + minutes 4 . sift mcts , magnesium silicate and lecithin into a planetary mixer ( e . g . hobart ) or v - blender tumbler through # 18 mesh screen . mix for 8 + minutes 5 . sift cellulose powder into a planetary mixer ( e . g . hobart ) or v - blender tumbler through # 18 mesh screen . mix for 8 + minutes 6 . sift magnesium stearate and silicone dioxide through # 40 mesh screen into the mixer , mix for 4 + minutes . for example , indole - 3 - carbinol ( i3c ) and its dimer 3 , 3 ′- diindolylmethane ( dim ), obtained from dietary consumption of cruciferous vegetables , have multiple biochemical activities . both compounds have been reported to be clinically effective in treating precancerous lesions of the cervix and laryngeal papillomas , pathologies with a human papillomavirus ( hpv ). various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description . such modifications are also intended to fall within the scope of the appended claims . in a preferred embodiment this invention provides a preparation ( or poebaca ), comprising ocular drug delivery vehicle of an oil - in - water submicron emulsion consisting essentially of about 0 . 5 to 50 % of a first component of an oil , about 0 . 1 to 10 % of a second component of an emulsifier , comprising a phospholipid , about 0 . 05 to 5 % of a non - ionic surfactant and an aqueous component , said submicron emulsion having a mean droplet size in the range of 0 . 05 to 0 . 5 . mu . m , and a weight ratio of surfactant to oil of about 1 : 1 or less . in a preferred embodiment this invention provides a method for transferring ingredients making up a preparation of encapsulated bioavailable chelating agents ( i . e . poebacai ) across a cellular membrane by encapsulating said ingredients within liposomes and carrying said poebacai to the cellular membrane where the liposomes will be taken up by the cells , thereby transferring the poebacai across the cellular membrane . poebacai can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed , releasing the poebacai to the interior of the cell . the released poebacai will complex intracellularly deposited toxic heavy metals , permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism . in a preferred embodiment this invention provides a method of transferring poebacai across a cellular membrane comprising : encapsulating said poebacai within liposomes ; and carrying said liposome encapsulated poebacai to said cellular membrane , whereby said liposome encapsulated poebacai will transfer across said cellular membrane . in a preferred embodiment this invention provides a method of introducing a poebacai into the interior of a cell in accordance with the method of claim 1 wherein said cellular membrane is the membrane wall of said cell and said encapsulated poebacai passes through the membrane wall of said cell into the interior of said cell , wherein said liposomes will be decomposed , thereby releasing said poebacai to the interior of said cell . in a preferred aspect this invention provides a method wherein said cell is a cell of a living organism and said poebacai is carried to said cell by injecting a saline suspension of said liposome poebacai into the blood stream of said living organism whereby said poebacai is carried to the cell within the blood in a preferred embodiment this invention provides a method for the removal of intracellularly deposited toxic heavy metals comprising : introducing said liposomal poebacai into the blood system by one or more of the following routes : oral administration , intravenous injection , transdermal patch ; whereby said liposome poebacai is carried to said body cells within said blood system ; said liposome poebacai is passed through the cell wall into the interior of said body cell ; said poebacai is released to the interior of said cell by the biological degradation of said liposome by lysosomal enzymes , said released poebacai complexing said intracellularly deposited toxic metal ; said complexed toxic metal is passed through the cell wall into said blood stream ; and said complexed toxic metal is removed from said blood stream and the body by normal body processes . in a preferred embodiment this invention provides a preparation or poebaca wherein said liposomes are prepared from a mixture of lecithin and cholesterol . in a preferred embodiment this invention provides a poebacai comprised of a member chosen from the group consisting of edta , egta , and dtpa . in a preferred embodiment this invention provides a detoxification method wherein said toxic heavy metals are selected from the group consisting of plutonium , gold , mercury , and lead , beryllium , and cadmium . any gel can be used in the practice of the present invention . the materials which can be used to form such gels include but are not limited to : carbohydrates such as cellulosics , methylcellulose , starch and modified starch , agarose , gum arabic , ghatti , karay , tragacanth , guar , locust bean gum , tamarind , carageenan , alginate , xanthan , chickle , collagen , polyacrylamide , polysiloxanes ( polyanhydrides , e . g ., malic anhydride copolymers , polyacrylates , e . g ., hydroxyethylpolymethycrylate polymethylmethacrylate , polyethylethacrylate polymethacrylate , ethylenevinylacetate copolymers , ethylenevinylalcohol copolymers , polyorthoesters , . epsilon .- caprolactones , amino acid polymers such as gelled albumin , amino acid polymers and copolymers and gelatins , and other organic or inorganic polymers which can be mixed with liposomes in vitro . after the mixture forms a gel the resulting liposome - gel matrix can be implanted in tissues . in a particularly useful embodiment of the present invention soft gel matrices such as agarose , collagen and the like containing sequestered liposomes may be injected in vivo . alternatively , gels such as methylcellulose can be formed in the tissues after inoculation of liposomes in a suspension containing the gel material . after inoculation the suspension forms a gel and the liposomes remain sequestered in the gel matrix rather than dispersed and cleared . regardless of the method used for preparing and implanting the gel matrix , the release of a liposome entrapped bioactive chelating agent or other poebacai is prolonged and the relative concentration of the agent at the site of inoculation is increased . virtually any poebacai ( including chelating agents ) as well as virtually any other bioactive agent can be entrapped within the liposomes for use according to the present invention . such agents include but are not limited to antibacterial compounds , antiviral compounds , antifungal compounds , anti - parasitic compounds , tumoricidal compounds , proteins , toxins , vitamins , trace minerals , heavy metals , enzymes , hormones , neurotransmitters , lipoproteins , glycoproteins , immunoglobulins , immunomodulators , dyes , radiolabels , radio - opaque compounds , fluorescent compounds , polysaccharides , cell receptor binding molecules , anti - inflammatories , antiglaucomic agents , mydriatic compounds , anesthetics , nucleic acids , polynucleotides , etc . in fact , if concurrent therapy is desired , two or more poebacai ( including chelating agents ) or other bioactive agents may be entrapped in one liposome population which is sequestered in the gel matrix . alternatively , two or more liposome populations ( of the same or different types of liposomes , e . g . mixtures of splvs , mpvs , suvs , luvs , revs , etc .) which each entrap the same or different poebacai ( including chelating agents ) or other bioactive chelating agents may be sequestered in the gel matrix . in yet another embodiment of the present invention the gel can be used as a vehicle for the same or different bioactive chelating agents and other poebacai than those entrapped by liposomes . in certain therapeutic applications it may be desired to deliver a relatively high dose of a drug compound ( i . e ., compound a ) followed by a sustained dose of the same or another compound ( i . e ., compound b ). according to the present invention , this is readily accomplished by entrapping compound b in liposomes , sequestering the liposomes in a gel matrix containing compound a , and administering the same in vivo in a single inoculation . thus , rapid delivery of compound a by diffusion from the gel , and slow sustained delivery of compound b by release from the liposomes is effected the release of the bioactive chelating agents may be controlled by the type of liposomes used and the membrane composition of the liposome bilayers as well as by the type and porosity of the gels used . the rate of release is also dependent upon the size and composition of the bioactive chelating agent itself . the liposome itself is the first rate limiting factor in the release of entrapped bioactive chelating agents . the rate of release may depend upon the number of bilayers , the size of the liposomes and most importantly the bilayer composition . a number of researchers add “ stabilizers ” such as sterols , cholesterols and the like to the phospholipid bilayers in order to alter the permeability of the liposome ( papahadjopoulos , d ., kimilberg , h . k ., 1974 , in progress in surface science , ed . s . g . davison , pp . 141 - 232 , oxford : pergamon ; demel , r . a ., bruckdorf , k . r ., van deenan , l . l ., 1972 , biochem . biophys . acta , 255 : 331 - 347 ). for the present invention it is important that the stable liposomes will release their contents upon contact with body fluids or culture media . the rate of release may be controlled by modifying liposome membranes accordingly using known methods . the liposome - gel compositions of the present invention may be used for sustained delivery of a bioactive chelating agent to cells and / or fluids in vivo and in vitro . when used in vivo , the liposome - gel compositions of the present invention may be administered before or after gel formation . routes of administration include but are not limited to : inoculation or injection , ( e . g ., intraperitoneal , intramuscular , subcutaneous , intra - aural , intra - articular , intra - mammary , etc . ), topical application ( e . g ., on areas , such as eyes , ears , skin or on afflictions such as wounds , burns , etc . ), and by absorption through epithelial or mucocutaneous linings ( e . g . vaginal and other epithelial linings , gastrointestinal mucosa , etc .). for example the liposome - gel preparations of the present invention may be inoculated in vivo to provide for the sustained systemic release of the bioactive chelating agent . such applications may be particularly useful for the systemic release of drugs such as hormones ( e . g ., to control growth , fertility , sugar metabolism , etc .) or antimicrobials to control and treat infections , etc . in an alternative example , the liposome - gel preparation may be applied topically . topical application may be particularly useful for the treatment of wounds ( either surgical or non - surgical wounds ) where the sustained release of poebacai ( including chelating agents ), antimicrobials and / or blood clotting factors may be helpful in the healing process . similarly , the liposome - gel preparation may be topically applied to burns for the sustained release of poebacai ( including chelating agents ), antimicrobials and / or cell growth factors . the liposome - gel preparation may also be applied in the ear to treat infections by providing sustained release of poebacai ( including chelating agents ), antimicrobials ; this would reduce the necessity of repeated applications of the bioactive chelating agent in the form of ear drops . in another alternative embodiment , a liposome - gel preparation may be administered orally for sustained release . such application may be useful for sustained release to oral epithelium and other oral tissues and for sustained release to epithelia of the alimentary tract . the liposome - gel preparations of the present invention may also be used in vitro to provide for sustained release of a poebacai ( including chelating agents ) into the cell or tissue culture medium . such poebacai ( including chelating agents ) may also include but are not limited to nutrients , drugs , hormones , growth factors , etc . the liposome - gel preparation may be used as a support for cell adhesion and growth ; for instance , a liposome - collagen gel may be especially useful for culturing muscle cells , nerve cell , or liver cells . when the liposome - gel preparation is applied as an overlay , a liposome - agarose gel may be particularly useful . many methods for making preparations comprising the ingredients provided herein as well as methods for making preparations comprising micropsheres or liposomes are many in the art . for particularly useful references regarding these methods , see the references listed below , which are hereby incorporated by reference in their entirety . the following us patents are hereby incorporated by reference herein in their entirety : u . s . pat . nos . 5 , 990 , 153 5 , 000 , 887 ; 4 , 994 , 213 ; 4 , 981 , 692 ; 4 , 975 , 282 ; 4 , 963 , 297 ; 4 , 952 , 405 ; 4 , 944 , 948 ; 4 , 927 , 637 ; 4 , 927 , 571 ; 4 , 923 , 854 ; 4 , 906 , 476 ; 4 , 897 , 384 ; 4 , 895 , 719 ; 4 , 891 , 208 ; 4 , 885 , 172 ; 4 , 880 , 635 ; 4 , 873 , 088 ; 4 , 861 , 580 ; 4 , 839 , 175 ; 4 , 837 , 028 ; 4 , 828 , 837 ; 4 , 822 , 777 ; 4 , 818 , 537 ; 4 , 804 , 539 ; 4 , 781 , 871 ; 4 , 766 , 046 ; 4 , 762 , 915 ; 4 , 752 , 425 ; 4 , 737 , 323 ; 4 , 721 , 612 ; 4 , 714 , 571 ; 4 , 708 , 861 ; 4 , 698 , 299 ; 4 , 668 , 638 ; 4 , 666 , 831 ; 4 , 610 , 868 ; 4 , 588 , 578 ; 4 , 564 , 599 ; 4 , 522 , 803 ; 4 , 483 , 929 ; 3 , 932 , 657 ; 3 , 909 , 284 ; and 3 , 576 , 663 . the following references are also hereby incorporated herein in their entirety : 1 . walaszek z , szemraj j , narog m . metabolism , uptake , and excretion of a d - glucaric acid salt and its potential use in cancer prevention . cancer detect prev 1997 ; 21 : 178 - 90 [ review ]. 2 . walaszek z , hanausek - walaszek m , minton j p , webb t e . dietary glucarate as anti - promoter of 7 , 12 - dimethylbenz [ a ] anthracene - induced mammary tumorigenesis . carcinogenesis 1986 ; 7 : 1463 - 6 . 3 . walaszek z , hanausek m , sherman u , adams a k . antiproliferative effect of dietary glucarate on the sprague - dawley rat mammary gland . cancer lett 1990 ; 49 : 51 - 7 . 4 . walaszek z , hanausek - walaszek m , webb t e . dietary glucarate - mediated reduction 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