AU2015200115A1 - L-sugar colon cleansing agent and uses thereof - Google Patents

Abstract

Abstract Disclosed is L-glucose monohydrate and compositions thereof. Also disclosed are methods for making L-glucose monohydrate and compositions thereof. Further disclosed are methods for colonic cleansing using L-sugars, such as L-glucose monohydrate, and compositions and kits useful for colonic cleansing.

Description

L-SUGAR COLON CLEANSING AGENT AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS [0001] The present application is a divisional application of Australian Application No. 2010256491, which is incorporated in its entirety herein by reference. [0001a] This application claims the benefit of priority to U.S. Provisional Application Nos. 61/183,596, filed June 3, 2009, and 61/233,722, filed August 13, 2009, both of which are incorporated herein by reference. BACKGROUND [0002] In 2006, an estimated 55,170 people in the United States died from colorectal cancer and 148,650 new cases were diagnosed. According to the National Cancer Institute, colon cancer is the second most deadly cancer in the United States. Of great importance in each case is early and accurate diagnosis, in which case colonoscopy is the standard tool for examination. Colonoscopy screening has been shown to reduce the expected morbidity and mortality of colorectal carcinoma by 76% to 90% (American Cancer Society. Colon and rectal cancer treatment guidelines for patients. Version 1, March 2000, (00-80M-No. 9409-HCP)). The U.S. Centers for Disease Control and Prevention estimates only an 8.5 % chance of survival if the disease is diagnosed at an advanced stage. [0003] Colon cleansing (colonoscopy preparation) is a required prerequisite for successful colonoscopy. With the requirement to identify flat lesions (nonpolypoid colorectal neoplasms) there is now an even greater need for proper colon preparation. Flat or recessed lesions are much more difficult to spot than raised polyps with traditional colonoscopy, because their appearance is similar to normal tissue. Recent research has shown that these flat lesions may be more likely to be cancerous than polyps (Soetikno et al., "Prevalence of Nonpolypoid (Flat and Depressed) Colorectal Neoplasms in Asymptomatic and Symptomatic Adults," J. Am. Med. Assoc. 299(9): 1027- 1035, 2008). [0004] Colonoscopy preparation is commonly achieved with polyethylene glycol (PEG) solutions or oral sodium phosphate (NaP) solution or tablets. Both preparations have their limitations. Subject non-compliance because of an unpleasant taste and a necessary large fluid volume in combination with the drug ingestion has resulted in inadequate intake of PEG 1 solution and poor colonoscopy preparation. Side effects of the PEG solution, such as bloating and nausea, are also common. Some subjects may tolerate the NaP solution or NaP tablets better than the la PEC solution; however, the NaP solution has a acidic say taste and i add ition to causing common gastrointestina side effects; the use of NaP preparations has been associated with various fluid and electmlyte disturbances (Sharma ef at. "Controlled study of pretreatment with magnesitun citne oen the q i colonoscopy preparation with polyethylene glycol electrolyte lavage solution (.asroines Eoidosc 46(6:541 3 1997; Caswell et a, 'Tb time course and effect on serum electrolytes of oral sodiumn phosphates solution in healthy male and female volunteers, Can J in Phannaco! 43):e260 20; Caswell e! a1' owel preparaton with ora sodium phosphate and renal diseausef Aadosopv (852 2006; Caswetll _atl "Phosphate salt bowel preparation regmens alter perioperative acid-base and electrolyte bhalance" Jm Anaeuth 53( 9 1, 2006 [000] iU-glucose, the mirror image of the molecule D-glucose, cannot be metabolized by cells in the biochemical process known as glycolysis. k-glucose has been long recognized as a potential replacement for D-glucose because like its enantiorner it has sinlar organolepe properties ie, sweetness and the bulk properties of l)ggucose when used in food preparation, [0006] Similarly k-glucose has been studied for colon cleansing colonoscopy preparation), which is a required prerequisite for successful colonoscopy; The use of Lglucose as an oral fornnulation for colon cleansing has been hampered by the dissolution properties of anhydrous glucose, the form that is currently manufactured. As such, when water is added to anhydrous k-glucose, clumping and slow dissolution are encountered. Tis fact has been a barrier: to providing dry coln cleaning compositions to consumersfor in home use. When faced with clmping and poor dissolution of -glucose compositions. consumers may not receive the adequate dosage of -glucose necessary to fully cleanse the colon prior to medical procedures because of the undisso ved residue that remains behind in the container used to reconstitute the L-glucose containing composition. [0007] in light of the limitations associated with currently available colonic cleanser, and the importance of proper colon preparation for colonoscopy, alternatives for colon cleansing are needed. For example, there is a need for new forms of Lglicose that are easily and more quickly dissolved in water. The compounds. compositions, methods and kits disclosed herein address these needs and other needs 2 SUNIMA RY [O08 'The present inventors have discovered a new rapidly dissolving form ot L gucose, specifically -glucose monohydrate -- glucose monohydrate is particularly well suited as a "ready to dissolve colon cleansgi or Waxa composition for home and medical use' The rapid dissolution results in easier preparation of oral solutions of Lglucose from solid Lgcose. less cl jumping in the solution, and more accurate dosing than anhydrous Vglucose, and, in turn, improved colon cleansing andlaxative performance. [0009] In one aspect the present invention relates to L-glucose ronohydrate and to compositions thereof (e g, pharmaceuti cal compositions containing -glucose monohydrate) lKrther disclosed is a method for preparing and/or isolating Lgiucose monohydrate Yetfurther disclosed are conposidons and kits for use by consumers or medical personnel wherein a rapid, and fully dssoI ved solution comprising Vgl ucose is desired. The present inventors have surprisingly discovered that at a suffieitlv high dosage; particularly when administered as a split dose (eg, where each dose is 6g or greater oa the weight basis of the base sugas such as.1,gl ose provide enhanced colon cleansing, and can be used fo colonoscopy preparation, Unlike PEG and NaP bowel cleansing preparations--sugars such as glucose have a pleasant, sweet taste. low volume intake, and an absence of or mild intensity of common cathartic-associated adverse events (s), making them an especiallyadvantageous alterative to current avadable preparations for colon cleansing prior to colonoscopv [00i1] In another aspect, the present invention relates to methods of using Lsugarssue-h as iUglucose monohydrate ascolon ceansing agents. Further disclosed are compositions and kits containing Lsugars, such as L--eglucose monohydrate for use in colon cleansing [0012] One embodiment is a method for colon cleansing in a subject (such as a subject undergoing a col onoscopy) by( a administering to the subject an aqueous solution containing from about 36 to about 72 g-glucose (based on the weight of base -glucose) at night (e g the night before the colonoscopy) and (b)administering to the subject an aqueous solution containing" from) about 36 to about 72 a rOnIlg emrfn f c i-a3o t g chose the following morning (e.gthe morning of, 3) but prior to, the colonoscopy The aqueous solutions may be prepared by dissing a powder of L,_glucose monohydrate in water. [0013] One preferred embodiment is a method for colon cleansing in a subject (such as a subject undergoing a colonoscopy) by (a) adinistering to the subject an aqueous solution containing about 48 g U-glucose (based on the weight of base b-glucose) (or 52.8 g -- glucose monohydratewhich contains an equivalent amount of base I>glucose) at night (eg, the night before a colonoscopt and (b) administering to the subject an aquecus solution containing about 48 g Aglucose (5r2,ggguoemate)the next morning (e g. the morning of. but prior to, the colonoscopy The aqueous solutions may be prepared by dissolving 52,8 g S glucose monohydrate (which is equivalent to about 48 g of base Lglucose) in water (for instance 8 tuid ounces of water). [0014] Additional advantages will be set forth in part in the description that follows, and in part wAll be obvious from the description, or may be learned by practice of the aspects described below.'The advantages described below will be realized and attained by means of the elements and combinatons particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive BRIEF DESCRIPTION OF THE FIGURES [00:15] The accompanying dating, which is incorporated in and constitutes a part of this specification, illustrates several aspects described below, [00161 Figure 1 depicts the Xray powder diffraction pattern of ghucose mnoohydrate. DETAILED DESCRIPTION [00171 The materials, compounds, compositions articles devices, and methods described herein can be understood more readily by reference to the foilowng detailed description of specific aspects of the disclosed subject matter and the Examples included therein. [0018] Before the present compounds, devices, and/or methods are disclosed and described, it is to be understood that they are not limited to specific synthetic methods unless otherwisespeciied, or to particular reagents unless otherwise specified. as such can, of course, vary, It is also to be understood that the terminology used herein is for the purpose of describing 4.

partikuar aspects only and is not intended to be limiting Athough any methods and materials similar or equivalent to those desired herein can be used in the practice or testing of the present mention, example methods and materials are now described, [00191 Also, throughout tis specfcation various publications are reference Ihe disclosures of these publications in theirenireties are hereby incorporated by reference ito this application in order to more fully describe the state of the art to which the disposed matter pertains. The references disclosed are also individually and specificalyincorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon, [0020] in this specification and in the claims that foow reference will be made to a nuibe.r of terms, which shall be defined to have the foIlowing ineaings: [0021 throughout the description and claims of this spcification the word "comprise" and other fons of the word, such as "comprising" and "comprises," means including but not lianted to, and is not intended to exclude, for example, other additives, components, integers or s tps, [00221 M used in the specification and the appended clairris, the singular forms "a," "an" and "the" include plural referents uess the context clearly dictates otherwise Thus for example. reference to "a component includes mixtures of two or more components. [00231 Ranges can be expressed herein as from "about" one pauticular value, and/or to "about" another particular value. When such a range is expressed, another aspect ime s fiom the one particular value and/or to the other particular value. Sinilarly, when values are expressed as appoximati'ons by use of the antecedent "about." it will be understood that the particular value forms another aspect. It will be father understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independency of the other endpoint t Salso understood that there are a number of values disclosed herein and that each value is also herein disclosed as "about" that particular value in addition to the value itself For example, if the value "10" is disclosed, then "about 10" i also disclosed. It is also understood that each unit between two particular units are also disclosed For example, if 10 and 15 are disclosed, then I11 12 1'3 and 14 are also disclosed, 5 [0024] As used herein, the terms "optional" or "optionally" means that the subsegently described event or circumstance can or can not occur and that the description includes instances wIere said event or ciumstance occurs and instances where it does not. [00251 "Subject as used herein, means an individual In one aspect, the subject is a mammal such as a primate, and, in another aspect. the subject is a human. The term "subject" also includes domesticated animals (epg., cats, dogs e),and livestock (e., cattle, horses, pigs, sheep, goats eta), [00261 By "rate of dissolution" and "dissolution rate" or other forms thereof is meant, the speed or quickness that a given amount of a solid fully dissolves in a given amount of water at a particular temperature. [0027] Reference will now be made in detail to specific aspects or the disclosed niaterials, compositions, ticles, and methods, examples of which are illustrated in the accompanying Examples L-Suarsi [0028] Disclosed hereini are uses ofsugars. An Lsaugar is defined as a monosaccharide in which the hydroxyl group at the lowest chiral carbon atom in a Fischer projection structure is on the left, [00291 Examples of sugars include, but are not limited to, aadosesketoses. aldopentoses aldohexoses.ketopentoses, andtketohexoses.aadopentoses nclude bose.xylose and lyxose.aldohexoses include L-allose aitrose Liucose, vguloseg, idose ijol Se, and vtalose, Lketopenoses include ribulose and Vxylulosendecohexoses include Jluctose, Lpsicose. usorbose and utagatose. Further examples ofi.sugars include L aido'exses and k.etobexoses, Still further examples of aidohexoses includeiglucose and gulose Examples of .etohexoses incudei-fructose and Isorbose Due to the fact that these L hexose monosaccharides are either not metabolized by the body or they are metabolized to such a small extent by the body and colonc bacteria, the y will not produce hazardous gases i the colon, A preferred LUsugar is -- glucose. 6 Ldlcoe sMonohvdate [00301 In one particular embodiment, the ugaris -gucose monohydrate, [0031] While not wishing to be limited by theory, it has been found that the rate of dissohtiuon of ,glu-cose formulations is an important paraneter when formulating "ready to dissolve" colon cleansing or laxative compositions for home or medical use. Because of the greater rate of dissoluuom of (glucose ionohydrate relative to other reported forms of 1, glucose, compositions for use as either a colon cleansing formulation or laxative can be more easily prepared by the consumer or medical protessional. [0032] The vgiucose monohydrate described herein has the empirical fornula; Cd1: or ('15 fH 2 The LGlucose monohydrate comprises approximately 36,6 % carbon 7,12 % hydrogen and 56k61 % oxygen; ported as C 36.36. H 7.12, 0 56.51. The irghacose monohydrate has an exact mass of8 9.953 g/not The wrghcose rnonohydrate has an average molecular weight of about 198. 17115 ghoi. [00331 In one embodimen, the ghacose monohydrate is characterized by an Xray powder diiffraction (XFRPD) pattern having one or more characteristic peaks at about 9,24 about 18.46. about 19.78, about 20.24. and about 28.36 ± 0.2 degrees 20, In another embodiment. the tgucose monohydrate exhibits peaks at two or more of theaforementioned values. in yet another enibodi ment he glCose onohydrate exhibits peaks at three or more of the aforementioned values, in yet another embodiment the Lgiucose monohydrate exhibits peaks at four or more of the aforementioned vahes [00k34] In a further embodiment the egucose monohydrate is characterized by an Xray powder diffraction (XRPD) pattern having characteristic peaks at about 9,24, about 18.46, about W28 about 2024, and about 28.36 ± 0.2 degrees 20, [003S] In another e-mbodiment, the r. IU-cse monohydrate ischaracterizd by an X-ray powder difraction (XRPD) pattern having one or more characteristic peaks at about 9,24, about 12.7, about 140 about 16.48, about 1846 about 19.32 about 978, about 20.24 bout 20.6 about 21.70 about 22,84,about 23.50 about 25.52, about 26.56. about 27.62. about 2784 about 2836, about 29 4 0, about 30.80 about 30.98 about 31.22 about 3238 about 33.44. about 33. bo 35,24, about 5.72, about 36.96, and about 40,18+ 0.2 degrees 20. in 7 another ermbodimentthe glaCose monohydrate exhibits peaks at two or more of the aforementioned values, in yet another enibodimet the [-glucose nonohydrate exhibits peaks at three or rmore of the aforementioned values, in yet another embodiment the 1glucose monohydrate exhibits peaks at four or moe of the aforementioned values. In yet anot her embodiment, the -ghucose monohydrate exhibits peaks at ive or more of the aforementioned values, i yet another embodiment, the i- gIucose monohydrate exhibits peaks at six or more of the aforementioned values [00361 In another embodiment the .glucose onohydrae is characterized by an X-ay powder diffraction (RPD) pattern having characteristic peaks at about 924; about 12., about 1460, about 16,48, about 18A6. about 19.32 about 1938, about 20.A about 20.56 about 217 about 224 about 23.0, about 25.52 about 26.56, about 27.62, about 27.84, about 2836 about 29.0 about 3080 about 3O198, about 312 3 about 3344. about 33,82, about 324 about 3572, about 36.96, and about 418 ± 0.2 degrees 2 [00371 1n a further embodiment, the -glucose rmonhydrate can be characterized by an X-ray powder diffraction pattern substantially as shown in Figure 1, I038] With respect to the term "substanally one skilled in the art would understand that the relative intensities of the peaks can vary depening upon the sample preparation technique, the sample mounting procedure and he narticuiar instrument employed. Moreover, instrument variation and other factors can affect the 20 vahes. Therefore. the XRPD peak assignments can vary by plus or minus about 0.2 degrees 20, [10391 The rghlcose mondrate can be substantial free(eg., contain 3% or less, 2% or less. 1% or less, 0.5% or less or 2 or less, based on the total amount of glucose by weight) or free from -glucose and/oraglucose monohydrate The [glucose monohydrate can also be substantially free or free front other impurities as other Iugars or iTsugars, In one embodiment, the [-glucose monohydrate is at least about 99% pure, such as at about least 999% at least about 9999% or at least about 99:999% pure, based on the total amount of sugars present; [0040] in one embodiment, the specific optical rotation of the glucose monohydate is about -52.5 to about -3.3 degrees, calculated with reference to anhydrous glucose. The specific optical rotation can be calculated according to the following procedure. vGlucose 8 moanohydrate (10 g) is dissolved in de-ionized triply distilled water80 ri) Concentrated ammonia (41 g) is diluted to a volume of 100 mL with de-ionized triply distilled water. To the solution of guose ''monohydate iad OW 2 ml, oth flte4 ammonia Soluion This solution of Lelucose monohydrate and dilute ammonia is allowed to stand for 30 minutes after which time the solution is further diluted with deionized triply distilled water to a volme of 100 mU. [0041] in one embodiment, the [gucose monohydrate disclosed herein has a rate of dissolution in 100 ml of water at 25 ?C7 of at least about 18 ghni. In a further embodiment, the rate of dissolution of lucose monohydrate in 100 mL of water at 25 T is at least about 23 g/min, n another embodiment, the rate of dissolution of v-glucose [nonohydrate in 100 nL of water at 25 *C is at least about 26 gmin. In a yet further embodiment the rate of dissolution of ghucose monohyirate in 100 m of water at 2 TC is at least about 30 g/min In a still further emrbodhnent the rate of dissolution of L-glucose monohvdrate n100 ml of water at 25 i is at least about 455 gAnm. In a yet still further embodiment, the rate of dissolution of L-glucose mionohydrate in 100 ml of water at 25 C is at least about 60 g/nrin. In a vet another embodiment, the ate of dissolution of glucose monohydrate in 100 mL of water at 25 n is at least about 9-1 ghian. However, the disclosed glucosee monchydrate can have any rate of dissolution from at least about 18 g&nin, to latest about 91 g/rin Non limiting examples of rates include at least about 18 g/mnin, at least about 19 gimi, at least about 20 g/umin., at least about 2 g /m.in at least about 22 g/min, at least about 23 g/mm. at least about 24 g/mim, at least about 25 g/min., at least about 26 gmin., at least about 27 /min, at least about 28 g/min., at least about 29 g/min at least about 30 g/mm, at least about 31 g/rn.41, at least about 32 g/rine, at least 3at least about 34 / .in at least about 35 g/nin., at least about 36 g/rin., at least about 37 g/min. at least about 38 g/run., at least about 39 g/am. at least about 40 g/im at least about 41 gmn., at least about 42 g/mil..at least about 43 g/mini at least about 44 g/min, at least about 45 g/min, at least about 46 g/min,, at least about 47 g/in. at least about 48 g/inm at least about 49 g/mhin. at least about 50 g/min at least about 51 g/muin. at least about 52 g/min., at least about 53 g/min, at least about 54 ghnin., at least about 55 g/rin., at least about 56 p/min, at least about 57 g/ruin., at least about 58 i east about 59 a/min, at least about 60 g/min, at least about 61 g/min. at least about 62 .nn at least about 63 grien. at least about 64 ghrain, at least about 65 g/nrn, at ).east about 66 g/rin. 9 at least about 67 g/mi.n at least about 68 ghni, at least about 6 g/minteiast about 70 g/rnin, at least about 7 i /min., at least about 72 gmin .at least about 73 /min., at least about 74 ghni, at least about 75 g/min, at least about 76 ghian, at least about77 g/rnn, at least about 78 gAin, at least about 79 gnin, at least about 80 ghnin at least about 81mhninat least about 82 g/min, at least about 83 g/i at least about 84 gnrin, at least about 85 /in at least about 86 g/ein, at least about 87 g/mein, at least about 88 ghnin., at least about 89 g/min, at least about 90 g/min, at least about and at least about 91 ghin. In addition any fractional value in this ruge is also contemplated, for example, at least about 253 g/mrei, at least about 44.56 g/min., and at least about 73.22 g/min, Synthesis of-Sunars [0042] Many 1sugars are commercialy available or can be prepared by methods known in the art, See, for example, U.S Patent Nos t,'30618; 3,677,818; 4,471J14; 4.58114?; 4,718 405 815,445; 4837,315 4.900.667: 49304; 4,959,467; 4,9702302; and 5,O0,794, which are all incorporated by reference herein for their teachings of sugar preparations. 100)431 The following procedures can be used to prepare -- giucose monoydrate from a source of 1 glucose The source can be commercial anhydrousaucose or the -glucose can be obtained from a known commercial process or laboratory scale preparation For eanple, a source of giucose can be obtained by modification of the procedure of Isbell, R+S1.., ea,.. synthesisis oft) ucse*-C and D-Mannose-i -'" Aournal oResearch of the Naionl Bureau of StUd- 483 pga. 163-171 (1952) include herein byreference in its entiety [0044] In one embodiment, the process comprises (a) adding L-glucose to water. heating the resulting mixture under reduce pressure to form a sohuion and (b) cooling the resulting solution to induce crystallization, and optionally adding an organic solvent such as ethanol. [0045] In another embodimen the process comprises: a)dispersing an amount fronm about 0.9 moles per liter to about 1,5 moles per liter Of a source of -glucose in water at a temperature of from about 55 T to not more than about 65 'C at a reduced pressure of at least about 700 nm hig less than atmospheric pressure, reducing the amount of vater present such that the amount of water present is from about 28% to about 30% by weight ofte souton, and heating the dispersion to a temperature of from abont 80 *C to about 82 C to form a solution; 10 and b) cooling the solution to a temnerture ot from about 50 *C to about 55 *C to induce crystallization, further cooling the resulting shrry to a temperature of from about 25 C to about 30 *Cand adding an amount of ethanol that is froi about 4,5 mof ethanol to about 5 maL of ethanol per gram of h-glucose dispersed in step (a) to form .- glucose monohydrate, [00461 in a further embodiment, the h-glucose monohydrate formed in step (b) is optional isolated in a further step kc), [00471 In one embodiment, in step (ax h-glucose is dissolved. dispersed, or suspended in water at a temperature of from about 55 IC to not more than about 65 *C under reduced pressure; The reduced pressure is at least about ) mm Fg less than atmospherd but can be adjusted upwards or downward depending upon the specific conditions available to the formulator. The final glucose concentration is from about 35 Mto about 4 M, ione embodiment, the concentration is fom about 3.77 N to about 389 N in another embodiment, the concentration is from about 3,5 Ni to about 3.9 N, [00481 The sol nation of vglucose can be stirred or agitated under reduced pressure while heating occurs. Once the solid has been dissolved, the formulator can increase the temperature to less than about 65 'C to begjn adjusting the amount of water present in the solution The formulator, knowng the original concentration of the 1-glucose can determine the concentration of the heated solution by collecting or otherwise determining the amount of water removed under reduced pressure The amount of water present in the solution is reduced to an amount from. about 28% by weight to about 30% by weight of the solution. The resuming slurry is then heated to a temperature of from about 80 C to about 82 *C and held until all of the Ighucose has dissolved.. [00491 Because the source of -gluose used for this step can have larger or smaller crystal szes, th slurry that can be heated to a temperature of lionm about 8 C to about 82C7 should be stirred or agitated at that temperature range for a greater or lesser amount of time.The forul ator canu alow the solution to stir for a longer period of time provide, the amount of water present remains in the range of from about 28% by weight to about 30% by weight of the solution [00501 In one emnbodirnent of step (b), the solution resulting from step (a) is gradually cooled to a temperature of ion about 50 C to about 55 $C( with continued agitation while aoaton or stirring is continued, After the solution reaches this temperature it is held there util crystaliization begis. Once crystallization begins, the solution is lowered to a temperature of from about 25 'C' to about 30 'C, in one embodiment, the formuulator Can induce crystallization by adding crystals of vglucose monohydrate in another embodinent, the fomulator can allow the solution to self nucleate [051] In furher embodiments ethanol can be added to the solution to enhance crystalization. The amount of ethanol added is, for example, from about 4.5 mL of ethanol to about 5 mL of ethanol per gram of -glucose used in step (a), For processes that introduce glucose as a wet mixture rom a processthis amount of ethanol is calculated upon the actual mass of I-ghicose entering into step (al For example, in the case wherein anhydrous -glucose is used as the starting material in step (at one embodiment of the disclosed process utilizes about 4.S mi of ethanol per gram of anhydrous .ghicose dissolved in step (a), The ethanol is added at any rate that allows for formation of neady homogeneouscystals, However the formulator can adapt he rate of addition of ethanol to any rate that is compatible with the conditions, equipment, or desired crystal size [00521 After allowing crystallization to occur, the solid that forns can be isolated in a further step(c The formulator can use any means available for obtaining the crystals, for exaie, vacuum filtration centrifugation and telike. Once isolated the crystals may be washed with onetenth the amount of ethanol used to further nucleation for example, from about 0.45 mL of ethanol to about 0U mL of ethanol per grain of vghcose used in step (a) [0053 The obtained crystal can then be dried under a vacum o for exampleat least about 650 mm Hg at a tenoerature of from about 15 'C to about 20 C. however the formulator can adjust the vacuum and temperature to provide approximately equiva.ent conditions. Composi tignsContaininagLugagrs [0054] In additional aspect the present invention relates to compositions comprising h-sugars (such as compositions comprising glucose monohydrate). These compositions are peferably pharmaceutical compositions. [00551 in one aspect, the compositions comprise at least about. 10% by weight of I glucose rnonohydwrate' and b) one or more adjunct ingredients. positionss according to this 12 aspect cnompose any value for exarrmpie. at least about 10%. about 20%, about 30%. about 40% up to at least about 99*999% or greater by weight of glucose monohydrate. [00561 in one embodiment, the compositions compose at least abouI50% by weight of v glucose monohydrate, in a another embodiment, the compositions comprise at least about 10% by weight of t-giucose monohydrate. i a further embodiment, the compositions comprise at least about 75% by weight gh f i.-gTucose mronoh ydrate. hi a still furher embodiment the compositions comoipse at least about 80% by weight of 1-glucose monohydrate. In a vet further embodinnt, the compositions cornmse at least about 85% by weight of -guche monohydrate In a further embodiment the compositions comp'kse' at least about 90% by weight of .ghucosen monohydrate. In another enibodiment the compositions compise at least about 95% by weight of .4Agucose monthydrate. In one embodiment, the compositios comprise at least about 99% by weight of Lgiucose monohydrate, for example at least about 99,9%, at least about 99.99% or at least about 99.999% by weight-lucose monohydrate, [00571 In additional nonKimnitimg examples the compositions comprise about 1%, about 2%. about 3%, about 4%; about 5, about 6% about 7%, about 8%, about 9%, about 10%. about 11 %,bout 12%,about I% about 14% about 15% about 16%, about 17%, about 18%, about 19%.about 2%,about 21 % about 22%, about 23%. about 24%- about 25%. about 26% about 27% about 28%, about 29%, abot 30% about a1 bti t'2% about 33%. about 34% about 35% about 36%. about 37% about 38%, about 39% about 40% about 41%, about 42% about % aboui4% about45% about 46%, about 47%, about 48%, bout49%. about about 51 bout 52%. about 53%. about 54%. about 55%. about 5%6%- about 57%, about 58%, about 59% about 60% about 61%, about 62% about 63%. about 64% about 65%. about 66%. about 67% about 68% about 69%. about 70%, about 71%. about 72 about 731, about 74%, about 75% about 76%, about 77% about 78%, about 79%, about 80% about 81 %, about. about 83%, about 84%, about 85%, about 86%, about 87% about 88% about 89%a bout 90%, about 91% about 92%, about 93%., about 94%.,about 95% about 96 .bout 97% about 98% about 99% about 99.9%, about 999% or about 99.999% by weight glucose nonoh ydrate lee any of the stated values can form an upper or lower endpoint of a range. In addition. any fractional value in this range is also contemplated, for example, about 0 1% about 43%, about 25.7%. about 44,56%, and about 99,98%. 13 [058 The composions described herein have an increasedrae of dissohiton versus anhydrous tIgjucose. The compositions encompassed have a rate of dissolution in 100 mL of water at 25 C of at least about h8 gniinlI a further embodiment the rate of dissolution ofI glucose monohydrate containing components have a rate of solubility in 100 mL of water at 25 IC of at least about 23 gfhn.iI anotherembodament the rate of dissolitio of i.glucose monohydrate containing components have a rate of solubi ity in 100 t of water at 25 *C of at least about 26 ghnin In a yet further embodiment, the rate of dissoltJon of .ughcose mlonc~hy date containing comnponernave a rate of solubility in 100 maL of waterat 25 '' ofat least about 30 ghnin. In a still further embodiment, the rate of dissolution of Vglucose rmonohydrate cotaimnig components have a rate of solubilhty in 100 rml of water at 25 C of at least about 45 g/min. In a yet still further embodiment, the rate of cssolution of t.acose monobydrate containng components have a rate of solubility in 100 aL of water at 25 C of at least about 6) gmin, In a yet another ernbodient. the rate of dissolution of-glucose monnhydate contaning components have a rate of solbility in 100 mL of water at 25 CT of at least about 91 g/n-in, [0059] In further enbodiments. compositions described herein can have any rate of dissolution from at least about 18 g/min to at least about 91 g/min. Noniun examples of rates include at least about 18 gnin, at least about 19 c/rnin, at least about 20 gnmin.; at least about 21 g/mi.., at least about 22 gimn at least about 23 g/min..

4 at least about 24 g/min at least about 25 g/mi-in. at least about 26 g/min, at least about 27 g/mi. .at least about 28 grain, at least about 29 g/min., at least about 30 gmin. at least about 31 g/min, at least about 332 gn/rrnn at least about 33 g/.rin at least about 34 g/main at least about 35 g/r.rnu. at least about 36 g/min, at least about 37 g/min, at least about 38 <min, a least about 39 gnmin, at least about 40 g/rin, at least about 4.1 gimin, at least about 42 g/min.at least about 43 rans at least about 44 g/inn at least about 45 g/min, at least about 46 g/main, at least about 47 nn at least about 48 g/nin, at least about 49 ghihn, at least about 50 g/min., at least about 51 gnin, at least about 52 grin, at least about 53 gniain, at least about 54 g/nin., at least about 55 g/rnin, at least about 56 g/min, at least about 57 g/min, at least about 58 glnain, at least about 59 gmin at least about 60 gtp/in, at least about 61 g/mr. at least about 62 ran at least about 63 g/min., at least about 64 g/rin, at least about 65 g/rini, at least about 66 ghnin., at least about 67 ghni at least about 68 grain, at least about 69 p/rin., at least about 70 14 g/rnin, at least about 71 ghnin, at least about72. ait least about 73 g/min, at least about 74 g/min, at least about75 gmin, at least about 76 g/min. at least about 77 g/min., at least about 78 g/min at least about 79 ruin., at least about 80 g/anim, at least about 81 ghinn a least about 82 g/minm at least about 83 gimin.. at least about 84 g/m.in at last about 85 g/mn. at Least about 86 g/min, at least about 87 g/min, at least about 8$ grn.at least about 89 ginin.. at least about 90 gmini, at least about and at least about 91 g/ni where any of the stated values can form an upper or lower endpoint of a range. in addition, any fractional vahve in this range is also contemplated, for example. at least about 252 g/in -at least about 4456 g/min, and at least about 73.22 g/in. [0060] The disclosed compositions can comprise one or more adjunct ingredients By 'adgunet ingredient" is meant a chemical compound or chemical species that is not I glucose monotnydrate in one embodiment, the adjunct ingredient is anhydrous --glucose, In another enbodirent, the adjunct ingredient is a stabilizer or material that insures the flowability of the composition n a further embodiment, the adjunct ingredient can be any unknown impurity. 1[1061) In a vet further embodiment, when the i,..-glucose mionohvdr-ate isprepared, according to a process described hereli, and dependig upon the source of Ihc se d in step (a) of the process desCribed herein a saccharide impurity, for example, D ai-- or any of its forms D-gicose or any of its forms, Dor Ig.,aactose or any of its forms Dor .

galactouronic acid or any of its forms, or any other D.- or i-pentose, D- or .hexose and the like, can be present as an adjunct ingredient. 10062] in a yet still further embodiment, the adjUnct ingredient can be ethanol. or any other suitable processing solvent. Non-imiting examples of solvents that can be an adjunct ingredient indde methanol, thanol, propanol, iso-propanol, butanol, dioxane, peitane, iso pentan, aeptane, octane, sooctane benzene, nitr benzene, toinene, and Xylene chlorosforrT, carbon ttahrI de dichioromnethane.blroorricabo te. loide 1 -ichloroethane. 1 2.dichloroethane. trichloroethane acetone, methyl ethyl k-etone 3pentanone, nitromethane, tetrahydrofuran. aCetonAile, dioxane methvytpyrrolidone. dimethyl sulfoxide. NNi methiformamide, dA' dethylacetamide, and hexamnethryiphosyphoric trianide. [00631 In a et still another embodiment, the adjunct ingredient can be a colorant, non limiting examples of which include FD&C Red 3 ED&C Red 40. D&C Yellow 5 FD&C 15 Yellow 6 FD&C Blue 1, D&C Bue 2. FD&C Green ttanium dioxide, Beet Root Red, Lycopene, Carotena Carotennc, Paprika Extrac, Annatto Carotenes, Caramel, Brdliant Blue FCr, hidigotine, Allira Red AC, Erythosine, Ponceau. Carmoisine, Sunset Yellow PC~T 'artrazine, and Inurneric [0064] in another aspect, the composition comprises (al at least about 10% by weightof 1-glucose mnohydrate and b) aiydrous .- g] ucose hr further enbodinents compositions according to this aspect can comprise any value for exanple at least about I0% about 20%. about 30% about 4-0% up to at least about 99,999% by weight of i-gucose monohyderte and the corresponding balance anhyvdrousL-ucose, [0065] In one embodiment, the compositions can comprise at least about 50% by weight of ugstgcosem monohydrate and the balance anhydrous -glucosein a yet a further embodiment. the compositions can comprise at Ieast about70% byweh ofgose mronhydrate and the balance anhydro us -glucose, in a still another embodiment the compositions can comprise at least about 75% by weight of nlucose monohyarate and the balance anhydrous h-glucose, I a still further embodiment. the compostions can comprise at least about 80% by weight of v glucose monohydrate and the balance anhydrous glucose. In a yet further emlbodiment, the compositions can compose at least about 85% by weigtof glucose mohydrate and the balance anhydrous Ingcsedn a further enibodiment, the compositions can comprise at least about 90% by weight of -gleucose nonohydrate and the balance anhydrous v-glucose. In another embodimen, the conposi dons can comprise at least about 95% by weight of -glucose monohydrate and the balance anhydrous v-glucose. In one embodiment of this aspect, the compositions can comprise at least about 99%s, or at least about 99,999% by weight of L.-glucose nimonohydrate and the balance anhydrous glucose [0066] Non -imiting examples of amounts of glucose monohydrate in the compositions described herein include aboa but 3"' bout3 about 4%. about 5%, about 6%.about 7% about 8%, about 9%, about 109 ,about i11iabout 12%,about 13%, about 14%,about % )Thabout I6%. about 17% about 1 8%. about 19% about 20%, about 2:1%. about 22%. about 23%.about 24%. about 25%, about 26%. aboabo% about 28% about 29%, about 30%, about 31% about 32% about 33%, about 34%, about 35 about 36%; about 37%, about 38%, about 39%; about 40%; about 41 % A 2% abot 43%t42% about 45%, about 46%, about 16 47%, about 48%, about49 %. aboit 50% aboit %, about 52%, about 53%. about 54%, about 5,aoU56,, about 57 about AN8 about 59%;, about 60%7 la about about 62%'v. about about 64% about 65% about 66%, about 67%. about 68%. about 69%---, about 70%, about 71% about 72% about 73% about 74% ut bout 76% about 77%, about 78%, about 79% about 0%. about 81 %, about 82%, about 83%, a 84% au 85%, about 86% about 87% about 88%, aboutbo9%t a9o1% 90%, about 9 a 9b about 93%, about 94%, about 9% bout % about 97%. abou bout 99% about 99 )% about 99.99% and about 99099%. where any of the stated values can form an upper or ower endpoint of a range. In addition. any fractiona Value in this range is also contemplated, for example about 0.1%, about 4% about about 446% and about 99/98%, [00671 In certain embocments, te composition s described herein can result frm the formulator varying the procedures kfo preparing Lglucose monohydrate and thus forming a composition that can cornpise any amount of Aydus gcose Inz addional embodiments. the tormulator can prepare a composition that provides Lgiucose monohydrate, but the composition isstored or trnsponred i a rnanner hat the composition reverts o a nature of . glucose monohydnate and n [0068] In one embodiment, the amount of anhydrous glucose present in the comnpoition.is inot pAriiary to the perfo-rniance (ie, the rate of dis.soltion of the comnpoSitiOn) due to one or more factors, For example the fiial concentration of an aqueow sdhion of the composition is such that the rate of diss&aidion of Te anhydrous ,- glucose i not a lmiting facor. An example of this is the circumstance wherein the mxture of IgQucose monohydrate arid anhydrous ,-glucose is ftniulated with a material tht has a higher rate of dissolution. In some instances, the mixture can be formnlated with another ingredient that has greater heat of sol uUti, i. A!] > 19 ki/mol, thereby requiring warming of the admnIitr [0069] in another aspect, disclosed are compositions for use hn colonic cleansing, coIuprising '1) fro about 0.01% to about 999% by weight tf an active componient. ComnprisingA i) from about (O 01% to about 99,999% by weilt of gL2ucose monohydrate and ) tfz- rf LabYt 0T00 1% to about 99,199% by weight of anhydrous Ligucose; and b) the balance adj~nct ingrediernts 100701 A further enbodinent of this aspect relates to a composition for use as a laxative, comparing: a) from about 0.01 to about P999% by weight of an active component, comnpoisingd) from about 0,001% to about 99,999% by weigt ofonhydrate and ii) from about 0.001% to about 99.999% by weightofhydro glucose and b) the balance adjumct ingredients; 100711 By "actve component' as it relates to this aspect is meant that the adjunct ingredients are not known oi understood to have colon cleansing or laxative activity.is such, the adjunct ingredieits can be stabilizers, colorants, flavorants, and the like. [00721 in addHion to having a rapid rate of dissointion in water, the disclosed compositions have a high solubility in water, for example. a solubility in water of from about 0.85 g/nit> to about 1,5 g/mL,, at 25 *C, In another embodiment. the compositions have a solubility in water of from about 0.9 g/mL to about 1.2 g/mL at 25 'C' In a further embodiment the compositions have ability in water of from about 092 g/mL to about 0.98 ghnt at 25 in a yet further embodiment, the compositions have a solubiitvin water of from about 0.91 ghito about 093 g/L at 25 W 100731 A further embodiment of the disclosed compositions relates pharmaceutical compositions comprising a) from about 0.01% to about 9999% by weight of a non-absorbable saccharine component. comprising: i) from about 0.01% to about 99 99% by weight of I ghucose monohydrate;, and ii) from about 0,001 % to about 50% by weight of anhydrousI gl ucose:and h one or more pharmaceutically active ingredients. 100741 By "non-absorbable saccharide component" is meant compounds that axe not readily absorbed by the body. for example.glucose or compounds that are sweet to the taste, but because of their high sweetness index, do not add bulk or mass to the composition and thus to not interfere with the colon cleansing embodinents, As such, although iAglucose is understood not to be absorbed, the formulator can indude other ingredients that have the desirable organoleptic property of sweetness. but which are not absorbed or that are minirnaliy absorbed by the body or which are recognized as non-caloric sweeteners Non-imiting examples of non calorc sweeteners include acesulkune and salts thereor, aspartame. neotame, saccharin. sueralose. stevia. and tagatose In addition other non-absorbable sugars inchde xylhtol arid the like. 18 100751 The compositions may further include one or more pharmaceutically active ingredients, By pharmaceutical active ingredient" is meant a substance that provides a medical benefit to the consumer but does not affect the colonic cleaInsing or laxative properties of the composition, For example, the pharmaceutically active ingredient can be a substance that relieves anxiety. In addition. the active ingredient can counteract any stomach or esophageal reaction due to fasting. [0076| In one embodiment, the compositions comprise:i) from about 10%. to about 90% by weight of La-lucose nonob ydrate; and ii) from about 10% to about 50% by wemht of anhydrousg ucose [0077] in another embodiment. the compositions comprise: i) from about 20% to about 80% by weight ofghicose mnonohydrate; and ii).from about 20% to about 50% by weight of anhydrous 1giucose. [0078] in a further embodiment the compositions comprise: i) from about 30% to about 70% by weght of -gluouse mrtonohlydrate; and ii)from about 30- to about 50% by weight of anhydmous aogheose [0079] In a still further embodi-ment, the compositions comprise; i) from about 40% to about i0% hguose mnohidrate; and ii) from about 40% to about 50% by weight of anhydrous D-glucnse, [0080] In a yet further embodiment, the compositions comprise: about 50% by weight ofi-gucose monchydrate: and ii) about 50% by weight of anhydrous glucose monohydrate [00811 I one em)bodint, the compositions can comprise from about 10% to about 90% by weight of the pharmaceutticallactive. componentss, In a further embodiment the composions of this aspect ca comprise from about 10% to about 90% by weight of the pharmaceutical aciveco'mponentts), In another embodiment the compositions of this aspect can compose froim about 20% to about 90% by weight of the pharmaceuticly active componentss. in a further embodiment; the compositions of this aspect can comprise from about 30% to about 90% by weight of the pharmaceuticals active component(s), I a yet further embodiment, the compositions of this aspect can comprise front about 10% to about 80% by weight of the pharmaceutically active componentIsn ina still further embodiment, the 19 compositions of this aspect can comprise from about 10% to about 70% by weight of the pharmaceutically active componentss. [0082] in various embodiments, the glucose monohydrate is used in a pharmaceutical composition, for example a composition for use in colon cleansing, For example, a colonic cleansing method can comprise orally admnistering to a subject in one or more doses a composition cOmprising an amount ofone or more Lesgars that is greater than about 48 g wherein one of the L-sugars isliucose monohydrate. or wherein the L-stigars consist solely of iglose monohydrate. [00831 The compositions fr colonic cleansing can mi ude the sugar in a compositions, such as a food product. For example, a colonic cleansing composition in the fom of a gel can include combining ater. s ugar and a gCing agent. GC1litg agents nilude for example gelatin, such as Gelatin, Type A, 25 Bloom, 50 mesh. from Great Lakes Gelatin. PO Box 91!. rayslake, IL; agar such as Sigma brand Agar A-7002 Lot 7 1 K0093; and commercially available products that include flavorings, such as JELL 0 brand desert mixt and the like. In one aspect, about 85 g ofELL&V' can be boiled in about 1 30) mL. of water and combined with a near boiling mixture containing 45 i. of nugar dilUted with about 65 ni of water and the flavoringincorporation of a laxative agent into a gel is described, for example, in US Publication No 2004/0071779 A I, whib i-s incorporated by reference herein inits entirety. [0084] A composition for colonic cleansing and/or a kit for colonic cleansing, as disclosed herein, comprises an L- sugar; The composition and/or kit can also include one or more other ingredients such as flavoring, colorards, andior dispersants, The i-sugar can be in the form of, for example, a solution, a suspension a colloid a dispersion,a sury or a gel A composition for colonic cleansing can include the sugar in solid form including a powdered soid, a granulated solid, or one or more tablets. When present as a solid, the sugar can be anhygins, or can be present as a hydate Ig monohydratel ,for example I glucose monohydrate; al amounts Of sugars and L-ghucose referred to herein exclude w' ater of hydration and any other compounds that can be present in the specific form of sugarsed, The -sugar can be in one or more containers, such as bottles, tubs sachets, envelopes packets tubes and ampoules, 20 10085] in certain aspects, the v sugar is dissolved in water (or other comestible liquid.) The rate of dissolution is diecdy proportional to surface area of the solute, Thus. it can be adantageous to use very fine powders of the anhydrous form i issgarssice they have large surface areas. Thushen a subject adds water to the anhydrousugar and stirs for a few minutes thel material will dissolve. If, however, a subject does not suiciently stir the solids can chunp and dissolution rate can become quite slow. [00861 While not wishing to be bond b theory. it is believed that the reason for this phenomenon is allowance for local supersatuation of glucose in water to occur near the crystals front which dissolution is occurring. hisreststin the rapid growth and deposition oft glucose monohydrate crystals onto the anhydrous material, and a dramatic reduction of the overall surface area upon which dissolution rate depends. [0087] The advantage of .- glucose monohydrate (or similarly the nionohydrate of other Laugars) is that dhere is no longer a transition of Crystal forns afecting the overall surface area. If one begins with high surface area of glucose monohydrate they can add vater and apply even minimal stining to accomplish rapid dissolution , w within 1 minute or so), As such, in certain enibodiments herein the sugar that is provided in the kits is in the monohydrate form. [00881 In an additional aspect the present invention relates to kits comprising Ungars such as compositions comprising Uelucose monohydrate) In one ebodiment the kit comprises a package and an amount of an -sugar (eg glucose monohydrate) effective for colon cleansing in the package, [00891 In a further embodiment the kit conripses at least two separate pre--measured doses of L-sugarsuch as a first dose and a second dose, preferably in separate containers In some examples the kit can include two containers of Usugar, each container having an amount of U-sugar appropriate to combine with water to form an orally administrable first or second dose, In a further example the sugar can be present as a powder contained in two packets, the packets corresponding to a first and second dose of colon deansing agent. In a still further example, the kit can conpise a container containing a pre-measured amount of -sugar into which water can be added to dissolve the .sugar to the desie volume. A kit can contain one, 21 two, or more such containers, The disclosed kits can aiso comnprise instructions for colonoscopy preparation, [0090] in certain embodiments, the total amount of Lsugar in the kit is greater than 48 g, In further embodiments, the total amount of I*sugar in the kit is from greater than about 48 g to about 200 g; 10091] In another embodiment. the first dose in the kit comprises at least 36 g L-sugar and the second dose comprises at least 30 g L-sugar, For example, the first does in the kit conprises from about 36 g to about 80 g L-sugar and the second dose comprises from about 3g to about 80 girsugar. [00921 Ia one emi odiment the Irsugar is hgjucose. In another embodiment. the .Lsugar is Iglucose monohydrate. [0093 One or more anorectal wipes optionally can be present in the kit, Anorectal wipes can be made from any suitable substrate such as cloth, paper. or combinations thereof, and can be wetted with an aqueous mixture that can inchide one or more actve ingredents, Examples of active ingredients include a local anesthetic such as pramoxine hydrochloride, and a potectant such as glycerin. The aqueous mixture also can include one or more inactive ingredients, such as cetylpyridinium chloride, citric acid disodium EDTA, eucalyptol, menthol, octoxyno>9 sodium benzo ate, te 'he anorectal wipes can be in the form of pads and the like such as EEELT PainRelief Pre Moistened anorectal pads. In one aspect, four individually wrapped wipes are preferred. The anorectal wipes can be rectangular in shape, having dimensions of about 4 cm by about 7 cm. The anorecta wipes can be present in the kit i one or mom containers. such as bottles tubs, sachets envelopes, packets, tubes, and the like, For example, the kit can inci ude two packets containing one or more. anorectal wipes each .In one embodiment, the kit includes at least two anorectal wipes packets, each packet containing two anorectal wipes. Mthmos of ramn [0094 In prec iinical studies, there was no metabolism of glucose in any mamalian species studied. in mice, rats, dogs, rabbitsand monkeys. the major route of Vglucose elimination was urinary exretion, Food restrction had no significant effect on the metabolism of ghcose. A dietary study in Sprague Dawley rats showed that there was no overt evidence of 22 toxitcty fon the continuous administration of ..- glucose fbr 90 days The maximurn tolerated dose in rats was determined to be 10% dietary level of Lgiucose [0093j Clinical studies have shown that -ghcose is moderately absorbed from the human intestine. Breath hydrogen results in humans were comparable with results obtained from in Uwr studies, indicating that colonic bacteria do not metabolize glucose The major routes elinnation of -glucose in hunrans are fecal and No icant glucose or insulin response was noted after the adnin istration of 1.-glcose. Mild upper gastrointestinal yptos Suti.as coming nasea belchingrifting, and bloating occurred in a minority of subjects. Lower gastrointestial symptoms, such as cramping and gas/flatus, occurred in a majority of subjects, but symptoms were mild and did not interfere with their daily activities Subjects reported that the taste of uglucose was generally perceived as pleasant [0096] Despite these generally advantageous properties of L-sugars. tey have not been found to be satisfactory as a colonic cleansing agent in various tests. For example, an open-label. historically controlledsingle-dose study of a 24-g dose oft glucose was conducted to determine the safety and effectiveness of glucose as a colon-cieansing agent before colonoscopy (Raymer etal- 'An opendabelrial of glucose as a colon-cleansing agent before colonoscopv Gst roines Endow 5( K305. 2003).Based on the results of the colonoscopies the majority of subjects (80%, had a colonoscopy preparation grade ofsee~nt" or "good. However, the 80% success rating reported was less than that observed with conventional PEG compositions, which in turn are less effective than coloic cleansing agents based on phosphate saltsJism et at, leta-anal ysis and cost comparison of polyethylene glycol lavage versus sodiurn phosphate for colonoscopy preparation," astroimesdnalndoscop 48(% 276-282 1998) It is further noted that the 8ep O c success rathng qui talent to a 20% failed rating, which is not acceptable especially when one considers that each failed colonoscopy possibly means a missed diagnosis, not to mention great expense and inconvenienceto the doctor and patient when rescheduning the colonoscopy [0097] The methods discosed herein use compositions comprising i.sugars in doses that produce signincanty improved colonic cleansing. [00981 Ia one embodiment, disclosed herein are methods for colonic cleansing that comprise orally administering to a subject in one or more doses (e.g. within a 24 hour period) a 23 composition comprmag an amount Of an sugar that is greater than about 48 g, FOexamle an -sugar can be administered in an amount from greater than about 48 g to about 200 g of the sugar, from about 50 g to about 150 g of the sugar from about 60 g to about 140 g ofthe V sugar, from about 70 g to about 130 g of the sugar. from about $0 g to about 120 g of the Q sugar or from about 90 g to about I10 g of the r sugar. 10099] In other examples, an sugar can be admiistered in an amount of about 49, about 50, about 51, about 52,about 53, about 54, about 55. about 56, about 57 about 58. about 59, about 60, about 61, about 62, about 63. about 64. about 65, about 66bout 67, about 68, about 69, about 70, about 71, about 72 about 73, about 74. about 75 About 76, about 77, about 78, about 79, about 80, about 81, about 82, about 83, about 84, about 85 about 86, about 87, about 38. about 89. about 90. about 91, about 92. about 93, about K about 95, about 96, about 97, about 98, about 99, about 100, about 101. about 102, about 103, about 104, about 105, about 106, about 107, about 108 about 109, about I 10, about I 11, abo ut 112, aboat 113, aboat 114, about i15, about i16. about 117, about I18, about 119, about 120, about 121, about 122, about 123, about 124, about 125, about 126, about 127, about 128 about 129. about 130, about 131, about 132, about 133, about 134, about 135, about 136, about 137, about 138 about 139. about 140. about 141, about 142, about 143, about 144, about 145, about 146, about 147, about 148, about 149, about 150, about 151, about 152. about 153, about 154, about 155 about 156, about 157, about 158, about 159, about 160, about 1 61, about 162, about 163, about 164, about 165, about 166, about 167, about 168 about 169, about 170, about 171 about 172, about 173. about 174, about 175, about 176, about 177, About 178, About 179, about 180, about 181, about 182, about 183, about 184, about 185, about 186, about 187, about 188. about 189, about 190. about 191, about 192, about 193 about 194, about 195, about 196, about 197. about 198, about 199, or about 200 gof the -sugar.vhere any of thestated values can form an upper or lower endpoint of a dosage range, [06i0] Also disclosed herein are methods for colonic cleansing that comprise adininisterug a first dose of a com'posion compsing an i.sugar and then a second dose of a composion comprising an sugar For example one can administer a first dose comprising at least about 36 g of the Usugar and a second dose comprising at least about 30 g of the Irsugar, a fbast dose compdsing om about 36 g to about 80 g of the I--sugar and a second dose comprising from about 30 g to about 80 g of the sugar a fust dose comprising from about 40 g to about 60 24 g of the Ls'ugar and a second dose comping from about. 40 g to about 60 g of the sugar a first dose comprising from about 45 g to about 55 g of the sugar and a second dose comprising from about 45 g to about 55 g of the v-sugar, a first dose comprising fromn about 40 g to about 50 g of the sugar and a second dose comprising from about 30 g to about 40 g of the [-sugar, or a first dose comprising at least about 48 g of the Lsugar and a second dose comprising at least about 8 g of the sugar, [00101] In certain embodiments. the second dose is administered at least about 2. about 4. about 6, about 8, about 10, or about 12 hour\ after the first dose. [00102} in certain etbodiments of the methods described herein, the U-sugar is L glucose In other embodiments of the methods described herein, the IUsugar is U-glucose znon ohydrate. [001031 In one embodiment, the methods described herein include administering a first dose comprising about 48 g L glucose (which is equivalent to about 52. 8 U-glucose monobydratef and a second dose comprising about 48 g U-glucose (or about 528 g L-glucose monohydrate) Preferably, the first and second doses re aqueous solutions of the Lglucose. [00 04] In one embodiment the present invention relates to a method for colon cleansing m a subject undergoing a colonoscopy; that includes administering to the subject an aqueous solution containing about 32,8 g 1, glucose monohydrate (which is equivalent to about 48 g of active glucose) the night before the colonoscopy, and adnunistering to theus acttoe sh,'ubject an aqueu solution containing about 52.8 g U--glucose monohydrate the morning of, but prior to, the colonoscopy, [001 051 In fune boitiets, each dose of LUglucose mionohydrate is dissolved in 8 ounces of water prior to administration to the subject [00106] In one embodiment, the first dose of L-glucose nonohydrate is administered at about 6 pm the night before the colonoscopy. in another enbodinent, the second dose of L glucose mono'hydrate is administered at about 6 am the day of the colonoscopy. In a father embodiment, the first dose of Lucose monohydrate isadministered at about 6 pm the night before the Colonoscopy and the second dose of l-giucose monohydrate is administered at about 6 am the day of the colonoscopy, 25 I0107 in additional embodrwnt& adTinistration of a composition comprising an v sugar can be accomplished by dissolving the composition comprising the b-sugar in water (or other comestible) and admnisteing orally. Alternatively tablet s) capsule(s) sachets powders, grnules suspensions. emulsions, or solutions in water or non-aqueous media cat be ingested by or administered to a subject. Thickeners.flavorings, diluents emiulsifers dispersing aids or binders can be used. The disclosed compositions can also be administered by enema. [0010S] The following examples are merely illustrative of the present invention and shoul not be construed as lirniting the scope of the invention in any way as many variations and equivalents that are encompassed by the present invention will become apparent to those skilled in the art upon reading the present disclosure. EXAMPLES [001091 glucose (144 kg. 800 rol) is dissolved in water (600 L) in a sealed vesseland the pressure reduced by approximately 700 mm Hg. The solution is heated to less than about 65 'C and the water content reduced to about 28% to about 30% by weight. f he solution is then heated to a temperature from about 80.C to about 82 a"n until the observed solids are dissolved. The solution is then gradually cooled and held at a temperature of from about 50 C to about 55 *C until crystallization occurs. Once crystaization is initiated the solution is further cooled to a temperature of from about 25 C to about 30 IC with continued aguation. Crystallization is allowed to continue fr about 12 hours, Ethanol (7() L) that has been denatured with isopropanol, is added over approximately 30 minutes. [00110] After about 90 minutes, the resulting crystal slurry is ceritrfuged and the solid is collected, washed with denatured ethano.a L) and transferred to a tray dried rhe crystals are tied under a vacuum of at least about 650 mm Hg at a temperature from about '5/C to about 20 K7 to afford 110 kg (694% yield) of -glucose monohydrate. Karl Fischer water analysis of final product found that there yas approximately 9% water present. thereby affirmin ghlcose monovhydrate. The remaining lujcose can be recycled to obtain additional glucose monohydrate 26 euoemonohydrate(oipsi.on Ex ate [00111] The following are nonlintting exemplary conposilons contaiinng L-glucose monohythate. The following are solid compo;sitiofns that ame dissolved in 100 mL to make up a colon cleansing and/or laxative composition. The following amounts are in grams. Composition Examples 15 Ingredients 1 2 3 4 L-,lucose monohydrate 48 48 48 4 48 sdivdrous ULccose -0,05 0.07 A I. 0U25 Compositii Exampes 6 10 nredients 6 7 8 9 10 L-ucose monobiydrate 50 50 o 50 so anhydrous Ugiucose 0.05 0075 l 0125 Composition Examples 1&15 ingredients 16 17 18 19 20 Lqglucose monohydrate 70 60 0 70 70 anhydrous ucose 0075 0 0 "2 015 Com~poStIon Examples 21 2 ngirdients 21 22 23 24 25 Le g cose monohydrae 80 20 80 80 80 anhyous L-gluose mo 0.1 0 25 80 0o)7S Cornposition Exampls 26-30 ngeins26 27 2S 293) 1.gh cose m''-lonobydrate 90 90 90 9() 90 anhydrous tg ncose 0 0125 015 0175 [001121 The Lglucose monohYdrate can have a rte of sohbilh tnt increases with increasing temperatunte As such ompositions conmpising ughcose nouhydrate can be waited by the user to increase the rate of dissolution. [001131 The following describes methods for determining the increased dissolution rate of i'-glcose mnonohydrate comprising compositions. [00114] To separate 600 mL beakers is charged Uglucose onobydrate (53 g -and anhydrus -lucose (48 g Each sample composes approximately an equivalent amount ofA glcose on a weight basis. Carefully, to avoid agitation and mixing, doubly distilled water (240 nL is added to each beaker. In one example, the sohition is stirred immediately after addition of water, In a second example. the solutions are allowed to stand for 5 mines before agitation. The stiring was conductedin a manner duplicautng the way a consurner is expected to stir a sample prior to use. The following Table summaries these experiments which were conducted in duplicate. Samle Time' Observationis Sample f!kuiy dissol ved after 2.5 mi. of strng L-- glucose nonhiirate No delay Several clusters of solid at I min . Final solution was clear, colorless and homogeneous Sample fully dissolved after 235 min, of stirring, L- glcose monohydrate 5 d ever clusters of solidadt Iin Final solution was clear, colorless and homogeneous -glucose N y Fully dissolved after 2 min. of string Final inhsosemoohydrate No dela solutin was clear, colorless and homogeneous Fully dissolved after mia of stirrint Final L- gh cose, m.onohydr-ate 5 m n d solution was clear, colorless and homogeneous 2S Most of the sampve dissoIved after 5 min of anhdrous Lglacose No delay stirring, Cear sohdion results with patent insoluble particles present. Material chtmped into a hard mass during ime delay, Most of the sample dssohed after S in ahvdrous Lglucose 5 mmn delay of stirring. 0ear solution results with latent usoluble particles present, 1, Sample obtained frm Darisco Inc, Lot # MiS> -0408A, 2. Sanpl obtained from Arch Phanalabs Lmtd. Lot # VILGC-0 17090001. 3. Saipit obtained from Danisco Mc., Lot # DeLS5J9208A, 4 Sampes with no delay are immediately stirred in a manner consistent with the practice of consumers, ie use of a spoon or stirring stek Samples with a time delay are not agitated until the end of the time delay, [0015] Because of the increased rate of dissolution of Uglucose monohydrate it can be used for formuladins whereinrapid dissoluon ofhe cou position mnredients is desired For example, the LVglucose monohydrate can be formulated into a composition that is taken orally for colonic cleansing, The coniposition can be used by the consumer or by, medical pesonnel The composition for colonic cleansing can include the glucose monohydrate in solid form. including a powdrd s a granulated solid, or one or more tablets. When present as a soid, the u-ghcose monohydrate can be in one or more containers.such as bottles, tubs, sachets, envelopes, packets tubes and ampoule.s Bowel Preparation Scals [00116] The American Society for Gastrointestinal Endoscopy (ASGE) and the American College of Gastroenterology Taskforce on Quality in Endoscopy have published guidelines for procedural documentation that include a recommendation to assess bowel cleansing quality in all colonoscopy report-s (Rex ew al Quality indicators for colonoscopy; A I (astrocerei 101 87385, 2006) Unfortunately, there is no industryawide standard for assessing the adequacy of bowel preparation fbr colonoscopy. Previously published scales differ significantly in their deign (global s segmental scoring system (cateconcal vi numerical) an d application (before 29 or after washi-ng and cleansing) Advantages and disadvantages of each scoring method are shown in Table 1. Table 1 Thoeia1avnae and isdaiweofbowel prprto crn vb n AdntagesDisadvantae Design global Has v to use Diffult to accout fo EaF tsy to understand segmental differences Segment Accounts for segmenta More complex difference in cleansing y (hallenging to validate by quality that occur with v idetape review A segments 'l preps aent designated *Permits independent study of right colon Ceansing, a postulated factor in missed colon cancers Scoring sten Catego e Ea s to understand rying defitions of Standard language of excellent ood Exce~ient - Good" and "Poor" prohibi t cross generaly considered tial comparisons successful prep in Literature ______________________ Numerical * asy to statistical y Non-descriptive ayRequires an arbitrary ntmrincal threshold to determine adequacy oi inadequacy Smali but statistically ~gnificant differences in uunerjcal score ;n ht not be Application Before Reflects true cathatc Fails to account for ease of ashing/Suctionng effects of bowel hearing residual fluid or ________________prep_____aratiorn kees AfUtr WasbingSuclioning *R 'fleets ability of * oe.not account f'or tume colonoscopist to view the spent in clearing coon a colonic mcosa a significant efficiency ator uical endooit 30 [0071 Historcallbowel preparation manufacturers have relied u pon their own unique scales to assess the adequacy of bowel cleansing in headituhead clinical trials. These scales differ widely in their desigasmaking cross-trial compartsons impossible Futher. the lack of reliable, validated definitions of categorical descrptions of bowelleansing (A "Eceleat" "ood% Ot- and "PooIrendersany guideline for the documentation of boweI preparation adeoquacy impractical to implement. [001181 AppUcants have relied upon a combination of a categorical, 4-point scale and a muneical. egental scorig system to assess bowel cleansing quality (Balaban et at "Low volume bowel preparation for colonoscopy: randomized, endoscopist-blinded trial of liquid sodam phosphate versus tablet sodium phosphate," Am I (uterol 98:82732 2003 The basic 4- point scale, known as the Global Preparation Assessment OPA) is essentially the same as the original scale used in the first randomized controlled triA Af PHOS PH SODA as a bowel cleansing agent published in 1990 by Wanner m td. ( randonized prospective trial comparing oral sodium phosphate with standard polyethylene glyconbased lavage solution (Golytely) in the preparation of patients for colonoscopyv Am Gastroenterai 85;422-7 1990), The numerical scoring system known as the Residual Stool Score (RSS is a continuously variable averaged segmental scoring instrument that assesses both the amount and consistency ofres iduaa stool before suctioning (a measure of the cathartic activity of the bowel cleansing regimen) as well as the percent of the bowel wail seen after washing and cleansing (a measure of the utimate endpoint for bowel preparation success). The two scales are shown below. weRent= clean colon or small volume of leariquid Good =moderate to large volume of clear to seniclear liquid Pir =some semisolid stool suctioned or washed away Poor semisolid or solid stool unable to be suctioned or washed away Reidual IStool *SCor [001191 Effectiveness variables include assessment of the amount and consitency of stool in the bowel and the percent bowel wall visualized. Segnental evaluations are done at the level 31 of the rectumi descending colon. transverse colon. ascCnding colon nid cnc un according to the scales below Stool Amount: Stool Consistency: Percent Wall Visualized: 0= None 0 = None 0 >95% . Z Minimd I = Clear yellow liquid .1 =85% to 94% 2 Small 2 Muddy liquid 2= 75% to 84% 3 Moderate 3 = Particulate stool 3 = 50% to 74% 4= Large 4= Solid Stool 4 <50% [00120] Amount Of stool and stool consistency is scored before washing and suctioning. while percent bowel wal visualized is scored after washing and suctioning The surn of the three ratings constitutes the score for each segment 'he final RSS is determined by calculating a mean of the scores for all segments seen. If the colonoscopy does not proceed through the five sections of the colon, the segment where the colonoscopy coded and the reason for stopping is noted, and the segments are rated as viewed up to that point. I001211 The GPA scale includes representative colonoscopic images of each cleansing grade as a visual aid.. The 4 point GPA has been demonstrated to have a hig degree of statistical correlation wah the segmental RSS10(r px <001) (alaban et Am3 (aistine ol 988272 2003) [001221 The bowel preparation assessments described in the Examples below em ployed two scales to describe the amount and consistency of residual stool as well as the ability of the endoscopist to clear the stool for complete examination, Certain eienents of thescoring method were completed before suctioning and washing and reflected the ability of the bowel preparation to provide a dry and clean prep, which is advantageous to minzize time of additional lavage and suctioning during the exam The other elements were completed after suctioning and washing and rejected the ability to completely examinethe colon. [001231 Other published bowel preparation scales focus either exclusively on visualization of the colon or on a description of residual stool but do not permit independent assessment of each of these elements. Furthermore, the absence of a segmental component in some scales 32 precludes important evaluations of the relative efficacy of cleans-ig in theright and left consideration for endoscopists. [001241 Incremental modifkicions of the language of the GPA and RSS scales from dozens of researchers over the past 7 years has resulted in descriptions that are free of the anbiguity that hampers the utility of other scales. As an example the scale employed by Raymer e, a! includes a description of 'smail bits of adherent fecl fluid> inthe Excellencategory, it is not clear whether "bits" refers to a solidcomponent.as one might expect or a liquid component hihis described by "fd Of note, solid feces are not permissible i either the Excellent or Good scores used in the examples below, which indicates that the scale used in the examples below is morerigorous, V)4MU125] Applicants method for bowel cleansing assessment inching the Global Preparation Assessment and the Residual Stool Score, addresses unique and complementary elements of bowel cleansing for colonoscopy. By using both scales the metod permits a complete analysis of fecal dearanceincluding the ease with which complete colonoscopic exam can be achieved. Comr-pared to other published scoring systems Applica-nts method is more. rigorous in its language and more complete in its description of bowel preparation adequacy [001261 A muiticenter. doubie~-blind. deangeminding study to evaluate the effectiveness and safety of tghucose as a colon-cleansing agent before colonoscopy was conducted, Doses used in this study were 12 g, 16 g, 20 g, and 24 g. The assessment of h preparations was based on the scale used in Hsu 4 atl, 'Meta-analysis and cost comparison of polyethylene glycol savage versus sodium phosphate for colonoscopy preparation," Gasinsinal Anihdacop y 48):276-282 1998, wherein small bits of fecal material in the colon vere allowed in an "xceflen$" score. Thus, the 24 g dose experiments were similar to the highest dose experiments of Ravmer et at The results indicated that I-glucose in single doses within these ranges was not acceptable as a colonic cleanser. 33 ComnparativeExample 2 [00127j A randomized ,single-blind study designed to determine the cLinical effectiveness of glucose as a bowel preparation before colonoscopy s perfrmed. Three dose regimens were evaluated: 24 g in the evening only, 30 g in the evemrig oly and 24 g in the evening followed by 12 g in the miorning (36 g total) Here. Applicant's GPA scale described herein was used to evaluate the preparations. In is studythe 2 eve nri-only doses (24 g and 30 g) were suspended for lack of effectiveness. This study showed that t-glucose given as a split dose had greater clinical effectiveness of bowel cleansing. In fact the split dose schedhle was statistically superior to the single close schedule:(PA showed a significant difference in efficacyg < 0{) between a split-dose as compared to the single-dose schedule. Clinical efficacy (defined as a combination of ecsdleon e an godt assessments) for the split-dose schedule was 19127 (70% t as compared to 7/1 23%) in the single--dose scheduled (p 0.001). Commonly reported adverse events were generally absent or mild, and there were no clinically significant changes i laboratory test results, Nerly all subjects reported the -glucose cleansing solution as easy and convenient to use. The taste was favorably rated as very pleasant to somewhat pleasant; Overall tolerance to the bowel preparation was rated as good or very pod and most subjects reported they were willing to repeat the regimen. 1001281 As noted above in the description o Applicant's OPA scale, the criteria for determining whether a preparation was deemed "ctexUt" or "good" was respectively defined as "clean colon or small volume of clear liquid' or "moderate to large e of Clear to semi clear iiquid"'V These crieria are more strngent than the rating system used by Raymerat a!. discussed rpra since Raynr s MUeent" and "god ratings were respectively defined as "no more than small bits of adhererntfecal fIid and "small amounts of fece-s or fluid not interfering with the examination Thus Rayner "eedlent" rating would likely not qualify as even a "good" rain in Applicant's GPA scale. [001291 This open-label, 2-site study employed a dose-escalating design using 3 split doses of -glucose (24 g124 g, 36 g16 g, and 48 g8 g) The doses were administered the night beforeand the morning of a scheduled colonoscopy The study was conducted in Phase I 34 facihties to control for administration of Lglucose aid adherence to the dietary and hydrationz regimen, [.0030J Three dose cohorts of 24 sbjs were evenly divided between males and females for each cohort. Subjects who were scheduled to undergo an elective coionoscop who met the study entrance critelria, and who gave their consent to participate in the study were enroled. Study subjects who met the inclusion criteria and did not meet the exclusion criteria were enrolled into the lowest dose cohort first. Each subject observed a strict diet and hydration regimen as part of the study medicatioiadinistradon. [001311 The she pharmacist prepared the i glucose preparation based on the study medication preparation manual provided. Each. subject, regardless of dose cohort, received the dose in 8 ounces of water, which was to be consumed within a 10VrinAe period Dose cohots proceeded in a dose-escalating fashion starting with the lowest dose (24 g/24 g) and escalated according to a dose escalaton decision tree, [001321 The physician performing the colonoscopy utilized Applicant's GPA scale to evaluate the quality of bowel preparation as before suctioning and washing If the colonoscopy did not proceed through the colon to the ecum for anatomicalor medical reasons and not because of retained stool the location where the colonoscopy ended was noted and the preparation was rated as viewed up to that point. When the colonoscopy did not proceed through the colon to the cecum for reasons of inadequate bowel preparation, because of the presence of retained stool, the GPA was rated as "poo" [001331 The Residal Stool Score (RSS) described above was also used to assess bowel cleansing in each of the 5 segments of the bowel (rectum, descending colon, transverse colon, ascending colon, and cecum }. As noted, assessnients included the amount of stool present, the consistency of the stool, and the estimated percentage of the bowel walvisualized in each segment. [01341 Por reasons of inadequate, bowel preparation, sections of the bowel that were not directly examined during colonoscopy were rated as "pot' on all three measures listed previously, 35 [00135 A total of 24 subjects were enrolled into each of the thee dose cohorts. All 72 subIects were included in the inent-to-treat (FIT) and safety populations. [00136 There were 23(95.8%) subjects in each dose cohort who had a complete col OnIosCopy (endoscopiSt was able to reach to the level of the cecum). The nean (SD) of GPAs were 3.29 (08 1) for the 24 g/24 dose cohort 342 (0 83) for the 36 g/36 g dose cohort and 3,88 (0,45) for the 48 g/48 g dose cohott The GPA scores were rated exef For at least half of the subjects in each of the 3 dose cohorts including 12 (500%) subjects in the 24 g/24 dose cohort. 14 (58,3%) subjects in the 36 g/36 g dose cohort and 22 (9L7%) subjects in the 48 g/48 g dose cohort. Only 1 42% subject in the 36 g/36 g dose cohort had a CPA score that was rated "por;" Table 2 summarizes the GPA results. Table 2 Sunnary of Global Preparation Assessment by Dose &ohort (ntent-to-Treat Population) 4 g'4 36 g/36 g 48 /4-8 g (Ichort Cohort Cohort ~ oa (N 2 24) (= 24) (n=24) Global Preparation A ssessment N 24 24 24 72 Mean (SD) 329 (0.81 3 42 (0.) 88 (),45) 353 (0.75) Median 3 50 4.00 4,00 4.00 Min. Max 2.00. 400 100, 4,00 2.00. 4,00 100, 4,00 Excellent 12 (50.0) 14,583) 22 (9 1) 48 (667) Good 7 (29.2) 7 (292) (42) 15 (20) Fair 5 (20.8) 2 (83) 1(42) 8 (1 1.) Poor 0 (n) 1 (12) 0 (00) 1 (IA) SD =sidard dc-a.n= niam ,a~x njxi um N:Pecentages arc based onikeIm'r d 3jts in each dose cohort [001371 There were 30 (96,8%) subjects at Site 01 and 39 (95 1% subjects at Site 02 who had a complete colonoscopy The mean (SD) GPA was 3.68 (035) for Site 01 and 3. (034) for Site 02. The CPA scores were rated excdem" for more than half of the subjects at Site 01 (25 subjects 80.7%) and Site 02 (23 subjects, 56.1%,,\ Only 1 (3.2%) subject at Site 01 had a GPA score. that was rated "'poor 36 [001381 The results of the efficacy analysis demonstrated the following, The GPA scores were rated txceen for at Least half of the subjects in all 3 dose cohorts including 12 (5.0%) subjects in the 21 g/24 g dose cohort, 14 i58.39subjects ithe 36 g136 g dose cohort, and 22 91%) sub jets in the 48 g/48 g dose cohort, There were 23(9i8%) subjects in each dose cohort who had a complete colonoscopy Tne dose that achieved the greatest eticy was the 48 g/ 48 g dose, based on the high percentage of eueln" examinations observed at both sites, supported by the shortest time to the first watery bowel movement, Further, the 48 g/48 g dose provided a more robust bowel cleansing, based on the higher percentage of "ee/lent" examination; at lower doses there were differences in GPA ratings, demonstrating a less robust bowel cleansing. The results indicate that split doses mow than 36 :/36 g resut in. signifcantly better colon cleansing than lower split doses, and especially lower single doses Ferther when one takes into account the more stringent criteria used in this study to asses the preparation CsPAand RSS scales). the results obtained are -even more dramatic, [001391 It will be apparent to those skilled in the art that various modifications and varations can be made in the present vention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from cosmidention of the specification and practice of the invention disposed hereint is intended that the specification and examples be considered as exemplary only, with a tme scope and spirit of the invention being indicated by the folowing claims. 37

Claims (18)

1. L-gicose rmonobydrate.

2. The INgh cose monohydrate of c iIhaving an X-ray powder diffraction (XRPD) pattern comprising one or more characteristic peaks at about 9.24 about] 846, about 19.78. about 20,24 and about 28,36 ± 0,2 degrees 29.

3. The L-giucose monohydate of ciaim i having an X-ray powder diffraction (XRPD) pattern comprising characteristic peaks at about 9.24 about 1846, about 19.7 about 20.24 and about 2836 ± 0,2 degrees 20, 4; The Lglcose monohydrate of claim I having an X ry power diffraction (XRPD) patten comprising one or more characteristic peaks at about 9U4, about 1238, about 14.60, about 16,48. about 18 46 about 19.32.about 1978, about 2) 2 about 2056, about 21 7&about 2 84,abut 2350; about 25,52, about 26 56 about 27.62 about 27,84, about 2836 about

29.40, totd0,80, about 3098, about 31.22 about 52,38. about 32.4 about 33 82 about 3524, about 35,72, about 36.96 and about 40.18 degreess 2.6. a Ihe L Alicose monohydrate of claMn 1 having an X -- ray powder diffractionXRPD) pattern comprising characteristic peaksa at about 9.24. about 12, 8 dbout 14,60 about 1648, about 1846. about 19. a bout 19.78 about 20.24, about 20 56 about 213 about 284 about 2350 about 2532 about 236 about 2762, aut ?.84, about 2836 about 2940 about 3080 about 309 about 31 22. about 32.38, about 3.34 About 3382; about 352,J)out 3532 about 36.96 and about 40 8 ± 02 degrees 20, 6. The glucoe nonohydrate of claim 1 having an X-ray powder diffraction pattern substantially as shown in Figure L The L--glucose monohvdrate of claim 1 having an optical rotation of from about -- 52.5 to about -533 degrees, calculated with reference to anhdrous L-glucoe. 8. The Iglucose rnonohydrate of c ain I, which is free front D-glucose and D-gIucose monohydrate 38 9, The L ucos monohydrate of ciain I which is at least about 99% pure. 10. "The glucose mnhydrate of clam I. which is at least about 99,999% pure, Ipi A process for preparing L-gucose nonhvdrate comiipsing (a) adding Lgline to water and heating under reduced. pressure, and (b) cooling the resultant solution to form glucose nionohydrate, 12, A process for preparing L-glucose monohydrate, compnsing: (a) dispersing an amount from about 0;9 moles per iluer to about 1.5 moles per liter of a source of i-lucose in water at a temperature of from about 55 *C to not nore than about (5 *C at a reduced pressure of at least about 700 nun Hg less than atmospheric pressure, reducing the amount of water present such that the amount of water present is from about 28% to about 30% by weight of the solution, and heating the dispersion to a temperature of from about 80 'C to about 82 0 C to form a solution; and (b)cooling the solution to a temperature of from about 50 "O to about 55 TC to induce crystallizaion, further cooling the resulting s urry to a temperature of from about 25 *T to about 30 "C, and adding an amount of thanol that is from about 4.5 ml. of ethanol to about 5 ml of ethanol oof Lglucse dispersed in step (a) to form L-glucose monohydrate. 13 The process according to claim 12, further conprisria (cI isolating the U-glucose monohydrate formed in step (b), 14 The press cording to claim 12 wherein the amount of L-glucose provided in step (a) is about 1.33 moles ofUglucose per liter of water. 15 The process according toclaim 12 wherein Lglucose monohydrate is added in step (b) to induce crystallizaon. 16. The process according to clain 12, wherein the amount of ethanol added in step (b) is about 85 mL per gram of I-glucose used in step (a). 39 17. The process according to claim 13, where the U glucose mooh ydrateis isolated by centrifugation. 18. glucose monohydrate prepared by a process according to claim i or claim 12. 19. A composition comprising at least about 509 by weight of glucose monohydrate and one or nom adjunct ingredients, 20, A composition comprising a) at least about 50% by Weight of .elucoSe monohydrate; and b) anyidrous Lrglucose, 21. The composition according to claim 20, comprising at east about 70% by weight of L glucose monohydratc. 22. The composition according to claim 20, comprising at least about 75% by weight of L- lucose monohydrate. 21 The composition accddng to claim 20, comprising at least about 80% byweight of L glucose monohydrate, 24. The composition according to claim 20, comprising at least about 85% by weight of L ghucose monohydrate. 21 The composition according to claiT 20. comprising at least about 90% by weight of I, glucose ruonohydrate. 2.6. The coinpositicn according to claim 20, comprising at least about 95% by weightof L~ glucose monohydratc. 27. The composition according to caim 20, comprising at least about 99% by weight of L glucose moohydrate 28. The composition according to Claim 20, comprising at least about 99.999% by weight of L-glucose nmonohydrate, 40 29. A method for colonic cleaing compring g administering to a subject in one or more doses a composition comprising an amount of an L-sugar that is greater ian about 48 a. 30 The method of claim 29. wherein the amount of an Lugar is from about 48 g to about 200 g, 31, The method of claim 29. wherein the amount of an Lsugar is from about 50 g to about 150 g, 3 The method of clain 29, wherein the amount of an L-sugar is from about 60 g to about 140 g,

33. The method of claim 29, Wherein the amount of an L-sugar is from about 70 g to about 130 g, '34 "The method of clain 29, wherein the amount of an L.sagar is from about 80 g to about 120 g,

35. The method of claim 29. wherein the amount of an L-sugar is from about 90 g to about 110 g 36, The method of claim 29, where the L-sugar comr L gcose

37. The method of claimi 9, wherein the h-sugar comprises .- ghcose monohydrate 38 The method of claim 29.wherein the administering comprises administedng a first dose of the composition comprising the L-sugar and a second dose of the composition composing the U-sugar:

39. The methodof claim 38, Wherein the first dose courses at least about 36 g of the L sugar, and hs close comprises at least about 30 g of the L sugar.

40. The method of claim 38, wherein the first dose comprises from about 36 g to about 80 g of the L gr and the second dose comprises from about 30 g to about g to 60 g of the h-sugar, and the second dose composes from 40 a to 60 g of the hLs sugar, 41 41 The method of caim 38, wherein the first dose compares from about 40 g to about 50 g of the L-su grand the second dose comprises from about 30 g to about 40 g of the I-sugar. 42 1he method of claim 38, wherein the first dose comprises from about 45 g to about 55 g of the laugar, and the second dose comprises from about 45 g to about 55 g of the Usugar. 43 The method of claim 38. wherein the first dose comprises at least about 48 g of the L sugar, and the second dose composes at oast 48 g of the -Isgalr.

44. The method of claim 38, wherein the first dose comprises about 528 g -glucose mon ohydrate, and the second dose comprises about 52,8 g L-ghucose nonohydrate.

45. The method of claim 44, wherein the first dose is administered the night before the subject undergoes a colonoscopy, and the second dose is administered the morn of.but prior to. the colonoscopy. A The method of clain 44 e wherein each dose of Lglucose monohydrate is disolved in about 8 ounces of water. 47 The method of claim ., wherein the administration to the subject is prior to the subject undergoing: a colonoscopy. 48 A method for colon cleansing in a subject comprising: (a) administering to the subject an aqueous solution containing from about 36 to about 72 g L-glucose (based on the weight of base Igiucose) at night and (b) administering to the subject an aqueous solution containing from about 36 to about 72 g Lgiucose the frolowingt morning; 49 The method of claim 48 wherein the subject is undergoing a colonoscopy; step (a) is performed the night before the colonoscopy. and step (b) is performed the moving of but prior to. the colonoscopy.

50. A method for colon cleansing in a subject comprising: (a) dissol ving bglucose monohydrate in water to form a first aqueous soition, wherein the amount of b--glucose ranges from about 36 to about 72 g (based on the weight of the base L- 42 gtucose') (b; adminstering to the subject the first aqueous solution at night, (c) dissoivi'n-g L smonohydrate inwater tO fann a second aqueous solution, wherein the amount of L.glucose ranges from about 36 to about 72 g (based on the weight of the base Lghcoseh and (d) admiristeng to the subject theecond aqueous sotion the following moving,

51. A method for colon cleansing in a subject undergoing a colonoscopy comprising: (a) administering to the subject an aqueous solution containing about 48 g L-glucose (based on the weight of base -glucose) the night before the colonoscopy, and (b) administering to the subject an aquecos solution containing about 48 g U-glucose the morm.ng of, but pror to, the colonoscopy

52. An method for colon cleansing in a subject undergoing a colonoscopy comparing; (a) dissoling 528 g L gucose mnonohydrate in about 8 fluid ounces of water to form a first aqueous solution, (b) administering to the subject the first aqueous solution the night before the colonoscopys (c) dissolving 52,g 8 -glucose ronohydrate in about 8 fluid ounces of water to form a second aqueous solution, and (d) administering to the subject the second aqueous solution the .oedag of but prior to, the colonoscopy

53. A colonic cleansing kit comprising a package and an amount of an iUsugar effective for colonic cleansing in the package, wherein the amount of Lsugar comprises a first pre-measured dose and a second pre-measured dose,

54. The kit of claim 53, wherein the total amount of the L-sugar is greater than about 48 g,

55. The kit of cli 53, Wherei the total amount of the U-sugar is from greater than about 48 g to about 200 g, 56 The kit of claim 53, wherein the first dose comprises at least about 36 g of the L-sugar, and the second dose composes at least about 30 g of the L-sugar, 43 57 The kit of claim 53. wherein the firt dose comprises from about 36 g to abou80 g of the L-su gar, and the second dose comprises from 30 g to 80 g of the L-sugar

58. The kit of claim 53. wherein the L-sugar comprises L-glucose 59 The kit of claim 53. wherein the L-sugar comprises i-glucose mnoohydrate 60 The kit of claim 59, further conmprising anhydrous s I-glucose. 61 The kit of claim 48, further comprising instructions for colonoscopy preparation. 44