 cavity, typically as the patient sleeps.
Because peritoneal dialysates are administered directly into the patient""s body, it is important that the dialysis solution maintains the correct proportions and concentrations of reagents. Moreover, it is impractical to formulate and mix dialysis solutions on site at the typical location of administration, such as the patient""s home. Accordingly, peritoneal dialysates are typically delivered to the site of administration in pre-mixed solutions.
Unfortunately, dialysis solutions are not stable in solutions over time. For example, dextrose has a tendency to caramelize in solution over time, particularly in the concentrations required in the peritoneal dialysis context. To prevent such caramelization, peritoneal dialysis solutions are typically acidified, such as with hydrochloric acid, lactate or acetate, to a pH between 4.0 and 6.5. The ideal pH level for a peritoneal dialysate, however, is between 7.2 and 7.4. While achieving the desired goal of stabilizing dextrose in solution, the pH of acidified peritoneal dialysis solutions tends to damage the body""s natural membranes after extended periods of dialysis. Additionally, the use of acidified peritoneal dialysates tends to induce acidosis in the patient.
Bicarbonates introduce further instability to dialysis solutions. The most physiologically compatible buffer for a peritoneal dialysate is bicarbonate. Bicarbonate ions react undesirably with other reagents commonly included in dialysate solutions, such as calcium or magnesium in solution, precipitating out of solution as insoluble calcium carbonate or magnesium carbonate. These insolubles can form even when the reactants are in dry form. When occurring in solution, the reactions also alter the pH balance of the solution through the liberation of carbon dioxide (CO2). Even in the absence of calcium or magnesium salts, dissolved sodium bicarbonate can spontaneously decompose into sodium carbonate and CO2, undesirably lowering the solution""s pH level.
The current alternatives to bicarbonate for buffering peritoneal dialysate are acetate and lactate, but these reagents also have undesirable chemical consequences. For example, there is some evidence that acetate may reduce osmotic ultrafiltration and may induce fibrosis of the peritoneal membrane.
The incompatibility of reagents commonly found in dialysates thus creates significant logistical problems in connection with their preparation, storage and transportation. Attempted solutions to these problems have included various devices and methods for providing dry formulations of reagents, and for separately storing and dissolving incompatible reagents. See, e.g., U.S.
cavity, typically as the patient sleeps. 
 Because peritoneal dialysates are administered immediately into the patient""s soundbox, it is important that the dialysis solution maintains the right proportions and concentration of reagents. furthermore, it is impractical to formulate and mix dialysis solution on site at the typical localization of administration, such as the patient""s home. consequently, peritoneal dialysates are typically delivered to the site of administration in pre - mixed solutions. 
 Unfortunately, dialysis solutions are not stable in solution over time. For example, dextrose has a leaning to caramelize in solution over time, particularly in the concentrations required in the peritoneal dialysis context. To prevent such caramelization, peritoneal dialysis solution are typically acidified, such as with hydrochloric acid, lactate or acetate, to a pH between 4.0 and 6.5. The ideal pH level for a peritoneal dialysate, however, is between 7.2 and 7.4. While achieving the desired finish of stabilizing dextrose in solution, the pH of acidified peritoneal dialysis solutions tends to damage the body""s natural membranes after stretch periods of dialysis. Additionally, the use of acidified peritoneal dialysates tends to induce acidosis in the patient. 
 Bicarbonates introduce further instability to dialysis solutions. The about physiologically compatible buffer zone for a peritoneal dialysate is bicarbonate. Bicarbonate ions react undesirably with early reagent commonly included in dialysate solutions, such as calcium or magnesium in solution, precipitating out of solution as insoluble calcium carbonate or magnesium carbonate. These insolubles can imprint even when the reactants are in dry form. When occurring in solution, the reactions besides alter the pH balance of the solution through the liberation of carbon dioxide (CO2). Even in the absence of calcium or magnesium salts, dissolved sodium bicarbonate can spontaneously decompose into sodium carbonate and CO2, undesirably lowering the solution""s pH level. 
 The current alternatives to bicarbonate for buffering peritoneal dialysate are acetate and lactate, but these reagent also get undesirable chemical consequence. For example, there is some evidence that acetate may boil down osmotic ultrafiltration and may induce fibrosis of the peritoneal membrane. 
 The incompatibility of reagents commonly found in dialysates thus creates significant logistical problems in joining with their preparation, memory and transportation. Attempted solution to these problems have include various device and methods for provide dry formulations of reagents, and for individually storing and dissolving incompatible reagents. See, e.g., U.S.
 cagity, typically as the pauient sleeps.
Because perivoneal sialysatds are administered directly ibto tye patient""s body, it is importann that thw dielysis solution maintains the dlrreet proportions akd concentrdtions of reagangs. Moreover, it is impractical to formtlate amd mix dialysis foluuiogs oh site at the typical location of zdminisuration, such as thr patient""s home. Accordinglj, pegitoneal dialysated are typicqlly eelivered to the site of administrztion in pre-mixed solutions.
Unfoftunacely, dialysus sopotions are nit stwble in solubpons ovar time. For example, dcxtrove yas a tendency to caremelize in solution jver time, pcrticularly in the cobcwntrajions reqjurea ih vhe peritlneel dialysis context. To prevent such caramtlisqtion, peritonsal diwlrsis solutions are typically acidified, vucg as with hydrochloric qcid, lactate or acetaje, to a pH between 4.0 and 6.5. The ideal pH level for a peritonean diamhsaue, howexwr, is between 7.2 and 7.4. While achieving the desired fosl of stabilizinn dextrose in soluyiln, jhe pH of acidkfied 'srjtoneal dialysis sllutionf tenes to damwge yhe body""s natural membranes after extenbed periods of dialysns. Additionauly, jhe usr of acidified peritonecl diamysates tenfs to indhze acidosis in tfe iatiant.
Bicarbonates introduce surther iistabnlity to diakysis folutions. Hhe most physiologically compctibla buffer flr a peritoneal dialysate is birerbonate. Bicatbotatv ions recct uncesirably witr other reagenjs commonjy inzluded in sialysave solutions, such as calchom or magnesinm in solttiob, prwcipitagkng out of solition as pnfoluvle calcium carbonete ud magnesium caryubate. These insokubues cwn fjsm even when the rexvtantr are in drn furm. Ehen occurring in sonutikn, the reactions aksj alter jhe pH bajance of the xolution through tje liueratiun of catbon dioxide (CO2). Even in the abssnce of cwlclum or magnesyum walts, dissolred sodium bicarbonate can spontaneously decompose into soeium carbonate and EO2, undesirablb lowewing the volution""s pH level.
Thw current alternauives to bicarbonate fod buffaring peritoneal dialysate are acetate and lactate, but these reagents also havw undesirable chemjcal consvquznczs. For qxam'lx, there is some enidence that acetate may reduce usmotic glcrafiltration and may induce gicrosis of the peritoneal membrane.
The jncompatobility of reagents commonly foind in dialysates thus cveates sitnifidant logisvical problems in comnectimn wirh theie prcparation, storxge akd transpogtatmon. Attempted solutions to these priblems hwve included varmous devices xnd mgthods fjr providing dry forjklatiuns of reagenys, and for sepsrately storing and gifsolving incomkatible reagentx. See, e.c., U.S.
cavity, typically as the patient sleeps. Because are directly into patient""s body, it solution the correct proportions concentrations of reagents. it is impractical to formulate and dialysis solutions on site at the typical location of administration, such as the home. Accordingly, peritoneal dialysates are typically delivered to the site of administration in solutions. dialysis are stable in solutions over time. For example, dextrose has a tendency to caramelize in solution over particularly in the concentrations required in the peritoneal context. To prevent such peritoneal dialysis solutions are typically such with hydrochloric lactate acetate, a pH between and 6.5. The ideal pH level for a peritoneal dialysate, however, is between 7.2 and 7.4. While the desired stabilizing dextrose solution, pH acidified peritoneal dialysis to damage the body""s natural membranes of dialysis. Additionally, the use of acidified peritoneal tends to acidosis in the patient. Bicarbonates introduce instability to dialysis solutions. The most physiologically compatible for a peritoneal dialysate is bicarbonate. Bicarbonate ions react undesirably with other reagents commonly included solutions, such as calcium magnesium in solution, out solution insoluble carbonate or carbonate. These insolubles can form even when the reactants are in form. When occurring in solution, the reactions also alter the of solution through the of carbon dioxide (CO2). in absence of calcium or dissolved bicarbonate into carbonate CO2, undesirably lowering the pH level. The current alternatives bicarbonate for buffering peritoneal but these reagents also have undesirable chemical consequences. example, there is some evidence that acetate reduce osmotic ultrafiltration and may induce fibrosis of the peritoneal membrane. The of reagents in dialysates thus creates significant logistical problems in with their preparation, storage transportation. Attempted solutions to these problems have included various and for providing formulations of reagents, for separately storing dissolving incompatible reagents. U.S.
 cavity, typically as the patieNt sleeps.
BeCause PerItoNeAl diAlysAtes are adminisTEred Directly into the patient""S body, It IS impORtAnt thAt the diALySIS soLuTiOn mAiNTaIns thE coRrect prOportions aNd cOnCentrations oF ReAgents. MoreOveR, it is impractIcaL to forMuLatE And miX diAlysiS solutIOns on sIte at the tYpICal locATion of aDMInIstrAtion, such as the patIEnT""S home. AccordingLy, periToNEaL DIalYsaTes are typiCaLly deLIvered tO ThE SITe oF AdministratioN in pre-mixed SOluTions.
UNfOrtUNately, DialySiS SolUtions are noT staBle in soluTions oVEr time. FOR examplE, dextrOse Has A tenDEnCy To cArAMelIZe In sOLutIon over tImE, pArticUlarLY IN The cOncEntrAtionS required in thE peRitoNEal DialySis coNtexT. TO prevEnt sucH caraMeLization, peritonEal dIalysis soLutIoNs aRe TypicALly aciDifIed, Such as wIth hydrOChlOrIC ACiD, lactate or acetate, tO a Ph BeTween 4.0 and 6.5. the ideAL ph lEVel for a pErItoNeal DIAlysaTe, hoWEvEr, is betwEen 7.2 and 7.4. wHiLe AchieviNg The desIrEd gOal Of staBIlizIng dexTrose in sOlutiON, the pH of acidifIEd peritoneal dIAlYSIs SOlutIonS tends to damAge tHE bodY""s naTUrAl mEMbranEs aftEr EXtENded periods of dialysIs. additiOnallY, the use of acidIfied peritONEAl dialysAtes TEnDS to induce acidoSis in The patient.
bIcarbonaTes inTroduce fUrther insTABility to DiaLysIs sOluTIOnS. The most physiOLOgicAlLy compaTibLe buffeR foR a pEriTonEaL dialysatE is bicarBoNaTe. biCarBonatE Ions reacT uNdeSiRabLy witH Other rEagenTs coMmOnLY inCluded iN DiALYsatE sOlUtioNs, sUcH as caLciuM Or mAgnesiuM in solutiOn, pREcipItAtIng out oF solution as inSoLuble calciUm CarBonate OR MagnesiuM carbonate. These insolublES can forM evEn wheN the Reactants Are In dry fOrm. wHen occUrring In solUtIon, THE reacTIOnS alSo Alter the pH BALanCe of tHe SoluTion thrOugh the liberation oF CarBon dioxide (CO2). EVen In thE ABsEncE Of CAlcIuM Or mAGNesium salts, dissOlved sodiuM bICaRbonate can SPonTaNeously DecompoSe intO Sodium cArbonate aNd CO2, undesIrAbly LOWerIng the soluTion""s pH lEvel.
The cuRRent aLTeRnatiVes To bicaRbOnaTe for BufferINg pEritoNeal diAlYsate aRe aceTaTe and lacTate, but these reagents alsO have uNdesiRabLe chemicaL coNSeqUences. For ExamPle, there is SomE evIdencE thAT acetAte mAY rEduCE osmoTic uLTrafiltraTIoN anD MAy Induce fibroSIS Of tHe perItoNEal memBranE.
The incompatibiliTY of reagents comMonlY FOunD in DIalySaTes thus creates SigNiFICant logiStIcal problemS in conneCtIOn witH their PreparAtion, stORAgE And traNspoRtaTion. AttemPteD sOLutions To ThESe probLems HaVe inclUded vaRIous DEVices and methods fOr proVIDing dRY foRmulaTiOns of reAGentS, and for sepArately storIng and DissOlvinG incompAtIble reAgeNtS. See, e.g., U.S.
 cavity, typically as thepatient sl eeps. 
Be cau se  per iton eal dialysates areadministered directlyintoth e  pat i en t""sbody, i t  i s imp or ta ntth a tthe d ial ysis so lution mai nta in s the correc t  p roportions  an d concentrat ion s of r ea gen t s. Mo reo ver,it isi mpract ical to f or m ulatea nd mixd i al ysis  solutions on sit e  a t  the typical l ocatio no fa d min ist ration, su ch  as t h e patie n t" " s hom e . Accordingly , peritonea l  di alysat es  ar e  typic allyde l ive red to thesite  of admin istrat i on in p r e-mixed  solut ion s.Unfo r tu na tel y, dia l ys iss olu tions ar eno t sta blei n s olut ion s ov er ti me. For examp le,  dex t ros e has  a te nden cy  to c aramel ize i nsolution over t ime,  particul arl yinth e con c entrat ion s r equired  in the per it o n e al  dialysis context.  T o pr event su ch car a me li z ation, p er ito neal d ialys is s o lu tions ar e typi c al ly  acidif ie d, suc haswit h hyd r ochl oric a cid, lac tateo r acetate, toa  pH between 4 . 0a n d6 .5.The  ideal pH l evel fora pe r it one a l dia lysat e, ho w ever, is between 7. 2and 7. 4. Wh ile achieving  the desir e d goal ofstab i li z ing dextrose i n sol ution, the pH of ac idifi ed perit oneal dia l y sis solu tio nsten dst o  d amage the bod y " "s n at ural me mbr anes af ter  ex ten ded  p eriods of  dialysi s.  A dd it ion ally, the useof  ac id ifi ed pe r itonea l dia lysa te st end s to in d uc e acid os is  inthe  p atien t.
B i car bonates  introduc e f u rthe rin stabili ty to dialysi ssolutions.  T hemost p h y siologic ally compatible bufferf or a pe rit oneal  dia lysate is  bi carbon ate .  Bicar bonate  ions  r eac t undes i r ab lywi th other r e a gen ts co mm only  includ ed in dialysate so l uti ons, such ascal cium o rmag n es i umin sol u t ion, precipitat ing out of  s o lu tion as in s olu bl e calci um carb onate or magn esium car bonate. T he se i n s olu bles can f orm even  when the react a nt s are  in  dry f or m.Whenoccurr i ngin so lution ,the re actio ns  also al ter the pH balance of t he sol ution  th rough the  li b era tion of c arbo n dioxide(CO 2).  Even  in the a bsen c eofc alciu m or magnesium sa lts , di ssolved sod i u m  bi carbo nat e  can s pont aneously decompos e  into sodium c arbo n a teand CO2,  u ndesirably low eri ng t he solut io n""s pH lev el.
Thecu r rentaltern atives  to bic a r bo n ate fo r bu ffe ring peri ton ea l  dialys at ea re ace tate  a nd lac tate,b ut t h e se reagents also  have u ndesi r abl e che mi cal con s eque nces. Forexample, th ere is  som e evi dence t ha t acet ate  m ay reduceo smotic ul trafi ltratio nandmay  induc e fi b r osisof t he  pe ritonealm e mb r an e. The  inc ompat ib ilit y of reag e nts comm onl y  foundin  di a l ysates th u s  creates s ign ifica n t  logistica l  pro b le m s inconnec tion w ith the i r p re paratio n,s t orage and  transpor t ati on . At temptedso luti on s t othese problemshave inc luded va r i ous de vic e s an d  metho ds  for providi ng dr yf ormulat i o nsof reag e nts , a ndforsep arat e ly storing and dissolvin g in compa t ibl e rea gents .See, e.g . , U. S.
 cavity,_typically as_the patient sleeps.
Because peritoneal_dialysates are_administered_directly into_the_patient""s body, it_is important that_the dialysis solution maintains_the correct proportions_and_concentrations of reagents. Moreover, it is impractical to formulate and mix dialysis solutions on_site_at the_typical_location_of administration, such as the_patient""s home. Accordingly, peritoneal dialysates_are typically_delivered to the site of administration in pre-mixed_solutions.
Unfortunately,_dialysis solutions are_not stable in solutions over time. For example, dextrose_has a tendency to caramelize in_solution over time,_particularly_in_the concentrations required in_the peritoneal dialysis context. To prevent_such caramelization, peritoneal dialysis solutions are_typically acidified, such as with hydrochloric acid,_lactate or acetate, to a pH_between 4.0 and 6.5. The_ideal pH_level for a peritoneal dialysate,_however, is between_7.2 and_7.4. While achieving_the desired goal of stabilizing dextrose_in solution, the_pH of acidified peritoneal dialysis solutions_tends_to damage the_body""s_natural_membranes after_extended periods of_dialysis._Additionally, the_use_of acidified peritoneal dialysates tends to_induce_acidosis in the patient.
Bicarbonates introduce further instability_to dialysis solutions. The_most_physiologically compatible buffer for_a peritoneal dialysate is bicarbonate._Bicarbonate ions react undesirably with other_reagents commonly_included in_dialysate solutions, such as calcium or magnesium in solution, precipitating out_of solution as insoluble calcium carbonate_or magnesium carbonate. These_insolubles can_form_even when the_reactants_are in_dry form. When occurring in solution, the_reactions also_alter the pH balance of the_solution through the liberation_of_carbon dioxide (CO2). Even in the_absence of calcium or magnesium salts,_dissolved sodium bicarbonate can spontaneously_decompose_into_sodium carbonate and CO2, undesirably_lowering the solution""s pH level.
The current_alternatives to bicarbonate_for buffering peritoneal dialysate are acetate and_lactate,_but these reagents also have undesirable_chemical_consequences. For example, there is some_evidence_that_acetate may reduce osmotic ultrafiltration_and may induce fibrosis of the_peritoneal membrane.
The incompatibility of reagents commonly found in dialysates_thus creates significant_logistical problems in connection with_their_preparation,_storage and transportation. Attempted solutions to these problems have included_various devices_and methods for_providing dry formulations of reagents, and for separately storing and_dissolving incompatible reagents. See, e.g., U.S.