Peritoneal therapeutic fluid

Abstract

Peritoneal therapeutic fluid comprising one or more of a biocompatibility enhancing agent (BCA) that is selected from the group consisting of a polyphenolic compound, a metabolite of a polyphenolic compound which is obtained by metabolization in the human or animal body, a salt or a glycoside of a polyphenolic compound.

1 . A peritoneal therapeutic fluid comprising one or more of a biocompatibility enhancing agent (BCA) that is selected from the group consisting of a polyphenolic compound, a metabolite of a polyphenolic compound which is obtained by metabolization in the human or animal body, a salt of a polyphenolic compound, a glycoside of a polyphenolic compound, a derivative of a polyphenolic compound, polyethylene glycol (PEG), or a derivative of a polyethylene glycol, for use as a peritoneal dialysis fluid, or as a peritoneal therapeutic fluid with decreased cytotoxicity on human peritoneal mesothelial cells. 
     
     
         2 . A peritoneal therapeutic fluid according to  claim 1 , wherein the biocompatibility enhancing agent is selected from the group of stilbenoids, derivatives of stilbenoids, phenolic acids, and flavonoids. 
     
     
         3 . A peritoneal therapeutic fluid according to  claim 1 , wherein the biocompatibility enhancing agent is resveratrol, a resveratrol derivative, dihydro-resveratrol, piceid, piceatannol, pterostilbene, piceid glucoside, caffeic acid, luteolin, or delphinidin. 
     
     
         4 . A peritoneal therapeutic fluid according to  claim 1 , wherein the resveratrol derivative is selected from following compounds 1-12, 15, 16, 17, 18: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein in compound 2 and compound 3 
         R1=R2=R4=OH, R3=R5=R6=H; or 
         R1=R2=R4=OCH3, R3=R5=R6=H; or 
         R1=R2=R4=OCH3, R3=R5=H; R6=OH; or 
         R1=R2=R3=R5=OCH3, R4=R6=H; or 
         R1=R2=R3=R5=OCH3, R4=H, R6=OH; or 
         R1=R2=R3=R4=OCH3, R5=R6=H; or 
         R1=R2=R3=R4=OCH3, R5=H, R6=OH; 
         wherein in compound 4 R is one of the following moieties: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein in compound 5 
         R1 is hydrogen or a group of formula 
       
       
         
           
           
               
               
           
         
         R2 is hydrogen or forms together with the oxygen to which it is bound an acyl group (—OCO—R3), wherein R3 is a C1-C22 alkyl group or a C2-C22 alkenyl group, wherein, if R2 is hydrogen R1 forms a group of above-shown formula, 
         wherein in compound 6, R is one of the following moieties: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein X −  is a free soluble anion, 
         wherein in compound 8 
         R1=OCH3, R2=OH, R3=O-Glucose; or 
         R1=OCH3, R2=H, R3=O-Glucose; or 
         R1=OCH3, R2=OH, R3=OH; or 
         R1=OCH3, R2=H, R3=OH; or 
         R1=OH, R2=OH, R3=O-Glucose; or 
         R1=OH, R2=OH, R3=OH; 
         wherein in compound 12 
         R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently chosen from 
         hydrogen, hydroxyl, hydrocarbyl, substituted hydrocarbyl, hydrocarbyloxy, substituted hydrocarbyloxy, and sulfoxy; provided that at least one of the R groups is a hydroxyl or substituted hydroxyl group; and provided that if compound 12 is monomeric, then compound 12 is other than resveratrol, 
         wherein in compound 15 
         R1, R2 and R3, independently from one another, represent H or (C1-C3)alkyl; R4 and R5 are identical or different and represent hydrogen, linear or branched (C1-C5)alkyl, 
         a prenyl group —CH2-CH═C(CH3)2, 
         a geranyl group —CH2-CH═C(CH3)(CH2)2CH═C(CH3)2 or R4 and R1, and independently R5 and R2, together with the atoms they are linked to, form one of the following groups: 
       
       
         
           
           
               
               
           
         
         with the provisos that R4 and R5 are not both hydrogen and that when R1=R2=R3=H, R4 and R5 are not a prenyl group and hydrogen, respectively, 
         wherein in compound 18 X, Y, and Z are either hydrogen or a protective group, provided that at least one of X, Y, and Z is the protective group. 
       
     
     
         5 . A peritoneal therapeutic fluid according to  claim 1 , wherein the biocompatibility enhancing agent is a compound of formula 19: 
       
         
           
           
               
               
           
         
         wherein in compound 19 
         R4 is selected from one of the following groups 
       
       
         
           
           
               
               
           
         
         wherein R1, R2, R3, R5, R11, R12, R13, R14, R15, R21, R22 and R31 are independently from each other selected from 
         —H, —OH, —O—R Alk , —CHO, —COR Alk , —COOH, —COO—R Alk , —CO—NH—C n H 2n —COOH, —CO—NH—C n H 2n —COO − , 
         —CN, —Cl, —Br, —I, —NO 2 , 
         —C n H 2n CN, —C n H 2n —Cl, —C n H 2n —Br, —C n H 2n —I, —C n H 2n —NO 2 , 
         —O—PO 3   2− , —O—PO 3 H − , —O—PO 3 H 2 , —NH2, —NHR Alk , —NR Alk1 R Alk2 , —N + H 3 , —N + H 2 R Alk , —N + H R Alk1 R Alk2 , —N + R Alk1 R Alk2 R Alk3 , 
         —CN, —B(OH) 2 , —OCHO, —O—COR Alk , —OCF 3 , —O—CN, —OCH 2 CN, 
         wherein R Alk , R Alk1 , R Alk2 , and R Alk3  are alkyl residues which are independently selected from each other, preferably CH 3 , C 2 H 5 , C 3 H 7  or C 4 H 9 , 
         wherein in C n H 2n  n is an integer, and C n H 2n  preferably is CH 2 , C 2 H 4 , C 3 H 6 , C 4 H 8 ; 
         or wherein R1, R2, R3, R5, R11, R12, R13, R14, R15, R21, R22 and R31 are, independently from each other, one of the following moieties: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein X −  is a free soluble anion, 
         or wherein R 1 , R 12 , R 13 , R 14  or R 15  are a mono or oligo saccharide-residue, with the proviso that 
         at least two of R1, R2, R3, R11, R12, R13, R14 and R15 are independently selected from —OH, —O—R Alk , —O—COR Alk , —OCF 3 , —O—CN, and —OCHO. 
       
     
     
         6 . A peritoneal therapeutic fluid according to  claim 1 , wherein the biocompatibility enhancing agent is selected from the group comprising:
 epsilon-viniferin, pallidol, trans-diptoindonesin B, hopeaphenol, oxyresveratrol, or 4′-methoxy-(E)-resveratrol 3-O-rutinoside, phenolic acids such as gallic acid, ellagic acid, vanillic acid; propyl gallate, protocatechuic acid, p-coumaric acid, danielone, syringic acid, salicylic acid, gentisic acid, p-hydroxy benzoic acid, rosmarinic acid, rosmanol, quinic acid, sinapic acid, epi-isorosmanol, E-anethol, 3,4-dimethoxycinnamic acid, ferulic acid; phenolic diterpenes such as carnosol and carnosic acid; coumarines such as coumarin, ombelliferon, herniarine, esculedol, scopoletol, scopanone, fraxetol and their glucosides such as 7-O-glucosyl-ombelliferone, 6-O-glucosyl-esculetol, 7-O-glucosyl-esculetol, 7-O-Glucosyl-6-methoxycoumarine, dihydroxyisocoumarins such as 6-methoxymellein, as well as prenyloxycoumarines such as 7-geranyloxy coumarine, 7-methoxy-6-(3-methyl-2-butenyl)-coumarine, 7-methoxy-8-(3-methyl-2-butenyl)-coumarine; naphtoquinones such as 1,2-naphtoquinone, 1,4-Naphtoquinone, 2,6-Naphtoquinone, alkannin, hexahydroxy-1,4-naphthalenedione, juglone, lapachol, lawsone, menatetrenone, 2-methoxy-1,4-naphthoquinone, nigrosprin B, 2,3,5,7-tetrahydroxy-1,4-naphtalenedione, menadione, 5,8-Dihydroxy-1,4-naphtoquinone and other dihydroxynophtoquinones, atovaquone; flavonoids: anthoxanthins including flavonols such as quercetin, kaempferol, myricetin, fisetin, galangin, isorhamnetin, pachypodol, rhamnazin pyranoflavonols and furanoflavonols, flavones such as apigenin, and tangeritin, flavonoides including flavanones such as hesperetin and naringenin, eriodictoyl, homoeriodictoyl and sakuranetin, flavanonols such as taxifolin, dihydrolquercitin and dihydrokaempferol, flavans such as flavan-3ol (including Catechin, Gallocatechin, catechin 3′-gallate, gallocatechin 3-gallate, epicatechin, epigallocatechin, epicatechin 3-gallate, Epigallocatechin 3-gallate, theaflavin, theaflavin-3-gallate, theaflavin-3,3′-digallate, thearubigin, proaanthocyanidins, flavan-4-ol and flavan-3,4-diol; anthocyanins such as cyanidin, malvidin, pelargonidin, peonidin, petunidin, cyanin-3-rutinoside and delphinidin-3-rutinoside; isoflavonoides including isoflavones such as genistein, glycitein and daidzein, further including isoflavanes, isoflavenes, coumestans and pterocarpans stilbenoides including stilbene and aglycones such as piceatannol, pinosylvin, pterostilbene, or a mixture of two or more thereof.   
     
     
         7 . A peritoneal therapeutic fluid according to  claim 1 , wherein the biocompatibility enhancing agent is solubilized through pegylation with Polyethyleneglycol (PEG) or Methoxy-Polyethyleneglycol (mPEG), provided that the BCA is not polyethylene glycol (PEG) or a derivative of a polyethylene glycol. 
     
     
         8 . A peritoneal therapeutic fluid according to  claim 1 , wherein the PEG, or the derivative of PEG has a molecular weight above 400 Da. 
     
     
         9 . A peritoneal therapeutic fluid according to  claim 1 , wherein the PEG or the derivative of PEG is selected from the group comprising PEG 600, mPEG 600, PEG 1000, mPEG 1000, PEG 1450, mPEG 1450, PEG 3350 and mPEG 3350, or the like. 
     
     
         10 . A peritoneal therapeutic fluid according to  claim 1 , wherein the one or more biocompatibility enhancing agent is/are present in a concentration of 0.001 mg/L to 5 g/L. 
     
     
         11 . A peritoneal therapeutic fluid according to  claim 1 , comprising one or more of an ingredient which is selected from the following: alkali metal ions, alkaline earth metal ions, an osmotic agent, and/or a pH-buffer. 
     
     
         12 . A peritoneal therapeutic fluid according to one or more of the preceding claims, comprising one or more of a saccharide, wherein the saccharide may be a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, or any mixture thereof. 
     
     
         13 . A peritoneal therapeutic fluid container or kit comprising at least one liquid containing compartment, wherein liquid of at least one compartment contains a biocompatibility enhancing agent as claimed in  claim 1 , wherein the biocompatibility enhancing agent is solubilized. 
     
     
         14 . A peritoneal therapeutic fluid container or kit comprising at least two compartments, wherein at least one compartment contains a biocompatibility enhancing agent as claimed in  claim 1 , wherein the biocompatibility enhancing agent may be in solubilized form or may be solubilized by contacting with a liquid from one of the other compartments, preferably just before application. 
     
     
         15 . A peritoneal therapeutic fluid container or kit according to  13  for use in peritoneal dialysis.