Peritoneal dialysates

Inactive Publication Date: 2004-05-20
JAPAN SCI & TECH CORP
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

0072] (Effects of Protein Cross Linkage Splitter)
0073] Human serum albumin was dissolved in phosphate buffer solution at 50 mg/ml, wherein 3-deoxyglucosone was added at 50 mM/l, thence the solution was incubated at 37.degree. C. for 7 days, followed by the determination of fluorescent intensity. Residual 3-deoxyglucosone was removed by membrane dialysis with phosphate

Problems solved by technology

However the same means can not be applied to peritoneal dialysis, therefore an osmotic agent is added into the dialysate so as to rais the osmotic pressure of the dialysate over that of plasma.
However, adverse effects were recognized as serious problems, such as disfunctioning of peritoneum, due to the absorption of large quantity of glucose into the patient body and the reaction with amino acids, peptide and protein, followed by the formation of AGEs, progress of collagen synthesis, and cross linki

Method used

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Examples

Experimental program
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Effect test

example 1

[0052] For estimating the suppression effect on protein cross linking sensitively, glyoxal was used. This chemical is one of glucose degradation products and much greater promoter to accelerate AGE formation than glucose does. Glyoxal (20 mM / l) was added into phosphate buffer solution, in which human serum albumin (50 mg / ml) was dissolved. As a test specimen, mercapto compound, listed in Table 1, was added into the solution at 20 mM / l, then incubated at 37.degree. C. as long as for two weeks. Fluorescent intensity (FI) of the cross linked albumin in the incubated solution was determined at 440 nm (excitation: at 370 nm) by fluorescence meter (Nihon Bunkou Co.). The suppression effect was estimated as follows; dividing the increase in the fluorescent intensity through the incubation in the case of "test specimen added", by that of "no test specimen added (control 1) ".

[0053] The result is shown in Table 1.

[0054] [Control 1]

[0055] In Control test 1, the fluorescent intensity was deter...

example 2

[0056] Methylglyoxal in place of glyoxal as GDP (Glucose Degradation Products) in Example 1 was used under the similar conditions as Example 1. Sodium bisulfite and sodium sulfite were tested as protein cross linking suppressors. Fluorescent intensity was determined in the same manners as in Example 1. The results are shown in Table 2.

[0057] [Control 2]

[0058] No protein cross linking suppressor, but methylglyoxal alone was added to human serum albumin. Fluorescent intensity was determined in the same manners as Example 2. The results are shown in Table 2.

2 TABLE 2 Increase Specimen (Cross linking suppressors) in FI (%) Example 2 (a) Sodium bisulfite 46 (b) Sodium sulfite 61 Example 3 (a) Acetyl salicylic acid 53 (b) Ascorbic acid 86 Example 4 (a) Quercetin dihydrate 19 (b) Catechin hydrate 64 (c) Epicatechin 72 Example 5 Heparin 96 Example 6 Amino guanidine hydrochloride 31 Example 7 N-Phenacyl thiazolium bromide 28 Example 8 (a) N-(2-thiazolyl)-sulfanylamide 45 (b) 2-mercapto-4-met...

example 3

[0059] The cross linking suppressors in Example 2 were replaced by acetylsalicylic acid and ascorbic acid and other conditions were similar to those in Example 2. The increase in fluorescent intensity was determined to estimate relative ratio to those of Control 2.The results are shown in Table 2.

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Abstract

In peritoneal dialysis, a therapy for end stage renal disease patients, glucose has been used mainly as an osmotic agent in the dialysate. However due to the oxidation and decomposition of glucose, protein cross linking reaction progress to cause peritoneum sclerosis, resulting in cease of this therapy The present invention relates to the dialysate comprising protein cross linking suppressor(s) and/or protein cross linkage splitter(s) for the solution of the problem. Effective suppressors or splitters may be reductants, anti-oxidants, mercapto compounds, sulfide, hydrosulfide, salt of reductive sulfur oxyacid, thiourea and its derivatives, hydroxyl and/or carboxyl residue(s) containing cyclic compounds flavonoids, nitrogen containing heterocyclic compounds, hydrazyl compounds and uronic acid containing mucopoly-saccharides and the like. The dialysate is prepared by sterilizing the dialysate under high temperature and pressure separately from the suppressors and by adding the suppressors, that is sterilized separately, into the dialysate. By use of the dialysate in the present invention, peritoneal dialysis can keep on without suffering from problem,

Description

[0001] The present invention relates to the dialysate for peritoneal dialysis, that is, therapy for end stage renal disease, more specifically, the dialysate for peritoneal dialysis to suppress protein cross linking due to sugar osmotic agents, such as glucose and the like.BACKGROUD OF THE INVENTION[0002] The peritoneal dialysis has been applied as an effective therapy for end stage renal disease patients. The dialysis is proceeded by infusing dialysate into peritoneal cavity through a catheter, which is implanted in the patient's peritoneal cavity, and storing it for a certain period, thence withdrawing the dialysate out through the catheter. This procedure is repeated a few times every day.[0003] This dialysis has a few advantages over hemodialysis in physiological point of view, as it purifies blood continuously through the patient's' peritoneum, while hemodialysis purifies blood though an artificial membrane intermittently. Also peritoneal dialysis enables the patients' social a...

Claims

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Application Information

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IPC IPC(8): A61L2/06A61K9/08A61K45/06A61M1/14A61M1/28
CPCA61K9/08A61M1/287A61K45/06A61K31/70
Inventor SAKAI, ASAHINAKAYAMA, MASAAKI
Owner JAPAN SCI & TECH CORP
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