Dialysis solution for peritoneal dialysis

Details Dialysis solution for peritoneal dialysis Dialysis solution for peritoneal dialysis

1997-03-11

2001-09-04

Kim, John (Department: 1723)

Liquid purification or separation

Processes

Liquid/liquid solvent or colloidal extraction or diffusing...

C210S646000, C514S060000, C514S929000, C536S111000, C604S029000

Reexamination Certificate

active

06284140

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to dialysis solutions for peritoneal dialysis, containing hydroxyethyl starch as the osmotically-active substance, electrolytes and/or conventional additives.
DISCUSSION OF BACKGROUND INFORMATION
In solutions for peritoneal dialysis, for example continual ambulatory peritoneal dialysis (CAPD) or continual cycling peritoneal dialysis (CCPD) it is the usual practice to make use of glucose as the osmotic carrier substance or osmotic active substance. However, these solutions have the disadvantage that glucose when used as the carrier substance is strongly resorbed, because of which the glucose blood level is increased, which is very disadvantageous in the presence of disturbances of carbohydrate metabolism. Dialysis solutions for peritoneal dialysis, e.g. the continuous ambulant peritoneal dialysis (CAPD) or the continuous cycling peritoneal dialysis (CCPD) are disclosed in (cf. “Praxis der CAPD”, published by F. Scheler and C. Fuchs, Bibliomed, Medizinische Verlagsgesellschaft mbH Melsungen, 1981, p. 1-139).
For this reason attempts have been made over long periods of time to replace the glucose in dialysis solutions for peritoneal dialysis with other substances which do not possess the disadvantages occurring when glucose is used as the osmotic active substance, that is to say, with which there is no undesirable resorption, and with which it is also possible to have longer dwell times and, therefore, a change is only necessary after longer intervals of time. A restricted choice of replacements for glucose can be made from poly-anionic substances and glycerin. However, poly-anionic substances have the disadvantage that they can cause alteration in the size of the membrane pores, thus having a negative influence on the dialysis. Studies with poly-anionic substances have not yet progressed beyond the stage of animal experiments. Also, substantial doubts exist about the utilisation of glycerin, because glycerin has a nephrotoxic effect and, since it can be resorbed because of its low molecular weight, it can disturb the residual kidney function.
According to the DE-OS 34 28 201, an hydroxyethyl starch with a molecular weight≧3×10
4
Dalton and a degree of substitution in the range from 0.25 to 0.7 is proposed as the osmotic active substance in solutions for peritoneal dialysis.
However, the utilisation of such an hydroxyethyl starch, with regard to the problems of poor metabolisation of eventually absorbed hydroxyethyl starch, is unfavourable.
Hydroxyethyl starches are known from EP-A-0 402 724, which have a mean molecular weight in the range from 60,000 to 600,000, a degree of substitution MS and DS in the range from 0.15 to 0.5 and a substitution ratio C2/C6 in the range from 8 to 20. However, only the use of plasma expanders is described and no reference is made to the utilisation of hydroxyethyl starch in peritoneal dialysis.
However, from investigation, referred to in Nephron 1992, 61, 120 and in which the breakdown of hydroxyethyl starches of different molecular weights in various organs was compared, it can be gleaned that hydroxyethyl starches do not appear to be suitable for use as osmotically active substances in continuous ambulatory peritoneal dialysis.
Therefore, there still exists, as formerly, the need for dialysis solutions which contain osmotically active substances and with which the disadvantages of the known solutions do not occur.
SUMMARY OF THE INVENTION
The objective of the present invention is therefore the preparation of dialysis solutions for peritoneal dialysis which do not exhibit the disadvantages of known dialysis solutions, but which contain an osmotically active substance which is only slightly resorbed or scarcely at all, is readily metabolised, has no harmful effect for the peritoneum and possesses good osmotic activity.
DETAILED DESCRIPTION
Very surprisingly, it has been found that dialysis solutions which are characterised by the fact that they contain an hydroxyethyl starch having a molecular weight Mw in the range from 10,000 to 150,000, a degree of substitution MS in the range from 0.10 to 0.40, a degree of substitution DS in the range from 0.09 to 0.35 and a substitution ratio C2/C6≧8, do not display the disadvantages of the known dialysis solutions.
The hydroxyethyl starch utilised in the inventive dialysis solutions preferably has a molecular weight Mw in the range from 10,000 to 55,000, in particular from 20,000 to 29,000, for example 29,000. The degree of substitution MS of the hydroxyethyl starch is preferably in the range from 0.10 to 0.24, in particular from 0.20 to 0.24, for example 0.23. The degree of substitution DS of the hydroxyethyl starch used is preferably in the range from 0.09 to 0.23, whilst the ratio C2/C6 of the starch utilised is preferably in the range from 8 to 25.
For purposes of the present invention as disclosed herein, the weight average of the molecular weights of hydroxyethyl starch was measured with MALLS-or LALLS-high pressure GPC (HPGPC, high pressure size exclusion chromatography).
Conditions of separation:
Stationary phase:
Precolumn
Spherogel TSK PWHR (4 cm×6 mm)
Separation columns
2×Spherogel TSK GMPWHR (30 cm×7.8 mm)
Temperature 30° C.
Mobile phase:
Acetate-buffer
18.7 g sodium-acetate 3 H
2
O and 1,72 g sodium-azide dissolved in approximately 4 1 H
2
O (bidest.) adding 34.5 ml acetic acid and filling it with H
2
O (bidest.) up to 51.
Flow rate:
0,5 ml/min.
a flow rate of 0.5 mi/min means that 0.5 ml acetate buffer passes within 1 minute through a Precolumn (4 cm×6 mm) and two Spherogel TSK GMPWHR (30 cm×7.8 mm) columns.
The production of the inventive hydroxyethyl starch utilised is effected in the manner known per se by hydrolytic and/or enzymatic degradation of a starch, in particular a starch rich in amylopectin, to a specified molecular weight and partial etherification to the desired degree of substitution. For production of the dialysis solution, a solid hydroxyethyl starch obtained for example by spray drying or vacuum drying can be utilised, or else the hydrolysis solutions obtained by purification, in particular by diafiltration, can be utilised.
An example of a process for preparing an hydroxyethyl starch is disclosed in U.S. Pat. No. 5,218,108, SOMMERMEYER et al., the disclosure of which in its entirety is incorporated by reference thereto herein. As used herein, unless otherwise disclosed, the terms molecular weight, average molecular weight, mean molecular weight, substitution degree MS (molar substitution), substitution degree DS (degree of substitution), and the ratio of substitution of C
2
to the substitution of C
6
(the ratio C
2
/C
6
) have the same meaning as disclosed in U.S. Pat. No. 5,218,108.
The dialysis solution in accordance with the present invention contains the hydroxyethyl starch, preferably in an amount in the range from 3 to 10 percent by weight, based on the final solution.
The medium for the dialysis solution can be, for example, one used for peritoneal dialysis, in particular the conventional medium for peritoneal dialysis with glucose as the osmotically active carrier substance, for example Ringer's solution.
As used herein, a “Ringers Solution” includes sodium-, potassium-, calcium-, and chloride-ions, as disclosed in a) CANTOR (ed),
ROTE LISTE
1989, Verzeichnis von Fertigarznelmitteln der Mitglieder der Bundesverbandes des Pharmazeutlischen Industrie e.V.; Herausgeber: Bundesvverband der Pharmazeutischen Industrie e.V.; Aulendorf/Wurtt; and b) Fresnius, “Infusionstherapie und Klinische Ernahrung”, Aug. 8, 1993. An example of a conventional Ringers solution, is disclosed in
Hawley's Condensed Chemical Dictionary,
LEWIS, Jr. (ed), Twelfth Edition, Van Nostrand Reinhold Company, New York, 1993, page 1010.
Along with hydroxyethyl starch as the osmotically active substance, the inventive solutions for peritoneal dialysis may contain additional substances, in particular those conventional ingredients for dialysis solutions such as, for example, the components of

Affiliated with

Also associated with

Rating

Dialysis solution for peritoneal dialysis does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Dialysis solution for peritoneal dialysis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Dialysis solution for peritoneal dialysis will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2520103