Method of peritoneal dialysis using glucose polymer solutions

Details Method of peritoneal dialysis using glucose polymer solutions Method of peritoneal dialysis using glucose polymer solutions

1992-09-30

2001-06-19

Peselev, Elli (Department: 1623)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

C514S054000, C514S060000

Reexamination Certificate

active

06248726

ABSTRACT:

This invention relates to a new form of polymer, a method for its production and compositions containing it.
Maltodextrins (glucose polymers) are produced by the hydrolysis of pure starch isolated from various natural products, e.g. wheat, rice, tapioca etc. In a typical process a pure isolated starch is produced by a multi-stage separation process involving removal of protein, oil, fibre and glutens before being hydrolysed.
As no single number can adequately characterise the molecular weight of a polymer, such as a maltodextrin, various averages are used. The most commonly used are the weight average molecular weight ({overscore (M)}
w
) and the number average molecular weight ({overscore (M)}
n
):
M
_
w
=
∑
n
i
⁢
M
i
2
∑
n
i
⁢
M
i
M
_
n
=
∑
n
i
⁢
M
i
∑
n
i
where n
i
is the number of molecules of molecular weight M
i
. {overscore (M)}
w
is particularly sensitive to changes in the high-molecular-weight content of the maltodextrin polymer whilst {overscore (M)}
n
is largely influenced by changes in the low molecular weight of the sample.
We have now found that it is possible to monitor starch hydrolysis and in particular to stop the hydrolytic action when the hydrolysate contains the maximum amount of molecules in the desired molecular weight range. The monitoring may be carried out by a technique known as size exclusion chromatography. Furthermore, fractionation of the starch hydrolysate can be monitored by size exclusion chromatography and a weight average molecular weight, a number average molecular weight and a molecular weight distribution of the products can be determined using chromatographic columns calibrated with dextran standards (Alsop et al Process Biochem 2 10-15 (1977) and Alsop et al J. Chromatography 246, 227-240, (1982)).
We have also found a method for optimising the yield of a glucose polymer with a preselected molecular weight range.
Glucose polymers are often characterised by the expression “degree of polymerisation” (DP). In this terminology a product may be described as having 20% of its weight comprising molecules with a DP greater than 10, ie. 20% has a molecular weight greater than 1656 (a polymer comprising 10 glucose units).
British Patent Application 2132914A describes a glucose polymer mixture having at least 15% by weight of glucose polymers of DP greater than 12 for use in continuous ambulatory peritoneal dialysis (CAPD). PCT/US Application 82/00774 describes a CAPD solution comprising glucose polymers of DP of at least 4.
European Patent Application 0076355 A2 discloses glucose polymer mixtures having at least 99% of glucose polymers of DP less than 12 for use in CAPD.
It has now surprisingly been found that certain polydisperse glucose polymer mixtures of high molecular weight are useful in medicine, e.g. in CAPD and in prevention of post-operative adhesions.
According to the invention we provide a glucose polymer mixture (I), wherein at least 50% by weight of the polymer is of molecular weight in the range 5000 to 30000.
We particularly prefer a glucose polymer (I), wherein at least 80% by weight of the polymer is of molecular weight in the range 5000 to 50,000.
We prefer the glucose polymer (I) to have a weight average molecular weight in the range of from 5000 to 100000, preferably of from 5000 to 50000, more preferably of from 12000 to 25000, and most preferably of from 14000 to 20000.
We prefer the glucose polymer (I) to have a number average molecular weight of less than 8000, preferably less than 5000, more preferably less than 4000 and most preferably less than 2900.
We prefer the content of mono-, di-, and tri-saccharide compounds present in the glucose polymer (I) to be less than 5% by weight, more preferably less than 2% and most preferably 0% by weight. By 0% we mean an amount which is undetectable by conventional methods.
We further prefer that the content of glucose polymers with molecular weight greater than 100000 in the glucose polymer (I) should be less than 5%, preferably less than 3% and most preferably less than 1% by weight.
We prefer the glucose polymers to be substantially free from endotoxins and nitrogenous contaminants arising from the original starch, or from the enzyme preparations used for its hydrolysis.
We particularly prefer the endotoxin level to be less than 0.25 endotoxin units/ml, more preferably less than 0.12 endotoxin units/ml and most preferably less than 0.06 endotoxin units/ml as determined by the Limulus Lysate Test (US Pharmacopoeia).
We prefer the nitrogen content of the glucose polymers to be less than 0.01% w/w, more preferably less than 0.001% w/w and most preferably zero as determined by the Kjeldahl method (British Pharmacopoeia)
We also prefer the glucose polymers to be substantially free of undesirable metals, e.g. aluminium. Thus we prefer the level of aluminium to be less than 500 ppb, more preferably less than 200 ppb and most preferably less than 100 ppb.
We also prefer an aqueous solution comprising 10% w/v of the glucose polymer to be substantially clear and colourless. Thus we prefer such a solution to have a turbidity value of less than 30 EEL units (US Pharmacopoeia), more preferably less than 20 EEL units and most preferably less than 10 EEL units. We also prefer such a solution to have no substantially visible colour. We particularly prefer the solution to have a visible colour of less than 10 APHA Hazen units and more preferably less than 5 APHA Hazen units. The content of colour precursors such as 5-hydroxymethyl furfural can be measured by absorption of ultraviolet light of wavelength 275 or 284 nm. We prefer the absorbance to be less than 0.5, more preferably less than 0.25 and most preferably less than 0.15. The transmission of ultraviolet light measured at a wavelength of 430 nm is preferably greater than 90% and more preferably greater than 95%.
It is a further feature of this invention to provide a glucose polymer (I) having up to 20% by weight of glucose polymers with a molecular weight of from 800 to 10,000, preferably of from 1500 to 4000. We particularly prefer a glucose polymer (I) having up to 20% by weight of glucose polymers with a molecular weight of from 1500 to 2500, more preferably up to 10% by weight and most preferably up to 7% by weight.
According to the invention we also provide a method for the production of a glucose polymer (I), which comprises
a) fractional precipitation of an aqueous solution of a glucose polymer containing polymer (I) with a water miscible solvent, and/or
b) filtration of an aqueous solution of a glucose polymer containing polymer (I) through membranes possessing an appropriate molecular weight cut-off range. The molecular weight cut-off range may be determined empirically.
In process a) the process parameters used are interdependent and each parameter may vary depending upon the desired quality of the product, the desired molecular weight range, etc. The water miscible solvent may be an alcohol, eg an alkanol, such as ethanol. The solvent may be present in an aqueous solution which is mixed with an aqueous glucose polymer. The concentration of the solvent in the aqueous solution before mixing may be from 60 to 100%v/v, preferably from 75 to 90%v/v, and most preferably about 85%v/v.
The concentration of the aqueous glucose polymer solution before mixing may be from 0 to 80% w/v, preferably from 15 to 65% w/v, and most preferably from 30 to 40% w/V.
The fractionation may be carried out at a temperature of from 10 to 40° C. and more preferably from 20 to 30° C.
In process b) the type of membrane material used may vary with the particular molecular weight distribution which is desired. A chemically inert plastics material may be used for the membrane, eg. a cellulose acetate or polytetrafluoro-ethylene. We particularly prefer to use a material which is mechanically stable at high temperatures and pressures, eg. a polysulphone.
A series of membranes may be used consecutively such that both a high and a low molecular weight fractionation is carried out. The membrane fractionation may be carried out at elevated

Affiliated with

Also associated with

Rating

Method of peritoneal dialysis using glucose polymer solutions does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method of peritoneal dialysis using glucose polymer solutions, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of peritoneal dialysis using glucose polymer solutions will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2443654