U.S. patent application number 09/882187 was filed with the patent office on 2001-11-22 for peritoneal dialysis solution containing modified icodextrins.
Invention is credited to Casu, Benito, Naggi, Annamaria, Petrella, Enrico, Torri, Giangiacomo.
Application Number | 20010044424 09/882187 |
Document ID | / |
Family ID | 22764822 |
Filed Date | 2001-11-22 |
United States Patent
Application |
20010044424 |
Kind Code |
A1 |
Naggi, Annamaria ; et
al. |
November 22, 2001 |
Peritoneal dialysis solution containing modified icodextrins
Abstract
The present invention provides a peritoneal dialysis solution
that contains heat stable osmotic agents such as D-glucitols,
gluconic acids and alkylglycosides produced the reduction,
oxidation or glycosylation of icodextrins respectively. As a
result, osmotic agents that are stable under autoclaving or heat
sterilization conditions are provided which reduces the amount of
bioincompatible materials in the sterilized peritoneal dialysis
solutions. Methods of preparing the D-glucitols, gluconic acids and
alkylglycosides are disclosed.
Inventors: |
Naggi, Annamaria; (Legnano,
IT) ; Petrella, Enrico; (Mirandola, IT) ;
Torri, Giangiacomo; (Milano, IT) ; Casu, Benito;
(Milano, IT) |
Correspondence
Address: |
Charles R. Mattenson, Esq.
Renal Division
Baxter International Inc.
One Baxter Parkway
Deerfield
IL
60015
US
|
Family ID: |
22764822 |
Appl. No.: |
09/882187 |
Filed: |
June 15, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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09882187 |
Jun 15, 2001 |
|
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09206063 |
Dec 4, 1998 |
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Current U.S.
Class: |
514/54 ; 514/58;
536/102; 536/103; 536/104; 536/105; 536/124 |
Current CPC
Class: |
A61P 7/08 20180101; A61K
31/718 20130101 |
Class at
Publication: |
514/54 ; 514/58;
536/102; 536/103; 536/104; 536/105; 536/124 |
International
Class: |
A61K 031/715; C08B
031/00; C08B 031/18; C07H 001/00; C07H 003/00 |
Claims
What is claimed is:
1. A sterilized peritoneal dialysis solution comprising: a starch
comprising a glucose polymer selected from the group consisting of
5wherein R is selected from the group consisting of CH.sub.3,
CH.sub.3CH.sub.2, (CH.sub.2OH).sub.2CH, CH.sub.2(OH)CH(OH)CH.sub.2,
and [CH.sub.2(OH)CH(OH)CH.sub.2(OH)]CH, and wherein the polymer is
linked by .alpha.-1,4 bonds, that comprise at least 85%, by number,
of the linkages.
2. The peritoneal dialysis solution of claim 1 wherein the solution
is substantially free of formaldehyde.
3. The peritoneal dialysis solution of claim 1 wherein the solution
is substantially free of furfurals.
4. The peritoneal dialysis solution of claim 1 wherein the
partially hydrolyzed starch is substantially of terminal aldehyde
groups.
5. A method of administering an autoclavable osmotic agent to a
subject in need thereof wherein the osmotic agent is prepared by
the steps comprising: providing a solution of starch dissolved in
water; and adding NaBH.sub.4 to the starch solution to reduce the
starch.
6. The method of claim 5 further comprising the step of purifying
the reduced starch solution by passing the reduced starch solution
through an anionic exchange resin.
7. The method of claim 5 wherein the dissolving and adding steps
are carried out at room temperature.
8. The method of claim 6 further comprising the following step
after the adding step and prior to the purifying step: allowing the
solution to stand for about 10 hours.
9. The method of claim 5 wherein the starch is maltodextrin.
10. The method of claim 5 wherein the starch is reduced to an
icodextrin linked predominately by .alpha.-1,4 bonds and having the
formula: 6
11. A method of administering a sterilizable osmotic agent to a
subject in need thereof wherein the osmotic agent is prepared by
the steps comprising: providing a solution of starch dissolved in
water; providing a solution of NaOCl; and adding the NaOCl solution
to the starch solution to oxidize the starch.
12. The method of claim 11 further comprising the step of purifying
the oxidized starch solution by passing the oxidized starch
solution through a gel permeation chromatograph.
13. The method of claim 11 wherein the adding step is carried out
at room temperature.
14. The method of claim 12 further comprising the following step
after the adding step and prior to the purifying step: allowing the
solution to stand for about 2 hours.
15. The method of claim 11 wherein the starch is maltodextrin.
16. The method of claim 11 wherein the starch is oxidized to an
icodextrin linked predominately by .alpha.-1,4 bonds and having the
formula: 7
17. A method of administering a sterilizable osmotic agent to a
subject in need of same wherein the osmotic agent is prepared by
the steps comprising: dissolving starch in an acid and an alcohol
selected from the group consisting of methanol, butanol and
glycerol.
18. The method of claim 17 further comprising the step of stirring
the starch, alcohol and acid for about 2 hours.
19. The method of claim 17 wherein the stirring step is carried out
at a temperature of about 100.degree. C.
20. The method of claim 17 wherein the starch is maltodextrin.
21. The method of claim 17 wherein the acid is HCl.
22. The method of claim 17 wherein the starch is glycosylated to an
icodextrin linked predominately by .alpha.-1,4 bonds and having the
formula: 8wherein R is selected from the group consisting of
CH.sub.3, CH.sub.3CH.sub.2 and (CH.sub.2OH).sub.2CH.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 09/206,063 which was filed on Dec. 4,
1998.
BACKGROUND OF THE INVENTION
[0002] The present invention relates generally to peritoneal
dialysis and solutions for the same. More specifically, the present
invention relates to the use of modified icodextrins in peritoneal
dialysis solutions as an osmotic agent and as an alternative to the
use of glucose as an osmotic agent. The present invention also
relates to methods of preparing peritoneal dialysis solutions that
are stable under autoclaving conditions.
[0003] Dialysis provides a method for supplementing or replacing
renal function in certain patients. Principally, hemodialysis and
peritoneal dialysis are the two methods that are currently
utilized.
[0004] In hemodialysis, the patient's blood is passed through an
artificial kidney dialysis machine. A membrane in the machine acts
as an artificial kidney for cleansing the blood. Because it is an
extracorporeal treatment that requires special machinery,
hemodialysis is fraught with certain inherent disadvantages such as
the availability of dialysis machines and the possibility of
infection and contamination.
[0005] To overcome the disadvantages associated with hemodialysis,
peritoneal dialysis was developed. Peritoneal dialysis utilizes the
patient's own peritoneum as a semi-permeable membrane. The
peritoneum is a membranous lining of the abdominopelvic walls of
the body. The peritoneum is capable of acting as a natural
semi-permeable membrane because of its large number of blood
vessels and capillaries.
[0006] In operation, a peritoneal dialysis solution is introduced
into the peritoneal cavity utilizing a catheter. After a sufficient
period of time, an exchange of solutes between the dialysate and
blood is achieved. Fluid removal is achieved by providing a
suitable osmotic gradient from the dialysate to the blood to permit
water outflow from the blood. This allows the proper acid-base,
electrolyte and fluid balance to be achieved in the blood. After an
appropriate dwell period, the dialysis solution or dialysate is
drained from the body through a catheter.
[0007] Conventional peritoneal dialysis solutions contain glucose
as an osmotic agent to maintain the osmotic pressure of the
solution higher than the physiological osmotic pressure (about 285
mOsmol/kg). Glucose is a preferred osmotic agent because it
provides rapid ultrafiltration rates. However, certain
disadvantages have become associated with the use of glucose.
[0008] For example, glucose is known to decompose to
5-hydroxymethyl-furfural (5-MHF) in an aqueous solution during
autoclaving or steamed sterilization. Smith, et al. AM.J. Hosp.
Pharm., 34:205-206 (1977). Because 5-HMF is considered to be
harmful for the peritoneum (Henderson, et al., Blood Purif.,
7:86-94 (1989)), it would be desirable to have a peritoneal
dialysis solution with an osmotic agent as effective as glucose but
which does not produce 5-HMF or other harmful decomposition
products during autoclaving or sterilization. In short, a
substitute osmotic agent for glucose is needed.
[0009] One family of compounds capable of serving as osmotic agents
in peritoneal dialysis solutions is icodextrins, including
maltodextrins. However, while these compounds are suitable for use
as osmotic agents, they are also known to degrade during heat
sterilization to aldonic acids and formaldehyde. Because the
presence of formaldehyde in peritoneal dialysis solutions is
inappropriate due to its poor biocompatibility, the use of
icodextrins, including maltodextrins as a substitute for glucose as
an osmotic agent is unsatisfactory.
[0010] Accordingly, there is a need for an improved peritoneal
dialysis solution which utilizes an osmotic agent other than
glucose and which is stable under autoclaving or steam
sterilization conditions.
SUMMARY OF THE INVENTION
[0011] The present invention provides a solution to the aforenoted
need by providing a sterilized peritoneal dialysis solution
comprising a glucose polymer linked predominately by .alpha.-1,4
bonds. The term "predominately" is used because it is anticipated
that within polymer molecules, other bonds such as .alpha.-1,6
bonds will be present as well, but in lesser amounts. Accordingly,
as used herein, the term "predominately" means at least 85%. Thus,
a glucose polymer linked predominately by .alpha.-1,4 bonds
includes at least 85%, by number, .alpha.-1,4 bonds.
[0012] In an embodiment, the glucose polymer linked predominately
by .alpha.-1,4 bonds is selected from the group consisting of
D-glucitol having the formula 1
[0013] wherein R is selected from the group consisting of CH.sub.3,
CH.sub.3CH.sub.2 and (CH.sub.2OH).sub.2CH,
CH.sub.2(OH)CH(OH)CH.sub.2, and (CH.sub.2OH)
(CHOHCH.sub.2OH)CH.
[0014] In an embodiment, the glucose polymers, linked predominately
by .alpha.-1,4 linkages, of the peritoneal dialysis solution may
include up to 10% of other linkages including, but not limited to,
.alpha.-1,6 linkages.
[0015] In an embodiment, the peritoneal dialysis solution of the
present invention is substantially free of formaldehyde.
[0016] In an embodiment, the peritoneal dialysis solution of the
present invention is substantially free of furfurals.
[0017] In an embodiment, starch utilized as the osmotic agent is
substantially free of terminal aldehyde groups.
[0018] In an embodiment, the present invention provides a method of
preparing a stabilized osmotic agent of a peritoneal dialysis
solution comprising the steps of providing a solution of starch
dissolved in water and adding NaBH.sub.4 to the solution of
partially hydrolyzed starch to reduce the starch.
[0019] In an embodiment, the method of the present invention
further comprises the step of purifying the reduced starch solution
by passing the reduced starch solution through an anionic exchange
resin.
[0020] In an embodiment, the dissolving and adding steps of the
method of the present invention are carried out at room
temperature.
[0021] In an embodiment, the method of the present invention
further comprises the step of allowing the solution to scan for
approximately 10 hours after the NaBH.sub.4 is added to the starch
solution to reduce the starch.
[0022] In an embodiment, the starch of the present invention is
maltodextrin.
[0023] In an embodiment, the method of the present invention
reduces maltodextrin to D-glucitol linked predominately by
.alpha.-1,4 bonds and having the formula 2
[0024] In an embodiment, the present invention provides a method
for preparing a stabilized osmotic agent of a peritoneal dialysis
solution which comprises the steps of providing a solution of
starch dissolved in water, providing a solution of NaOCl, and
adding the NaOCl solution to the starch solution to oxidize the
starch.
[0025] In an embodiment, the method of the present invention
further comprises the step of purifying the oxidized starch
solution by passing the oxidized starch solution through a gel
permeation chromatograph.
[0026] In an embodiment, the oxidation of the starch is carried out
at room temperature.
[0027] In an embodiment, the combined solutions are allowed to
stand for approximately 2 hours.
[0028] In an embodiment, the starch is maltodextrin.
[0029] In an embodiment, the method of the present invention
oxidizes the maltodextrin to a gluconic acid linked predominately
by .alpha.-1,4 bonds and having the formula 3
[0030] In an embodiment, the maltodextrin can be oxidized
electrochemically.
[0031] In an embodiment, the present invention provides a method of
preparing a stabilized osmotic agent for a peritoneal dialysis
solution which comprises the steps of dissolving the starch in an
acid and an alcohol selected from the group consisting of methanol,
butanol, glycerol or other alcohols.
[0032] In an embodiment, the method further comprises the step of
stirring the starch, alcohol and acid for 2-16 hours.
[0033] In an embodiment, the method further comprises the step of
stirring the starch, alcohol and acid at a temperature of about
100.degree. C.
[0034] In an embodiment, the starch is maltodextrin.
[0035] In an embodiment, the acid is hydrochloric acid or other
acids such as sulfuric acid.
[0036] In an embodiment, the method of the present invention
hydrolysizes and alkylates the starch to an alkylglycoside linked
predominately by .alpha.-1,4 bonds and having the formula 4
[0037] and wherein R is selected from the group consisting of
CH.sub.3, CH.sub.3CH.sub.2 and (CH.sub.2OH).sub.2CH. When
hydrolysis is performed on starch pre-treated with periodate, R is
the remnant of a glycol-split glucose unit.
[0038] It is therefore an advantage of the present invention to
provide an improved peritoneal dialysis solution which is stable
under autoclaving and steam sterilization conditions.
[0039] Another advantage of the present invention is that it
provides an improved osmotic agent as an alternative to
glucose.
[0040] Yet another advantage of the present invention is that it
provides improved methods of preparing peritoneal dialysis
solutions.
[0041] Yet another advantage of the present invention is that it
provides improved osmotic agents for peritoneal dialysis solutions
which are stable under autoclaving or steam sterilization
conditions.
[0042] Additional features and advantages of the present invention
are described in, and will be apparent from, the detailed
description of the presently preferred embodiments and upon
reference to the accompanying figures.
BRIEF DESCRIPTION OF THE FIGURES
[0043] FIG. 1 is a graphical illustration of the .sup.13C NMR
spectrum of an osmotic agent prepared by glycosylation in
accordance with the present invention; and
[0044] FIG. 2 is a graphical illustration of the .sup.13C NMR
spectrum of an osmotic agent prepared by glycosylation in
accordance with the present invention.
DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS
[0045] The present invention provides a peritoneal dialysis
solution with osmotic agents that are stable under autoclaving and
steam sterilization conditions. The stable osmotic agents of the
present invention may be prepared by reduction, oxidation or
glycosylation. When an icodextrin having reducing-end units are
employed, such as maltodextrin, the reduction, oxidation or
glycosylation procedures of the present invention transform the
icodextrin to corresponding D-glucitols, gluconic acids and
alkyglycosides respectively.
EXAMPLE 1
[0046] A reduced icodextrin was prepared by starting with 15 grams
of maltodextrin dissolved in 20 ml of water. One gram of NaBH.sub.4
was added to the solution at room temperature and the solution was
allowed to stand for 10 hours. The solution was then purified by
passing it through an anionic exchange resin.
[0047] Three different maltodextrin starting materials were
utilized. A low molecular weight (LMW) having a 3% degree of
polymerization (DP) was utilized that contained 1% glucose, 37%
maltose, 20% maltotetraose and 42% high molecular weight
oligosaccharides. Second, a high molecular weight maltodextrin
(HMW1) having a 14% degree of polymerization was utilized and
contained 1% glucose, 2% maltose, 4% maltotetraose and 94% high
molecular weight oliogosaccharides. Third, a second high molecular
weight maltodextrin (HMW2) with a 9% degree of polymerization
containing 1% glucose, 3% maltose, 7% maltotetraose and 90% high
molecular weight oliogosaccharides was utilized. The products and
starting materials were analyzed using .sup.13C NMR spectroscopy.
The signals associated with the reducing end units of the starting
materials completely disappeared in the specter of the products.
Some depolymerization was observed.
[0048] The products were tested for stability under sterilization
conditions at neutral pH. A significant reduction of absorbance
variation at 284 nm (.DELTA.Abs) after sterilization is observed
for the reduced compounds. The reduced compounds from Example 1 are
listed as HMW1 red, HMW2 red and LMW red in Table 1.
EXAMPLE 2
[0049] Utilizing the three different samples of maltodextrins
discussed above with respect to Example 1, oxidation reactions were
carried out on each sample by dissolving 15 grams of maltodextrin
in 30 ml of water and combining the starch solution with an
effective amount of NaOCl in 70 ml of a solution containing sodium
hydroxide and having a pH of 8.+-.0.5 at a temperature of
43.degree. C. The combined solutions were allowed to stand for
approximately 2 hours and the product solution was purified by gel
permeation chromatography. Again, the products were analyzed using
.sup.13C NMR spectroscopy and were tested for stability under
sterilization conditions as illustrated in Table 1. While the
oxidation products, HMW1 ox HMW2 ox and LMW ox show contrasting
results, this is attributed to the high molecular weight oxidized
products not being completely purified.
1TABLE 1 Absorbance (284 nm) variation after sterilization
(121.degree. C. 45 min) of 5% Icodextrin and modified Icodextrin
solutions Number of .DELTA.Abs .DELTA.Abs CODE experiments (pH
6.5-7.5) (pH 5.5) HMW1 6 0.65 .+-. 0.30 0.59 .+-. 0.35 HMW1 red 6
0.31 .+-. 0.10 0.20 .+-. 0.07 HMW1 ox 2 1.83 .+-. 0.21 1 78 .+-.
0.13 HMW2 8 1.21 .+-. 0.71 0 62 .+-. 0.71 HMW2 red 7 0.13 .+-. 0.09
0.09 .+-. 0.06 HMW2 ox 4 0.76 .+-. 0.31 0.79 .+-. 0.19 LMW 8 1.96
.+-. 0.87 1.33 .+-. 0.86 LMW red 8 0.18 .+-. 0.11 0.17 .+-. 0.07
LMW ox 3 0.01 .+-. 0.01 0.02 .+-. 0.01 Reference compounds Glucose
4 2.54 .+-. 0.78 2.36 .+-. 0.96 *Glucose 2 0.98
*D(+)-Gluconolactone 1 0.01 *Glucose and D(+)-Gluconolactone
solutions are 2.5% at pH 7 .DELTA.Abs = difference between
absorbance after and before sterilization
EXAMPLE 3
[0050] In a third method of preparing stable osmotic agents in
accordance with the present invention, icodextrin were
glycosylated. The glycosylation reactions were performed using
starch as the starting material and alcohol as the alkylating
agent. Butanol and glycerol were chosen because of their
biocompatibility. The molecular weight of the reaction products
depends upon the temperature, time and acid concentration used.
[0051] The hydrolysis with methanol and butanol were performed by
stirring a suspension of 200 mg of starch in 540 mg of alcohol
containing 60 mg of acid at a temperature of about 100.degree. C.
for approximately 2 hours. The .sup.13C NMR spectrum of the two
products obtained from this reaction with methanol and butanol
respectively are shown in FIGS. 1 and 2. Table 2 presents the
degree of polymerization (DP) and the percentage of non-substituted
reducing ends as a function of the reaction conditions. This data
was obtained from the ratio between the appropriate NMR signals
(.sup.1H NMR for DP values and .sup.13C NMR for the percentage of
nonsubstituted reducing ends).
2TABLE 2 Glycosylation reaction with MeOH and ButOH % non Acid
substituted Sample No. Alcohol M/ D.P. glucose 1 MeOH
H.sub.2SO.sub.4 4.1 8.7 2 MeOH HCl 5.2 11.2 3 ButOH H.sub.2SO.sub.4
1.3 41.6 4 ButOH HCl 1.4 13.0
EXAMPLE 4
[0052] In the case of alcoholysis with glycerol, the reactions were
performed using 1 gram of undried starch (humidity 9%) and 2.7
grams of glycerol and stirring the mixture at 100.degree. C. with
different amounts of hydrochloric acid for different time periods.
Glycerol excess was eliminated by evaporation under reduced
pressure and further purification was performed by gel filtration.
The results are shown in Table 3.
3TABLE 3 Glycosylation reaction with glycerol (Standard reaction
conditions: undried starch 1 g, glycerol 2.7 g) % non Temperature
Time HCl Yield substituted Compound .degree. C. h Mol/L % DP red.
end 5* 80 2 1.27 n.d. 8.5 9.8 6** 100 2 1 27 96 1.4 4.8 7 100 2
1.27 n.d. 4.7 0 8 100 2 2.54 77.1 1.6 10.4 9 100 2 5.08 87.7 1.7
28.2 10 100 2 5.08 81.9 2.0 26.8 11 100 2 5.08 79.3 2.1 25.7 12 100
4 1.27 98 1.5 6.4 13 100 4 5.08 95.8 1.2 19.2 14 100 4 5.08 85.7
1.2 20.9 15 100 16 1.27 99.3 1.4 0 16*** 100 16 1.27 93.1 1.2 0 17
100 16 5.08 78.9 1.0 13.4 18 100 16 5.08 79.6 1.0 0 19 100 24 5.08
82.1 1.0 4.6 20 60 16 1.27 n.d. 1.35 17.1 21 60 16 1.27 n.d. 1.10
23.9 22 80 16 0.32 88.7 1.11 13.9 23 80 16 0.32 79.4 1.10 11.3 24
80 16 0.32 89.1 1.15 10 6 25 80 16 0.64 94.2 1.04 17.9 26 80 16
0.64 n.d. 1.03 21.7 27 80 16 0.64 n.d. 1.10 9.7 28 80 16 1.27 n.d.
1.03 11.4 29 80 16 1.27 99.8 1.01 8.6 30 80 16 1.27 n.d. 1.01 4.9
*Reaction conditions: starch 200 mg, glycerol 540 mg **Reaction
conditions: starch 600 mg, glycerol 1.62 g ***Reaction conditions:
dry starch 1 g, glycerol 2.7 g
[0053] The .sup.13C NMR spectrum of the completely depolymerized
product and of one with a degree of polymerization of 4.7 are shown
in FIG. 2. It is possible to observe the glycosidic anomeric
signals .alpha. (100.9 ppm) and .beta. (105.1 ppm), the CH.sub.2
signals of both substituted (.alpha.=71.3 ppm, .beta.=73 ppm) and
non substituted (65.3 ppm) primary hydroxyl groups of glycerol, the
CH signals (.alpha.=81.5 ppm, .beta.-83 ppm) of secondary
substituted hydroxyl group of glycerol.
[0054] The stability of one product shown in Table 3 was tested for
stability under sterilization conditions and the observed variation
at 284 nm is compared with that of glucose and methyl
glycoside.
4TABLE 4 Absorbance (284 nm) variation after sterilization
(121.degree. C. 45 min) of glycerol derivative and methyl glycoside
number of .DELTA.Abs neutra .DELTA.Abs acid Sample % (w/v)
experiments (pH 6.5-7.5) (pH 5.5) No. 6 5 4 0.46 .+-. 0.32 0.35
.+-. 0.15 glucose 5 3 2.43 .+-. 0.9 n.d. Methyl glycoside 2.5 1
0.01 n.d. glucose 2.5 1 0.07 n.d.
[0055] In an in vitro test predictive of the dialytic efficiency of
the osmotic agents described above, small dialysis bags with
Spectra Pore membrane with a cut-off 500 Dalton (diameter 15 mm, 15
cm high) were filled with 3 ml of water solutions at different
concentrations (2.5, 5.0% w/v of the samples). The bags were
immersed in 200 ml of distilled water and 37.degree. C. while
stirring the extra dialysis solution. At given 10 times (0, 1, 2,
3, 4, 5, 6 hours), the increase in the volume inside the dialysis
bag was evaluated by weight and expressed as a percentage increase
compared to the starting volume (.DELTA.w %). The mean results are
shown in Table 5 and are compared with the results for glucose and
glucose-1-phosphate.
5TABLE 5 Volume increase in vitro dialysis test of modified
icodextrins N of .DELTA.w % .DELTA.w % .DELTA.w % .DELTA.w %
.DELTA.w % .DELTA.w % Samples Moles/L experiments 1 h 2 h 3 h 4 h 5
h 6 h LMW red 0 071 5 29.9 43.0 53.8 66.2 76.7 88.3 LMW ox n.d 5 20
2 29.2 39.3 46.0 56.4 63 4 HMW 1 red 0 016 3 50 8 67.4 74.7 81 5
85.7 91.2 HMW 1 ox n.d 3 22.8 43.3 60.2 77.0 89.6 104.2 HMW 2 red
0.049 3 6 7 10.0 15.7 19 2 21.2 26.3 HMW 2 ox n.d. 4 32 2 52.9 69 7
84 2 96.0 106.4 No. 6 (5%) 0.215 1 33.2 68.2 98.1 119.5 140.5 159 8
.alpha.-methyl-gluc. (5%) 0 257 1 30.9 60.7 86 5 107.9 123 2 142 0
.beta.-methyl-gluc. (5%) 0.257 1 45 76 1 103 0 129 7 151.7 174.9
No. 6 (25%) 0.108 2 22.9 34.4 50.0 63.0 77.2 87.7
.alpha.-methly-gluc. (2.5%) 0.128 3 21 8 39 2 55.4 67 64 79.5 92.1
.beta.-methly-gluc. (2.5%) 0 128 3 34.0 50.3 63.7 67 6 77.7 86.5
glucose (2 5%) 0.138 3 15.3 34.2 43.4 57.3 74.2 90.9 gluc-1-phos.
(2.5%) 0.069 3 35 8 53 6 76.3 95.9 120.1 144.1
[0056] Accordingly, the present invention provides a number of heat
stable osmotic agents that provide a suitable substitute for
glucose, improved peritoneal dialysis solutions containing stable
osmotic agents as well as a variety of methods of producing
improved peritoneal dialysis solutions.
[0057] It should be understood that various changes and
modifications to the presently preferred embodiments described
herein will be apparent to those skilled in the art. Such changes
and modifications may be made without departing from the spirit and
scope of the present invention and without diminishing its
attendant advantages. It is, therefore, intended that such changes
and modifications be covered by the appended claims.
* * * * *