POLYMERS FOR ADVANCED TECHNOLOGIES

Polym. Adv. Technol. 10, 69±73 (1999)

Novel Composite Adsorbent for

Adsorption of Urea
Linqi Shi1*, Yuzhong Zhang2 and Binglin He1
1
State Key Laboratory of Functional Polymer Materials for Adsorption and Separation, Institute of Polymer
Chemistry, Nankai University, Tianjin 300071, China
2
Tianjin Institute of Textile, Tianjin, China

ABSTRACT W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W metabolism and excrement while circulating

through the body. Once the liver or kidney is in
A urea adsorbent with an aldo structure was obtained by failure, some excessive chemical components,
the oxidation of a crosslinked b-cyclodextrin polymer. including small molecules and middle molecular
The highest urea adsorption capacity reached 50.6 mg/g substances, accumulate in the blood and cause
in 0.05 M aqueous phosphate buffer at 37°C and pH=7.4, many kinds of disease. The symptoms improve
and decreased to 4.0 mg/g in aqueous human serum when the toxins are removed from the patient's
albumin. The novel composite adsorbent was prepared by blood. Hemoperfusion and hemodialysis are effec-
the oxidation of a crosslinked b-cyclodextrin and tive methods to remove the toxin from the blood,
cellulose dialytic membrane. It was found that the and adsorbents and dialytic membranes are used to
composite adsorbent had a higher urea adsorption clear the poisonous substances. One of the major
selectivity and capacity compared with that of the challenges in blood purification is the separation
oxidation of a crosslinked b-cyclodextrin adsorbent when selectivity and clearance efficiency. The disadvan-
urea is in aqueous human serum albumin.  1999 John tages of current techniques are many and varied.
Wiley & Sons, Ltd. Some processes, such as hemodialysis, remove the
toxins depending only on the molecular weight
with a lack of specificity: they cannot remove just
KEYWORDS: hemoperfusion; blood puri®cation; com- the macromolecular poisonous substance. Other
posite adsorbent; urea; albumin techniques, such as urea adsorbents [1±3] with
active groups are used to remove the urea of the
blood of uremia, and often interact with serum
albumin, and consequently are not entirely satis-
factory for use in hemoperfusion. A need remains
INTRODUCTION W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W for an adsorbent with better characteristics for the
adsorption of urea. Furthermore, a better under-
Blood carries nutrients to the tissues of human standing of the interactions between the adsorbents
body and brings waste to the liver and kidney for and urea is required for the design of such
materials. The goal of this work is to study the
* Correspondence to: Linqi Shi, State Key Laboratory of Functional interactions of urea with specially designed adsor-
Polymer Materials for Adsorption and Separation, Institute of bents. These adsorbents consist of a dialytic
Polymer Chemistry, Nankai University, Tianjin 300071, China.
Contract grant sponsor: National Natural Science Foundation of membrane and an adsorbent with cyclopolyaldo
China groups to improve purification selectivity.

Received 12 August 1997

CCC 1042±7147/99/010069±05 $17.50 Revised 2 November 1997
 1999 John Wiley & Sons, Ltd. Accepted 10 November 1997
70 / Shi et al.

TABLE 1. The Composition and Aldehyde Content of

Oxidation Crosslinked b-Cyclodextrin (O-b-CDP)

Aldehyde
Mole feed ratio content
Sample epichlorohydrin: b-CD (mmol/g)

O-b-CDP1 1:10 2.72

O-b-CDP2 1:8 2.03
O-b-CDP3 1:5 1.77
O-b-CDP4 1:3 1.40
O-b-CDP5 1:2 1.37
O-b-CDP6 1:1 1.01

EXPERIMENTAL W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W
Material
b-Cyclodextrin (b-CD) was recrystallized and dried
in vacuum at 100°C for 24 hr before use. Aqueous
human serum albumin (20%) is from Spain's
Barcelona Grifols Laboratories. All other materials
and solvents are analytical reagent grade.

Preparation of Crosslinked b-CD Polymer FIGURE 2. Isotherms of adsorption of urea by two

adsorbents: 1, O-b-CDP2; 2, O-b-CDP4.
b-Cyclodextrin (10 g) was dissolved in 300 ml of
water in a 1000 ml round-bottomed flask at 80°C.
The calculated amounts of the epichlorohydrin and excess of cool water. The product was purified by
sodium hydroxide were added. Then the solution thorough Soxhlet extraction and dried in vacuum at
was stirred at 80°C for 16 hr. The crosslinked b- 100°C for 24 hr.
cyclodextrin polymer was precipitated from a large
Oxidation of Crosslinked b-Cyclodextrin Polymer
(O-b-CDP)
b-CDP (5 g) was swollen in 50 ml of water for 24 hr.
Then a solution of NaIO4 (1.0 M) in 50 ml of water
was gradually added. The mixture was shaken and
kept in the dark for 72 hr at 4°C. For the
determination of the periodic consumption, an
aliquot of this solution was diluted 10 times and
the adsorption band was measured with a UV
spectrophotometer at 222.5 nm. After oxidation was
complete, the O-b-CDP was washed with 10 ml of
ethylene glycol and distilled water until no UV
absorption could be detected. The aldehyde and
carboxylic acid content of O-b-CDP was deter-
mined using a hydroxylamine technique [4] and an
acid± base titration method [5], respectively.

Adsorbed Urea Determination

Dry adsorbent (0.5 g) was added to 25 ml of urea
solution at a concentration of 130 mg/dl in Na2H-
PO4 buffer solution (pH 7.4) and was shaken at
37°C for 4±10 hr. The amount of urea adsorbed was
calculated according to [6].

RESULTS AND DISCUSSION W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W

FIGURE 1. Rates of adsorption of urea by three One molecule of b-CD has seven rings. Each ring
adsorbents at C0=130 mg/dl, 37°C and pH=7.4: 1, O-b- has hydroxyl groups at C-2, C-3 and C-6, and may
CDP2; 2, O-b-CDP3; 3, O-b-CDP4. be crosslinked at C-6 with epichlorohydrin. With

 1999 John Wiley & Sons, Ltd. Polym. Adv. Technol. 10, 69±73 (1999)
 Novel Composite Adsorbent for Adsorption of Urea / 71

FIGURE 3. Rates of adsorption of HSA by three

adsorbents at C0=40 mg/dl, 37°C and pH=7.4: 1, O-b- FIGURE 4. Isotherms of adsorption of HSA by two
CDP2; 2, O-b-CDP3; 3, O-b-CDP4. adsorbents: 1, O-b-CDP2; 2, O-b-CDP4.

an increase in the reaction time or in the ratio of
epichlorohydrin to b-CD, the degree of crosslinking
of the product also increases. Oxidizing the cross-
linked b-CD gives a new adsorbent with an aldo
group. The cleavage of the ring of b-CD with NaIO4
proceeds by the splitting of the bond between C-2
and C-3 of each glucose unit. No formaldehyde or
formic acid was produced during the oxidation.
The product thus obtained has a cyclopolyalde-
hyde structure. Table 1 shows that the aldo group
content of O-b-CDP decreases with an increase in
the degree of crosslinking during the oxidation of
b-CDP.
and reached sorption equilibrium after 1 hr only.
The adsorption isotherms of HSA, at 37°C, for O-b-
CDP with different aldehyde content are shown in
Fig. 4. The adsorption isotherm for the HSA was
rather similar to that for the urea. An increase in the
aldehyde content raised the adsorption capacity for
HSA.
HSA exists in the blood. It is composed of 584
amino acid residues with a molecular weight of
approximately 66,000. HSA molecule and urea
coexist in the blood of uremia. For successful use
in hemoperfusion, an adsorbent should be capable
of removing the urea under the coexistence of HSA.

Adsorption for Urea

The rates of adsorption of urea by selected TABLE 2. The In¯uence of HSA on the Adsorption
adsorbents, under identical stirring, are shown in Capacity of O-b-CDP for Urea
Fig. 1. Experimental results showed that the
Adsorption ca-
adsorbent containing aldo groups can adsorb urea.
Sample Concentration of pacity for urea
O-b-CDP had a high adsorption rate and reached
HSA (mg/dl) (mg/g)
equilibrium after 3 hr. The adsorption isotherms, at
37°C, of adsorbents with aldo group with different O-b-CDP2 0 50.6
aldehyde content are shown in Fig. 2. There was a O-b-CDP2 20 16.6
steady increase in capacity as aldehyde content O-b-CDP2 40 10.2
increased. The highest urea adsorption capacity O-b-CDP2 100 4.0
reached 50.6 mg per gram of adsorbent at 37°C and O-b-CDP2 0 30.4
pH7.4, and the concentration of urea in the buffer O-b-CDP4 20 10.4
solution was 150 mg/dl. O-b-CDP4 40 6.2
O-b-CDP4 100 3.9
Adsorption for Human Serum Albumin
Adsorption condition: concentration of urea 130 mg/
Figure 3 shown the rates of adsorption of human dl, pH=7.4, 0.5 M aqueous phosphate buffer, temp
serum albumin (HSA) by three O-b-CDP. The 37°C, time 6 hr.
results show that O-b-CDP adsorbed HSA rapidly,

 1999 John Wiley & Sons, Ltd. Polym. Adv. Technol. 10, 69±73 (1999)
72 / Shi et al.
FIGURE 5. Mechanism of Transport of Composite Adsorbent.
Adsorption experiments were performed by add-
ing the O-b-CDP to urea solutions containing
various concentrations of HSA. The results are
listed in Table 2, and indicate that, under the
influence of HSA, as in the human blood, the two
adsorbents adsorb only a small amount of urea. The
adsorption capacity of urea was as high as 50.6 mg
per gram of O-b-CDP2 while the capacity was
reduced to 4.0 mg per gram in an HSA concentra-
tion of 100 mg/dl.
Composite Adsorbent
The composite adsorbent consists of cellulose
dialytic membrane and O-b-CDP. The O-b-CDP
(urea adsorbent) as ªinteriorº phase never actually
contacts the ªexteriorº phase (blood), the dialytic
membrane acts as a partition between the ªinteriorº
phase and ªexteriorº phase. An example of this
type of separation is shown in Fig. 5. The macro-
molecule (HSA) is unable to diffuses through the
membrane and stay in the blood. A small molecule
such as urea diffuse through the membrane and
conjugates with O-b-CDP. The other small mole-
cules are unable to conjugate with O-b-CDP, and
rapidly reach diffuse equilibrium. Since there is
very little free static urea in the interior phase, the
TABLE 3. The Adsorption Capacity of Composite Adsorbents for Urea at Aqueous
HSA
Sample Composite adsorbents
M-O-b-CDP2 O-b-CDP2/dialytic membrane
M-O-b-CDP3 O-b-CDP3/dialytic membrane
M-O-b-CDP4 O-b-CDP4/dialytic membrane
Concentration urea 130 mg/dl, temp. 37°C, time 8 hr. The data in brackets are
the adsorption capacity of OXY-b-CDP for urea at pH 7.4 buffer.
 1999 John Wiley & Sons, Ltd.
driving force for separation and partition into the
interior phase is very high.
Adsorption experiments were performed by
adding the composite adsorbent to a previously
prepared urea solution containing HSA. The results
are listed in Table 3, and indicate that the composite
adsorbent can avoid the influence of HSA. The
composite adsorbent has a substantially higher
urea adsorption capacity compared to that of O-b-
CDP.
CONCLUSION W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W
A urea adsorbent with aldo structure was obtained
by the oxidation of crosslinked b-cyclodextrin
polymer. The highest urea adsorption capacity
reached 50.6 mg per gram of adsorbent at 37°C
and pH 7.4. The composite adsorbents for urea
have been prepared by the cellulose dialytic
membrane and the oxidation of a crosslinked b-
cyclodextrin polymer. The composite adsorbents
can effectively avoid adsorbing HSA, and have a
substantially higher adsorption capacity for urea
than O-b-CDP under the coexistence of HSA. It is
an ideal adsorbent and might be used to remove
excess urea from the human body with hemoperfu-
sion.
Adsorption
capacity for
Concentration of urea
HSA (mg/dl) (mg/g)
40 36.4 (10.2)
40 29.4 (6.2)
40 22.5 (5.4)
Polym. Adv. Technol. 10, 69±73 (1999)
 Novel Composite Adsorbent for Adsorption of Urea / 73

ACKNOWLEDGMENT W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W W 3. B. L. He and X. B. Zhao, Reactive Polymers, 18, 229

(1992).
4. D. K. A. Gilles, J. K. Hamilton, P. A. Rebers and F.
This project was supported by the National Natural Smith, Anal. Chem., 28, 350 (1986).
Science Foundation of China. 5. B. Qian and W. L. Liu, The Application Handbook of Ion
Exchangers, Chemical Industry Publishing House,
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 1999 John Wiley & Sons, Ltd. Polym. Adv. Technol. 10, 69±73 (1999)