Method of preparing urea adsorbent

A urea adsorbent and a method for its production are disclosed, the adsorbent comprising hollow microspheres each having an outer layer formed of a urea-permeable polymer and an inner layer formed of a polymer containing a polyoxyalkylene glycol derivative expressed by the following formula: EQU --(CH.sub.2).sub.n --O--.sub.m R wherein R stands for hydrogen or a methyl group and n is an integer of 2-5 and m is an integer of at least 3. The adsorbent can selectively adsorb urea with a high adsorbing activity and does not interact with other substances than urea and, therefore, is useful as an artificial kidney. The adsorbent may be prepared by subjecting a w/o/w type emulsion to polymerization wherein a radical polymerizable polyoxyalkylene glycol derivative is dissolved in the inner aqueous phase of the emulsion and an oil-soluble radical polymerizable monomer is used as the outer oil phase.

BACKGROUND OF THE INVENTION 
1. Field of the Invention: 
This invention relates generally to a urea adsorbent and, more 
particularly, to a novel polymer-based urea adsorbent suitable for use as 
an artificial kidney. 
2. Description of the Prior Art: 
Artificial kidneys currently used include those of a dialysis type, 
filtration type, adsorption type and enzyme-fixation type. While these 
known artificial kidneys have certain merits, they suffer from some 
drawbacks too. Thus, there have not been developed yet artificial kidneys 
satisfactorily used for chronic or acute kidney troubles. 
For example, an artificial kidney of a dialysis type, which is now most 
widely used, constantly requires a fresh dialysate. Further, the 
artificial kidney of this type is generally large in size and is 
inconvenient because patients are inevitably restrained in a hospital for 
a long time. 
An artificial kidney of a filtration type has a great drawback because 
serum containing useful components is discarded together with effete 
matters. 
An artificial kidney of an enzyme-fixation type, which is recently 
developed rapidly, has a problem of the inactivation of the enzyme at or 
after the fixation of urease. In addition, its performance is susceptible 
to environment conditions such as temperature and acidity. 
An artificial kidney of an adsorption type is convenient because it is 
small in size and light in weight. However, the adsorbent, generally 
activated carbon, is not effective for the adsorption of urea which is a 
main ingredient secreted in urine, though it effectively adsorbs organic 
effete or waste matters. 
At present, it has become an important problem to develop a urea-removing 
substance for use in an artificial kidney of an adsorption type. Oxystarch 
(Kobunshi Ronbunshu 39, 629) and a product obtained by reaction of a 
hydrazide-containing polymer with formaldehyde or glyoxal (Publication of 
Unexamined Japanese Patent Application No. 69489/1976) have been proposed 
as such an adsorbent but are not satisfactory in practice. 
SUMMARY OF THE INVENTION 
The present inventor has made an extensive study on selective urea 
adsorbent for the purpose of solving the above-mentioned problems and has 
found that a specific polyoxyalkylene glycol derivative is useful as a 
urea adsorbent. In accordance with the present invention there is provided 
a urea adsorbent comprising hollow microspheres each including an outer 
layer formed of a urea-permeable polymer, and an inner layer formed of a 
polymer containing, as its component, a polyoxyalkylene glycol derivative 
expressed by the following formula (I): 
EQU --(CH.sub.2).sub.n --O--.sub.m R (I) 
wherein n is an integer of 2-5, m is an integer of at least 3 and R stands 
for hydrogen or a methyl group. 
The method for the preparation of the urea adsorbent according to the 
present invention is not specifically limited. However, an emulsion 
polymerization method is preferable because of the ease and simplicity 
simpleness of the preparation steps. Especially, a w/o/w type emulsion 
method using a radical polymerizable polyoxyalkylene glycol derivative of 
the formula (II) or (III): 
##STR1## 
wherein n is an integer of 2-5, m is an integer of at least 3, R stands 
for hydrogen or methyl group and R' stands for hydrogen or a hydrocarbon 
group having 1-10 carbon atoms, is most preferable. 
The urea adsorbent in the form of hollow microspheres may be suitable 
obtained by emulsion polymerization of a w/o/w type emulsion in which the 
radical polymerizable polyoxyalkylene glycol derivative of the formula 
(II) or (III) is dissolved in the inner aqueous phase and an oil soluble 
radical polymerizable monomer is used as the oil phase. 
During the course of the polymerization, the polyoxyalkylene glycol 
derivative of the general formula (II) or (III) is co-polymerized with the 
oil soluble radical polymerizable monomer. Since the radical polymerizable 
polyoxyalkylene glycol derivative is dissolved in the inner aqueous phase 
of the w/o/w type emulsion, the resulting hollow microspheres each have an 
inner layer formed of a polymer mainly composed of the radical 
polymerizable polyoxyalkylene glycol derivative of the formula (II) or 
(III) and an outer layer formed of a polymer composed mainly of the oil 
soluble radical polymerizable monomer. The outer layer may be other 
polymer than the polymer of the oil soluble radical polymerizable monomer 
as long as the outer layer permits the permeation of urea therethrough. 
A polyoxyalkylene glycol derivative generally has a property to interact 
with and adsorb (remove) useful components in human bodies, such as 
vitamin B-12 and polypeptides, besides waste matters. To prevent the 
removal, by adsorption, of the useful components in human bodies, it is 
effective to reduce the contact between the useful components and the 
polyoxyalkylene glycol derivative. This can be achieved by the use of the 
hollow microspheres with the above-described structure. As described 
previously, the outer layer of the hollow microspheres is formed of an 
urea permeable polymer such as a polymer of an oil soluble radical 
polymerizable monomer. The outer layer serves as a separating membrane. 
That is, due to the molecular sieve effect of the membrane (outer layer), 
high molecular weight and middle molecular weight substances which are 
effective components in human bodies cannot pass therethrough, permitting 
the passage of low molecular weight substances such as water, urea, metal 
ion, therethrough. The low molecular weight substances, after passage 
through the outer layer, are then brought into contact with the inner 
layer of the polyoxyalkylene glycol derivative and urea is selectively 
adsorbed thereby. 
The method of the preparation of the urea adsorbent is described below. A 
mixture containing an oil soluble radical polymerizable monomer, a 
nonionic surfactant, a radical polymerization initiator and, if necessary, 
a crosslinking agent is mixed with an aqueous solution containing a 
radical polymerizable polyoxyalkylene glycol derivative of the formula 
(II) or (III) and the mixture is vigorously agitated to form a w/o 
emulsion. The w/o emulsion is then added into water containing a cationic 
or anionic surfactant with stirring to form a w/o/w emulsion. The w/o/w 
emulsion is then heated with stirring under nitrogen atmosphere to effect 
the polymerization. The stirring is conducted at a rotational speed so 
that the w/o/w emulsion is not destroyed, preferably at a rotational speed 
of 100-300 r.p.m. 
The nonionic surfactant may include, for example, polyoxyethylene oleyl 
ether, polyoxyethylene nonylphenyl ether, polyoxyethylene sorbitan 
trioleate, polyoxyethylene sorbitan monooleate, or polyoxyethylene 
glycerin monostearate. The amount of the noionic surfactant used varies 
with the amount of the radical polymerizable polyoxyalkylene glycol 
derivative of the formula (II) or (III). Since the compound of the formula 
(II) or (III) has a property as a nonionic surfactant, the above-described 
nonionic surfactant is used only when otherwise a stable w/o/w emulsion is 
not obtainable, in a minimum required amount. 
The anionic surfactant may include, for example, sodium laurylsulfate, 
sodium cetylsulfate, sodium dodecylbenzenesulfonate, sodium 
laurolylsarcosine or sodium polyoxyethylene lauryl ether phosphate. These 
anionic surfactants may be used singly or in combination of two or more. 
The cationic surfactant may include, for example, cetylpyridinium chloride, 
benzalkonium chloride, or cetyltrimethylammohium chloride. These cationic 
surfactants may be used singly or in combination of two or more. If 
desired, inorganic salts(e.g. sodium hexametaphosphate) may be used in 
conjunction with the above anionic or cationic surfactant. 
As a result of the polymerization of the oil soluble radical polymerizable 
monomer and the radical polymerizable polyoxyalkylene glycol derivative of 
the formula (II) or (III), hollow microspheres having an outer, 
urea-permeable layer formed of a polymer composed mainly of the oil 
soluble radical polymerizable monomer and an inner layer formed of a 
polymer containing, as its component, a polymer of the polyoxyalkylene 
glycol derivative of the formula (II) or (III) crosslinked with the 
polymer of the outer layer. 
The thus obtained microspheres are separated from the reaction mixture by 
sedimentation, centrifugation, vacuum filtration, pressurized filtration, 
or so on. The separated microspheres are washed with water and then with 
methanol and dried by hot air or in vacuum. The resulting microspheres 
have a size of 2-100 .mu.m and a high mechanical strength. Further, the 
microspheres are stable in air and under dried conditions so that the 
microspheres withstand long-period storage. The microspheres have a hollow 
structure with a wall thickness of about 1-10 .mu.m. The hollow structure 
may be confirmed by photomicroscopy after crushing the microspheres. 
It is deduced from the below-described facts that the hollow microspheres 
thus obtained have an outer layer formed of a polymer composed mainly of 
the oil soluble radical polymerizable monomer and an inner layer formed of 
a polymer containing the polyoxyalkylene glycol derivative crosslinked 
with the polymer of the outer layer. Thus, the adsorbent according to the 
present invention is prepared by w/o/w type emulsion polymerization, in 
which the outer oil phase contains the oil soluble radical polymerizable 
monomer and the inner aqueous phase contains the radical polymerizable 
polyoxyalkylene glycol derivative of the formula (II) or (III). The fact 
that the polyoxyalkylene glycol derivative is contained in the inner layer 
which does not contact directly with the useful substances in human bodies 
is also deduced by the fact that, while microspheres (Comparative Example 
2) formed from a polyethylene glycol and a crosslinking agent by a method 
disclosed in Publication of Unexamined Japanese Patent Application 
No.55009/1985 interact with vitamins or hormones, the hollow microspheres 
according to the present invention do not interact with such vitamins and 
hormones. 
The hollow fine microspheres as such may be used as a urea adsorbent. It is 
possible to modify them for imparting hydrophilicity thereto or to 
subjecting them to a hydrophilic polymer coating treatment or plasma 
treatment before using them as a urea adsorbent. 
Illustrative of suitable radical polymerizable polyoxyalkylene glycol 
derivatives expressed by the general formula (II) are polyoxyethylene 
glycol mono(metha)acrylate, polyoxytrimethylene glycol 
mono(metha)acrylate, polyoxytetramethylene glycol mono(metha) acrylate, 
.omega.-methoxylpolyoxyethylene glycol mono(metha)acrylate, 
.omega.-methoxypolyoxytrimethylene glycol mono(metha)acrylate, and 
.omega.-methoxypolyoxytetramethylene glycol mono(metha)acrylate. 
Illustrative of suitable radical polymerizable polyoxyalkylene glycol 
derivatives expressed by the general formula (III) are 
.alpha.-(p-vinylbenzyloxy)-polyoxyethylene glycol, 
.alpha.-(p-vinylbenzyloxy)-polyoxytrimethylene glycol, 
.alpha.-(p-vinylbenzyloxy)-polytetramethylene glycol, 
.alpha.-(p-vinylbenzyloxy)-.omega.-methoxypolyoxyethylene glycol, 
.alpha.-(p-vinylbenzyloxy)-.omega.-methoxypolyoxytrimethylene glycol and 
.alpha.-(p-vinylbenzyloxy)-.omega.-methoxypolyoxytetramethylene glycol. 
Examples of the polymers containing as their component a polyoxyalkylene 
glycol derivative of the formula (I) include a copolymer of ethyl 
methacrylate/polyoxyethylene glycol dimethacrylate (number average 
molecular weight: 400)/polyoxyethylene glycol monomethacrylate, a 
copolymer of styrene/ethylene glycol 
dimethacrylate/.omega.-methoxypolyoxyethylene glycol monomethacrylate, a 
copolymer of ethyl methacrylate/polyoxyethylene glycol 
dimethacrylate/.alpha.-(p-vinylbenzyloxy)polyoxyethylene glycol, and a 
copolymer of methyl 
methacrylate/divinylbenzene/.alpha.-(p-vinylbenzyloxy)-.omega.-methoxypoly 
oxyethylene glycol. The hollow microsphere adsorbent of the present 
invention is composed of the above-exemplified polymer and has an outer 
layer formed of a urea-permeable polymer composed mainly of an oil soluble 
monomer such as ethyl methacrylate or styrene and an inner layer formed of 
a polymer composed mainly of a radical polymerizable polyoxyalkylene 
glycol derivative expressed by the general formula (II) or (III). 
The radical polymerizable polyoxyalkylene glycol derivative of the formula 
(II) or (III) may be produced by any known method. For example, the 
derivative of the formula (II) in which the terminal group is hydrogen may 
be obtained by adding an alkylene oxide to a hydroxyalkyl acrylate in the 
presence of stannic chloride, as disclosed in Japanese Patent Publication 
No. 15493/1978. In the case of the derivative of the formula (II) in which 
the terminal group is methyl may be prepared by the transesterification of 
an acrylate with a polyoxyalkylene glycol whose one terminal hydroxyl 
group is substituted by a methoxy group (Kobunshi Ronbunshu 39, 165). 
The radical polymerizable polyoxyalkylene glycol derivative of the formula 
(III) may be obtained by reacting a corresponding polyoxyalkylene glycol 
with sodium hydroxide to form a sodium salt, followed by the reaction with 
chloromethylstyrene (Publication of Unexamined Japanese Patent Application 
No. 121730/1978). The thus synthesized polyoxyalkylene glycol derivative 
of the formula (II) or (III) may be used singly or in combination of two 
or more. 
The number average molecular weight of the polyoxyalkylene glycol 
derivative of the formula (II) or (III) is generally 120-50000, preferable 
200-10000. A number average molecular weight of less than 120 is 
insufficient to impart appreciable urea adsorbing properties to the 
resulting polymer of the general formula (I). Further, the glycol 
derivative with such too low a molecular weight becomes poor in 
hydrophilicity so that it becomes difficult to dissolve the glycol 
derivative in the inner aqueous phase of the w/o/w type emulsion, 
especially when polyoxytetramethylene glycol derivative is employed as the 
alkylene glycol of the formula (II) or (III). On the other hand, if the 
number average molecular weight is greater than 50000, the urea absorbing 
power of the polymer tends to be lowered and the mechanical strength of 
the microspheres becomes low. 
The amount of the polyoxyalkylene glycol derivative of the formula (II) or 
(III) used is preferably 1-50 weight % based on the oil soluble monomer. 
Too small an amount causes insufficient urea absorbing power while too 
large an amount fails to produce microspheres with desired structure. 
As described above, the terminal group of the polyoxyalkylene glycol 
derivative of the formula (II) or (III) is hydrogen or methyl. Generally, 
in an artificial kidney, the control the concentration of potassium and 
sodium ion is one of the important problem. A great difference exists in 
the ion adsorbing power between the hydrogen-terminated polyoxyethylene 
glycol derivative and the methyl-terminated polyoxyethylene glycol 
derivative, i.e. the former glycol derivative has a greater adsorbing 
power. By converting a portion of the terminal hydrogen into methyl, 
however, it is possible to obtain microspherical adsorbent having a 
desired ion adsorbing power. 
The oil soluble radical polymerizable monomer is not specifically limited 
in the present invention. Illustrative of suitable monomers are aromatic 
radical polymerizable monomers such as styrene, .alpha.-methylstyrene, 
.beta.-methylstyrene, and p-vinyltoluene; ester type radical polymerizable 
monomers such as methyl acrylate, methyl methacrylate, ethyl acrylate, 
ethyl methacrylate, propyl acrylate, propyl methacrylate, butyl acrylate, 
butyl methacrylate and methyl .alpha.-ethylacrylate; and vinyl type 
radical polymerizable monomers such as vinyl chloride, vinyl acetate and 
methyl vinyl ether. These oil soluble polymerizable monomers may be used 
singly or in combination of two or more. 
A crosslinking agent may be used, if desired. Examples of the crosslinking 
agents include divinylbenzene, ethylene glycol dimethacrylate, 
polyoxyethylene glycol dimethacrylate, polydimethylsiloxane 
dimethacrylate, polyamide dimethacrylate. The amount of the crosslinking 
agent is 0-50 wt % based on the oil soluble radical polymerizable monomer. 
An amount of the crosslinking agent over 50 wt % is undesirable because of 
the lowering of the permeation rate of water and urea of the hollow 
microspherical adsorbent. 
The microspherical adsorbent produced by w/o/w type emulsion polymerization 
and formed of a polymer containing as its component a polyoxyalkylene 
glycol derivative of the general formula (I) should allow the passage of 
water and urea in a facilitated manner. For this reason, it is preferable 
to use an ester-type radical polymerizable monomer capable of providing a 
polymer of a high permeability such as methyl acrylate, methyl 
methacrylate, ethyl acrylate or ethyl methacrylate and to use 
polyoxyethylene glycol dimethacrylate as a crosslinking agent. When 
chloromethylstyrene, which is hydrophobic in nature, is used as the 
radical polymerizable monomer, it is effective to convert its 
polymerization product into an ammonium salt so as to impart 
hydrophilicity thereto. It is also effective to use glycidyl methacrylate 
as the radical polymerizable monomer and to react, after the radical 
polymerization, the polymerized product with a nucleophile so as to impart 
hydrophilicity by opening the three membered rings. 
Illustrative of suitable radical polymerization initiators are peroxides 
such as cumene hydroperoxide, dicumylperoxide, benzoylperoxide and 
lauroylperoxide; azobis-type initiators such as azobisisobutyronitrile and 
azobis-2,4-dimethylvaleronitrile; and redox initiators such as a 
combination of peroxodisulfate and sodium hydrogen sulfite. Both water 
soluble and oil soluble polymerization initiators may be used for the 
purpose of the present invention. 
The urea adsorbent obtained in the foregoing manner has a potent urea 
adsorbing property. For example, when 0.5 g of the urea adsorbent is 
immersed in 50 ml of an aqueous urea solution having a urea concentration 
of 100 mg/dl for 1 hour, the urea concentration is decreased to about 
half. In addition, the urea adsorbent is advantageous because the 
adsorbent having adsorbed urea may be regenerated by washing with hot 
water for the desorption of the urea, followed by filtration and drying.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The present invention will now be described in detail below by way of 
examples. It is to be understood, however, that these examples are not to 
be considered as limitting the scope of the invention. 
EXAMPLE 1 
Into a mixture containing 19 g of ethylmethacrylate, 2 g of tetraethylene 
glycol dimethacrylate [NK Ester 4G (trademark) manufactured by 
SHIN-NAKAMURA CHEMICAL Co., LTD.], 2 g of sorbitan monooleate and 0.01 g 
of azobisisobutyronitrile were added 10 ml of an aqueous solution 
containing 2 g of polyoxyethylene glycol monomethacrylate and the 
resulting mixture was vigorously stirred to obtain a w/o type emulsion. 
To a four-necked flask equipped with a stirring bar, a condenser, a tap 
funnel and a nitrogen feed pipe were charged 1 g of sodium dodecylsulfate, 
2.5 g of sodium hexametaphosphate and 450 ml of water and the mixture was 
heated to 70.degree. C. while introducing nitrogen gas. Then the above w/o 
type emulsion was added, dropwise from the tap funnel, into the flask at 
70.degree. C. with stirring. After the addition of the w/o type emulsion, 
the mixture within the flask was reacted at 80.degree. C. and at a 
stirring rate of 300 r.p.m. for 5 hours. The precipitate formed by the 
polymerization was recovered by filtration under vacuo, washed five times 
with water and thrice with methanol, and dried under a reduced pressure to 
obtain hollow microspheres each having an outer layer formed of a 
copolymer composed mainly of ethyl methacrylate and tetraethyelene glycol 
dimethacrylate and an inner layer formed of a copolymer composed mainly of 
polyoxyethyelene glycol monomethacrylate and tetraethylene glycol 
dimethacrylate and crosslinked with the copolymer of the outer layer. 
The hollow microspheres were found to have an average size of 100 .mu.m and 
a wall thickness of about 2 .mu.m. The hollow structure was confirmed by 
optical microscope (Optiphoto XF-BD manufactured by Nikon Inc.) after 
crushing the sample microspheres. FIG. 1 is a microphotograph of the 
microspheres according to the present invention, in which a broken 
microsphere appears at the center and unbroken microspheres appear 
therearound. The hollow microspheres are insoluble in water and in usual 
organic solvents. The microspheres have good dispersibility in water. 
The hollow microspheres as such were used as urea adsorbent to measure the 
amount of urea adsorbed thereby in the following manner: To an aqueous 
solution (50 ml) containing 100 mg/dl of urea were added 0.5 g of the 
adsorbent and the mixture was agitated at 37.degree. C. for 2 hours and 
centrifuged. The supernatant thus obtained was recovered and 
colorimetrically analyzed to determine the concentration of urea according 
to the diacetyl method using a spectrophotometer (150-20 type manufactured 
by Hitachi Ltd.; wavelength: 480 nm). As a result, the concentration of 
urea was found to decrease to 60 mg/dl. For the purpose of comparison, a 
similar test was conducted using activated carbon in place of the hollow 
microspheres, revealing that the urea concentration was reduced to 95 
mg/dl. 
The foregoing results indicate that the urea absorbent according to the 
present invention which is composed of a polymer containing 
polyoxyethyelne glycol as its component has an excellent urea adsorbing 
property. 
EXAMPLE 2 
Into a mixture containing 19 g of ethyl methacrylate, 1 g of ethylene 
glycol dimethacrylate, 2 g of sorbitan monooleate and 0.01 g of 
azobisisobutyronitrile were added 10 ml of an aqueous solution containing 
2 g of methoxy-terminated polyoxyethylene glycol monomethacrylate [NK 
Ester-M-230G (number aaverage molecular weight: ca. 1000) manufactured by 
SHIN-NAKAMURA CHEMICAL Co., LTD.] to obtain a w/o type emulsion. The 
emulsion was reacted in the same manner as Example 1 to obtain hollow 
microspheres formed of a polymer containing methoxyterminated 
polyoxyethylene glycol as its component. Each microsphere has an outer 
layer formed of a copolymer composed mainly of ethyl methacrylate and 
ethylene glycol dimethacrylate and an inner layer formed copolymer 
composed mainly of methoxy-terminated polyoxyethylene monomethacrylate. 
The microspheres were found to have an average size of 70 .mu.m and a wall 
thickness of 3 .mu.m. The hollow structure was confirmed by optical 
microscope in the same manner as in Example 1. The microspheres were found 
to be insoluble in water and in usual organic solvents and have good 
dispersability in water. The microspheres were tested for adsorbing 
property in the same manner as in Example 1, revealing that the 
concentration of urea of the aqueous urea solution after the treatment 
with the microspheres was reduced to 80 mg/dl. The urea adsorbing property 
of the microspheres of Example 2 is thus inferior to that of the 
microspheres of Example 1 but is far superior in comparison with activated 
carbon. 
EXAMPLE3 
Into a mixture containing 19 g of ethyl methacrylate, 1 g of ethylene 
glycol dimethacrylate, 2 g of sorbitan monooleate and 0.01 g of 
azobisisobutyronitrile were added 10 ml of an aqueous solution containing 
2 g of mono(p-vinylbenzyloxy)tetraoxyethylene glycol to obtain a w/o type 
emulsion. The emulsion was reacted in the same manner as Example 1 to 
obtain hollow microspheres formed of a polymer containing 
hydroxyl-terminated polyoxyethylene glycol as its component. Each 
microsphere has an outer layer formed of a copolymer composed mainly of 
ethyl methacrylate and ethylene glycol dimethacrylate and an inner layer 
formed of a copolymer composed mainly of 
mono(p-vinylbenzyloxy)tetraoxyethyelene glycol. The microspheres were 
found to have an average size of 45 .mu.m and a wall thickness of 3.5 
.mu.m and to be insoluble in water and in usual organic solvents and good 
in dispersability in water. The hollow structure was confirmed by optical 
microscope. The urea adsorbing property of the microspheres was tested in 
the same manner as in Example 1, revealing that the concentration of urea 
of the aqueous solution after the treatment with the microspheres was 
reduced to 70 mg/dl. The microspherical adsorbent according to the present 
invention exhibits a high urea adsorbing power even if the molecular 
weight of the polyoxyethylene glycol is relatively small. Comparative 
Example 1 
Into a mixture containing 19 g of ethyl methacrylate, 1 g of ethylene 
glycol dimethacrylate, 5 g of sorbitan monooleate and 0.01 g of 
azobisisobutyronitrile were added 10 ml of water to obtain a w/o type 
emulsion. The emulsion was reacted in the same manner as Example 1 to 
obtain hollow microspheres having an average size of 50 .mu.m and a wall 
thickness of 5 .mu.m. The hollow structure was confirmed by optical 
microscope. The microspheres were composed of a copolymer of ethyl 
methacrylate and ethylene glycol dimethacrylate and did not contain a 
polyoxyalkylene glycol derivative. Using the thus obtained microspheres as 
an adsorbent, a urea adsorbing test was carried out in the same manner as 
in Example 1 to reveal that the urea concentration of the aqueous urea 
solution after the treatment was 100 mg/dl and the microspheres had no 
urea adsorbing property. The foregoing results suggest that the presence 
of a polyoxy- alkylene glycol derivative is essential for adsorption of 
urea. 
COMATIVE EXAMPLE 2 
In 50 ml of methyl ethyl ketone were dissolved 37.5 g of polyoxyethylene 
glycol monomethacrylate with a number average molecular weight of 400 
(Blenmer PE350 manufactured by Nippon Oil and Fats Co., Ltd.), 12.5 g of 
ethylene glycol dimethacrylate and 0.1 g of azobisisobutyronitrile to form 
a first solution. On the other hand, 15 g of sodium chloride and 10 g of 
polyvinyl alcohol were dissolved in 500 ml of water to give a second 
solution. The first solution was then added into the second solution which 
was previously heated to 70.degree. C., and the mixture was agitated to 
form a suspension. The suspension was allowed to react for 10 hours. The 
precipitates formed by the polymerization were collected by means of a 
glass filter, washed thrice with water and thrice with acetone and dried 
under vacuum to obtain microspheres with an average size of 30 .mu.m. The 
microspheres had no hollow structure and were formed of a copolymer of 
polyoxyethylene glycol monomethacrylate and ethyelene glycol 
dimethacrylate. Using the microspheres as an adsorbent, a urea adsorbing 
test was carried out in the same manner as described in Example 1 to 
reveal that the concentration of urea in the aqueous urea solution was 
decreased to 70 mg/dl. 
The microspheres were then tested for adsorption of creatinine (aqueous 
solution with a concentration of 10 .mu.g/ml), albumin (aqueous solution 
with a concentration of 100 .mu.g/ml) and vitamin B-12(aqueous solution 
with a concentration of 10 .mu.g/ml). The tests were conducted in the same 
manner as in urea adsorption test by adding 0.5 g of the microspheres in 
50 ml of each of the above aqueous solutions and agitating the mixture at 
37.degree. C. for 2 hours. The mixture was then centrifuged to recover a 
supernatant. Each supernatant was subjected to colorimetric analysis. The 
maximum absorption wavelengths of the creatinine, albumin and vitamin B-12 
aqueous solutions are 234, 279 and 550 nm, respectively. By the treatment 
of the microspheres, the maximum absorption wavelengths of the creatinine 
and albumin solutions were shifted to 225 and 275 nm, respectively. No 
change was observed in the case of the vitamin B-12 aqueous solution. The 
above results indicate that some change occurred in creatinine and albumin 
upon the treatment with the microspheres. 
Similar tests were carried out using the hollow microspheres obtained in 
Examples 1-3. No changes in concentration or in maximum absorption 
wavelengths were observed on the creatinine, albumin and vitamin B-12 
solutions treated with the hollow microspheres. 
The foregoing results suggest that microspheres whose surfaces are formed 
of a polyoxyalkylene glycol derivative interact not only with urea but 
also with other ingredients and give undesirable results. In contrast, 
with the hollow microspheres having an outer layer formed of a 
urea-permeable polymer composed mainly of an oil soluble radical 
polymerizable monomer and an inner layer formed of a polymer composed 
mainly of a polyoxyalkylene glycol derivative, the undesirable interaction 
between the latter polymer and the ingredients other than urea can be 
effectively prevented and urea alone can be selectively adsorbed. 
The urea adsorbent according to the present invention has an excellent urea 
adsorbing power and can selectively adsorb urea. Thus, the adsorbent is 
suitably utilized as an artificial kidney.