United States Patent (19) 11 Patent Number: 4,940,665

Iijima et al. 45 Date of Patent: Jul. 10, 1990

54 METHOD FOR GRANULATION OF FOREIGN PATENT DOCUMENTS
ENZYME
75) Inventors: Hitoshi Iijima; Kunio Nishimura, 0256127 12/1986 European Pat. Off. .
both of Tokyo, Japan 1935233 1/1970 Fed. Rep. of Germany ... 252/DIG.
12
73) Assignee: Showa Denko K. K., Tokyo, Japan 1802465 5/1970 Fed. Rep. of Germany .
2030531 12/1971 Fed. Rep. of Germany .
21) Appl. No.: 103,550 57-165497 10/1982 Japan.
60-168385 8/1985 Japan.
(22 PCT Filed: Dec. 26, 1986
(86 PCT No.: PCT/JP86/00661 Primary Examiner-Robert A. Wax
Attorney, Agent, or Firm-Oblon, Spivak, McClelland,
S 371 Date: Aug. 4, 1987 Maier & Neustadt
S 102(e) Date: Aug. 4, 1987 57 ABSTRACT
87 PCT Pub. No.: WO87/04184 A product obtained by granulating an enzyme powder
PCT Pub. Date: Jul. 16, 1987 must avoid emitting dust, possess high strength, exhibit
the property of quickly dissolving in water where such
30 Foreign Application Priority Data ready solution is necessary for the intended application,
Dec. 27, 1985 JP Japan ................................ 60-2931.67 defy absorption of moisture or deformation for a long
51) int. Cl. ............................................... C12N 9/98 time, and preserve without a sacrifice of activity. The
52 U.S. C. ............................... 435/187; 252/74. 12; method of this invention produces granules of raw en
252/DIG. 12 zyme powder possessed of the qualities mentioned
58 Field of Search ................... 435/187; 252/17412, above by admixing the enzyme powder with polyethyl
252/DIG. 12 ene glycol or polyoxyethylene-polyoxypropylene block
polymer of specific quality as a binder and granulating
(56) References Cited by agitating the resulting combination at a temperature
U.S. PATENT DOCUMENTS not lower than the melting point of the binder. This
3,749,671 7/1973 Gedge, III .......................... 435/187 method is suitable for production of enzyme-containing
3,775,331 11/1973 Borrello ... ... 252A17412 granules for use in detergents, medicines, etc.
4,106,991 8/1978 Markussen et al. ... 435/187
4,572,897 2/1986 Amutz et al. ....................... 435/177 5 Claims, No Drawings
 1.
4,940,665
2
time consumed in laundering, these granulated enzymes
METHOD FOR GRANULATION OF ENZYME must be capable of being quickly dispersed and dis
solved to release the enzymes in water in a span of
TECHNICAL FIELD several minutes. Even if a granulated enzyme has high
This invention relates to a method for the granulation mechanical strength, therefore, it cannot be used as a
of an industrial grade raw enzyme powder. More partic good product if it possesses poor solubility in water.
ularly, this invention relates to a method for the granu When an enzyme product having inferior storage stabil
lation of a raw enzyme powder, characterized by the ity is kept in storage for a long time, this enzyme prod
fact that spherical particles having diameters in a de O
uct absorbs moisture and consequently swells and de
sired range can be obtained in a high yield with mini forms, undergose disintegration and coalescence, suf
mum inactivation ratio and without entailing any me fers from loss of flowability and decline of activity, and
chanical trouble and the produced granules possess sustains other forms of degeneration, to the extent of
proper strength, produce almost no dust, excel in stor being deprived of its commercial value. The granulated
age, and dissolve quickly in water preparatory to actual 15
enzymes, therefore, must possess sufficient solubility in
Se water as described above and, on the other hand, absorb
BACKGROUND ART moisture only nominally and exhibit satisfactory mois
ture resistance.
The industrial grade enzymes which are used in ma Further, in the granulation of enzyme powder, there
chines, foods and drinks, textiles, leather, detergents, is entailed a peculiar important problem. Enzymes are
and various other applications are broadly divided into 20 generally liable to be inactivated by heat and water. In
those obtained by extraction from animals and plants numerous cases, their inherent activity is impaired by
and those obtained as products of fermentation by mi the heat and water to which the enzymes are exposed
croorganisms. Generally the enzymes of the former during the course of granulation.
type are economically utilizable only to a limited extent Therefore, it is important for granulation method of
because of limited sources of supply, whereas those of 25 an enzyme powder to attain the granulation under con
the latter type are extensively used because they have ditions not capable of inactivating the enzyme, i.e.
virtually infinite sources of supply and are producible under conditions using a low temperature and a small
relatively economically. amount of water sufficient to preclude the inactivation
Generally the enzyme powders, no matter whether of enzyme.
they originate in animals and plants or in microogan 30 Quite naturally, further, the operational conditions
isms, which hawve been obtained by separation and involved in the work of granulation such as, for exam
purification are rarely put to use in their unaltered form. ple, length of the time required for the granulation,
Most of these enzyme powders are granulated by them
selves or in combination with an extender, a stabilizer, presence or absence of such mechanical troubles as
and other substances and put to use. 35 adhesion of the raw material to the wall of the granulat
The granulated enzymes are generally in demand in ing machine, amount of such adjuvants as a binder to be
particle sizes in the range of about 0.5 to 1.5 mm. Fur used, and yield of the granulation (yield of acceptable
ther, as in any other field, the granulated enzymes are product), viz. the conditions which may well be termed
required to be uniform in particle size, shape, and con as economic factors, are equally important elements to
stituent makeup, rich in flowability, excellent in me 40 be fulfilled.
chanical strength, and rigid enough to avoid sustaining Thus, the method adopted for the granulation of the
cracking and chipping during storage or transportation. enzyme powder can hardly be called satisfactory when
Besides these general requirements, the granulated en it fails to fulfill all at once the numerous requirements
zymes must fulfill the following requirements. mentioned above which, in a sense, turn out to be mutu
It has been pointed out that enzymes, particularly 45 ally incompatible requirements.
proteases (proteolytic enzyme), may cause allergic reac Various methods have been heretofore proposed as
tions in some workers and users handling them when means for the granulation of enzyme powders. Substan
the dust of the enzymes comes in contact with the eyes, tially all of these methods, however, contemplate using
nose, and skin, for example. Therefore, as much as pos water or an aqueous solution of a binder substance as
sible, it is necessary to prevent generation of dust during 50 the binder for the granules to be produced. Industrial
storage, transport, uses etc. grade enzymes, particularly those various enzymes
Mechanical strength and dust emission are not neces which are obtained by the culture of microorganisms,
sarily directly related. For example, some granules are generally contain impurities to a certain extent. These
so rigid as to offer fair resistance to disintegration and impurities manifest strong viscosity in the presence of
yet emit a fine dust and other granules are highly disin 55 water. When water is added to the raw material being
tegrable into minute particles and yet are not reduced granulated, therefore, it manifests its function as a
into a fine powder. Generally, the so-called elutriation binder. Since the binding force (binder property) of
method is used in the determination of the dust-emitting these impurities is variable with their composition, it is
property of granulated enzymes. It is held that granu difficult to attain effective granulation of the enzyme
lated enzymes are desirable when the amount of dust 60 powder under a fixed set of conditions, making it neces
emitted thereby as determined by this method is not sary to study the conditions for the granulation for each
more than 150 GU/60 g (Ton den Ouden, Tenside De production lot of the enzyme powder. When the work
tergents, 14(1977) 4, P209-210). of granulation is to be carried out in an automated oper
In virtually all cases, the granulated enzymes are put ation, therefore, quality control of the product of this
to use as dissolved in hot water or cold water. Particu 65 operation is difficult to obtain because the granulated
larly, in the case of granulated enzymes intended for use enzyme acquires dispersed properties. A still more in
in detergents which form a main application for the portant problem arises from the fact that when an en
industrial grade enzymes, from the point of the overall zyme powder is granulated in the presence of water, the
 3
4,940,665
4.
produced granules must be dried as by heating for ex enzymatic properties by such additives as a binder are
pulsion of the water inevitably incorporated therein. equally important considerations besides the problem of
Most enzymes be nature are relatively unstable and are loss of activity during the course of granulation. Need
liable to be inactivated in the presence of water. Thus, less to say, economy constitutes another equally impor
the presence of water itself can pose a problem. The tant consideration. The methods heretofore known to
subsequent exposure of the produced granules to the the art indeed possess some superior properties and
heat applied thereto for the purpose of drying aggra exhibit improved qualities to some extent as described
vates the inactivation of an enzyme which inherently is above. None of the conventional methods, however,
rather unstable with respect to heat. Thus, the enzy can fulfill all the aforementioned considerations at once.
matic activity is inevitably lost more or less during the 10 All of them have some fault or other of their own.
course of the granulation.
Methods have been proposed for granulating enzyme DISCLOSURE OF INVENTION
powders in a non-aqueous medium using a waxy sub An object of this invention is to provide a method for
stance as a binder without the presence of water. The the granulation of a raw enzyme powder, characterized
methods heretofore known to the art have a disadvan 15 by the fact that, in the granulation of the enzyme pow
tage that they require use of a third substance such as a der alone or of a powder consisting of the enzyme and
core substance or fibrous substance during the work of such additives as extender, stabilizer, and coloring agent
granulation and necessitate provision of a complicated (hereinafter referred to as "raw enzyme powder"),
apparatus. spherical particles having a particle size in a desired
The method of Japanese Patent Pulbication SHO 20 range can be produced in a high yield without entailing
46(1971)-4259, for example, effects the granulation of an any mechanical trouble and with the inactivation during
enzyme powder by tumbling the raw material while the granulation repressed to the fullest possible extent
using a viscous waxy substance such as a nonionic sur and the produced granules possess sufficient strength,
factant. Since this method requires to use a core sub excel in storage stability, produce almost no dust, and
stance, it produces granules with an insufficient enzyme 25 dissolve quickly in water preparatory to actual use.
content and further suffers from poor productivity. The inventors continued a diligent study in search of
Japanese Patent Publication SHO 52-47033 discloses a method for the granulation of an enzyme powder,
a method which effects the granulation of an enzyme by which is capable of attaining the object described
preparing a liquid containing the enzyme and a wax as above. As a result, they have found that the granulation
a binder, dispersing this liquid with centrifugal force, 30 of an enzyme powder effected by agitating the enzyme
and cooling the dispersed drops of the liquid. This powder in a non-aqueous system using a specific wax in
method does not permit a desired increase in the en an amount falling within a limited range enables uni
zyme concentration in the produced granules because it form and substantially spherical particles to be pro
requires use of the wax in an amount of at least 50% by duced quickly in a high yield without either requiring
weight based on the total amount of the materials for 35 addition of a fibrous substance or entailing deposition of
the granulation. It suffers from poor economy because an irremovable layer on the inner wall of the apparatus
the apparatus used therefor is voluminous and compli during the course of granulation and that the produced
cated. granules possess satisfactory strength, excel in storage
Japanese Patent Publication SHO 58(1983)-26315 stability, produce almost no dust, and dissolve quickly
discloses a method for the granulation of an enzyme, in water preparatory to actual use. This invention has
which requires to use cellulosic fibers in an amount in been perfected as the result.
the range of 2 to 40% by weight and a waxy substance To be specific, the present invention is directed to a
and/or water as a granulating agent in an amount in the method for the granulation of a raw enzyme powder by
range of 50 to 70% by weight. This publicatgion dis the agitating of the raw enzyme powder admixed with
closes the granulation of alkalase by the use of a water 45 a wax which method comprises adding to the raw en
insoluble ethoxy aliphatic alcohol, as a working exam zyme powder in a substantially dry state at least one
ple using a waxy substance as a sole granulating agent. member in the amount of 10-35 wt % selected as a wax
For this method, use of cellulosic fibers having an aver from the group consisting of polyethylene glycol and
age length in the range of 50 to 160 and an average polyoxyethylene-polyoxypropylene block polymer
width in the range of 20 to 30 is an essential require 50 having melting points in the range of 40' to 100' C. and
ment. The addition of these cellulosic fibers is claimed agitating and granulating the product of the addition at
to preclude deposition of an irremovable layer on the a temperature not lower than the melting point of the
inner wall of the granulating machine and facilitate the added wax.
control of the granulation. From the practical point of BEST MODE FOR CARRYING OUT THE IN
view, however, this method has a disadvantage in that 55 VENTION
the presence of such fibers requires the waxy substance Now, the method of the present invention will be
to be used in a relatively large amount, elongates the described more specifically below.
time to be spent for the granulation, and aggravates the The enzyme to be granulated by the method of the
surface irregularity of produced granules and conse present invention is not specifically limited. It can be
quently enhances the generation of dust due to friction 60 any of the enzymes which are generally used in medi
of granules. cines, foodstuffs, textiles, leather, detergents, and other
In the granulation of an enzyme powder, efficiency of industrial applications. The method for the granulation
the work of granulation, shape and flowability of the contemplated by this invention optimally suits enzymes
produced granules, uniformity in the particle size, to be used in detergents. The optimum enzymes for the
shape, and constituent makeup of the produced gran 65 purpose of this invention are represented by proteases,
ules, generation of dust, rigidity, storage stability, solu lipases, amylases, cellulases, and pectinases. One mem
bility of the granules in water preparatory to actual use, ber or a combination of two or more members selected
and avoidance of the adverse effects exerted on the from among these optimum enzymes can be used.
 4,940,665
5 6
The raw enzyme powder may solely comprise an a molecular weight of less than 3,000, do not exhibit
enzyme powder. Otherwise, it may comprise an addi good pelletization yields even when granulatable, and
tive such as an extender or a filler optionally incorpo the granules are deficient in storage stability. If the
rated as a diluent for the purpose of keeping the specific molecular weight exceeds 10,000, the molten material
activity of the produced granules at a presecribed level. prepared for the granulation possesses too high viscos
When the raw enzyme powder contains the afore ity to be efficiently granulated and, because of the ne
mentioned additive, the enzyme content in the raw cessity for keeping the temperature at a level high
enzyme powder is required to be at least 5% for the enough to lower the viscosity, the molten material en
purpose of enabling the enzyme to be homogeneously tails inactivation of the enzyme as a drawback during
contained in the produced granules and allowing the O the course of granulation and the granules are produced
produced granules to retain the enzymatic activity suffi in a low yield and the produced granules have an infe
ciently, though this enzyme content is not invariably rior shape. To be used in this invention desirably from
fixed because of the influence of the potency of the the practical point of view, therefore, the PEG is re
enzyme itself. Concrete examples of the extender or quired to possess a melting point in the range of 40 to
filler are as follows. 15 100 C. and an average molecular weight in the range of
Sulfates: Sodium sulfate, potassium sulfate, calcium 3,000 to 10,000. Preferably, the melting point is in the
sulfate, magnesium sulfate, zinc sulfate, ferrous sulfate, range of 45 to 70° C. and the average molecular weight
sodium thiosulfate, and aluminum sulfate. in the range of 4,000 to 8,000.
Hydrochlorides and bromides: Sodium chloride, po For substantially the same reason as given above, the
tassium chloride, calcium chloride, magnesium chlo 20 polyoxyethylene-polyoxypropylene block polymer is
ride, and potassium bromide. desired to have an average molecular weight in the
Carbonates: Sodium carbonte, sodium hydrogen car range of 7,000 to 24,000, preferably 8,000 to 15,000. If
bonate, potassium carbonate, calcium carbonate, and the melting point is lower, although the molten material
magnesium carbonate. can be granulated, the granules are produced in a yield
Phosphates: Sodium phosphate, sodium hydrogen 25
hardly called satisfactory and the produced granules are
phosphate, sodium dihydrogen phosphate, potassium deficient in storage stability. If the melting point is
phosphate, potassium hydrogen phosphate, potassium higher, the molten material is granulated with poor
dihydrogen phosphate, and sodium pyrophosphate. efficiency, entails inactivation of the enzyme as a draw
Silicates: Sodium silicate, sodium metasilicate, potas back during the course of granulation, and produces
sium silicate, and calcium silicate. 30
granules in a low yield, and the produced granules have
Boric acid (borates): Borax, potassium borate, and a poor shape.
boric acid.
The extender or filler is desired to have a particle size One member or a combination of two or more mem
of not more than 100 um, preferably not more than 20 bers selected from the group consisting of polyethylene
pum. One member or a combination of two or more 35 glycol and polyoxyethylene-polyoxypropylene block
members selected from the group of extenders and fill polymers can be effectively used herein. When two or
ers cited above can be used. more members are used in combination, the mixture is
Further, any of the coloring agents and stabilizing required to possess a melting point falling in the range
agents which are known in the fields of granulation and mentioned above.
enzyme preparation can be suitably used. Suitably, the amount of the waxy substance (hereinaf.
In the method of the present invention, one key to ter referred to simply as "waxy') to be incorporated in
successful granulation of an enzyme powder is the se the raw enzyme powder (the total amount of the materi
lection of a binder to be used in the raw enzyme pow als combined for the purpose of granulation) is in the
der. For perfect fulfillment of the requirement men range of 10 to 35% by weight, based on the amount of
tioned above, use of a polyethylene glycol (polyoxyeth 45 the raw enzyme powder. If this amount does not reach
ylene) or a polyoxyethylene-polyoxy propylene block 10% by weight, the granulation does not produce de
polymer having a melting point in the range of 40 to sired granules but only gives rise to minute particles. If
100 C. is indispensable. Various substances are con the amount exceeds 35% by weight, the granulation
ceivable for use in an operation which contemplates proceeds suddenly in a short span of time and entails a
using a simply waxy substance as a binder and effecting 50 disadvantage that the control of the granulation is not
the granulation in a non-aqueous system. The binders easily obtained and the granules are produced in an
other than those specified above as usable in this inven extremely low yield.
tion invariably have merits and demerits of their own During the granulation, the wax must be in a molten
and fail to meet the purpose of this invention. For exam state. Thus, the granulating machine is heated in ad
ple, such waxy substances as coconut oil monoethanol 55 vance to a temperature of not lower than the melting
amide, polyoxyethylene fatty acid ester, polyoxye point of the wax to be used. While the granulation is in
thylenealkyl ether, polyoxyethylenealkylphenol ether, progress, however, the temperature of the granulation
and glycerin fatty acid ester cannot be used because the machine is desired to be kept down to the lowest possi
granules obtained from the raw enzyme powders using ble level because this temperature, if elevated to an
them are invariably deficient in solubility in water. 60 unduly high level, can become a cause for inactivation
Then, such waxy substances as sorbitan fatty acid ester of the enzyme. Generally, the temperature of the granu
and sugar wax, mainly because of their high degrees of lating machine must be kept at a level higher by a mar
hygroscopicity, has a disadvantage that the produced gin in the range of 5 to 20 C. than the melting point of
granules are deficient in storage stability. the wax to be used. Desirably this margin is between 7
Even among polyethylene glycols (PEG) having a 65 C. and 12 C., preferably in the neighborhood of 10° C.
melting point in the vicinity of the aforementioned, The wax which is admixed with the other compo
those having an average molecular weight falling out nents for granulation is amply agitated therein for thor
side the range of 3,000 to 10,000, for example those with ough mixing with the other components. During this
 7
4,940,665
8
agitating, desired granulation is attained at the pre softening point of the coated granules exude to the
scribed temperature. surface and the finished product finally obtained does
The wax can be added in a molten state or in a solid not withstand actual use.
state to the other components for the granulation. In Although the amount of the binder to be used for the
either case, the outcome of the granulation is the same. aforementioned overcoating is suitably variable with
The procedure which comprises preparatorily heating the condition of surface finish of the granules, the com
the wax and subsequently adding the wax now in a position of the surface-covering agent, and the amount
molten state by spraying onto the other components for of this surface-covering agent to be used, it generally
granulation shortens the time required for the granula falls in the range of 6 to 8% by weight, based on the
tion and consequently improves the productivity. 10 weight of the produced granules.
For the granulation contemplated by this invention, it A white coloring agent to be used herein is desired to
is an essential requirement that the granulation should be a sparingly hygroscopic inorganic substance such as
be effected by agitating the molten material. None of titanium oxide, talc, and/or zeolite comminuted to a
the conventional methods available for granulation, can particle size in the range of 1 to 100 um. Although the
attain the desired granulation fulfilling the requirements 15 amount of the coloring agent to be used in suitably
set by this invention. variable, it generally falls in the range of 13 to 17% by
To be specific, the granulation of this invention is weight, based on the amount of the produced granules.
carried out by placing the raw enzyme powder (enzyme Other covering substances such as excipient, deodor
powder alone or combined with the other additives) ant, and antistatic agent may be added when needed.
and the wax powder in the granulating machine kept in 20 Where the property of dust emission must be re
advance at a temperature high enough to melt the wax pressed further or the storage stability must be in
used as the binder and agitating the contents of the proved further, the coated granules may be re-over
granulating machine. coated with the aforementioned binder.
As regards the water content of the raw enzyme Now, the method of the present invention will be
powder for granulation, if the water content is unduly 25 more specifically described below with reference to
high, the excess of water can be a cause for inactivation typical working examples. Needless to say, these exam
of the enzyme during the course of granulation. Practi ples are meant purely for illustration and not for limiting
cally, it must be kept not higher than 10% by weight, the present invention in any sense.
preferably not higher than 8% by weight. The tests for the determination of enzymatic activity
After the granulation is completed, the granules con 30 and for the evaluation of the results of granulation were
sequently produced are cooled, recovered from the carried out in accordance with the methods indicated
granulating machine, when necessary, withe aid of a below.
small amount of a release agent, and then overcoated to (1) Determination of activity of protease: The
give rise to a finished product. method disclosed in Japanese Patent Publication SHO
The overcoating of the produced granules is carried 35 60(1985)-55118.
out by keeping the granules tumbled in the agitating (2) Determination of activity of amylase: The
granulating machine or some other rotary machine, "method for testing industrial grade amylase for lique
adding a binder, namely a wax, in a molten state to the fying power" defined by JIS K 7001-1972.
granules in motion and, at the same time or subse (3) Determination of activity of cellulase: The
quently, adding thereto other surface-covering sub method described in "Handbook on Use of Enzymes',
stances such as, for example, a coloring agent, stabiliz page 298, compiled under supervision of Michio Kozaki
ing agent, excipient, deodorant, and antistatic agent. (published by Chijin Shokan).
The aforementioned binder may be added in a commi (4) Determination of activity of lipase: The method
nuted solid state and then heated and melted while
being rolled in conjunction with the granules in the 45 book. on page 230 of the aforementioned Hand
described
rotary machine. (5) Detemination of activity of pectinase: The method
The was to be used for the overcoating must be se described on page 338 of the aforementioned Hand
lected strictly for the same reason as already given with book.
respect to the binder which is used for the granulation. (6) Ratio of inactivation during granulation: The
As the binder to be used for overcoating the granules SO radio expressed bu the formula,
of this invention, one polyethylene glycol or a mixture
of two or more such polyethylene glycols and/or a
polyoxyethylene-polyoxypropylene block polymer or a
mixture of two or more such block polymers, each
possessing a melting point of not lower than 35 C. and 55 using the value (A) of the activity of a given raw en
not higher than the softening point of the binder which zyme powder fed and the value (B) of the activity of the
is used for the granulation, is used. One member or a enzyme in the recovered granules, both determined by
combination of two or more members selected from the the relevant method described above.
binders enumerated above can be used. (7) Bulk density: Method in compliance with JIS K
With any of the binders other than those cited above, 3362.
the coating desired to be attained by this invention (8) Whiteness: The method proposed by Hunter for
cannot be obtained for the same reason as already de the determination of whiteness.
scribed with respect to the binder for the granulation. (9) Solubility in water: The ratio expressed by the
If a binder is similar in kind to the binder used for the formula,
aforementioned overcoating but has a melting point 65
lower than 35 C., then the coated granules produced Value of activity of enzyme in solution
by the procedure of this invention is deficient in storage Value of activity of enzyme of sample x 100 (%),
stability. If a binder has a melting point exceeding the
 4,940,665
10
using the value of activity of a given enzyme powder for five minutes. After this mixing, the contents of the
and the value of activity of enzyme in a solution ob machine were discharged.
tained by agitating 1 g of the sample for 3 minutes in 100 The overcoated granules were recovered in an
g of water at 10 C., both determined by the relevant amount of 2305 g (100%), indicating that the ratio of
method described above. inactivation was 0%. They had a bulk density of 1.09
(10) Storage stability: The stability expressed by the and a Hunter's whiteness of 80%, a value representing
residual ratio of activity in percentage points (%), found ample whiteness (the whiteness held to be necessary
by the ratio of the values of activity of a given enzyme from the practical point of view is not less than 75%).
granule before and after two weeks standing under the O
By observation under an optical microscope, they were
conditions of 40 C. and 80% humidity, both deter found to be spheres having a smooth surface. The re
mined by the relevant method described above. The sults of test for static and impact strength indicate that
sample after the standing was further examined visually the overcoated granules possessed ample strength. In
as to change of shape and occurrence of coalescence of the test for solubility in water, they showed a solubility
granules. ratio of 99%, a value indicating highly satisfactory solu
(11) Property of dust emission: The method (elutria 15 bility in water. In the test for stability over two weeks'
tion) described in Ton den Ouden: Tenside Detergents, storage, the residual ratio of activity was found to be
14 (1977) 4, P209-210. 61%, a value representing ample stability. The property
EXAMPLE 1. of dust emission determined by the elutriation method
was 60 GU/60 g, a value amply satisfying the standard
In a jacketed agitating and granulating machine, 340 20 (150 GU/60 g) required to be met for the sake of safety
g of protease powder (API-21, 80nkatal/mg), 1,230 g of of handling.
anhydrous sodium sulfate, 80 g of titanium oxide, and As described above, the product obtained in the pres
350 g of polyethylene glycol (a product marketed under ent example met all the requirements expected to be
Code "PEG-5000', having an average molecular 25 possessed by a granulated enzyme, indicating that this
weight of 5,000 and a melting point of about 85 C.) product had highly satisfactory qualities.
were mixed by agitating for 2 minutes, with the main EXAMPLE 2
shaft of the machine operated at a rate of 250 rpm and
the chopper thereof at a rate of 3,000 rpm. Under the The aforementioned agitating and granulating ma
same agitating conditions as described above, the result chine was filled with 340 g of protease powder (API-21,
ing mixture was granulated as continuously heated by 30 80 nkat/mg), 25g of raw amylase powder (a product of
passing hot water at 70° C. through the jacket. Yamato Kasei, 220000 LJ/g, marketed under the trade
The granulation was completed in a total span of 31 mark of "Crystase M20'), 1155 g of anhydrous sodium
minutes. Then, 15 g of finely comminuted silica was sulfate, 80 g of titanium oxide, and 400 g of the same
added to the granules and agitated therewith and the 35 polyethylene glycol as used in Example 1, and granula
resultant mixture was discharged, cooled by fluidizying tion was performed by the same procedure as in Exam
and then recovered. Thus, 1,995 g of mixture was re ple 1. The whole procedure was completed in a span of
covered, indicating a recovery ratio of 99.0%. Substan 30 minutes.
tially no deposition of any material on the inner wall of The amount of produced granules recovered was
the granulating machine was recognized. 40 2003 g, representing a recovery ratio of 99.4%. Substan
The particle size distribution of the granules consisted tially no deposition of any material on the inner wall of
of 3.9% of 14-mesh on, 95% of 14-42 mesh, and 1.1% of the machine was observed.
42-mesh pass. The yield (yield of granulation) of the The particle size distribution consisted of 3.1% of
acceptable granules (14-42 mesh) was as high as 94.1%. 14-mesh on, 94.2% of 14-42 mesh, and 2.7% of 42-mesh
By observation under an optical microscope, these 45 pass. The yield of granulation was 93.6%. By observa
granules were found mostly to be spheres having a tion under an optical microscope, the granules were
smooth surface. The results of the test of these granules found substantially to be spheres having a smooth sur
for static and impact strengths indicate that they pos face. They showed ample static and impact strength.
sessed ample strength. The ratio of inactivation during The ratios of inactivation of protease and amylase
granulation was found to be 1.3%, indicating that sub 50 during granulation were 1.3% and 1.6% respectively,
stantially no inactivation occurred during the operation indicating that substantially no discernible inactivation
of granulation. was caused by the operation of granulation.
The acceptable granules obtained be sifting were The acceptable granules, 1,880 g, obtained by sifting
overcoated as follows. The granules, 1.890 g, were were overcoated by following the procedure of Exam
placed again in the aforementioned agitating and granu 55 ple 1, except that the amount of polyethylene glycol to
lating machine and heated to 45 C. Then, to the heated be used was changed to 113 g.
granules, polyethylene glycol (a product marketed The product of this overcoating had a bulk density of
under Code "PEG 1540', having an average molecular 1.08 and a Hunter's whiteness of 82%. By observation
weight of 1,500 and a melting point of about 43 C.) was under an optical microscope, the granules were found
added as a melt in an amount of (132 g) corresponding to be spheres having a smooth surface. They showed a
to 7% by weight, based on the amount of the granules. solubility ratio of 99%, indicating that they possessed
The contents of the machine were mixed by agitating highly satisfactory solubility in water. In the test for
for two minutes with the main shaft of the machine storage stability, the residual ratio of activity was 65%,
operted at a rate of 150 rpm (the chopper not used). a value representing ample storage stability. The prop
Thereafter, the granules and titanium oxide added 65 erty of dust emission determined by the elutriation
thereto in an amount (283 g) corresponding to 15% by method was 40 GU/60 g. Thus, the product obtained in
weight, based on the amount of the granules, were this example possessed highly satisfactory qualities for a
mixed under the aforementioned agitating conditions granulated enzyme.
 11
4,940,665
12
EXAMPLE 3 protease and amylase during granulation were 1.9% and
2.0% respectively, indicating that substantially no inac
Granules were produced by following the procedure tivation was caused by the operation of granulation.
of Example 1, except that polyethylene glycolpolypro The acceptable granules, 1,870 g, obtained by sifting
pylene glycol block polymer (a product of Dai-ichi 5 was overcoated by following the procedure of Example
Kogyo Seiyaku Co., Ltd., having a melting point of 1, except that 150 g of polyethylene glycol (a product
about 60' C. and marketed under trademark designation having a molecular weight of 1,900-2,000) marketed
of "Epan 785") was used in place of polyethylene gly under Code of PEG-2000 was used in place of the poly
col. The whole procedure was completed in a span of 32 ethylene glycol used in Example 1.
minutes. 10 The overcoated product had a bulk density of 1.08
The amount of granules recovered was 1,996 g, rep and a Hunter's whiteness of 81%. By observation under
resenting a recovery ratio of 99.1%. Substantially no an optical microscope, these granules were found to be
deposition of any material on the inner wall of the ma spheres having a smooth surface. The solubility ratio
chine was observed. The particle size distribution con was 98%, a value representing highly satisfactory solu
sisted of 4.5% of 14-mesh on, 93.7% of 14-42 mesh, and 15 bility in water. In the test for storage stability, the gran
1.8% of 42-mesh pass. The yield of granulation was ules showed a ratio of residual activity of 62%, a value
92.8%. By observation under an optical microscope, the representing ample storage stability. The property of
granules were found substantially to be spheres having dust emission determined by the elutriation method was
a smooth surface. They possessed ample static and in 63 GU/60 g.
pact strength. The ratio of inactivation during granula 20
tion was 1.8%, a value indicating that substantially no EXAMPLES 5, 67, and 8
discernible inactivation was caused by the operation of Granules were produced by following the procedure
granulation. of Example 1, except that other species of enzymes
The acceptable granules, 1,860 g, obtained by sifting were used in place of the protease used in Example 1,
was overcoated by following the procedure of Example 25 and the kind and amount of a binder and the kind and
1.
amount of a coating material were varied from those of
The overcoated product had a bulk density of 1.09 Example 1. The conditions of granulation and the re
and a Hunter's whiteness of 80%. By observation under sults are collectively shown in Table 1.
an optical microscope, these granules were found to be It is noted from this table that the times required for
spheres having a smooth surface. The solubility ratio 30 the granulation were invariably short and the granules
was 98%, a value representing highly satisfactory solu were obtained in high recovery ratios. The acceptable
bility in water. In the test for storage stability, the ratio granules obtained in high recovery ratios represent
of residual activity was 61%, indicating that the gran highly satisfactory yields of granulation. The ratios of
ules possessed ample storage stability. The property of inactivation during granulation were very low.
dust emission determined by the elutriation method was 35 By observation under an optical microscope, the
55 GU/60 g. granules obtained in the different runs were invariably
EXAMPLE 4 found substantially to be spheres having a smooth sur
face. They also showed ample static and impact
Granules were produced by following the procedure strength.
of Example 2, except that polyethylene glycolpolypro The finished products obtained by overcoating the
pylene glycol block polymer (Epan 785) was used in acceptable granules with the aforementioned coating
place of polyethylene glycol. The whole procedure was material were tested for various properties. The results
completed in a span 30 minutes. are shown collectively in Table 2.
The amount of granules recovered was 2,001 g, rep The values of Hunter's whiteness the coated products
resenting a recovery ratio of 99.3%. Substantially no 45 showed were invariably equal to or in excess of 80%
deposition of any material on the inner wall of the ma and the solubility ratios they showed were invariably
chine was recognized. The particle size distribution equal to or in excess of 97%, a value representing highly
consisted of 4.2% of 14-mesh on, 93.8% of 14-42 mesh, satisfactory solubility in water.
and 2.0% of 42-mesh pass. The yield of granulation was In the test for storage stability, while the product of
93.1%. By observation under an optical microscope, the 50 Example 7 showed a relatively low value of 58%, the
produced granules were found substantially to be products of the other examples showed high values
spheres having a smooth surface. They showed ample exceeding 60%, a level representing satisfactory stabil
static and impact strength. The ratios of inactivation of ity.
TABLE 1.
EXAMPLES EXAMPLE 6 EXAMPLE 7 EXAMPLE 8
Binder PEG-4000 PEG-6000 PEG-4000 PEG-6000
(molecular weight (molecular weight (molecular weight (molecular weight
3000-3700) 7800-9000) 3000-3700) 7800-9000)
Weight (%) 12.0 2.5 30.0 S.0
Melting point (C.) 43.5-5.5 60-63 43.5-57.5 60-63
Coating material PEG-540 PEG-2000 PEG-1500 PEG-540
(moleuclar weight (nolecular weight (molecular weight (molecular weight
1300-1600) 1900-2100) 500-600) 1300-1600)
Weight (%) 8.0 7.0 7.0 6.0
Melting point (C.) 43-46 50-53 38-4 43-46
Time required for completion of 30 32 31 33
granulation (min.)
Amount recovered (g) 1994 1997 2001 1994
Recovery ratio (%) 99.0 99.1 99.3 99.0
Deposition of material on inner wall Ione noe none role
 4,940,665
13 14
TABLE 1-continued
EXAMPLE 5 EXAMPLE 6 EXAMPLE 7 EXAMPLE 8
Particle size distribution (%
Above 14 mesh 3.7 4. 3.6 4.2
Between 14 and 42 mesh 94.0 94. 93.6 94.2
Below 42 mesh 2.3 1.8 2.8 1.6
Yield of granulation 93.0 93.3 92.9 93.2
Ratio of inactivation during 1.8 2.0 1.5 1.7
granulation

TABLE 2
EXAMPLE5 EXAMPLE 6 EXAMPLE 7 EXAMPLE 8
Bulk density 09 1.10 1.07 1.08
Hunter's whiteness 80.0 81.0 8.0 80.0
Solubility in water 98.0 98.0 97.0 99.0
Storage stability 6 60 58 61
Property of dust emission 55 60 80 45
(GU/60 g)

COMPARATIVE EXPERIMENT 2
COMPARATIVE EXPERIMENT 1 Granules were produced by following the procedure
In the aforementioned agitating and granulating ma of Comparative Experiment 1, except that the addition
chine, 360 g of protease powder (API-21, 80 nka 25 of cellulose was omitted and 1,110 g of anhydrous so
tal/mg), 910 g of anhydrous sodium sulfate, 60 g of dium sulfate and 160 g of water as a binder were added
titanium oxide, 200 g of cellulose (a product of Sanyo instead.
Kokusaku Pulp Co., Ltd. marketed under the trademark The amount of granules recovered was 1,865 g, rep
"KC Flock W-100"), and 500 g of talc were mixed by resenting a recovery ratio of 79%. There was observed
agitating for three minutes. While the contents of the 30 heavy deposition of material on the inner wall of the
machine were kept agitated under the same conditions granulating machine. The particle size distribution of
as those of Example 1, except that the temperature was the produced granules consisted of 66.6% of 14-mesh
changed to 35 C., 300 g of water as a binder was added on, 30.7% of 14-42 mesh, and 2.7% of 42-mesh pass.
by a two-flow spray to the agitated contents over a Granules rejectable because of excessive particle size
period of 10 minutes. To the contents held under obser 35 accounted for the major part of the produced granules.
vation for growth of particles, water was gradually The yield of acceptable granules was 24.3%. By obser
added as a binder. The whole procedure of granulation vation under an optical microscope, these produced
was completed in a span of 39 minutes. The total granules were found to be uneven in shape, comprising
amount of water thus added was 360 g. The produced spheres and ellipsoids having an irregular surface.
granules were discharged, dried by being fluidized at an These results indicate that the present procedure
inlet gas temperature of 80 C. for 15 minutes, and then using water as a binder and not using cellulose entailed
recovered. The amount of granules thus recovered was many disadvantages such as heavy deposition of mate
2,195 g (recovery ratio of 93%). There was observed rial on the inner wall of the machine, unduly large diam
heavy deposition of material on the inner wall of the eters of produced granules, and an extremely low ratio
machine, as compared with the operation of Example 1. 45 of granulation.
The particle size distribution of the produced gran COMPARATIVE EXPERIMENT 3
ules consisted of 15.0% of 14-mesh on, 80.1% of 14-42
mesh, and 4.9% of 42-mesh pass and the yield of granu Granules were produced by following the procedure
lation was 74.5%. These results are inferior to those of of Example 1, except that 370 g of protease powder
the granules of Example 1. By observation under an 50 (API-21, 80 nkatal/mg), 860 g of anhydrous sodium
optical microscope, the produced granules were rela sulfate, 60 g of titanium oxide, 200 g of cellulose (a
tively uneven in shape, comprising spheres and ellip product of Sanyo-Kokusaku Pulp Co., Ltd. marketed
soids both having an irregular surface. The ratio of under the trademark “KC Flock W-100'), and 510 g of
inactivation during granulation was 3.7%, a value polyethylene glycol (PEG-5000) were used instead.
larger than that of the granules of Example 1. 55 The whole procedure of granulation required 65 min
The acceptable granules, 1,000 g, obtained by sifting utes. The produced granules were discharged and re
were overcoated by following the procedure of Exam covered in the same way as in Example 1. The amount
ple 1. of granules recovered was 1,830 g, representing a re
The overcoated product had a bulk density of 1.04 covery ratio of 91%. The deposition of material to the
and a Hunter's whiteness of 79%. By observation under 60 inner wall of the machine was slightly heavier than in
an optical microscope, the granules are found to be the operation of Example 1.
spheres having a smooth surface. The solubility ratio The particle size distribution of the produced gran
was 90%, a value smaller than that of the granules of ules consisted of 6.9% of 14-mesh on, 83.6% of 14-42
Example 1. In the test for storage stability, the coated mesh, and 9.5% of 42-mesh pass. The yield of granula
product showed a ratio of residual activity of 60%. The 65 tion was 75.9%, a value appreciably inferior to the
property of dust emission determined by the elutriation value of the granules of Example 1. By observation
method was 140 GU/60 g, a value larger than that of under an optical microscope, the granules were found
the product of Example 1. to be relatively uneven in shape, comprising spheres and
 15
4,940,665
16
ellipsoids having an irregular surface. The results of the The amount of granules recovered was 1,993 g, rep
test for static and impact strength indicate that the gran resenting a recovery ratio of 98.9%. Substantially no
ules possessed ample strength. The ratio of inactivation deposition of any material on the inner wall of the gran
during granulation was 1.5%, a value representing sub ulating machine was recognized. The particle size dis
stantial absence of inactivation by the operation of gran tribution consisted of 5.1% of 14-mesh on, 84.0% of
ulation. 14-42 mesh, and 10.9% of 42-mesh pass. The yield of
The acceptable granules, 1,450g, obtained by sifting the acceptable granules was 83.1%, a value about 10%
were coated by following the procedure of Example 1 lower than that of the granules in Example 1.
to give rise to a finished product. By observation under an optical microscope, the
The overcoated product possessed a bulk density of 10 produced granules were found substantially to be
1.05 and a Hunter's whiteness of 81%. By observation spheres having a smooth surface. They showed ample
under an optical microscope, the granules were found static and impact strength. The ratio of inactivation
to comprise spheres and ellipsoids having a smooth during granulation was 1.8%, indicating substantial
surface. The solubility ratio was 98%, a value represent absence of inactivation by the operation of granulation.
ing highly satisfactory solubility in water. In the test for 15 The acceptable granules, 1,660 g, obtained by sifting
storage stability, the ratio of residual activity was 60%, were overcoated by following the procedure of Exam
indicating ample stability. The property of dust emis ple 1 with PEG-1000 (molecular weight 1,000 and melt
sion was 136 GU/60 g, a value inferior to that of the ing point 40' C.) used as a coating wax, at a temperature
granules of Example i. of 40' C.
COMPARATIVE EXPERIMENT 4 20 The overcoated product showed signs of exudation
of a coloring component in the raw enzyme powder to
Granules were produced by following the procedure the surface granules. The coated granules failed to as
of Example 1, except that 360 g of protease powder, sume a white color (Hunter's whiteness of 69%) suffi
1,160 g of anhydrous sodium sulfate, 80 g of titanium cient for the intended use of the product. In the test for
oxide, and 400 g of coconut oil monoethanol amide 25 storage stability, the produced granules underwent par
were charged into and granulated by the aforemen tial coalescence. The ratio of residual activity was
tioned agitating and granulating machine and the tem 27.0%, a value representing appreciably heavy inactiva
perature of the hot water was changed to 77' C. The tion.
whole procedure of granulation required 53 minutes.
The amount of granules recovered was 1,955 g, rep 30 COMPARATIVE EXPERIMENT 6
resenting a recovery ratio of 97.0%. The deposition of Granules were produced by following the procedure
material on the inner wall of the machine was slight. of Example 1, except that polyethylene glycol (a prod
The particle size distribution consisted of 16.2% of uct having a molecular weight of 2,000 and a melting
14-mesh on, 82.8% of 14-42 mesh, and 1.0% of 42-mesh point of about 49' C. and marketed under Code "PEG
pass. The yield of granulation was 80.3%. 35 2000') was used in place of the polyethylene glycol
The yield of granulation was low and not satisfactory (Code “PEG-5000").
as compared with that of the granules of Example 1. The amount of granules recovered was 1,992 g, rep
By observation under an optical microscope, the resenting a recovery ratio of 98.9%. Substantially no
produced granules were found to be spheres having a deposition of any material on the inner wall of the gran
smooth surface. They showed ample static strength. 40 ulating machine was observed. The particle size distri
The ratio of inactivation during granulation was 1.9%, bution of the produced granules consisted of 6.0% of
indicating substantial absence of inactivation by the 14-mesh on, 82.3% of 14-42 mesh, and 11.7% of 42
operation of granulation. mesh pass, indicating that the yield of granulation was
The acceptable granules, 1,000 g, obtained by sifting 81.4%. This value is about 10% lower than that of the
were overcoated by following the procedure of Exam 45 granules obtained in Example 1. By observation under
ple 1. an optical microscope, the produced granules were
The overcoated product possessed a bulk density of found substantially to be spheres having a smooth sur
1.09. By observation under an optical microscope, the face. They showed sufficient static and impact strength.
granules were found substantially to be spheres having The acceptable granules, 1,640 g, obtained by sifting
a smooth surface. In the test for storage stability, the 50 were overcoated by following the procedure of Com
ratio of residual activity was found to be 61%. The parative Experiment 1.
property of dust emission determined by the elutriation The overcoated product showed signs of exudation
method was 90 GU/60 g, representing a low level of of a coloring component in the raw enzyme powder to
dust emission from the practical point of view. The the surface of granules. The coated granules did not
solubility ratio was only 45%. 55 assume a white color (Hunter's whiteness 69%) suffi
The product obtained in this comparative experiment cient for the intended use of the product.
had a lower yield of granulation and a lower solubility In the test for storage stability, the produced granules
ratio than the product obtained in Example 1. Particu showed a ratio of residual activity of 58%.
larly in terms of solubility in water, the product was
unfit for actual use. COMPARATIVE EXPERIMENT 7
COMPARATIVE EXPERIMENT 5 Granules were produced by following the procedure
of Example 1, except that fructose (having a melting
Granules were produced by following the procedure point of 105 C.) was used in place of polyethylene
of Example 1, except that polyethylene glycolpolypro glycol and the temperature of heating was changed to
pylene glycol block polymer (a product of Dai-ichi 65 120' C.
Kogyo Seiyaku Co., Ltd. having a melting point of 35' The amount of granules recovered was 1,995 g, rep
C. and marketed under trademark designation of "Epan resenting a recovery ratio of 99.0%. Substantially no
465") was used in place of polyethylene glycol. deposition of any material on the inner wall of the gran
 4,940,665
17 18
ulating machine was observed. The particle size distri (1) Since it is a specific wax that manifests the binding
bution of the produced granules consisted of 20.2% of force required, the conditions of granulation are stable
14-mesh on, 71.1% of 14-42 mesh, and 8.7% of 42-mesh and need not be varied by the attributes of the raw
pass. The granules underwent coalescence to an extent enzyme powder to be used. Thus, the product of granu
of increasing the ratio of rejectable granules of 14-mesh 5 lation acquires properties with little variance.
on. The yield of the produced granules was notably (2) Since no water is added, the inactivation of en
lowered to 70.4%. The ratio of inactivation during zyme is very slight and the enzyme activity and the
granulation was 14.7%, indicating the occurrence of yield of granulation are high.
heavy inactivation by the operation of granulation. (3) Since the granulation can be carried out under
O substantially the same set of conditions even when the
COMPARATIVE EXPERIMENT 8 attributes of the raw material powder are varied, the
Granules were produced by following the procedure productivity of the granulation by the method of the
of Example 1, except that PEG-12000 (having a molec present invention is notably high.
ular weight of 12,000 and a melting point of about 63.0 15 (4) In the granulation in an aqueous system, when the
C.) was used in place of PEG-5000 and the temperature binder property originating in the raw enzyme powder
of heating was changed to 90' C. is manifested to an excessive extent, the deposition of
The amount of granules recovered was 1,994 g, rep material to the inner wall of the granulating machine
resenting a recovery ratio of 99.0%. Substantially no occurs heavily and the number of times of cleaning of
deposition of any material on the inner wall of the gran 20 the granulating machine is consequently high. By the
ulating machine was observed. The particle size distri method of the present invention, the deposition of mate
bution of the produced granules consisted of 21.1% of addition be
rial can substantially eliminated without requiring
of fibers.
14-mesh on, 73.5% of 14-42 mesh, and 5.4% of 42-mesh
pass. Because of the occurrence of coalescence of gran to (5) The amount of a wax to be used is small, the time
be spent for granulation is shortened to half, and the
ules, the ratio of rejectable granules of 14-mesh on was 25 yield of granulation is high as compared with the con
increased. The yield of granulation was 72.8%, repre ventional
senting a significant decline. The ratio of inactivation duced are granulation
uniform in
using fibers. The granules pro
shape and have a smooth surface.
during granulation was 15.1%, indicating heavy inacti Thus, they enjoy a good appearance and yield to the
vation by the operation of granulation. phenomenon of dust emission due to friction of granules
COMPARATIVE EXPERIMENT 9 30 to an extremely limited extent.
Granules were produced by following the procedure (6) The produced granules have low hygroscopicity,
of Example 1, except that 1,420 g of anhydrous sodium exhibit satisfactory storage stability, and excel in solu
sulfate and 160 g of PEG-5000 were used instead and bility in water. The granulated product, therefore, man
the time for granulation was increased to 120 minutes. ifests its effect as soon as it is put to use.
No acceptable granules could be produced.
35 (7) When two or more species of enzymes, such as
protease and amylase, are used in a mixed state, they do
As to the particle size distribution of the produced not interact within the produced granules while the
granules, all the granules passed a 42-mesh sieve. granules are kept in storage, unlike the granules pro
The same operation of granulation was repeated duced in an aqueous system. Thus, the granules have no
using PEG-species having different molecular weights 40 possibility of being inactivated during the storage.
of 3,000 to 10,000. No granules were obtained in any of The method of this invention for the granulation of an
the test runs. enzyme powder will find extensive utility in medicines,
COMPARATIVE EXPERIMENT 10 foods and drinks, textiles, leather, detergents and nu
merous other applications.
Granules were produced by following the procedure 45 We claim:
of Example 1, except that 820g of anhydrous sodium 1. A method for the granulation of a raw enzyme
sulfate and 760 g of PEG-5000 were used instead. powder, comprising the steps of:
Two minutes after the temperature of the raw en adding to a raw enzyme powder in a substantially dry
Zyme powder in the granulating machine had reached state at least one wax selected from the group con
59 C., the molten material suddenly formed granules 50 sisting of (1) polyethylene glycol having a melting
and this formation of granules could not easily be con point in the range of 40-100° C. and an average
trolled. molecular weight in the range of 3,000-10,000 and
The ratio of recovery was 90% and deposition of (2) polyoxyethylene-polyoxypropylene block co
material on the inner wall of the machine was observed. polymers having a melting point within the range
The particle size distribution consisted of 70.7% of 55 of 40-100 C. and an average molecular weight in
14-mesh on, 29.1% of 14-42 mesh, and 0.2% of 42-mesh the range of 7,000-24,000, in an amount in the
pass. Thus, the particle sizes were notably concentrated range of 10-35% by weight based on the amount of
on the 14-mesh on. said raw enzyme powder to obtain a mixture;
The operation mentioned above was repeated using agitating said mixture at a temperature 5'-20° C.
PEG-species having different molecular weights of 60 higher than the melting point of said at least one
3,000 to 10,000 and fixing the amounts of addition at wax to obtain a granular material;
38%. The granulation which proceeded could not be cooling said granulated material; and
controlled in any of the test runs. adding to said cooled granular material at least one
molten binder selected from the group consisting
INDUSTRIAL APPLICABILITY 65 of (i) polyethylene glycol having a melting point of
By the method for granulation of enzyme powder not less than 35 C. and not higher than the soften
according to this invention, the following effects can be ing point of said wax and (ii) polyoxyethylene
obtained. polyoxypropylene block copolymer having a melt
 19
4,940,665
20
ing point of not less than 35 C. and not higher than C. and an average molecular weight ranging from
said softening point of said wax, while tumbling 4,000-8,000.
said cooled granular material, thereby overcoating 4. The method of claim 1, wherein said polyoxyethy
the granules of said material with said at least one lene-polyoxypropylene block copolymer has an aver
binder. 5
2. The method of claim 1, wherein the amount of said age molecular weight ranging from 8,000-15,000.
at least one binder added to the cooled granules is 6-8% 5. The method of claim 1, wherein the temperature at
by weight based on the amount of said cooled granules. which the mixture of raw enzyme powder and wax is
3. The method of claim 1, wherein said polyethylene agitated ranges from 7-12 C.
glycol wax has a melting point in the range of 45-70 10 K k

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