Title of Invention

FUNCTIONAL STARCH POWDER

Abstract Functional starch powder of 400% or more water retention capacity, 5 hr or more collapse time and 200 g or more gel indentation load. This functional starch powder is produced through the step of heating a starch raw material in the presence of water at 60 to 150°C so as to swell starch particles of the starch raw material and the subsequent step of drying the thus swollen starch particles so as to obtain a powder mixture comprising starch particles and, lying in the exterior thereof, amylose and amylopectin.
Full Text DESCRIPTION
FUNCTIONAL STARCH POWDER
TECHNICAL FIELD
The present invention relates to functional
starch powder, a composition including the functional
starch powder and one or more active ingredients, and a
method for producing the functional starch powder.
More particularly, it relates to functional starch
powder which permits control of the release of an
active ingredient(s) when used in medicines,
agrochemicals, fertilizers, feed, food, industry,
cosmetics, etc. The composition containing the active
ingredient (s) can be obtained as a sustained-release or
rapid-release composition, depending on the amount of
the functional starch powder incorporated into the
composition.
BACKGROUND ART
For compositions having sustained-release
properties, there are, for example, solid sustained-
release medicines. The solid sustained-release
medicines are very useful for controlling the blood
level of the active ingredient(s), reducing the
frequency at which the medicine must be taken;
prolonging the effect of active ingredients that have a
short half-life; and reducing the side effects of the

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active ingredients that have a narrow range between a
minimum effective blood concentration and a side effect
exhibition concentration. Regarding conventional solid
sustained-release medicine, there are matrix type
sustained-release tablets that use a hydrophilic
polymer capable of forming a gel upon contact with
water, and reservoir type sustained-release capsules
that enclose granules of medicine. The granules
within the capsules are formed by coating core
particles with an active ingredient(s) and then coating
the surface of the coated particles with a coating film
capable of imparting sustained-release properties.
Tablets are preferable to capsules and granules from
the viewpoint of ease of taking, but reservoir
sustained-release tablets have been disadvantageous in
that when the sustained-release granules are compressed
into the tablets, the coating film capable of imparting
sustained-release properties is destroyed, so that the
controlled release of the active ingredient (s) by
dissolving becomes difficult.
On the other hand, patent document 1 and the
like describe that hydrophilic polymers such as methyl
cellulose (MC), hydroxypropyl cellulose (HPC) and
hydroxypropylmethyl cellulose (HPMC) can be used as a
release-sustaining base ingredient used in the matrix
type sustained-release preparations. These hydrophilic
polymers are advantageous, for example, in that they
impart sustained-release properties by the formation of


a complete gel layer by hydration in a solution having
a low ionic strength, are hardly affected by pH, and
are excellent in the stability of release by
dissolution over a long period of time. They, however,
5 have a problem, which is called dose dumping. If dose
dumping occurs, it becomes impossible to hydrate the
polymer in a solution having an intermediate or higher
ionic strength, their gelation is suppressed, so that a
large portion of the active ingredient(s) of a
pharmaceutical preparation designed to have sustained-
release properties is rapidly released, thus, the
preparation exhibits no sustained-release properties.
When the dose dumping occurs, the resulting rapid
increase of the active ingredient(s) in the blood can
induce death, depending on the efficacy of the active
ingredient(s) that have a narrow range between the.
minimum blood level and the concentration where side
effects are exhibited. Since the value of ionic
strength in the gastrointestinal tract varies depending
on regions of the tract and the food consumed, there
has been a desire for a release-sustaining base
ingredient which makes it possible to avoid the dose
dumping in a wide ionic strength value range throughout
the gastrointestinal tract.
Patent documents 2 to 5 describe simultaneous
use of pregelatinized starch and a hydrophilic polymer
such as hydroxypropyl cellulose or hydroxypropylmethyl
cellulose as a means for avoiding the dose dumping.


However, the pregelatinized starch (preferably drum-
dried waxy corn starch) used in patent document 2 has
no sustained-release effect in itself and is such that
sustained-release properties are imparted by an
ingredient other than the pregelatinized starch. In
addition, the pregelatinized starch is disadvantageous
in that the pregelatinized starch has only auxiliary
effect on the release-sustaining base ingredient,
because both the base ingredient and this auxiliary are
necessary and the amounts added should be large,
resulting in an increased size of a preparation.
Patent documents 3 to 5 describe that the tablet
tensile strength of pregelatinized starch at a solid
fraction of 0.8 is 0.15 kN/cm2. They, however, do not
describe the upper limit of the tablet tensile
strength. The tensile strength of the pregelatinized
starch used in the comparative examples in these patent
documents is 0.220 to 0.323 kN/cm2, while the tensile
strength of the functional starch powder of the
invention is 0.7 to 1.5 kN/cm2. Thus, they are clearly
different. In patent documents 2 to 4, sustained-
release properties are imparted by a combination of
pregelatinized starch and hydroxypropylmethyl
cellulose. These documents, however, neither describe
nor suggest that starch having a tensile strength of
0.15 kN/cm2 or more imparts sustained-release properties
by itself. In addition, no starch having a tensile
strength of more than 0.323 kN/cm2 has been reported.


As starch used in the fields of medicines,
agrochemicals, fertilizers, feed, food, industry,
cosmetics, etc., there are pregelatinized starch,
partly pregelatinized starch, crosslinked starch and
the like. They are used as a disintegrating agent
mainly in the medicine field.
All of the starches described in patent
documents 6 to 15 rapidly collapse and do not impart
any sustained-release properties. They are essentially
different in the following respects from the starch of
the invention, from which tablets that contain 60 to
100% of the starch powder are not disintegrated in 3
hours or more. That is, the modified starch of patent
document 6 has a low degree of swelling of 2.5 to 12
and breadks down in 30 minutes. The tablets of patent
document 7 that contain waxy starch disintegrate such
that tablets containing 50% of the waxy starch are
disintegrated within 60 seconds. The tablets of patent
document β contain β-starch with an α-starch surface
and tablets containing 17 to 30% of the p-starch are
disintegrated within 2 minutes. The tablests of patent
document 9 containing p-starch having 1 to 4% of α-
starch adhered thereto disintegrate such that tablets
containing 17 to 87% of this β-starch are disintegrated
within 20 seconds. The starch of patent document 10,
which is obtained by 5 to 20% pregelatinization of the
surface of β-starch, breaks down within 2 minutes. The
modified starch of patent document 11 has a cold-water-


soluble matter content of 10 to 20%, and tablets
containing 64 to 80% of this modified starch are
disintegrated within 20 minutes. The processed starch
of patent document 12 has a low degree of swelling of
3.0 to 6.0 and the tablets containing 10% of this
processed starch are disintegrated within 6 minutes.
The processed starch of patent document 13 has a cold-
water soluble matter content of less than 10% by
weight, a small swelling volume of 3 to 15 ml/g and a
low water retention capacity of at most 610% and breaks
down within 2 minutes. The starch of patent document
14 is a cross-linked starch powder having a low
swelling property (swelling property in cold water: 3
to 25 ml) and breaks down more rapidly than Starch 1500
(Comparative Example 6). The processed starch of
patent document 15 has a small swelling volume of 3 to
15 ml and is the starch represented by PCS (Comparative
Example 5) and Starch 1500 (Comparative Example 6).
Thus, these starches are essentially different from the
starch of the invention.
Patent documents 16 to 20 describe a starch
is used as a matrix base ingredient. Patent document
16 describes that matrix tablets are made of a high-
molecular weight polysaccharide existing in nature.
This document, however, describes only working examples
relating to xanthan gum and no working example using
starch and does not specifically describe starch
capable of imparting sustained-release properties.


Patent document 17 describes that a matrix agent
substantially contains a crystalline straight-chain
glucan and a glucan-degrading reagent. The straight-
chain glucan, however, refers to amylose. The
functional starch powder of the invention is different
from the matrix agent because it contains amylopectin
besides amylose as described hereinafter. In addition,
in the case of the functional starch powder of the
invention, the glucan-degrading reagent is not
necessary for controlling the release of an active
ingredient. Patent document 18 describes that a matrix
raw material substantially contains a crystalline
straight-chain glucan. This document, however,
describes that amylopectin is removed from starch. The
functional starch powder of the invention is different
from the matrix raw material because it contains
amylose and amylopectin.
Patent document 19 describes that the core
tablets of film-coated tablets contain pregelatinized
starch having an average degree of pregelatinization of
35 to 95%. Since the average degree of
pregelatinization of the functional starch powder of
the invention ranges from 40 to 98%, it is difficult to
distinguish the starch of the invention from that of
patent document 19 only by the average degree of
pregelatinization. The functional starch powder of the
invention, however, is clearly different from the
latter, for example, in gel indentation load and the

amount of swollen or dissolved amylose and amylopectin.
The purpose of the starch of patent document 19 is to
prevent the tablets from being impregnated with a
liquid at the time of coating, and hence is obviously
different from that of the functional starch powder of
the invention. The coated tablets (the amount of the
starch used: 14 wt%) themselves have excellent
disintegrating properties. From these facts, it is
clear that the starch of patent document 19 does not
control the release of a drug. Patent document 20
describes spherical fine particles wholly or partly
composed of a water-insoluble cottony polysaccharide.
The fine particles of patent document 20 are produced,
for example, by a biocatalyst process using starch
synthase. On the other hand, the functional starch
powder of the invention is produced only by heat
treatment without using a catalyst such as an enzyme.
Thus, the functional starch powder is obviously
different from the fine particles of patent document
20. As to the shape of the functional starch powder of
the invention, the functional starch powder comprises
starch particles with a particle size of 50 to 100 µm
having a structure formed by indenting a sphere or an
oval in one or more parts thereof. Thus, the
functional starch powder is clearly different from the
fine particles of patent document 20, i.e., the
spherical fine particles of 1 nm to 100 µm having a
narrow particle size distribution. Patent document 21


describes starch particles obtained by drying an
emulsion of an active ingredient and starch which has
an amylopectin content of 65% or more and 80% by weight
or more of which has a limited molecular weight of 10
to 10000 kDa. This starch, however, is water-soluble
and the functional starch powder of the invention is
different from the starch because it contains a water-
insoluble component. Patent document 22 describes a
method for making starch and a material into a slurry
in a saturated aqueous salt solution and making the
slurry into capsules, which includes blowing steam
through starch at a pressure of at least 110 psi (0.78
MPa) in the presence of a salt to disperse the starch
completely, heating the resulting starch slurry to a
temperature of 120 to 180°C at 55 to 120 psi (0.39 to
0.84 MPa) or more, and immediately exposing the slurry
to atmospheric pressure to lower the temperature to
112°C or lower. However, when the salt is present,
amylose is precipitated, so that the product obtained
by the method is not the starch particles according to
the invention, i.e., starch particles with a particle
size of 50 to 100 µm having an indentation in one or
more parts thereof but a filmy and leaf-like product
formed by the crystallization of amylose. Therefore,
the product is different in shape from the fine
particles according to the invention.
On the other hand, pregelatinized starch is
used mainly in the food field as a thickening agent,


feed for eel breeding or the like has been
disadvantageous in that a gel formed by the starch is
destroyed in the presence of α-amylase, resulting in a
deteriorated release-sustaining capability, as reported
in Chem. Pharm. Bull., 35(10)4346-4350(1987). It has
been disadvantageous also in that at a high ionic
strength, and it loses release-sustaining properties.
Patent document 1: US6296873
Patent document 2: JP-T-2002-541090
Patent document 3: WO200410997
Patent document 4: WO200410998
Patent document 5: WO200411002
Patent document 6: JP-B-46-21471
Patent document 7: JP-A-48-68726
Patent document 8: JP-B-53-3275
Patent document 9: JP-B-62-7201
Patent document 10: JP-B-58-27774
Patent document 11: JP-B-56-11689
Patent document 12: JP-A-58-32828
Patent document 13: JP-B-59-47600
Patent document 14: JP-B-63-7531
Patent document 15: JP-A-6-100602
Patent document 16: JP-T-10-512873
Patent document 17: JP-T-7-508532
Patent document 18: JP-T-7-508533
Patent document 19: JP-A-2002-193792
Patent document 20: JP-T-2001-514315
Patent document 21: US20030180371


Patent document 22: US4755397
DISCLOSURE OF THE INVENTION
Problem to be Solved by the Invention
The invention is directed to provide starch
powder as a release-sustaining base ingredient used for
controlling the concentration of an active
ingredient(s) in medicines, agrochemicals, fertilizers,
feed, food, industry, cosmetics, etc., which has a
sufficient release-sustaining capability to constitute
a sustained-release preparation mainly for medicinal
use, assures pH stability and long-term stability, and
is convenient. In addition, the invention is directed
to providing a novel starch-based release-sustaining
base ingredient that is not affected by ionic strength
and is free from the dose dumping problem, so that it
permits accurate control of an active ingredient(s),
for example, throughout gastrointestinal tract.
Means for Solving the Problem
The inventors earnestly investigated the
water retention properties, disintegration properties
and gel characteristics of starch powder, and
consequently found a starch powder which has all of
sufficient release-sustaining capability, pH stability
and long-term stability and does not cause the dose
dumping because it is not affected by ionic strength,
thereby the invention has been accomplished. That is,


the invention is as follows.
(1) Functional starch powder having a water
retention capacity of 400% or more, a collapse time of
5 hr or more and a gel indentation load of 200 g or
more.
(2) Functional starch powder according to (1),
wherein when the powder was dispersed in water, the
amount of amylose and amylopectin, each of which is
present in a swollen or dissolved state, ranges from 10
to 90% by weight.
(3) Functional starch powder according to (1) or
(2), which includes starch particles with a particle
size of 50 to 500 µm having an indentation in one or
more parts thereof.
(4) A composition including functional starch
powder according to any one of (1) to (3) and one or
more active ingredients.
(5) A composition according to (4), wherein the
one or more active ingredients are selected from
pharmaceutically active ingredients, agrochemical
ingredients, ingredients for fertilizer, ingredients
for feed, ingredients for food, ingredients for
cosmetic, coloring maters, flavoring materials, metals,
ceramics, catalysts and surfactants.
(6) A composition according to (4) or (5), which
controls the release of the active ingredient(s) so
that the release may be sustained release or rapid
release.


(7) A method for producing functional starch
powder according to any one of (1) to (3), which
includes heating a starch raw material in the presence
of water at 60 to 100°C to swell starch particles of the
starch raw material and subsequently drying the swollen.
starch particles to obtain a powder mixture comprising
starch particles and amylose and amylopectin which are
present in the exteriors of these starch particles.
(8) A method for producing functional starch
powder according to any one of (1) to (3) , which
includes heating a starch raw material in the presence
of water at 60 to 100°C to swell some or all of starch
particles of the starch raw material at a volume ratio
of 10 or more and subsequently drying the swollen
starch particles to obtain a powder mixture comprising
starch particles having a structure indented in one or
more parts and amylose and amylopectin which are
present in the exteriors of these starch particles.
(9) A method for producing functional starch
powder according to any one of (1) to (3), which
includes heat-treating a starch raw material at 100 to
130°C under reduced pressure and subsequently heating
the starch raw material in the presence of water at 60
to 150°C to swell starch particles of the starch raw
material and drying the swollen starch particles to
obtain a powder mixture comprising starch particles and
amylose and amylopectin which are present in the
exteriors of these starch particles.


(10) A method for producing functional starch
powder according to any one of (1) to (3), which
includes a step of heat-treating a starch raw material
at 100 to 130°C under reduced pressure and then heating
the starch raw material in the presence of water at 60
to 150°C to swell some or all of starch particles of the
starch raw material at a volume ratio of 10 or more and
subsequently drying the swollen starch particles to
obtain a powder mixture comprising starch particles
having a structure indented in one or more parts and
amylose and amylopectin which are present in the
exteriors of these starch particles.
(11) A method according to any one of (7) to (10),
wherein the starch raw material is potato starch.

Advantages of the Invention
The present invention is novel starch powder
which has satisfactory release-sustaining properties
owing to its high α-amylase resistance not possessed by
conventional natural or processed starch, is excellent
in pH stability and long-term stability and, moreover,
is not affected by ionic strength, so that it is free
from the dose dumping problem in conventional release-
sustaining base ingredients and hence permits accurate
control of an active ingredient(s) .
BRIEF DESCRIPTION OF THE DRAWINGS
[Fig. 1] An electron micrograph (600 magnifications)


of starch powder B prepared in Example 2.
[Fig. 2] An electron micrograph (600 magnifications)
of starch powder F prepared in Example 6.
[Fig. 3] An electron micrograph (100 magnifications)
of the commercial potato pregelatinized starch used in
Comparative Example 1.
[Fig. 4] An electron micrograph (200 magnifications)
of the commercial corn pregelatinized starch used in
Comparative Example 2.



[Fig. 5] An electron micrograph (100 magnifications)
of the commercial high-amylose corn pregelatinized
starch used in Comparative Example 3.
[Fig. 6] An electron micrograph (200 magnifications)
of the commercial waxy corn pregelatinized starch used
in Comparative Example 4.
[Fig. 7] An electron micrograph (400 magnifications)
of the commercial partly pregelatinized starch (PCS)
used in Comparative Example 5.
[Fig. 8] An electron micrograph (400 magnifications)
of starch powder G prepared in Comparative Example 8.
[Fig. 9] A graph showing the particle size
distribution of granules A for tabletting produced from
starch powder F in Example 6.
[Fig. 10] A graph showing the particle size
distribution of granules B for tabletting produced from
a suspension of starch powder D in Example 7.
[Fig. 11] A graph showing the particle size
distribution of granules C for tabletting produced from
commercial hydroxypropyl cellulose (HPC-L) in
Comparative Example 9.
[Fig. 12] A graph showing the particle size
distribution of granules D for tabletting produced from
commercial hydroxypropyl cellulose (HPC-L) in
Comparative Example 10.
BEST MODE FOR CARRYING OUT THE INVENTION
The invention is explained below in detail.


The functional starch powder of the invention
should have a water retention capacity of 400% or more,
more preferably 500% or more, particularly preferably
700%. The term "water retention capacity" is defined
as the volume of pure water retained by starch after
the centrifugation (2000G, 10 minutes) of a dispersion
of 1 g of dry starch powder in pure water. When the
water retention capacity is less than 400%, the starch
powder is hydrated to form no gel, resulting in
disintegration of tablets, or the starch powder cannot
exhibit satisfactory release-sustaining properties
because of rapid diffusion of an active ingredient(s)
even when the starch powder forms a gel layer. The
gel-forming capability is enhanced with an increase of
the water retention capacity. When the water retention
capacity is high, the gel is desirably not destroyed
even at a high ionic strength, though the maximum water
retention capacity is dependent on characteristics of a
starch raw material and is at most 3000%.
In addition, the functional starch powder of
the invention should have a collapse time of 5 hours or
more. The term "collapse time" is defined as the
disintegration time, in a test solution, of a
cylindrical molded article with a diameter of 0.8 cm
obtained by compressing 0.2 g of starch powder at 50
MPa. Here, the test solution is the second solution
(pH 6.8) prescribed in the Japanese Pharmacopoeia, the
14th revision, p. 204 and a disintegration test is


carried out by the use of an auxiliary plate according
to the disintegration test method described in the
Japanese Pharmacopoeia (14th revision). When the
collapse time is less than 5 hours, no satisfactory
release-sustaining properties can be attained. The
upper limit of the collapse time depends on the desired
degree of release-sustaining properties and is at most
240 hours.
Furthermore, the functional starch powder of
the invention should have a gel indentation load of 200
g or more, preferably 300 g or more, particularly
preferably 4 00 g or more. The term "gel indentation
load" is defined as a maximum load applied when a
cylindrical adapter is pressed for 3 mm at a rate of
0.1 mm/sec into a gel formed by immersing, in pure
water for 4 hours, a cylindrical molded article with a
diameter of 1.13 cm obtained by compressing 0.5 g of
starch powder at 50 MPa. Here, the term "maximum load"
means the following: when a layer of the gel is broken,
the term means a load value at the time of the
breaking; and when the gel layer is not broken, the
term means a maximum load value which the adapter
applies before it intrudes for 5 mm into the
gelatinized cylindrical molded article. When the gel
indentation load is less than 200 g, the diffusion of
an active ingredient(s) in a gel layer formed by the
starch powder becomes rapid, so that no satisfactory
release-sustaining properties are exhibited. Although


the gel indentation load is preferably high because the
release-sustaining capability of the starch powder is
enhanced with an increase of the gel indentation load,
it is at most about 3000 g.
As to the shape of starch particles
constituting the functional starch powder of the
invention, the starch particles have more preferable
characteristic in that they have a structure formed by
indenting a sphere or an oval in one or more parts
thereof. As to the particle size of the starch
particles constituting the functional starch powder of
the invention, the functional starch powder preferably
includes starch particles having a particle size in the
range of 50 to 500 urn, preferably 50 to 300 µm, more
preferably 50 to 100 urn, when observed by SEM (scanning
electron microscope) at a magnification of 200 to 1500.
As to the content of such starch particles having a
structure formed by indenting a sphere or an oval in
one or more parts thereof, the functional starch powder
preferably contains such starch particles so that for
example, when it is observed at a modification of 600,
the proportion (% by the number of particles) of such
starch particles to all particles observable in the
field of vision may be 5% or more, preferably 10% or
more. The content (% by the number of particles)
measured by such observation is considered as the
content (% by weight) based on the weight of all the
starch particles. When particle size of the starch


particles having an indentation in one or more parts
thereof is less than 50 µm, the starch particles hardly
release, outside them, amylose and amylopectin which
can be swollen or dissolved in a sufficient volume of
water, and hence no sufficient sustained-release
properties can be imparted. This is not desirable.
When the functional starch powder is dispersed in
water, the amount of amylose and amylopectin, each of
which is present in a swollen or dissolved state, is
preferably in the range of 10 to 90% by weight based on
the weight of all the starch particles. When the
particle size of the starch particles having an
indentation in one or more parts thereof is more than
500 µm, the amount of amylose and amylopectin, which
are present in the exterior of starch particles,
exceeds 90% by weight based on the weight of all the
starch particles and hence the resistance to α-amylase
is decreased, so that no satisfactory sustained-release
properties can be imparted. This is not desirable.
The starch particles constituting the
functional starch powder of the invention have a
structure formed by indenting a sphere or an oval in
one or more parts thereof, have a particle size of 50
to 500 µm, and may be an aggregate having particles of
1 to 50 µm having a structure formed by indenting a
sphere or an oval in one or more parts thereof, as
particles adhered to a part of the exterior of the
aggregate.


The starch particles constituting the
functional starch powder of the invention are
preferably non-crystalline. The starch particles can
be judged to be crystalline or non-crystalline by a
polarization image (magnification: 10) under an optical
microscope. When the starch particles are crystalline,
a light polarization image (for example, an image
called "crisscross observed by polarization microscope"
in the case of raw starch) appears.
The bulk density of the functional starch
powder of the invention is preferably in the range of
0.1 to 0.70 g/cm3, more preferably 0.15 to 0.70 g/cm3,
and most preferably 0.20 to 0.70 g/cm3. When the bulk
density is less than 0.1 g/cm3, the fluidity is low, so
that segregation by weight is undesirably caused when a
composition comprising the functional starch powder and
an active ingredient(s) is tablets. On the other hand,
when the bulk density is more than 0.70 g/cm3, the
moldability of the composition is deteriorated, so that
a suitable practical hardness is undesirably
unattainable. The viscosity of the functional starch
powder of the invention is preferably 1000 mPa.s or
less, more preferably 500 mPa.s or less, and most
preferably 400 mPa.s or less, in an aqueous solution of
2% concentration at 25°C. When the viscosity is more
than 1000 mPa.s, handling of the functional starch
powder undesirably becomes troublesome when the
functional starch powder is added in the form of an


aqueous solution. The lower limit of the viscosity is
preferably as close to the viscosity of water of 1
mPa.s as possible.
A method for producing the functional starch
powder of the invention is described below.
The functional starch powder of the invention
is produced through a step of heating a starch raw
material in the presence of water at 60 to 150°C to
swell some or all of starch particles of the starch raw
material and a step of drying the resulting swollen
starch particles to obtain a powder mixture including
starch particles with an indentation in one or more
parts and amylose and amylopectin which are present in
the exteriors of these starch particles.
The starch raw material referred to herein is
not particularly limited so long as it contains a
starch material such as natural starch, aged starch or
crosslinked starch of rice, glutinous rice, corn, waxy
corn, amiro corn, sorghum, wheat, barley, taro, green
gram, potato, lily, dogtooth violet, tulip, canna, pea,
shiwa pea, chestnut, arrowroot, yam, sweet potato,
broad bean, snap bean, sago, tapioca (cassava),
bracken, lotus, water caltrop or the like. Potato is
preferred because its starch particles have a high
swelling property, so that the water retention capacity
can easily be controlled to be high.
A material obtained by subjecting a starch
raw material to wet heat treatment such as heat


treatment at 100 to 130°C under reduced pressure is
discussed in JP-A-4-130102 or JP-A-7-25902 and is
preferred because when such a material is used, the
gelatinization initiation temperature is raised, so
that the swelling properties of particles are enhanced.
That is, JP-A-4-130102 discusses (1) a method in which
starch is placed in a sealable container resistant to
both internal and external pressures and having both a
pressure-reducing line and a pressurized steam line
attached, and the pressure is reduced, followed by
application of pressure and heat by steam introduction,
or the above procedure is repeated, whereby the starch
is heated for a predetermined time, and then the heated
starch is cooled. JP-A-4-130102 discusses (2) a method
according to (1), wherein by adjusting the temperature
in a can to at least 120°C, starch having a very high α-
amylase adsorption capability is produced, which is
that when an aqueous suspension of the starch is
heated, it has substantially no viscosity though starch
particles expand. JP-A-4-130102 describes a method
according to (1) and (2), wherein cooling is conducted
under reduced pressure after the heating. JP-A-7-25902
discusses, for example, (1) a method for producing wet-
heat-treated starch grains obtained by wet heat
treatment of starch grains, which includes repeating at
least once a first step of subjecting starch grains
charged into a pressure container to pressure reduction
and a second step of introducing steam into the


container to conduct heating and pressurizing, after
the pressure reduction; and (2) a production method
according to (1), wherein in the above second step, the
heating is conducted at 80°C or higher for 5 minutes to
5 hours. Thus, the wet-heat-treated starch is composed
of particles each of which has a hollow interior and a
shell having an increased crystallinity. It is
characterized in that a polarization crisscross pattern
observed as a polarization image under an optical
microscope is vaguer than that observed in the case of
raw starch, namely, non-birefringent particles are
decreased. The hollow portion seems to have a
structure formed by the loosening of the crystalline
states of amylose and amylopectin, and the treated
starch is characterized in that its digestibility with
α-amylase is higher than that of raw starch. The
viscosity of an emulsion of the wet-heat-treated starch
adjusted to 5% concentration is preferably 400
Brabender units (BU) or less during heating from 50°C to
95°C, and the maximum viscosity of the emulsion is
preferably 1000 BU or less when the emulsion is
maintained at 95°C for 30 minutes. As the starch raw
material, one or a mixture of two or more of the above-
exemplified materials may be freely used. The size of
particles of the starch raw material is preferably as
large as possible from the viewpoint of ease of
expanding.
The term "in the presence of water" used


herein with respect to the starch raw material means a
state in which the starch raw material and water are
present and the water content is 40% by weight or more.
A method for heating in the invention is not
particularly limited so long as it is a well-known
method. As the method, one embodiment is a method of
placing the starch raw. material in the presence of
water in a jacketed reactor and introducing steam into
the reactor to heat the starch raw material; a method
of mixing the starch raw material in the presence of
water with steam; a method of heating the starch raw
material in the reservoir of a drum dryer; and a method
of carrying out gelatinization and spraying at the same
time during spray drying while supplying steam to a
starch slurry. The method of mixing the starch raw
material in the presence of water with steam is
preferable because it facilitates the assurance of time
for heating starch particles. The heating temperature
is any temperature so long as the temperature of a
liquid obtained by the gelatinization of starch by the
above methods is 60 to 150°C, preferably 90 to 140°C,
more preferably 90 to 130°C, and most preferably 100 to
120°C.
The functional starch powder of the invention
should be produced by heating the starch raw material
in the presence of water at 60 to 150°C to swell some or
all of starch particles of the starch raw material at a
volume ratio of 10 or more. The term "volume ratio" is


defined as [b/a]3 when the average particle sizes before
and after the swelling are taken as a (µm) and b (µm) ,
respectively. The average particle size referred to
here is calculated by summing up the maximum diameters
m (µn) of individual particles observed under an
optical microscope (magnification: 10, OPTIPHOT-POL
mfd. by Nikon) and dividing the sum by the number (n)
of particles subjected to the measurement (Σm/n). When
starch particles constituting the starch raw material
is heated in the presence of water, they expand near a
gelatinization initiation temperature intrinsic to the
starch particles. During the swelling, in the starch
particles of the starch raw material, the hydrogen
bonds of amylose and amylopectin, which constitute the
shells of the starch particles, are destroyed by the
heating, and water intrudes into the interiors of the
starch particles, so that amylose and amylopectin in
the interiors of the particles are decreased in
molecular weight by heat to be released to the
exteriors of the starch particles. The ratio between
amylose and amylopectin is intrinsic to the kind of the
starch raw material (the amylose content of potato
starch is about 25%). The ratio between amylose and
amylopectin is not changed even after they are released
to the exteriors of the starch particles. It is
inferred that the molecular weight distribution is
shifted to a low molecular weight side.
Whether or not amylose and amylopectin, which


constitute the interiors of the particles, have been
released to the exteriors of the particles during the
expansion can be confirmed by a photomicrograph
(magnification: 20 to 30) by adding several drops of a
1/50 to 1/200 normality iodine solution to a suspension
of starch subjected to the swelling treatment by
heating. In the field of vision of the
photomicrograph, portions stained blue other than the
starch particles are amylose and amylopectin released
from the interiors of the particles. When the starch
particles expand and then dried, a mixture of starch
particles and amylose and amylopectin released to the
exteriors of the particles from the interiors is dried
to become powder. When the amount of expanded or
dissolved amylose and amylopectin defined herein is
measured in the resulting dry powder, it can be
confirmed that the amount of amylose and amylopectin
released to the exteriors of the starch particles
ranges from 10 to 90% by weight.
When the swelling of the starch particles is
insufficient, the volume ratio in the swelling cannot
be 10 or more and the amount of amylose and amylopectin
released to the exteriors of the starch particles
becomes less than 10%, so that no satisfactory release-
sustaining properties can be exhibited. This is not
desirable. In addition, unless such starch particles
are added in a large amount of more than 10% like
partly pregelatinized starch, it becomes difficult to


bind an active ingredient(s) to other additives, which
is not desirable. An example of such starch particles
is partly pregelatinized starch such as the starch
particles of Comparative Example 5. As to the shape of
such starch particles after drying, indented particles
having a particle size of less than 50 pm are observed
in only a small amount, and most of the starch
particles become an aggregate in which indented
particles of less than 50 pm are aggregated to such an
extent that the boundary surfaces among constituent
particles are not clear. Such an aggregate has a size
of 50 to 100 pm but is utterly different from the
functional starch particles of the invention because
its particles cannot be distinguished from one another
as individual particles having clear boundary surfaces
among them.
The upper limit of the volume ratio in the
swelling is at most 400, preferably 100, though it
varies depending on the starch raw material. When the
volume ratio is more than 400, amylose and amylopectin,
which form the shell structure of starch, are also
expanded to be dispersed as molecules and are gradually
dissolved and released to the exteriors of starch
particles, so that the starch particles themselves
disappear. Therefore, the amount of amylose and
amylopectin, which are present in the exteriors of the
particles, exceeds 90% based on the total amount of the
starch particles, so that no sufficient gel strength is


attained, and moreover, the resistance to α-amylase is
lost, so that no sufficient release-sustaining
capability is exhibited. This is not desirable. When
the starch particles become unable to retain the shape
of their shell structures and substantially all of them
become amylose and amylopectin that can expand or
dissolved in water, they become flaky or massive
crystalline particles (showing a polarization image in
a photomicrograph) after drying, for example, because
swollen or dissolved amylose and amylopectin become β-
amylose and β-amylopectin. Such particles are clearly
different from starch particles constituting the
functional starch powder of the invention.
In the case of the functional starch powder
of the invention, starch particles are swollen by a
volume ratio of 10 or more by heating, so that the
particle size of the swollen starch particles after
drying is 50 to 500 µm. Although a method for drying
is not particularly limited, it includes, for example,
freeze-drying, spray drying, drum drying, tray drying,
air-drying, vacuum drying, and drying by solvent
replacement. Industrially, spray drying and drum
drying are preferred. The solid content of a liquid at
the time of the drying is approximately 0.5% to 60%.
When the solid content is less than 0.5%, the
productivity is undesirably deteriorated. When the
solid content is 60% or more, the viscosity becomes
high, so that the yield is undesirably decreased. The


solid content is preferably 1 to 30%, more preferably 1
to 20%.
When 1 g of the functional starch powder of
the invention is dispersed in 100 cm3 of pure water and
stands for 16 hours, the lower layer portion of the
dispersion separated into upper and lower layers is
observed under an optical microscope (magnification:
10), it is preferable that the shell structure inherent
in a starch raw material for the functional starch
powder is completely present without loss thereof. The
functional starch powder of the invention is
essentially different from a starch where nothing is
observed in the above-mentioned lower layer portion, or
a starch which has a flaky, massive or the shell-like
structure formed by the conversion of swollen or
dissolved amylose and amylopectin to β-amylose and (β-
amylopectin in the lower layer portion.
For imparting release-sustaining properties,
resistance to α-amylase and resistance to ionic
strength, the amount of amylose and amylopectin, each
of which is present in a swollen or dissolved state,
should be in a definite range. The term "swollen or
dissolved amylose and amylopectin" means amylose and
amylopectin expanded or dissolved by heating of a
starch raw material in the presence of water that are
so transparent or semitransparent that their shapes
cannot be observed under an optical microscope. Their
amount (% by weight) can be determined by dispersing 1


g of starch powder in 100 cm3 of pure water, allowing
the resulting dispersion to stand for 16 hours and
calculating the amount from the volume of the upper
layer portion of the dispersion separated into upper
and lower layers and the weight of solids in 30 cm3 of
the upper layer (the volume (cm3) of the upper layer
portion ÷ 30 x the weight (g/cm3) of solids in 30 cm3 of
the upper layer ÷ the dry weight (g) of 1 g of the
starch x 100). The amount in the case of the starch
powder of the invention ranges from 10 to 90% by
weight. When the amount is less than 10% by weight,
the water retention is insufficient, so that no
release-sustaining properties are exhibited. This is
not desirable. When the amount is more than 90% by
weight, the water retention is lowered, so that the
resistance to α-amylase, release-sustaining capability
and resistance to ionic strength are undesirably
deteriorated.
When the amount of swollen or dissolved
amylose and amylopectin is controlled to be within the
above range, the shell structures of starch particles
are not completely lost and can be clearly observed in
the lower layer portion in the above-mentioned
measurement. The term "degree of swelling" is defined
as the volume of the lower layer portion of a
dispersion separated into upper and lower layers which
is obtained by dispersing 1 g of starch powder in 100
cm3 of pure water, followed by standing for 16 hours.


The degree of swelling of the functional starch powder
of the invention is approximately 0.5 cm3 to 60 cm3 and
is preferably 10 cm3 to 50 cm3.
Pregelatinized starch and partly
pregelatinized starch, which are used mainly in
medicines, are obtained by gelatinizing natural starch
by heating and then drying the gelatinized starch. As
described in JP-B-59-47600, starch with excellent
disintegrating properties can be obtained with starch
mostly composed of particles with a shell structure and
inhibited as much as possible from releasing swollen
amylose and amylopectin by dissolution by heating at a
temperature, which is above 50°C and below a temperature
about 10°C higher than an intrinsic gelatinization
initiation temperature (which is a temperature lower
than 90°C though depending on the kind of starch) .
However, although such starch includes particles with a
shell structure, the particle size of a single swollen
particle in the starch is less than 50 µm and
sufficient water retention is impossible because of the
insufficient swelling in water, or because of the
amount of swollen amylose and amylopectin is
insufficient which results in an insufficient gel
indentation load. Therefore, such starch does not
exhibit release-sustaining properties.
Pregelatinized starch used mainly in food is
produced by a method such as drum drying at about 150°C
or extrusion with an extruder at 120 to 160°C under high


pressure. In pregelatinized starch obtained by such a
method, its particles are excessively swollen because
of too high a gelatinization temperature, almost no
particles having a shell structure are present, and its
particles have a flaky or massive shape different from
a shell structure inherent in starch particles, which
is the same as a flaky, massive or the like structure
formed by the conversion of swollen amylose and
amylopectin to (3-amylose and (β-amylopectin. That is,
in conventional pregelatinized starch, swollen or
dissolved amylose and amylopectin and flaky or massive
particles formed by the conversion to [β-amylose and β-
amylopectin are present at the same time, and only the
flaky or massive particles have a visually confirmable
shape. Starch particles composed mainly of amylose and
amylopectin swollen with loss of the shell structures
by such excessive gelatinization are not desirable
because they have a low gel indentation load and a low
resistance to α-amylase and do not exhibit release-
sustaining capability and resistance to ionic strength.
That is, the functional starch powder of the
invention is produced by heating a starch raw material
at 60 to 150°C to swell starch particles at a volume
ratio of 10 or more and then drying the swollen starch
particles to obtain a powder mixture including starch
particles and, lying in the exterior thereof, amylose
and amylopectin. Surprisingly, the functional starch
powder obtained by such a production process has a high


resistance to α-amylase, a high resistance to ionic
strength and a sufficient release-sustaining
capability, which are not possessed by conventional
pregelatinized starch and partly pregelatinized starch.
The composition of the invention including
the functional starch powder and one or more active
ingredients can be used for controlling the
concentration of the active ingredient (s) in the fields
of medicines, agrochemicals, fertilizers, feed, food,
industry, cosmetics, etc. The amount of the starch
powder of the invention incorporated into the
composition is approximately 0.1 to 99.99% by weight.
When the amount is less than 0.1% by weight, the
concentrate of the starch powder of the invention is
not controlled. When the amount is more than 99.99% by
weight, a sufficient amount of the active ingredient(s)
cannot be added, so that the therapeutic effect,
efficacy and the like of the active ingredient(s)
cannot be expected. The starch powder of the invention
is usually used in the range of 0.5 to 95% by weight,
preferably about 0.5 to about 90% by weight.
The active ingredient(s) referred to herein
includes the following, but is not limited to:
pharmaceutically active ingredients, agrochemical
ingredients, ingredients for fertilizer, ingredients
for feed, ingredients for food, ingredients for
cosmetic, coloring maters, flavoring materials, metals,
ceramics, catalysts, surfactants and the like. The


active ingredient (s) may be in the form of any of
powder, crystals, oil, a liquid, a semisolid and the
like. The shape may be any of powder, fine granules,
granules and the like. The active ingredient(s) may be
coated to control the rate of dissolution, to reduce
bitterness, or the like. The above-exemplified active
ingredients may be used alone or in combination. As
the active ingredient(s), the pharmaceutically active
ingredients are the most preferable.
For example, for the pharmaceutically active
ingredients orally administrable drugs such as
antipyretic analgesic antiphlogistics, hypnotic
sedatives, sleepiness inhibitors, dinics, infant
analgesics, stomachics, antacids, digestives,
cardiotonics, drugs for arrhythmia, hypotensive drugs,
vasodilators, diuretics, antiulcer drugs, drugs for
controlling intestinal function, therapeutic drugs for
osteoporosis, antitussive expectorants, antasthmatics,
antibacterials, drugs for pollakiuria, tonics, vitamin
preparations, and the like can be used. These active
ingredients may freely be used alone or in combination.
One of the functions of the functional starch
powder of the invention is its ability to control the
release of the active ingredient(s) in the composition
including the functional starch powder and the active
ingredient(s). Here, the phrase "control the release
of the active ingredient(s)" means controlling the
release so that the amount of the active ingredient(s)


released by the composition in a liquid medium may be
in a definite range at intervals of a definite tine; or
releasing the whole of the active ingredient(s) Within
a definite time. The phrase "controlling the release
so that the amount of the active ingredient(s) may be
in a definite range at intervals of a definite time"
means that for example, when the whole of the acnive
ingredient(s) is released in 10 to 12 hours, the
release is controlled so that the rate of release by
dissolution measured according to the release-by-
dissolution test method, which is the second method
(paddle method) described in the Japanese Pharmacopoeia
(14th revision) may be 20 to 40% after 1 hour, 40 to 60%
after 5 hours, and 70% or more after 7 hours. In
addition, when the whole of the active ingredient(s) is
released in a long time such as 12 to 240 hours, it is
also possible to control the release by properly
lengthening the intervals of 1, 5 and 7 hours. The
phrase "releasing the whole of the active ingredient(s)
within a definite time" means that the whole of the
active ingredient(s) is released in a short time such
as 30 minutes. Here, although the term "the whole"
means the whole of the theoretical amount of the active
ingredient(s) added, the release is considered as the
release of the whole when the amount of the active
ingredient(s) released is in the range of 95 to 105%,
inclusive of analysis errors.
In the case of the functional starch powder


of the invention, there are two possible, seemingly
different, ways to control the rate of dissolution, as
described above. By these ways of controlling the
release by dissolution, the so-called sustained-release
effect, an effect of controlling the release so that
the amount of the active ingredient (s) released may be
in a definite range at intervals of a definite time,
can be obtained (in other words, a sustained-release
composition containing the functional starch powder of
the present invention can be obtained) by incorporating
the functional starch powder into the composition in an
amount of, for example, approximately 10 to 95% by
weight based on the weight of the composition. In
addition, the so-called rapid-release effect, an effect
of releasing the whole of the active ingredient(s)
within a definite time can be obtained (in other words,
a rapid-release composition containing the functional
starch powder of the present invention can be obtained)
by incorporating the functional starch powder into the
composition in an amount of, for example, approximately
0.1 to 5% by weight based on the weight of the
composition.
The active ingredient(s) and optionally other
additives can be granulated by a well-known wet
granulation method such as high-speed stirring
granulation, extrusion granulation or fluidized-bed
granulation. In this case, when the functional starch
of the invention is used in the composition in an


amount of approximately 0.1 to 10% by weight,
preferably approximately 0.1 to 5% by weight, based on
the total weight of the composition, the amount of
amylose and amylopectin, each of which is in a swollen
or dissolved state, is in a specified range, so that it
becomes possible to bind the active ingredient(s) and
optionally other additives to the functional starch.
Moreover, granules having an average particle size in
the range of 50 to 500 urn can be obtained.
Furthermore, a sufficient hardness can be imparted to a
composition obtained by compression-molding the
obtained granules by a well-known method. When a
comparison is made at the same adding amount, the
functional starch powder of the present invention can
impart a higher hardness than do cellulose derivatives
such as hydroxypropyl cellulose. The functional starch
powder of the invention gives a sharp particle size
distribution when used either in the form of powder or
in the form of a suspension, solution or semi-solution
in a medium such as water. For obtaining granules
having a sharper particle size distribution, the
functional starch powder is preferably used in the form
of powder.
In addition, the functional starch powder is
advantageous in that it includes starch particles with
a particle size of 50 to 500 urn having a structure
formed by indenting a sphere or an oval in one or more
parts thereof, so that when the granules are compressed


into tablets, the disintegration time of the tablets
having a practical hardness of 40N or more can be
reduced because the starch particles are swollen in
water. In the case of a conventional binder such as a
cellulose derivative (e.g. hydroxypropyl cellulose),
when its amount is increased, coarse particles are
formed, so that the average diameter of granules is
increased. As a result, the disintegration of tablets
obtained by compressing such granules is slowed.
Therefore, the diameter of granules should be set at a
suitable diameter. The functional starch powder of the
invention is advantageous in that even when its adding
amount is increased, it can be granulated without
remarkable increase of the average diameter of
granules, so that the disintegration of tablets
obtained by compressing such granules is not slowed.
Most of pregelatinized starches in use as a binder are
completely gelatinized starches and do not include
starch particles with a particle size of 50 to 500 µm
having a structure formed by indenting a sphere or an
oval in one or more parts according to the inventon.
Therefore, they have been disadvantageous in that the
disintegration of tablets obtained by compressing
granules is slow. They have been disadvantageous
particularly in that the disintegration is slowed with
the lapse of time because they contain a large amount
of gelatinized amylose and amylopectin.
If necessary, the composition of the


invention may contain other components such as
disintegrating agents, binders, fluidizing agents,
lubricants, correctives, flavoring materials, coloring
matters, sweeteners, etc. besides the active
ingredient(s) and the functional starch powder. The
other components may be used as a diluent.
The binders are not particularly limited and
include, for example, sugars such as sucrose, glucose,
lactose, fructose, trehalose, etc.; sugar alcohols such
as mannitol, xylitol, maltitol, erythritol, sorbitol,
etc; water-soluble polysaccharides such as gelatin,
pullulan, carrageenan, locust bean gum, agar, konjak
mannan, xanthan gum, tamarind gum, pectin, sodium
alginate, gum arabic, etc.; celluloses such as
crystalline celluloses (e.g. "Avicel" PH-101, PH-101D,
PH-101L, PH-102, PH-301, PH-301Z, PH-302, PH-F20, PH-
M06, M15, M25, "Ceolus" KG-801 and KG-802, manufactured
by Asahi Kasei Corp.), powdered cellulose,
hydroxypropyl cellulose, methyl cellulose, etc.;
starches such as pregelatinized starch, starch paste,
etc.; synthetic polymers such as
poly(vinylpyrrolidone)s, carboxyvinyl polymers,
poly(vinyl alcohol)s, etc.; and inorganic compounds
such as calcium hydrogenphosphate, calcium carbonate,
synthetic hydrotalcite, magnesium aluminate silicate,
etc. These binders may be used alone or in
combination.
The crystalline celluloses usable as the


binder are preferably those having an excellent
compactibility. Use of the crystalline cellulose
having an excellent compactibility permics compression
into tablets at a low striking pressure. Therefore,
granule-containing tablets can be obtained which permit
retention of the activity of an active ingredient(s)
that is inactivated by striking pressure. Moreover, a
high hardness can be imparted by adding a small amount
of such crystalline cellulose, and hence, a bulky
active ingredient(s) or a drug containing various kinds
of active ingredients can be made into tablets. Such
crystalline cellulose is advantageous, for example, in
that in some cases, it permits reduction of the size of
tablets, is excellent in ability to support a liquid
component and can suppress hindrances in compression
into tablets.
The disintegrating agents are not
particularly limited and include, for example,
celluloses such as sodium croscarmellose, carmellose,
calcium carmellose, sodium carmellose, low-substituted
hydroxypropyl cellulose, etc.; starches such as sodium
carboxymethyl starch, hydroxypropyl starch, rice
starch, wheat starch, corn starch, potato starch,
partly pregelatinized starch, etc.; celluloses such as
crystalline cellulose, powdered cellulose, etc.; and
synthetic polymers such as crospovidone, crospovidone
copolymers, etc. These disintegrating agents may be
used alone or in combination.


The fluidizing agents are not particularly
limited and include silicon compounds such as hydrated
silicon dioxide, light silicic anhydride, etc. These
fluidizing agents may be used alone or in combination.
The lubricants are not particularly limited
and include magnesium stearate, calcium stearate,
stearic acid, sucrose fatty acid esters, talc, etc.
These lubricants may be used alone or in combination.
The correctives are not particularly limited
and include glutamic acid, fumaric acid, succinic acid,
citric acid, sodium citrate, tartaric acid, malic acid,
ascorbic acid, sodium chloride, 1-menthol, etc. These
correctives may be used alone or in combination.
The flavoring materials are not particularly
limited and include orange, vanilla, strawberry,
yogurt, menthol, oils (e.g. fennel oil, cinnamon oil,
orange-peel oil and peppermint oil), green tea powder,
etc. These flavoring materials may be used alone or in
combination.
The coloring matters are not particularly
limited and include food colors (e.g. food red No. 3,
food yellow No. 5 and food blue No. 11), copper
chlorophyllin sodium, titanium oxide, riboflavin, etc.
These coloring maters may be used alone or in
combination.
The sweeteners are not particularly limited
and include aspartame, saccharin, glycyrrhizic acid
dipotassium salt, stevia, maltose, maltitol, thick malt


syrup, powdered sweet hydrangea, etc. These sweeteners
may be used alone or in combination.
When the composition is used as a medicine,
the composition includes, for example, solid
pharmaceutical preparations such as tablets, powders,
fine granules, granules, extracts and pills. They can
be produced by well-known methods such as extrusion
granulation, crushing granulation, fluidized-layer
granulation, high-speed stirring granulation, tumbling
flow granulation and the like. The composition may be
utilized not only as medicines but also as foods (e.g.
confectionery, health food, texture improvers and
dietary fiber supplements), solid foundations, bath
agents, animal drugs, diagnostic drugs, agrochemicals,
fertilizers, ceramic catalysts and the like.
As an example of the composition, tablets are
preferably prepared from the viewpoint of productivity,
the ease of administration/ingestion and the ease of
handling. The tablets are obtained by a direct
tableting method, dry granule compression method, wet
granule compression method, wet granule compression
(extragranular addition of MCC) or the like. Although
the tablets may be multi-core tablets containing, as
inner cores, tablets previously obtained by compression
molding, they are preferably, in particular, tablets
obtained by direct tabletting, from the viewpoint of
cost and ease.
The composition of the invention makes it


possible to impart sustained-release properties to
pharmaceutical preparations by a simple method
including mixing one or more active ingredients with
the functional starch powder of the invention and
formulating the mixture into tablets, a powder,
granules, fine granules or the like using a known
method. Therefore, troublesome operations such as
coating of granules or tablets with a coating agent and
the time and the labor required for the assurance of
production conditions for a constant quality are
unnecessary. Thus, the composition is useful also from
the viewpoint of cost and productivity.
Pharmaceutical preparations containing the
functional starch powder of the invention may have a
coating for taste masking, dampproofing or the like. A
coating agent is not particularly limited and includes,
for example, cellulose type coating agents (e.g. ethyl
cellulose, hydroxypropylmethyl cellulose phthalate,
carboxymethylethyl cellulose, hydroxypropylmethyl
cellulose acetate succinate, cellulose acetate
succinate, cellulose acetate phthalate and cellulose
acetate), acrylic polymer type coating agents (e.g.
Eudragit RS, Eudragit L and Eudragit NE), shellac and
silicone resins. These coating agents may be used
alone or in combination. As a method for using these
coating agents, a well-known method can be adopted.
The coating agents may be dissolved in an organic
solvent or suspended in water. A suspension of the


coating agent in water may be granulated together with
a pharmaceutically active ingredient(s) and other
components.
The pharmaceutical preparations containing
the functional starch powder of the invention include
those which permit sustained release of an active
ingredient(s) by diffusion from a gel layer formed from
only the functional starch powder of the invention or a
gel layer formed substantially from the functional
starch powder of the invention used in combination with
another release-sustaining base ingredient. These
pharmaceutical preparations can be prepared by well-
known methods such as mixing, stirring, granulation,
particle size regulation, tabletting, etc. The phrase
"formed substantially from the functional starch powder
of the invention" means that the functional starch
powder of the invention is incorporated into the
pharmaceutical preparation in order to endow the
pharmaceutical preparation with the various functions
of the functional starch powder of the invention, such
as a function of increasing the resistance to α-
amylase, a function of enhancing the sustained-release
capability and a function of assuring the sustained-
release capability in a medium having a high ionic
strength. For example, if formulation into a
pharmaceutical form and the impartment of sustained-
release properties can be achieved by the addition of
the functional starch powder of the invention in a case


where a release-sustaining base ingredient such as
HPMC, methyl cellulose, HPC or the like is co-used
which does not bring about a sufficient sustained-
release effect under a high ionic strength, the
achievement can be considered to be attributable to the
effect of the functional starch powder of the
invention.
The invention is illustrated in detail with
the following examples, which should not be construed
as limiting the scope of the invention. Methods for
measuring physical properties in the examples and
comparative examples are as follows.
(1) Volume ratio
The term "volume ratio" is defined as [b/a]3
when average particle sizes before and after swelling
are taken as a (µm) and b (µm) , respectively. The
average particle size referred to here is calculated by
summing up the maximum diameters "m" -(µm) of individual
particles observed under an optical microscope
(magnification: 10, OPTIPHOT-POL mfd. by Nikon) and
dividing the sum by the number "n" of particles
subjected to the measurement (Σm/n). The average
particle size is calculated for each of the following:
starch particles before swelling, and starch particles
swollen by heating at 60 to 150°C.
(2) Water retention capacity (%)
Wo (g) (about 1 g) of dried starch powder is
placed in small portions in a 50-ml centrifuge tube


containing about 15 ml of pure water and dispersed in
the pure water while stirring until the dispersion
becomes transparent or semitransparent. Pure water was
added to fill the 50-ml centrifuge tube about 70% full
therewith, followed by centrifugation (2000G, 10
minutes). After completion of the centrifugation, the
separated upper layer is immediately discarded and then
the water retention capacity is calculated from the
weight W (g) of the residue as the lower layer (the
total weight of starch and pure water retained by the
starch) by the following equation:
Water retention capacity(%) = 100 x [W - Wo] /
Wo
(3) Collapse time (hr)
The term "collapse time" is defined as the
disintegration time, in a test solution, of a
cylindrical molded article with a diameter of 0.8 cm
obtained by compressing 0.2 g of starch powder at 50
MPa. The test solution is the second solution (pH 6.8)
described in the Japanese Pharmacopoeia (14th revision,
p. 204) and a disintegration test is carried out by the
use of an auxiliary plate according to the
disintegration test method described in the Japanese
Pharmacopoeia (14th revision).
(4) Gel indentation load (g)
The term "gel indentation load" is defined as
a maximum load applied when a cylindrical adapter is
pressed for 3 mm at a rate of 0.1 mm/sec with a


rheometer (RHEONER, RE-33005, mfd. by YAMADEN) into a
gel obtained by immersing, for 4 hours in pure water, a
cylindrical molded article with a diameter of 1.13 cm
obtained by compressing 0.5 g of starch powder at 50
MPa. The term "maximum load" means the following: when
a gel layer is broken, the term means a maximum load
value at the time of the breaking; and when the gel
layer is not broken, the term means a maximum load
value, which the adapter applies before it intrudes for
5 mm into the gelled cylindrical molded article. The
maximum load is calculated as the average of five
measurements.
(5) Amount (% by weight) of swollen or dissolved
amylose and amylopectin
The amount of swollen or dissolved amylose
and amylopectin is determined by dispersing about 1 g
of dried starch powder in 100 cm3 of pure water, allowing
the resulting dispersion to stand for 16 hours,
calculating the volume of the upper layer portion of
the dispersion separated into upper and lower layers
and the weight percentage of solids in 30 cm3 of the
upper layer, and calculating the amount by the
following equation:
The amount (% by weight) of swollen or
dissolved amylose and amylopectin = the volume (cm3) of
the upper layer portion ÷ 30 x the weight (g/cm3) of
solids in 30 cm3 of the upper layer ÷ the dry weight (g)
of the starch powder x 100


(6) Particle size (µm) of starch particles
The term "particle size of starch particles"
is defined as the maximum diameter of a single particle
when the starch particles are observed at a
magnification of 200 to 1500 by the use of SEM (JEOL
JSM-5510LV, mfd by JEOL LTD.; vapor deposition of Pt;
JEOL JFC-1600 AUTO FINE COATER, mfd by JEOL LTD.). If
single particles aggregate, then the diameter of the
multi-particle aggregate is not considered in the
particle size evaluation. However, even if particles
are aggregated, their diameters can be considered as
the particle size referred to when the boundary
surfaces among the particles are clear and the maximum
diameter of the single particle is clear because of,
for example, the small size of the aggregated
particles. The reason is that the maximum diameter of
a single particle among them is precise.
(7) Degree of swelling (cm3/g)
Degree of swelling is determined by
dispersing about 1 g of dried starch powder in 100 cm3
of pure water, allowing the resulting dispersion to
stand for 16 hours, and calculating the degree of
swelling from the volume V of the lower layer portion
of the dispersion separated into upper and lower
layers, by the following equation:
Degree of swelling (cm3/g) = V (cm3) / the dry
weight (g) of the starch powder
(8) Shell structure


As to the shell structure, 1 g of starch
powder is dispersed in 100 cm3 of pure water and after
standing for 16 hours, the lower layer portion of the
dispersion separated into upper and lower layers is
observed under an optical microscope (magnification:
10). In the case of the starch powder of the
invention, the shell structure inherent in a starch raw
material for the starch powder is completely present
without loss thereof. On the other hand, in the case
of pregelatinized starch, nothing is observed in the
lower layer portion, or a flaky, massive or the like
shell structure formed by the conversion of swollen or
dissolved amylose and amylopectin to (β-amylose and (β-
amylopectin is observed in the lower layer portion.
[Example 1]
A starch emulsion having a solid
concentration of 5% was prepared by using potato starch
as a starting material. The starch emulsion was
gelatinized by heating at 95°C for 45 minutes in a
jacketed agitation vessel (4 L), diluted 2-fold with
warm water at 60°C, and then continuously spray-dried at
a flow rate of 8.3 L/hr while being maintained at 60°C,
to obtain starch powder A. A cylindrical molded
article with a diameter of 0.8 cm was obtained by
compressing 0.2 g of prepared powder of acetaminophen
(APAP)/starch powder A/crystalline cellulose "Ceolus"
KG-802 (weight ratio: 10/60/30) at 60 MPa with a
static-pressure press, and was subjected to a release-


by-dissolution test. As test solutions, there were
used solution I (pH 1.2), solution II (pH 6.8, ionic
strength 0.14) and Mcilvaine solution (pH 7.2, ionic
strength 0.39) described in the Japanese Pharmacopoeia.
The test was carried out by adding α-amylase to each of
these solutions to a concentration of 5 µm/cm3.
Table 1 shows the physical properties of
starch powder A, and Table 2 shows the release-by-
dissolution test result of the molded article of the
prepared powder. The molded article containing starch
powder A was not disintegrated in the test solutions
even after the lapse of 8 hours. It had a sustained-
release capability equal to that imparted by release-
sustaining base ingredients which have been generally
used. In addition, the molded article was free from pH
dependence and the influence of ionic strength and
moreover, had a good stability over a long period of
time. Thus, it can be seen that the molded article is
an excellent pharmaceutical preparation.
[Example 2]
Potato starch was packed in a stainless-steel
vat (50 cm x 25 cm) to a thickness of 5 cm, subjected
to pressure reduction (600 mmHg) in a pressure
container for 5 minutes, and then treated with
compressed steam (120°C) for 20 minutes. Using the
treated potato starch as a starting material, a starch
emulsion having a solid concentration of 5% was
prepared. The starch emulsion was gelatinized by


heating at 95°C for 45 minutes in a jacketed agitation
vessel (4 L), diluted 2-fold with warm water at 60°C,
and then continuously spray-dried at a flow rate of 8.3
L/hr while being maintained at 60°C, to obtain starch
powder B. A cylindrical molded article with a diameter
of 0.8 cm was obtained by compressing 0.2 g of prepared
powder of acetaminophen (APAP)/starch powder
B/crystalline cellulose "Ceolus" KG-802 (weight ratio:
10/60/30) at 60 MPa with a static-pressure press, and
was subjected to a release-by-dissolution test. As
test solutions, solution I (pH 1.2), solution II (pH
6.8, ionic strength 0.14) and Mcilvaine solution (pH
7.2, ionic strength 0.39) were used as described in the
Japanese Pharmacopoeia. The test was carried out by
adding α-amylase to each of these solutions to a
concentration of 5 µm/cm3.
Table 1 shows the physical properties of
starch powder B, Table 2 shows the release-by-
dissolution test result of the molded article of the
prepared powder, and Fig. 1 shows an electron
micrograph (600 magnifications) of starch powder B.
Table 3 shows the result of subjecting the cylindrical
molded article to a release-by-dissolution test in the
same manner as above after storing the cylindrical
molded article in a sealed-in state at 40°C and 75%RH
for 2 weeks. The molded article containing starch
powder B was not disintegrated in the test solutions
even after the lapse of 8 hours. It had a sustained-


release capability equal to that imparted by release-
sustaining base ingredients that have been generally
used. In addition, the molded article was free from pH
dependence and the influence of ionic strength and
moreover, had a good stability over a long period of
time. Thus, it can be seen that the molded article is
an excellent pharmaceutical preparation.
[Example 3]
Potato starch was packed in a stainless-steel
vat (50 cm x 25 cm) to a thickness of 5 cm, subjected
to pressure reduction (600 mmHg) in a pressure
container for 5 minutes, and then treated with
compressed steam (120°C) for 20 minutes. Using the
treated potato starch as a starting material, a starch
emulsion having a solid concentration of 5% was
prepared. The starch emulsion was gelatinized (outlet
temperature: 105°C) by heating at 20 L/hr in a jet
cooker, continuously passed through a residence tube
(85°C) with a capacity of 3 L, and then spray-dried to
obtain starch powder C. The residence time was 9
minutes.
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using starch
powder C. Table 1 shows the physical properties of
starch powder C and Table 2 shows the release-by-
dissolution test result of the molded article of
prepared powder. The molded article containing starch


powder C was not disintegrated in the test solutions
even after the lapse of 8 hours. It had a sustained-
release capability equal to that imparted by release-
sustaining base ingredients that have been generally
used. In addition, the molded article was free from pH
dependence and the influence of ionic strength. Thus,
it can be seen that the molded article is an excellent
pharmaceutical preparation.
[Example 4]
Potato starch was packed in a stainless-steel
vat (50 cm x 25 cm) to a thickness of 5 cm, subjected
to pressure reduction (600 mmHg) in a pressure
container for 5 minutes, and then treated with
compressed steam (120°C) for 20 minutes. Using the
treated potato starch as a starting material, a starch
emulsion having a solid concentration of 5% was
prepared. The starch emulsion was gelatinized (outlet
temperature: 120°C) by heating at 20 L/hr in a jet
cooker, continuously passed through a residence tube
(120°C) with a capacity of 3 L, and then spray-dried to
obtain starch powder D. The residence time was 9
minutes.
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using starch
powder D. Table 1 shows the physical properties of
starch powder D, and Table 2 shows the release-by-
dissolution test result of the molded article of


prepared powder. The molded article containing starch
powder D was not disintegrated in the test solutions
even after the lapse of 8 hours. It had a sustained-
release capability equal to that imparted by release-
sustaining base ingredients that have been generally
used. In addition, the molded article was free from pH
dependence and the influence of ionic strength. Thus,
it can be seen that the molded article is an excellent
pharmaceutical preparation.
[Example 5]
Potato starch was packed in a stainless steel
vat (50 cm x 25 cm) to a thickness of 5 cm, subjected
to pressure reduction (600 mmHg) in a pressure
container for 5 minutes, and then treated with
compressed steam (130°C) for 20 minutes. Using the
treated potato starch as a starting material, a starch
emulsion having a solid concentration of 5% was
prepared. The starch emulsion was gelatinized (outlet
temperature: 115°C) by heating at 20 L/hr in a jet
cooker, and then spray-dried to obtain starch powder E.
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using starch
powder E. Table 1 shows the physical properties of the
starch powder and Table 2 shows the release-by-
dissolution test result of the molded article of
prepared powder. The molded article containing starch
powder E was not disintegrated in the test solutions


even after the lapse of 8 hours. It had a sustained-
release capability equal to that imparted by release-
sustaining base ingredients that have been generally
used. In addition, the molded article was free from pH
dependence and the influence of ionic strength. Thus,
it can be seen that the molded article is an excellent
pharmaceutical preparation.
[Example 6]
Potato starch was packed in a stainless-steel
vat (50 cm x 25 cm) to a thickness of 5 cm, subjected
to pressure reduction (600 mmHg) in a pressure
container for 5 minutes, and then treated with
compressed steam (120°C) for 20 minutes. Using the
treated potato starch as a starting material, a starch
emulsion having a solid concentration of 5% was
prepared. The starch emulsion was gelatinized (outlet
temperature: 100°C) by heating at 20 L/hr in a jet
cooker, continuously passed through a residence tube
(100°C) with a capacity of 3 L, and then spray-dried to
obtain starch powder F. The residence time was 9
minutes.
In an agitation granulator (Vertical
Granulator FM-VG-10, mfd. by Powrex Co.) 15 g of starch
powder F, 1120 g of 200M lactose (Pharmatose 200M, mfd.
by DMV International) and 480 g of official corn starch
(mfd. by Nippon Starch Chemical Co., Ltd.) were placed
and premixed for 3 minutes under conditions of a blade
revolution rate of 280 rpm and a cross-screw revolution


rate of 3000 rpm. Then, 400 g of pure water was added
all at once as binding water, followed by granulation
for 3 minutes under conditions of a blade revolution
rate of 280 rpm and a cross-screw revolution rate of
3000 rpm. The resulting granulation product was dried
on trays at 60°C for 16 hours and then sifted through a
screen having a screen opening of 1410 urn, and granules
that could pass through the screen were used as
granules A for tabletting. To granules A for
tabletting was added magnesium stearate in an amount of
0.5% by weight based on the weight of the resulting
mixture, and the mixture was compressed into tablets at
a compression pressure of 5 kN, 10 kN or 15 kN with a
rotary tabletting machine (Clean Press, correct 12HUK,
mfd. by Kikusui Seisakusho Ltd.) under the following
conditions: 54 rpm, attachment of a Φ8mm-12R pestle,
and open feed.
Table 1 shows the physical properties of
starch powder F and Fig. 2 shows an electron micrograph
(600 magnifications) of starch powder F. Fig. 9 shows
the particle size distribution of granules A for
tabletting and Table 4 shows physical properties of the
tablets obtained. Granules A for tabletting produced
by adding starch powder F in the form of powder showed
the sharp particle size distribution and the tablets
produced from granules A for tabletting had a high
hardness and excellent disintegrating properties.
The weight frequency (%) in Fig. 9 is

explained below. Using IS screens having screen
openings of 45, 75, 106, 150, 212, 250, 300, 500 and
710 µm, respectively, 10 g of the granules for
tabletting are sieved with a low-tap screen classifier
for 10 minutes, and the weight percentage of granules
remaining on each screen is calculated and converted to
a weight frequency (at intervals of 10 urn) in each of
the above screen opening ranges. For example, when the
weight percentage of granules for tabletting in the
screen opening range of 45 µm to 75 urn is a (%), the
weight frequency b is calculated to be [a/(75-45)] x
10(%) by conversion. The same applies to Figs. 10 to
12 described hereinafter.
[Example 7]
Placed in a vessel was 500 g of pure water,
and 40 g of starch powder E of Example 5 was added in
small portions while stirring at 5000 rpm in a TK
homomixer (Model MARKII, mfd. by Tokushu Kika Kogyo
Co., Ltd.). After the whole amount of starch powder E
was added, the resulting mixture was stirred for 30
minutes to obtain a homogeneous suspension of starch
powder E. In an agitation granulator (Vertical
Granulator FM-VG.-10, mfd. by Powrex Co.) were placed
1120 g of 200M lactose (Pharmatose 200M, mfd. by DMV
International) and 480 g of official corn starch (mfd.
by Nippon Starch Chemical Co., Ltd.), and premixed for
3 minutes under conditions of a blade revolution rate
of 280 rpm and a cross-screw revolution rate of 3000


rpm. Then, 400 g of the homogeneous suspension of
starch powder E obtained above was added all at once as
a binder, followed by granulation for 3 minutes under
conditions of a blade revolution rate of 280 rpm and a
cross-screw revolution rate of 3000 rpm. The
granulation product obtained was dried on trays at 60°C
for 16 hours and then sifted through a screen having a
screen opening of 1410 µm, and granules that could pass
through the screen were used as granules B for
tabletting. To granules B for tabletting was added
magnesium stearate in an amount of 0.5% by weight based
on the weight of the resulting mixture, and the mixture
was compressed into tablets at a compression pressure
of 5 kN, 10 kN or 15 kN with a rotary tabletting
machine (Clean Press, correct 12HUK, mfd. by Kikusui
Seisakusho Ltd.) under the following conditions: 54
rpm, attachment of a Φ8mm-12R pestle, and open feed.
Fig. 11 shows the particle size distribution
of granules B for tabletting and Table 4 shows physical
properties of the tablets obtained. Granules B for
tabletting produced by adding starch powder E in the
form of the suspension showed the sharp particle size
distribution and the tablets produced from granules B
for tabletting had a high hardness and excellent
disintegrating properties.
[Comparative Example 1]
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same


procedure as in Example 1 except for using commercial
potato pregelatinized starch (Matsunorin M, mfd. by
Matsutani Chemical Industry Co., Ltd.) in place of
starch powder A. Table 1 shows the physical properties
of the commercial potato pregelatinized starch, Fig. 3
shows an electron micrograph (100 magnifications) of
this pregelatinized starch, and Table 2 shows the
release-by-dissolution test result of the molded
article of prepared powder.
The commercial potato pregelatinized starch
had a collapse time of 5 hr or more and a sufficient
water retention capacity, but it could not have a
sufficient release-sustaining capability because of its
low gel indentation load and because it exhibited no
release-sustaining capability at a high pH or a high
ionic strength.
[Comparative Example 2]
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using commercial
corn pregelatinized starch (mfd. by Sanwa Cornstarch
Co., Ltd.) in place of starch powder A. Table 1 shows
the physical properties of the commercial corn
pregelatinized starch, Fig. 4 shows an electron
micrograph (200 magnifications) of this pregelatinized
starch, and Table 2 shows the release-by- dissolution
test result of the molded article of prepared powder.
The commercial corn pregelatinized starch had


a collapse time of less than 5 hr and a sufficient
water retention capacity but it had substantially no
release-sustaining capability because of its low gel
indentation load.
[Comparative Example 3]
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using commercial
high-amylose corn pregelatinized starch (mfd. by Sanwa
Cornstarch Co., Ltd.) in place of starch powder A.
Table 1 shows the physical properties of the commercial
high-amylose corn pregelatinized starch, Fig. 5 shows
an electron micrograph (100 magnifications) of this
pregelatinized starch, and Table 2 shows the release-
by-dissolution test result of the molded article of
prepared powder.
The commercial high-amylose corn
pregelatinized starch had a collapse time of 5 hr or
less and an insufficient water retention capacity and
exhibited no release-sustaining properties at all.
[Comparative Example 4]
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using commercial
waxy corn pregelatinized starch (mfd. by Sanwa
Cornstarch Co., Ltd.) in place of starch powder A.
Table 1 shows the physical properties of the commercial
waxy corn pregelatinized starch, Fig. 6 shows an


electron micrograph (200 magnifications) of this
pregelatinized starch, and Table 2 shows the release-
by-dissolution test result of the molded article of
prepared powder.
The commercial waxy corn pregelatinized
starch had a sufficient water retention capacity but it
had a collapse time of 5 hr or less and exhibited no
release-sustaining properties at all.
[Comparative Example 5]
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using commercial
partly pregelatinized starch (PCS, mfd. by Sanwa
Cornstarch Co., Ltd.) in place of starch powder A.
Table 1 shows the physical properties of PCS, Fig. 7
shows an electron micrograph (400 magnifications) of
PCS, and Table 2 shows the release-by-dissolution test
result of the molded article of prepared powder.
PCS had a sufficient water retention capacity
but it had a collapse time of 5 hr or less and
exhibited no release-sustaining properties at all.
[Comparative Example 6]
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using commercial
partly pregelatinized starch (Starch 1500) in place of
starch powder A. Table 1 shows the physical properties
of Starch 1500 and Table 2 shows the release-by-


dissolution test result of the molded article of
prepared powder.
Starch 1500 had an insufficient water
retention capacity and a collapse time of 5 hr or less
and exhibited no release-sustaining properties at all.
[Comparative Example 7]
A release-by-dissolution test on a molded
article of prepared powder was carried out by the same
procedure as in Example 1 except for using a commercial
release-sustaining base ingredient of non-starch type
(HPMC 60SH, mfd. by Shin-Etsu Chemical Co., Ltd.) in
place of starch powder A. Table 1 shows the physical
properties of HPMC 60SH and Table 2 shows the release-
by-dissolution test result of the molded article of
prepared powder.
HPMC 60SH was sufficient in collapse time,
gel indentation load, water retention capacity and
release-sustaining capability and desirably had no pH
dependence. But it was found that at a high ionic
strength, HPMC 60SH becomes unable to be sufficiently
hydrated, and exhibited no release-sustaining
properties at all.
[Comparative Example 8]
Official corn starch was made into a 3% by
weight slurry and the slurry was completely gelatinized
by heating at 90°C and sprayed into an atmosphere of an
inlet temperature of 180°C and an outlet temperature of
90°C at a slurry feed rate of 5 L/hr with a spray dryer


having a two-fluid nozzle, to obtain starch powder G.
A release-by-dissolution test on a molded article of
prepared powder was carried out by the same procedure
as in Example 1 except for using starch powder G in
place of starch powder A.
Table 1 shows the physical properties of
starch powder G, Fig. 8 shows an electron micrograph
(400 magnifications) of starch powder G, and Table 2
shows the release-by-dissolution test result of the
molded article of prepared powder. Starch powder G had
an insufficient water retention capacity and a collapse
time of 5 hr or less and exhibited no release-
sustaining properties at all.
[Comparative Example 9]
Granules C for tabletting were obtained by
the same procedure as in Example 6 except for using 4 8
g of commercial hydroxypropyl cellulose (HPC-L, mfd. by
Nippon Soda Co., Ltd.) in place of 15 g of starch
powder F. Tablets were produced by the same procedure
as in Example 6 except for using granules C for
tabletting. Fig. 10 shows the particle size
distribution of granules C for tabletting and Table 4
shows physical properties of the tablets obtained.
Granules C for tabletting produced by adding
HPC-L in the form of powder had the broad particle size
distribution, and the tablets produced from granules C
for tabletting had a lower hardness and a longer
disintegration time than did the tablets produced from


granules A for tabletting in Example 6.
[Comparative Example 10]
Granules D for tabletting were obtained by
the same procedure as in Example 7 except for using
commercial hydroxypropyl cellulose (HPC-L, mfd. by
Nippon Soda Co., Ltd.) in place of starch powder E.
Tablets were produced, by the same procedure as in
Example 7 except for using granules D for tabletting.
Fig. 12 shows the particle size distribution of
granules D for tabletting and Table 4 shows physical
properties of the tablets obtained.
Granules D for tabletting produced by adding
HPC-L in the form of a solution had the sharp particle
size distribution, but the tablets produced from
granules D for tabletting had a lower hardness and a
longer disintegration time than did the tablets
produced from granules B for tabletting in Example 7.







INDUSTRIAL APPLICABILITY
The functional starch powder of the present
invention has a high resistance to α-amylase, a high
resistance to ionic strength and a sufficient release-
sustaining capability. Therefore, the functional
starch powder is used in medicines, agrochemicals,
fertilizers, feed, food, industry, cosmetics, etc. in
the form of a composition comprising the functional
starch powder and one or more active ingredients
selected from pharmaceutically active ingredients,
agrochemical ingredients, ingredients for fertilizer,
ingredients for feed, ingredients for food, ingredients
for cosmetic, coloring maters, flavoring materials,
metals, ceramics, catalysts and surfactants, which
composition permits control of the release of the
active ingredient(s).


CLAIMS
[1] A functional starch powder having a water
retention capacity of 400% or more, a collapse time of
5 hr or more and a gel indentation load of 200 g or
more.
[2] A functional starch powder according to claim
1, wherein the powder was dispersed in water, and the
amount of amylose and amylopectin ranges from 10 to 90%
by weight and is in a swollen or dissolved state.
[3] A functional starch powder according to claim
1 or 2, which comprises starch particles with a
particle size of 50 to 500 urn having a structure
indented in one or more parts.
[4] A composition comprising functional starch
powder according to any one of claims 1 to 3 and one or
more active ingredients.
[5] A composition according to claim 4, wherein
the one or more active ingredients are selected from
pharmaceutically active ingredients, agrochemical
ingredients, ingredients for fertilizer, ingredients
for feed, ingredients for food, ingredients for
cosmetic, coloring maters, flavoring materials, metals,
ceramics, catalysts and surfactants.
[6] A composition according to claim 4 or 5,
which controls the release of the active ingredient (s)
so that the release may be sustained release or rapid
release.
[7] A method for producing functional starch


[7] A method for producing functional
starch powder according to any one of claims 1 to 3,
which comprises heating a starch raw material in the
presence of water at 60 to 100°C to swell starch
particles of the starch raw material, and subsequently
drying the swollen starch particles to obtain a powder
mixture comprising starch particles and amylose and
amylopectin which are present in the exteriors of these
starch particles.
[8] A method for producing functional
starch powder according to any one of claims 1 to 3,
which comprises heating a starch raw material in the
presence of water at 60 to 100°C to swell some or all of
starch particles of the starch raw material at a volume
ratio of 10 or more, and subsequently drying the
swollen starch particles to obtain a powder mixture
comprising starch particles having a structure indented
in one or more parts thereof and amylose and
amylopectin which are present in the exteriors of these
starch particles.
[9] A method for producing functional starch
powder according to any one of claims 1 to 3, which
comprises heat-treating a starch raw material at 100 to
130°C under reduced pressure, heating the starch raw
material in the presence of water at 60 to 150°C to
swell starch particles of the starch raw

material, and subsequently drying the swollen starch
particles to obtain a powder mixture comprising starch
particles and amylose and amylopectin which are present
in the exteriors of these starch particles.
[10] A method for producing functional starch-
powder according to any one of claims 1 to 3, which
comprises heat-treating a starch raw material at 100 to
130°C under reduced pressure, heating the starch raw
material in the presence of water at 60 to 150°C to
swell some or all of starch particles of the starch raw
material at a volume ratio of 10 or more, subsequently
drying the swollen starch particles to obtain a powder
mixture comprising starch particles having a structure
indented in one or more parts thereof and amylose and
amylopectin which are present in the exteriors of these
starch particles.
[l1] A method according to claim 7, 8, 11 or
12, wherein the starch raw material is potato starch.

Functional starch powder of 400% or more
water retention capacity, 5 hr or more collapse time
and 200 g or more gel indentation load. This
functional starch powder is produced through the step
of heating a starch raw material in the presence of
water at 60 to 150°C so as to swell starch particles of
the starch raw material and the subsequent step of
drying the thus swollen starch particles so as to
obtain a powder mixture comprising starch particles
and, lying in the exterior thereof, amylose and
amylopectin.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=lQHS0iWoDzbAyousQM05Og==&loc=wDBSZCsAt7zoiVrqcFJsRw==


Patent Number 271439
Indian Patent Application Number 2121/KOLNP/2008
PG Journal Number 09/2016
Publication Date 26-Feb-2016
Grant Date 22-Feb-2016
Date of Filing 27-May-2008
Name of Patentee SANWA CORNSTARCH CO., LTD.
Applicant Address 594, UNATECHO, KASHIWARA-SHI, NARA
Inventors:
# Inventor's Name Inventor's Address
1 KAZUHIRO OBAE 291-8, NATSUTAMACHI, NOBEOKA-SHI, MIYAZAKI
2 MICHIHIRO SUNAGO 15-6, TENMADAINISHI 2-CHOME, HAIBARACHO, UDA-GUN, NARA
3 JUNICHI TAKAHARA 17-1, MAMIGAOKA 5-CHOME, KASHIBA-SHI, NARA
4 MASAAKI ENDO 23-341, SAKURAZONOMACHI, NOBEOKA-SHI, MIYAZAKI
5 ICHIROU IBUKI 1-8, ASAHIMACHI 3-CHOME, NOBEOKA-SHI, MIYAZAKI
PCT International Classification Number A23K 1/16,C08B 30/12
PCT International Application Number PCT/JP2004/009841
PCT International Filing date 2004-07-09
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 2003-273176 2003-07-11 Japan