U.S. patent application number 11/808996 was filed with the patent office on 2008-02-21 for coated material and process for producing the coated material.
This patent application is currently assigned to Kirin Beer Kabushiki Kaisha. Invention is credited to Takahiro Eguchi, Takahide Kasai, Kimiko Takai.
Application Number | 20080044434 11/808996 |
Document ID | / |
Family ID | 38196762 |
Filed Date | 2008-02-21 |
United States Patent
Application |
20080044434 |
Kind Code |
A1 |
Kasai; Takahide ; et
al. |
February 21, 2008 |
Coated material and process for producing the coated material
Abstract
A coated material and a process for producing the coated
material which includes providing a coating agent comprising yeast
cell wall fractions, as a primary constituent, consisting of cell
residue of yeast which has been treated with enzymes, optionally
subsequently with acidic solution, and water to remove internal
soluble cell constituents; and coating a solid material with the
coating agent to provide a coating thereon.
Inventors: |
Kasai; Takahide;
(Takasaki-shi, JP) ; Eguchi; Takahiro;
(Takasaki-shi, JP) ; Takai; Kimiko; (Takasaki-shi,
JP) |
Correspondence
Address: |
VENABLE LLP
P.O. BOX 34385
WASHINGTON
DC
20043-9998
US
|
Assignee: |
Kirin Beer Kabushiki Kaisha
Tokyo
JP
|
Family ID: |
38196762 |
Appl. No.: |
11/808996 |
Filed: |
June 14, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09514312 |
Feb 28, 2000 |
7238355 |
|
|
11808996 |
Jun 14, 2007 |
|
|
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Current U.S.
Class: |
424/195.16 |
Current CPC
Class: |
A61K 9/5063
20130101 |
Class at
Publication: |
424/195.16 |
International
Class: |
A01N 63/04 20060101
A01N063/04 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 26, 1999 |
JP |
11-50291 |
Claims
1. A coating agent, characterized in which the primary component of
which comprises yeast cell wall fractions consisting of cell
residue obtained by removing the internal soluble cell components
of enzyme-treated yeast.
2. (canceled)
3. A coating agent according to claim 1, characterized in which
said coating agent further comprises a plasticizer.
4. A coated material, on which a coating treatment has been
conducted using a coating agent according to claim 1.
5. A coated material according to claim 4, characterized in which
wherein the coated material is a granular material such as fine
particles, granules, or tablets.
6. A coated material according to claim 4, characterized in which
the coated material is food products, food product materials,
pharmaceutical preparations, enzymes, microorganisms, seeds,
agrochemicals, fertilizers, fragrances, or pigments.
7. A coating film formed by a coating agent according to claim
1.
8. A coating film according to claim 7, characterized in which said
coating film further comprises a plasticizer.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of application Ser. No.
09/514,312, filed Feb. 28, 2000, and claims priority to Japanese
Patent Application No. 11-50291, filed Feb. 26, 1999, the entire
contents of each of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a coating agent which is
safe to use, which can be coated even in 100% water, which affords
a finish that is not sticky despite its viscosity, thus resulting
in coated particles that do not stick to each other, and which has
an extremely low oxygen permeation coefficient, as well as to a
novel, edible coating agent consisting of yeast cell wall fractions
with the function of controlling dissolution time, coated materials
comprising the use of such coating agents, and a coating film
formed from such a coating agent.
[0004] 2. Description of the Related Art
[0005] Fine particles, microcapsules, granules, tablets, and the
like, comprising useful coated substances in a variety of forms or
with various properties, such as colorless or colored dyes,
medicinal products, agrochemicals, fragrances, feed materials, and
food product materials, have conventionally been prepared for
industrial purposes. Known examples of bases for coating
fragrances, feed materials, food product materials, and the like,
specifically, coating agents, include waxes and other oils, natural
polysaccharides, proteins, shellac (natural resin secreted by the
lac insect living in plants such as the legumes) and other resins,
and the like. Chemically synthesized coating bases stipulated for
medicinal additives are also known in the case of medicinal
products.
[0006] Most of such conventionally known coating agents, however,
suffer from the drawback of poor handling; as a result of
stickiness or poor dispersion during the preparation of the coating
liquid. Additional problems with most medicinal additives such as
shellac, zein (corn protein), and ethylcellulose, are their bad
effects on the environment and their high cost because of the use
of solvents such as ethanol have been indicated. Although water
dispersion types of ethylcellulose-based coating agents have become
commercially available recently, these also suffer from problems in
terms of handling, such as the changes in solution properties
depending on temperature conditions during storage, and the
inability to release them in wastewater into rivers because they
contain various solvents. Still another problem is the poor
intestinal dissolution and the extremely slow dissolution speed of
the aforementioned zein which can be used in the field of food
products.
[0007] Attempts have meanwhile been made to develop film materials
from yeast. Japanese Patent Publication (Kokoku) S56-19971, for
example, discloses an edible protein film based on water-soluble
proteins produced by removing the yeast cell membrane components
from residual yeast which was produced by extracting nucleic acid.
Japanese Laid-Open Patent Application (Kokai) S53-45385 discloses a
method for producing a film, wherein the cells of a microorganism
such as yeast are heated and alkali treated, acid is added for
treatment involving isoelectric precipitation, the pH of the
resulting precipitate is adjusted to between 6 and 8, and a
plasticizer is added to the resulting gel-forming microorganism
cells to produce a constituent.
[0008] Methods are also known for decoloring and deodorizing
substances primarily comprising the cell walls left over in the
form of residue during the extraction of yeast extract. Japanese
Laid-Open Patent Application (Kokai) H4-248968, for example,
discloses a method for decoloring and deodorizing yeast extract
residue, wherein extract residue is treated with alkali and acid,
is then treated with 1000 to 2000 ppm ozone, and is treated with
ethanol before and after the ozone treatment. Japanese Laid-Open
Patent Application (Kokai) H9-103266 discloses a method for
eliminating the flavor and odor of a yeast autolytic insoluble
substance, wherein a yeast autolytic insoluble substance is
suspended in ethanol, and is stirred and treated in the presence of
an alkali.
[0009] However, it has not been known that excellent use as a
coating agent can be made, without additional chemical treatment,
of yeast cell wall fractions consisting of yeast extract residue,
for example, such as extract residue obtained after the components
in soluble cells have been removed following the autolysis of live
yeast cream at 40 to 50.degree. C., or that further treatment of
such yeast cell wall fractions with acidic aqueous solution affords
a coating agent with better enteric properties allowing the time at
which dissolution begins to be controlled.
[0010] That is, an object of the present invention is to provide a
coating agent with an extremely low oxygen permeation coefficient,
which remedies the drawbacks of conventional edible coating agents,
for example, by having a finish that is not as sticky, despite its
viscosity, as gums such as gum arabic, resins such as shellac, and
zein or Eudragit, and which results in coated particles that do not
stick to each other, as well as to a coating agent which can be
used as an enteric coating agent capable of controlling the time at
which dissolution begins.
[0011] In the course of research on yeast cell wall fractions
occurring in the form of extract residue of yeast extract,
particularly in the course of research on coating agents utilizing
such yeast cell wall fractions, the inventors unexpectedly found
that residue undergoing no ethanol treatment as described in
Japanese Laid-Open Patent Applications H4-248968 or H9-103266, or
any other chemical treatment during the treatment of the yeast
extract residue had better film-formability, that is, film-forming
properties, than that which had been treated with ethanol, and were
particularly better as coating agents which require film
properties, and that yeast cell wall fractions without any chemical
treatment can be used as an unexpectedly excellent coating agent.
Upon further research on such yeast cell wall fractions, the
present invention was perfected when it was discovered that an
excellent enteric coating agent capable of controlling the time at
which dissolution begins was unexpectedly obtained using only
acidic aqueous solution in varying concentrations, unlike
conventional conditions for treating yeast with both alkali and
acid treatments for deodorization and decolorization.
SUMMARY OF THE INVENTION
[0012] That is, the present invention relates to a coating agent,
characterized in which the primary component of which comprises
yeast cell wall fractions consisting of cell residue obtained by
removing the internal soluble cell components of enzyme-treated
yeast; a coating agent, characterized in which the primary
component of which comprises acid-treated yeast cell wall fractions
consisting of cell residue obtained by removing the internal
soluble cell components of enzyme-treated yeast, the aforementioned
residue being treated with an acidic aqueous solution to further
remove solubilized components; the aforementioned coating agents
which is characterized by further comprising a plasticizer; a
coated material; comprising a material coated with the
aforementioned coating agents; the aforementioned coated material,
characterized in which the coated material comprises a granular
material such as fine particles, granules, or tablets; the
aforementioned coated material, characterized in which the coated
material comprises food products, food product materials, medicinal
preparations, enzymes, microorganisms, seeds, agrochemicals,
fertilizer, fragrances, or pigments; a coating film formed by any
of the aforementioned coating agents; and the aforementioned
coating film, further comprising a plasticizer.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 gives the measured results in dissolving tests with
water using coating agents of which the primary component
comprising the yeast cell wall fractions of the present
invention;
[0014] FIG. 2 gives the measured results in dissolving tests with
water on varying amounts of coating agents of which the primary
component comprising the acid-treated yeast cell wall fractions of
the present invention;
[0015] FIG. 3 gives the measured results in dissolution tests with
artificial gastric juice on varying amounts of coating agents of
which the primary component comprising the acid-treated yeast cell
wall fractions of the present invention;
[0016] FIG. 4 gives the measured results in dissolution tests with
water at varying drying times using coating agents of which the
primary component comprising the acid-treated yeast cell wall
fractions of the present invention;
[0017] FIG. 5 gives the measured results in dissolution tests with
artificial gastric juice at varying drying times using coating
agents of which the primary component comprising the acid-treated
yeast cell wall fractions of the present invention.
[0018] FIG. 6 gives the measured results in dissolution tests with
water on coating agents of which the primary component comprising
the acid-treated yeast cell wall fractions with different acid
concentrations in the present invention;
[0019] FIG. 7 gives the measured results in dissolution tests with
artificial gastric juice at varying drying times using coating
agents of which the primary component comprising the acid-treated
yeast cell wall fractions of the present invention; and
[0020] FIG. 8 gives the measured results in dissolution tests with
water on granules coated with varying amounts of coating agents in
which the primary component comprising the acid-treated yeast cell
wall fractions of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0021] Starting Material Yeast
[0022] Any yeast taxonomically belonging to yeasts may be used as
the yeast serving as the starting material for the coating agent of
the present invention. Examples include brewer's yeast, wine yeast
and baker's yeast. More specific examples include Saccharomyces
cerevisiae, Saccharomyces rouxii, Saccharomyces carlsbergensis,
Candida utilis, Candida tropicalis, Candida lipolytica, and Candida
flaveri.
[0023] Such yeasts can be used alone or in combination. The use of
live yeast is preferred, although yeasts in configurations other
than live yeast such as dried yeast can also be used, and can, for
example, be treated in the same manner as live yeast by being
suspended in water or the like. The size or configuration of the
yeast that is used is not particularly limited, although the
configuration is preferably as close as possible to spherical, and
the size preferably ranges from between 1 and 20 .mu.m.
[0024] Yeast Cell Wall Fractions
[0025] Yeasts contain water- or polar solvent-soluble internal cell
components such as proteins, amino acids, saccharides, nucleic
acids, and organic acids. Such internal cell components are readily
solubilized in water, and when used as a coating agent without the
removal of such soluble internal cell components, not only is the
effect of delaying the time at which for dissolution begins
inhibited, but the coating strength is also compromised. It is thus
necessary to use yeast cell wall fractions obtained by removing the
soluble internal cell components from yeast in order to obtain a
coating agent with an effective time delay before dissolution
begins.
[0026] To obtain yeast cell wall fractions by removing such soluble
internal cell components from the yeast, it is necessary to
solubilize such internal cell components by enzyme treatment to
remove them from the cells. Any enzyme-treatment used during the
production of yeast internal cell components in the form of yeast
extract can be used as the enzyme treatment, such as so-called
autolysis featuring the use of the enzymes inside yeast cells;
methods for adding enzymes, in which external enzymes such as
proteases, nucleases, .beta.-glucanase, esterases, and lipases are
added; or combinations of such methods. This allows effective use
to be made of the extract residue of yeast extract in the
manufacture of common yeast extract, in the form of the yeast cell
wall fractions in the present invention. To speed up or the like,
the enzyme treatment, pretreatment for physically rupturing the
cell walls with a high pressure homogenizer or the like may be
carried out before the enzyme treatment of the yeast. When such a
high pressure homogenizer is used, the material is preferably
dispersed at a pressure of between 100 and 1,000 kg/cm.sup.2, for
example.
[0027] At the completion of the enzyme treatment, the yeast is
treated to remove the soluble internal cell components, such as by
centrifugation, to obtain yeast cell wall fractions in the form of
cell residue. The yeast cell wall fractions thus obtained without
any particular chemical treatment consist of a film that is
relatively durable in physical and chemical terms, consisting of
glucan, mannan, and chitin layers, and can thus be used as an
excellent coating agent capable of encapsulating greater amounts of
substances without compromising the function of protecting the
encapsulated substances. However, the yeast cell wall fractions can
also be prepared with the incorporation of yeast washing
treatments, adjustment of the pH, temperature, or pressure, and the
like as needed.
[0028] Acid-Treated Yeast Cell Wall Fractions
[0029] The acid-treated yeast cell wall fractions can be prepared
in the form of yeast cell residue by treating the yeast with an
enzyme treatment to remove the soluble internal cell components,
and treating the resulting yeast cell wall fractions with an acidic
aqueous solution to then further remove the solubilized components.
More specifically, the aforementioned yeast cell wall fractions can
be treated with 0.01 to 2 N, and preferably 0.1 to 0.5 N, acid such
as hydrochloric acid, sulfuric acid, or nitric acid, the resulting
suspension can be centrifuged or the like to separate the
supernatant and yeast cell residue, and the yeast cell residue can
be harvested to prepare the acid-treated yeast cell wall fractions.
The material is also preferably heated to around 80.degree. C.
during the acid treatment.
[0030] The resulting acid-treated yeast cell wall fractions consist
of a film that is relatively durable in physical and chemical
terms, consisting of glucan, mannan, and chitin layers, and can
thus be used as an excellent enteric coating agent or the like that
is capable of encapsulating greater amounts of a substance without
compromising the function of protecting the encapsulated substance,
and that also allows the time at which dissolution begins to be
controlled by changing the concentration of the acidic water that
is used.
[0031] Coating Agent
[0032] Coating agents in the present invention which are based on
yeast cell wall fractions or are based on acid-treated yeast cell
wall fraction include, in addition to coating agents consisting of
these yeast cell wall fractions and acid-treated yeast cell wall
fractions, coating agents comprising the addition of adjuvants as
needed to these yeast cell wall fractions and acid-treated yeast
cell wall fractions. These yeast cell wall fractions and
acid-treated yeast cell wall fractions can be used as such to
obtain excellent coating agents, but it is sometimes desirable to
use an adjuvant such as a plasticizer to enhance the spreading
properties, water resistance, or the like of the coating film.
Examples of such additives, in the field of food products, include
glycerin, sorbitol, amino acids, organic acids, monoglycerides,
diglycerides, triglycerides, and MCT-based oils, which can be used
specifically as plasticizers. Examples in the field of
pharmaceutical products include triacetin, triethyl citrate,
acetylated monoglycerides, and any other plasticizer given in lists
of pharmaceutical adjuvants.
[0033] Physical Properties of Coating Agents
[0034] The coating agents of the present invention have excellent
properties allowing them to be used as bitterness masking agents or
enteric coating agents which, compared to conventional edible
coating agents, have a nonsticky finish despite their viscosity,
resulting in coated particles that do not stick together, and which
are capable of controlling the time at which dissolution begins.
Coating layers (films) comprising the coating agents of the present
invention have an extremely low oxygen or other gas permeability
and moisture permeability, and are better than existing edible
films, making them suitable for use in a wide range of fields, such
as food products, pharmaceutical products, feed, agrochemicals, and
the like. Conventional coating agent solutions involve the use of
quasi viscous fluids of dissolved polymers or dilatant fluid such
as aqueous suspensions of starch, but the coating agents of the
present invention are plastic fluids, and have different physical
properties than conventional types.
[0035] Encapsulated Substances
[0036] Any substance that is a solid at ordinary temperature can be
used as the encapsulated substance coated by the coating agent of
the present invention. Examples include food products, food product
materials, enzymes, microorganisms, pharmaceutical products, seeds,
agrochemicals, fertilizer, fragrances, and pigments. Examples of
the aforementioned food products and food product materials include
starch food products, tableted food products, Western style
confectionaries (candies, sweets, chocolate, chewing gum, etc.),
Japanese style confectionaries (such as crackers), baked
confectionaries (such as castella, cookies, and crackers), gummy
candies, fried snacks (such as potato chips, snacks, and the like),
various sauces, soy sauce, miso sauce, mayonnaise, or dressings in
the form of powders or solids, various beverages (such as fruit
juices, nectars, carbonated beverages, sports beverages, teas,
coffee, cocoa, soups, and alcoholic beverages) in the form of
powders or solids, various powder extracts (meats such as beef,
pork, or chicken, seafood such as shrimps, scallops, corbicula,
kelp and any marine products, vegetables and fruits, plants, yeast,
etc.), oils and flavoring (vanilla, citrus, bonito, etc.) in the
form of powders or solids, powder spices and herbs (red pepper,
black pepper, Japanese sansho pepper, yuzu citron, basil, and the
like), powdered beverages (such as instant coffee, instant tea,
instant milk, instant soups and miso soups, etc.), various dairy
products (such as cheese), various nutrient and nutritional
supplement foods materials (such as Vitamins A, B, C, D, and E,
Edible microorganism of Bifidobacterium, Lactobacillus, Clostridium
butyricum and other useful bacteria, chlorella, calcium and
magnesium minerals, propolis, and the like), sprinkles, flakes,
toppings (such as croutons), processed soy (such as tofu and bean
curd dregs) in the form of solids, fresh and processed foods (such
as curry and stews) in the form of solids and frozen foods (plain
and coated), and various processed food products. The coating
agents of the present invention are suitable for use when the
encapsulated substance is in granulated form, such as fine
particles, granules, or tablets, or when the encapsulated substance
itself is in a form resembling granules, such as seeds. Such
encapsulated substances can be coated with the coating agent of the
present invention to obtain the coated material of the present
invention. Further, the coating agent of the present invention can
also be used to produce a film without coating an encapsulated
substance in order to obtain the coating film of the present
invention, which has an extremely low oxygen permeation coefficient
or moisture permeation coefficient.
[0037] Coating Process
[0038] The aforementioned encapsulated substances can be coated
with the coating agent of the present invention by producing the
aforementioned encapsulated substances, either individually or in
combination, in the form of granulated products having a suitable
diameter, such as fine particles, granules, or tablets, and coating
them with the coating agent of the present invention suspended in
water or a mixture of water and solvent. Specifically, a coating
device such as the Doria Coater (by Powrex Co., Ltd), for example,
can be used to spray coat the substance to be encapsulated with a
suspension of the coating agent of the present invention, although
any well-known coating method or device can be used.
[0039] The drying temperature during the coating process, that is,
the drying temperature after the encapsulated substance has been
coated with the suspension of the coating agent of the present
invention, is not particularly limited, although the substance
should ordinarily be dried at a temperature of between 60 and
90.degree. C. The drying temperature can be set according to the
temperature stability of the encapsulated substance. Additionally,
the drying time can be extended to obtain effects similar to the
curing effects of latex-type coating agents used in pharmaceutical
adjuvants. And the amount of coating agent is determined according
to the amount of the encapsulated substance that is used, the
intended application, and the like.
EXAMPLES
[0040] The present invention is described in further detail below
with reference to examples, but the technical scope of the present
invention is not limited to these examples. The amounts of the
yeast cells given in the examples are actual weight (dry
weight).
Example 1
[0041] Brewer's yeast-slurry by-product was procured from a beer
plant and was centrifuged for 10 minutes at 4500 rpm, and the
resulting slushy live yeast was suspended in water to a solids
concentration of 5 wt %. The suspension was allowed to undergo
autolysis for 17 hours at 50.degree. C., the product was
centrifuged again to remove the soluble internal cell components,
and the resulting autolysis residue was used as the yeast cell wall
fraction. Then the yeast cell wall fraction was dispersed in water
to a solids concentration of 10 wt %, and glycerin was dispersed as
a plasticizer to 15 wt % of the yeast cell wall fraction solids, so
as to prepare a coating liquid.
[0042] As the encapsulated substance, tablets consisting of 3.6 mg
acetaminophen, 112.8 mg lactose, 3.0 mg HPC-L, and 0.6 mg magnesium
stearate (total of 120 mg/tablet) were formed in advance, and these
tablets were spray coated with the coating liquid using a Doria
Coater (Powrex Co., Ltd) to a tablet:coating agent ratio of 80:20
(weight ratio), giving Samples 1. The resulting Samples 1 were
shelf dried for 0, 30, 60, 90, and 120 minutes at 80.degree. C.,
giving Samples 1-0, 1-30, 1-60, 1-90, and 1-120.
[0043] These samples 1-0, 1-30, 1-60, 1-90, and 1-120, and an
uncoated control (no coating) were tested in dissolution tests
(paddle method) based on the Japan Pharmacopoeia. 500 mL of
37.degree. C. water was used as the solvent in the dissolution
tests with each type of sample tablet to determine the dissolution
rate based on acetaminophen absorption (Abs 242). The results are
given in FIG. 1. FIG. 1 reveals that all of the samples had slower
dissolution than the uncoated control, thus confirming the coating
effects. It may thus be concluded that the present coating agent is
suitable for precoating bitterness masking agents or sugar-coated
tablets.
Example 2
[0044] Samples were prepared in the same manner as in Example 1
except that torula yeast was used instead of the brewer's yeast
used in Example 1. The same dissolution test (paddle method) based
on the Japan Pharmacopoeia revealed results similar to those for
Sample 1 in Example 1.
Example 3
[0045] Brewer's yeast slurry by-product was procured from a beer
plant and was centrifuged for 10 minutes at 4500 rpm, and the
resulting slushy live yeast was suspended in water to a solids
concentration of 5 wt %. 10,000 U of a Zymoliase 20T (Seikagaku
Kogyo) was added to 500 g of the suspension and allowed to act
thereon for 8 hours at 37.degree. C., the mixture was centrifuged
again to remove the soluble internal cell components, and the
resulting autolysis residue was used as the yeast cell wall
fraction. The yeast cell wall fraction was then treated in the same
manner as in Example 1 to prepare samples. The same dissolution
test (paddle method) based on the Japan Pharmacopoeia revealed
results similar to those for Sample 1 in Example 1.
Example 4
[0046] Yeast cell wall fractions obtained in the form of autolysis
yeast residue in Example 1 were suspended in 0.1 N hydrochloric
acid to a solids concentration of 5%, treated with acid for 20
minutes at 80.degree. C., and then centrifuged for 15 minutes at
4500 rpm to remove the solubilized components, and the resulting
residue was used as the acid-treated yeast cell wall fraction. The
acid-treated yeast cell wall fraction was then dispersed in water
to a solids concentration of 7 wt %, and glycerin was dispersed as
a plasticizer to 7 wt % of the yeast cell wall fraction solids, so
as to prepare a coating liquid.
[0047] The aforementioned tablets prepared in advance were then
spray coated with the coating liquid using a Doria Coater (Powrex
Co., Ltd) to a tablet:coating agent weight ratio of 90:10, 80:20,
70:30, and 60:40, giving Samples 2, 3, 4, and 5. The resulting
Samples 2 through 5 were shelf dried for 0, 30, 60, 90, and 120
minutes at 80.degree. C., giving Samples 2-0, 2-30, 2-60, 2-90, and
2-120, Samples 3-0, 3-30, 3-60, 3-90, and 3-120, Samples 4-0, 4-30,
4-60, 4-90, and 4-120, and Samples 5-0, 5-30, 5-60, 5-90, and
5-120.
Example 5
[0048] the dissolution rate based on acetaminophen absorption (Abs
242). The results are given in FIG. 4. FIG. 4 reveals that the
drying time following coating did not have much of an effect on
dissolution behavior when water was used as a dissolution solvent
for Sample 9.
[0049] Samples 9-0, 9-30, 9-60, 9-90, 9-120, and an uncoated
control (no coating) were tested in dissolution tests (paddle
method) based on the Japan Pharmacopoeia. The dissolution solvent
was Japan Pharmacopoeia XIII 1.sup.st fluid (pH1.2), and the
dissolution rate was determined for each sample tablet based on
acetaminophen absorption -(Abs 242) in 500 mL of 37.degree. C.
Japan Pharmacopoeia XIII 1.sup.st fluid (pH1.2). The results are
given in FIG. 5. FIG. 5 reveals that the drying time following
coating did not have much of an effect on dissolution behavior when
artificial gastric juice was used as a dissolution solvent for
Sample 9.
[0050] Samples 3-90, 7-90, 4-90, 5-90, 9-90, and an uncoated
control (no coating) were tested in dissolution tests (paddle
method) based on the Japan Pharmacopoeia. 500 mL of 37.degree. C.
water was used as the solvent in the dissolution tests with each
type of sample tablet to determine the dissolution rate based on
acetaminophen absorption (Abs 242). The results are given in FIG.
6. FIG. 6 reveals that the time at which dissolution began could be
controlled based on the acid treatment conditions. This suggests
that the coating agent of the present invention was also useful as
an enteric coating agent.
Example 6
[0051] Yeast cell wall fractions obtained in the form of autolysis
yeast residue in Example 1 were suspended in 0.5 N hydrochloric
acid to a solids concentration of 5%, treated with acid for 20
minutes at 80.degree. C., and then centrifuged for 15 minutes at
4500 rpm to remove the solubilized components, resulting in
acid-treated yeast cell wall fractions consisting of residue. The
acid-treated yeast cell wall fraction yield was 41.4%, and the
solids concentration was 9.8 wt %.
Example 7
[0052] Samples 10 through 13 were prepared in the same manner as in
Example 4, except that the concentration of the hydrochloric acid
that was used in Example 4 was changed from 0.1 N to 0.5 N, and the
dispersion medium that was used during the preparation of the
coating liquid was changed from water to 100% ethanol. These had
finctions similar to those of Samples 6 through 9. Additionally,
since ethanol was used as the dispersion medium when Samples 10
through 13 were used to coat the tablets, it was possible to set
the tablet product temperature lower than when Samples 6 through 9
were used to coat the tablets. It was thus evident that the coating
agent made lower temperature coating possible.
Example 8
[0053] 1 g agar and 1.47 g glycerin were added to 20 g acid-treated
yeast cell wall fraction prepared by the method described in
Example 5, water was then added to bring the total to 400 g, and
the ingredients were mixed to homogeneity to prepare a coating
liquid. Tablets were then spray coated in the same manner as in
Example 4 to a tablet:coating agent ratio of 100:2, 100:4, 100:6,
100:8, and 100:10, giving Samples 14, 15, 16, 17, and 18. These
samples and an uncoated control (no coating) were used in
dissolution tests (paddle method) based on the Japan Pharmacopoeia.
500 mL of 37.degree. C. Japan Pharmacopoeia XIII 1.sup.st fluid
(pH1.2) was used as the solvent in the dissolution tests with each
type of sample tablet to determine the dissolution rate based on
acetaminophen absorption (Abs 242). The results are given in FIG.
7. FIG. 7 reveals that the dissolution rates were similar with an
amount of coating agent of 100:6 or more, but with a lag time of 1
hour until dissolution started. This suggests that the encapsulated
substance was held by the coating agent, and that the dissolution
design could be changed by adding adjuvants.
Example 9
Manufacture of Dried Bonito Granules, and Coating Effects
[0054] The granule manufacturing step and coating step involved the
use of a Powrex Co., Ltd Multiplex MP-01 model. 135 g of
gelatinized corn starch aqueous solution was sprayed onto 528 g of
dried bonito meal for granulation to produce dried bonito granules.
Yeast cell wall fraction obtained in the form of autolysis yeast
residue in Example 1 was then suspended in 0.5 N hydrochloric acid
to a solids concentration of 5 wt %, it was treated with acid for
20 minutes at 80.degree. C., and it was then centrifuged for 15
minutes at 4500 rpm to remove the solubilized components, and the
resulting residue was used as acid-treated yeast cell wall
fractions. The acid-treated yeast cell wall fraction was then
dispersed in water to a solids concentration of 5 wt %, and
glycerin was dispersed as a plasticizer to 7 wt % of the
acid-treated yeast cell wall fraction solids, so as to prepare a
coating liquid, which was used to spray coat the dried bonito
granules at an air supply temperature of 60.degree. C., an exhaust
temperature of 30.degree. C., and a flow rate of 10 g/min. The
resulting coated product was clearly more effectively prevented
from losing flavor, with the aroma enclosed therein, than uncoated
products.
[0055] It was possible to coat the material even with the exhaust
temperature lowered to 30.degree. C. With shellac, for example, the
lowest exhaust temperature was 35.degree. C. under the same
conditions, and the lowest temperature was 40.degree. C. with
water-based coating agents (such as HPMC). This means that this
coating agent can be used to coat granules (food product materials)
which are extremely vulnerable to heat, such as chocolate or Edible
microorganism of Bifidobacterium.
Example 10
Bitterness Masking Effect on Granules
[0056] The granule manufacturing step and coating step involved the
use of a Powrex Co., Ltd Multiplex MP-01 model. Marker
acetaminophen was layered with 50 mesh DMV lactose, and then sorted
to a size ranging from 16 to less than 48 mesh to prepare
acetaminophen granules. Yeast cell wall fraction obtained in the
form of autolysis yeast residue in Example 1 was suspended in 0.5 N
hydrochloric acid to a solids concentration of 5 wt %, it was
treated with acid for 20 minutes at 80.degree. C., and it was then
centrifuged for 15 minutes at 4500 rpm to remove the solubilized
components, and the resulting residue was used as acid-treated
yeast cell wall fractions. The acid-treated yeast cell wall
fraction was then dispersed in water to a solids concentration of 5
wt %, and glycerin was dispersed as a plasticizer to 7 wt % of the
acid-treated yeast cell wall fraction solids, so as to prepare a
coating liquid. The coating liquid was used to spray coat 500 g
acetaminophen granules at an air supply temperature of 60.degree.
C., an exhaust temperature of 32.degree. C., and a flow rate of 12
g/min. The granules were coated in amounts of 5, 10, 15, and 20%
relative to the granules, giving Samples 19, 20, 21, and 22.
[0057] Samples 19, 20, 21, 22 and an uncoated control (plain
granules) were tested in dissolution tests (paddle method) based on
the Japan Pharmacopoeia. 500 mL of 37.degree. C. water was used as
the solvent in the dissolution tests with 50 mg of each type of
sample granule based on the uncoated weight to determine the
dissolution rate based on acetaminophen absorption (Abs 242). The
results are given in FIG. 8.
[0058] FIG. 8 reveals no drug dissolution with a 20% coating after
30 seconds. Since a lag time of 30 seconds is generally required
until a drug begins to dissolve for the purposes of masking the
bitterness of drugs, this example would be effective as a coating
agent for masking bitterness. These results are quantitative
measurement data, and may be considered more stringent data than
organoleptic evaluation by humans.
Example 11
Oxygen Permeation Test
[0059] Glycerin as a plasticizer was dispersed in water to 10 wt %
of the acid-treated yeast cell fraction solids concentration in a
solution with an acid-treated yeast fraction solids concentration
of 5 wt % prepared by the method in Example 5, and the ingredients
were homogenized to produce a coating liquid. The coating liquid
was then introduced into Petri dishes and dried over night at
40.degree. C., resulting in a cast film 0.059 mm thick. An oxygen
permeability test was conducted in accordance with JIS K 7126B. The
test device was an OX-TRAN 10/50 by Mocon (Modern Controls). The
conditions of measurement comprised a temperature of 23.degree. C.,
0% humidity, a test surface area of 50 cm.sup.2, and an oxygen
concentration of 100%.
Example 12
Water Vapor Permeation Test
[0060] The coating liquid prepared in Example 11 was used. In the
same manner as in Example 11, the coating liquid was introduced
into Petri dishes and dried over night at 40.degree. C., resulting
in a cast film 0.055 mm thick. A water vapor permeability test was
conducted in accordance with JIS Z 0208. The test devices were a
hygrothermalstatic chamber PL4SP by Tabaiesupekku Co., Ltd and
scales AE200 by Mettler-Toledo Ag. The conditions of measurement
comprised a temperature of 40.degree. C., a humidity of 50% RH, and
a test surface area of 28.26 cm.sup.2. The results revealed a
moisture permeability of 322 (g/M.sup.2dayatm) and a moisture
permeation coefficient of 17.6 (gmm/m.sup.2dayatm). These results
indicate that the coating film based on the coating agent of the
present invention had an extremely low moisture permeation
coefficient.
Comparative Example 1
[0061] The yeast cell wall fraction obtained in the form of
autolysis yeast residue in Example 1 was meanwhile suspended in 0.5
N sodium hydroxide to a solids concentration of 5 wt %, then
treated with alkali for 20 minutes at 80.degree. C., and then
centrifuged for 15 minutes at 4500 rpm to remove the solubilized
components, and the resulting residue was resuspended in 0.5 N
hydrochloric acid to a solids concentration of 5 wt %, treated with
acid for 20 minutes at 80.degree. C., and centrifuged for 15
minutes at 4500 rpm to remove the solubilized components, giving an
alkali- and acid-treated yeast cell wall fraction consisting of the
resulting residue. The yield of the alkali- and acid-treated yeast
cell wall fraction was 15.8%, and the solids were 7.3 wt %.
[0062] The yield of the yeast cell wall fraction in Comparative
Example 1 was about as low as 38% of that in Example 6. The
combined alkali and acid treatments dramatically lowered the yield
compared to that obtained with acid treatment alone. Whereas the
acid-treated yeast cell wall fraction of Example 6 had a viscosity
of 1 at a solids concentration of 10 wt %, the alkali- and
acid-treated yeast cell wall fraction of Comparative Example 1 had
a viscosity of 21.9 at a solids concentration of 10 wt %, and
because of this high viscosity, coating with the latter took about
1.34 times longer than it did with the former. Furthermore, the
alkali- and acid-treated yeast cell wall fraction was heated for a
long time in the presence of an alkali, resulting in a greater
possibility of producing greater amounts of lysinoalanine, which
induces renal cell hypertrophy, making it unsuitable for food
products and pharmaceutical products.
Comparative Example 2
[0063] 500 mL of 100% ethanol was added to 500 g (49 g solids) of
acid-treated yeast cell wall fraction slurry prepared in Example 6,
the ingredients were stirred for 30 minutes, and the mixture was
centrifuged to remove the solubilized fractions, further, 500 mL of
100% ethanol was again added, the ingredients were stirred for 30
minutes, and the mixture was centrifuged to remove the solubilized
components, resulting in a residue slurry (acid- and
ethanol-treated yeast cell wall fraction). The acid- and
ethanol-treated yeast cell wall fraction was then dispersed in
water to a solids concentration of 7 wt %, and glycerin was
dispersed as a plasticizer to 7 wt % of the acid-treated yeast cell
wall fraction solids, so as to prepare a coating liquid. The
aforementioned previously prepared tablets were coated with the
coating liquid using a Doria Coater (Powrex Co., Ltd) to a
tablet:coating agent weight ratio of 90:10, but the film
formability was lost compared to samples made using acid-treated
yeast cell wall fractions. The surface of the tablets thus became
powdery, and this example was -concluded to be unsuitable for a
coating agent.
[0064] The coating agents of the present invention afford the
following effects.
[0065] (1) Considering its viscosity, the finish is not as sticky
as gums such as gum arabic, resins such as shellac, or zein or
Eudragit or the like, so that the coated particles do not stick to
each other.
[0066] (2) The time at which dissolution begins can be controlled
according to the amount coated and the acid treatment conditions,
allowing the invention also to be used as an enteric coating
agent.
[0067] (3) The invention is readily dispersed in water, even
without the use of emulsifiers or the like, and is capable of
coating even in 100% water. It can also be used with a small amount
of a solvent mixed therein.
[0068] (4) It is also highly safe, since it is not harmful when
directly touched and is edible.
[0069] (5) It has an extremely low oxygen permeation coefficient,
is far better than any existing edible films, and is suitable in a
wide range of fields, such as food products, pharmaceutical
products, and feed.
* * * * *