U.S. patent application number 10/803873 was filed with the patent office on 2006-02-02 for method of treating diabetes and obesity using carbohydrate absorption inhibitors.
Invention is credited to Michio Aitani, Tsutomu Arimura, Yotaro Konishi, Hiromichi Murai, Tadashi Okada, Hiroshi Yamaguchi.
Application Number | 20060024396 10/803873 |
Document ID | / |
Family ID | 18725531 |
Filed Date | 2006-02-02 |
United States Patent
Application |
20060024396 |
Kind Code |
A1 |
Konishi; Yotaro ; et
al. |
February 2, 2006 |
Method of treating diabetes and obesity using carbohydrate
absorption inhibitors
Abstract
This invention provides carbohydrate absorption inhibitor
derived from evening primrose seed which is significantly effective
to prevent and cure diabetes mellitus and prevent obesity, and the
manufacturing method of the same. Carbohydrate absorption inhibitor
in this invention is characterized that the effective component is
an alcohol extract of evening primrose seed. The aforementioned
evening primrose seed is preferably a defatted evening primrose
seed. Extracting solvent of the aforementioned evening primrose
seed is preferably ethanol, or preferably a 70 to 85% (v/v) aqueous
ethanol. Also, this invention is characterized that the
carbohydrate absorption inhibitor is an effective component of
polyphenol derived from evening primrose seed. The polyphenol is
preferably one or more substances selected from among gallic acid,
ellagic acid, catechin, pentagalloylglucose, procyanidin, and
proantocyanidin. The manufacturing method of the carbohydrate
absorption inhibitor in this invention is characterized to be
composed of the following processes A to C. Process A: evening
primrose is compressed, oil is separated then the compressed cake
is obtained. Process B: The aforementioned compressed cake is
defatted in fat-soluble organic solvent, and defatted substance is
obtained. Process C: The aforementioned defatted substance is
extracted by alcohol, and then this extracted liquid is
concentrated or evaporated.
Inventors: |
Konishi; Yotaro; (Osaka,
JP) ; Aitani; Michio; (Hyogo, JP) ; Yamaguchi;
Hiroshi; (Aichi, JP) ; Arimura; Tsutomu;
(Osaka, JP) ; Okada; Tadashi; (Aichi, JP) ;
Murai; Hiromichi; (Aichi, JP) |
Correspondence
Address: |
CLARK & BRODY
1090 VERMONT AVENUE, NW
SUITE 250
WASHINGTON
DC
20005
US
|
Family ID: |
18725531 |
Appl. No.: |
10/803873 |
Filed: |
March 19, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10343488 |
Jan 31, 2003 |
6932990 |
|
|
PCT/JP01/06436 |
Jul 26, 2001 |
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10803873 |
Mar 19, 2004 |
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Current U.S.
Class: |
424/776 |
Current CPC
Class: |
C07D 493/06 20130101;
A61P 43/00 20180101; A61P 3/08 20180101; A61K 36/185 20130101; A61P
3/04 20180101; C07D 311/62 20130101; A61P 3/10 20180101 |
Class at
Publication: |
424/776 |
International
Class: |
A61K 36/30 20060101
A61K036/30 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 1, 2000 |
JP |
2000-232930 |
Claims
1-6. (canceled)
7. In a method of administering treatment to a patient suffering
from diabetes mellitus, the improvement comprising administering to
the patient an effective amount of an carbohydrate absorption
inhibitor comprising an effective component of solvent extract of
compressed cake derived from defatted evening primrose seed and
wherein the effective component contains polyphenol--essential
elements comprising ellagic acid, gallic acid, pentagalloylglucose
and catechin.
8. In a method of administering treatment to patients suffering
from obesity, the improvement comprising administering to the
patients an effective amount of the carbohydrate absorption
inhibitor comprising an effective component of solvent extract of
compressed cake derived from defatted evening primrose seed and
wherein the effective component contains polyphenol--essential
elements comprising ellagic acid, gallic acid, pentagalloylglucose
and catechin.
9. The method of claim 7, wherein an extracting solvent of the
compressed cake derived from the evening primrose seed is 55 to 99%
(v/v) aqueous ethanol.
10. The method of claim 8, wherein an extracting solvent of the
compressed cake derived from the evening primrose seed is 55 to 99%
(v/v) aqueous ethanol.
11. The method of claim 9, wherein an extracting solvent of the
compressed cake derived from the evening primrose seed is 70 to 85%
(v/v) aqueous ethanol.
12. The method of claim 10, wherein an extracting solvent of the
compressed cake derived from the evening primrose seed is 70 to 85%
(v/v) aqueous ethanol.
13. The method of claim 7, wherein a fat-soluble organic solvent is
used in when defatting the evening primrose seed.
14. The method of claim 8, wherein a fat-soluble organic solvent is
used in when defatting the evening primrose seed.
15. The method of claim 7, wherein patients receive the effective
amount of the carbohydrate either orally or by injection.
16. The method of claim 8, wherein patients receive the effective
amount of the carbohydrate either orally or by injection.
17. The method of claim 7, wherein oil is removed from the evening
primrose seed by first compressing the seed into a cake for oil
removal, and then using a solvent to remove remaining oil from the
cake.
18. The method of claim 8, wherein oil is removed from the evening
primrose seed by first compressing the seed into a cake for oil
removal, and then using a solvent to remove remaining oil from the
cake.
Description
FIELD OF THE INVENTION
[0001] This invention relates to carbohydrate absorption inhibitor
and method for manufacturing the same effective against e.g.
diabetes prevention, diet, and so forth.
BACKGROUND OF THE INVENTION
[0002] Polysaccharide (starch, glycogen or the like) contained in
food is hydrolyzed by .alpha.-amylase in saliva and pancreas and
converted into oligosaccharide such as maltose, isomaltose or the
like, then decomposed to glucose by disaccharide degrading enzyme
such as .alpha.-glucosidase or the like in the small intestine and
absorbed.
[0003] Thus, .alpha.-amylase and .alpha.-glucosidase perform an
important role as a digestive enzyme for carbohydrate in the body.
These enzyme activities affect the blood glucose level. Therefore,
it is important to control these enzyme activities for the
preventions and medical treatments of diabetes mellitus and
obesity.
[0004] There are two different types of diabetes mellitus. One is
insulin-dependent diabetes mellitus (Type I diabetes) and the other
is non-insulin dependent diabetes mellitus (Type II diabetes), and
the latter type accounts for more than 90% in the incidence of
diabetes mellitus.
[0005] The latter type (Type II diabetes) is caused by derangement
of carbohydrate and fat metabolism arising from an insufficient
insulin action (for instance, insulin-hyposensitivity in the organ,
insulin-hyposecretion in pancreas or the like) due to
overeating.
[0006] Non-insulin dependent diabetes mellitus (Type II diabetes)
should be basically controlled by diet therapy or exercise therapy
rather than medication. However, such self-control does not always
correct the aforementioned metabolic derangement, and medication is
very much counted on.
[0007] However, it is necessary to consider side effects, dosage
and usage of the medicine. In general, medicine is usually an
intermixture of various components. Therefore, it is necessary to
consider the side effect each component has and adverse effect
caused by a prolonged dosage of each component.
[0008] Extract from gymnema leaf, guava leaf, banaba leaf, mulberry
leaf or the like is widely known as a plant-derived extract which
is effective to correct the derangement of carbohydrate metabolism.
From the viewpoint of safety, these plant-derived extracts are
easily applied to food, drugs and medicines, or the like, therefore
effective components or the like of the said plant-derived extracts
are now being extensively researched.
[0009] Against this background, the inventors in this invention
have been investigating contents of polyphenol, SOD-like activities
or the like in regard to the various plant-derived extracts, then
finally came to focus on ethanol extract of evening primrose
seed.
[0010] After each of the aforementioned experiments has been
conducted, they came to know the fact that this extract contains
various polyphenol effective to inhibit the carbohydrate
absorption.
[0011] This invention aims at providing inhibitor of carbohydrate
absorption derived from evening primrose seed and method for
manufacturing the said inhibitor of carbohydrate absorption which
are significantly effective to prevent or relieve symptoms of
diabetes mellitus and to prevent obesity.
SUMMARY OF THE INVENTION
[0012] Carbohydrate absorption inhibitor which is the subject
matter in this invention is characterized by comprising an
effective component of solvent extract of compressed cake derived
from the defatted evening primrose, and wherein the said effective
component contains polyphenol such as ellagic acid, gallic acid,
pentagalloylglucose.
[0013] Carbohydrate absorption inhibitor in this invention is
characterized in that extracting solvent of the compressed cake
derived from the aforementioned evening primrose seed is aqueous
ethanol (water/ethanol=15 to 30/70 to 85% (v/v)).
[0014] Carbohydrate absorption inhibitor in this invention is
characterized in that defatting process is proceeded by using
fat-soluble organic solvent.
[0015] Chemicals in this invention are characterized in that the
aforementioned carbohydrate absorption inhibitor is contained.
[0016] Food and drink in this invention are characterized in that
the aforementioned carbohydrate absorption inhibitor is
contained.
[0017] According to the experiment conducted by the inventors, the
existing plant-derived extracts (guava, banaba and mulberry) have a
strong inhibitory action against amylase, however the enzyme
inhibitory activity against amylase is not sufficient.
[0018] On the contrary, extract (polyphenol) derived from evening
primrose as disclosed in this invention indicates strong enzyme
inhibition activities against amylase and glucosidase. Especially
the ethanol extract derived from the defatted evening primrose seed
comprises a strong inhibitory action and consistent safety.
Therefore it is appropriate to mix it with medicine to prevent
diabetes mellitus or to diet
[0019] Evening primrose is an annual grass, biennial grass or
herbaceous perennial of oenothera genus. In rare cases, stem of
evening primrose may be lignified and grow on bush. The followings
are four representative examples. [0020] {circle around (1)}
Oenothera laciniata [0021] {circle around (2)} Oenothera striata
[0022] {circle around (3)} Oenothera biennis [0023] {circle around
(4)} Oenothera erythrosepala
[0024] In this invention, species of evening primrose are not
limited. Any species can be used.
[0025] Oil obtained from evening primrose seed is widely known. The
evening primrose oil contains a large amount of .gamma.-linolenic
acid and is said to be effective against obesity, diabetes
mellitus, hypercholesterolemia, alcohol dependence, aging, and
disease caused by insufficient vitamin B.sub.6.
[0026] Also it is widely known that evening primrose oil is
effective to inhibit the action in which linolic acid is converted
into .gamma.-linolenic acid when virus infection is experienced, as
well as to provide a medical treatment for asthma and atopic
disease.
[0027] In regard to the fat-soluble component of evening primrose
seed, physiological activity is now being researched, however,
there is no report about the physiological activity of other
substance than fat-soluble component.
[0028] Some part of the compressed cake exhausted in the
manufacturing process of evening primrose seed is used as an animal
feeding staff, or is disposed of as an industrial waste.
[0029] In this invention, a new usage of other components than the
fat-soluble component of the evening primrose seed can be provided,
and at the same time the effective component can be extracted from
the compressed cake after taking out the evening primrose oil. It
is significant to extract the high value-added effective component
from the compressed cake and efficiently recycle the natural
resources.
[0030] To efficiently extract the effective component (polyphenol)
for the carbohydrate absorption inhibition, alcohol is used as an
extracting solvent for the aforementioned evening primrose seed.
Ethanol is especially recommended. If ehanol is used, effective
component (polyphenol) is efficiently extracted and can be used
both for external application and food. According to other usages
available, methanol, butanol or the like can be used.
[0031] The concentration of ethanol as an extracting solvent is
preferably 70 to 85% (v/v). If the concentration of ethanol is less
than 70% (v/V), polyphenol is not sufficiently extracted. And if
the concentration exceeds 85% (v/v), seed oil easily dissolves into
the extracting solvent.
[0032] Also, alcohol extraction should be repeated preferably at
different levels of concentration since the content ratio of
polyphenol is improved.
[0033] Furthermore, it is preferable to use the defatted evening
primrose seed for alcohol extraction since polyphenol is
concentrated in the defatted matter by removing oil from the seed.
For instance, it is preferable to separate the oil from the evening
primrose seed by compressing the said seed, and then to extract and
separate the remaining oil of the compressed matter by fat-soluble
organic solvent.
[0034] It is preferable to use hexane as a fat-soluble organic
solvent for defatting since the extracted oil can be used for
edible oil and also extract of defatted evening primrose seed can
be used for foodstuff or the like. If the extract is used for other
objectives than food, other non-polar solvent than hexane can be
also used.
[0035] The aforementioned polyphenol derived from the evening
primrose seed can be extracted preferably by solvent such as
ethanol, aqueous ethanol, water or the like. According to the
research by inventors, the extract contains gallic acid, ellagic
acid, catechin, pentagalloylglucose.
[0036] Medicine described in this invention is suitable for the
prevention of diabetes mellitus, i.e. the prevention or treatment
of non-insulin dependent diabetes mellitus (Type II diabetes), or
can be also used for the effective component of antiobesity drugs.
For instance, medicine in this invention can be orally administered
in any shape of soft and/or hard capsule, tablet, granule, fine
granule, or powder medicine. On the other hand, the medicine in
this invention can be administered by injection into body tissue,
dermis, subdermal muscle or vein,
[0037] Given dose varies depending on the mode of administration,
condition of the disease, age of the patient, or the like. Adults
can take the effective component of 0.5 to 5,000 mg per day and
children can take 0.5 to 3,000 mg per day.
[0038] Concentration of polyphenol component can be varied
according to various types of medicine. However, when the medicine
is used by oral administration or mucomembranous absorption, the
given dose should be 0.01 to 15.0 wt %. When the medicine is used
by non-oral administration, the given dose should be 0.01 to 10 wt.
The dose mentioned above is only an example and can be varied
according to various situations.
[0039] This invention suggests various embodiments of ordinary food
and drink including snack food (such as chewing gums, candies,
caramel candies (taffies), chocolates, cookies, jellies, gummy
candies, other tablet shaped candies, or the like), noodles (such
as Japanese buckwheat noodles called "Soba", Japanese wheat noodles
called "Udon", Chinese noodle or the like), dairy products (such as
milk, ice cream, yogurt or the like), seasoning (such as fermented
soybean paste called "Miso", soy sauce, or the like), soups and
drinks (such as juice, soft drinks including carbonated drinks,
coffee, black tea, green tea, isotonic drinks, or the like), of
healthy food (such as food in supplement in tablet, capsule or the
like), nutraceutical supplement (such as nutrition supplement
drinks or the like). Extract (polyphenol) derived from evening
primrose seed is accordingly applied to those above or convenience
food. For example, ethanol extract of evening primrose seed mixed
with powdered cellulose can be spray dried or freeze-dried and
converted into powder, granule, tablet, solution or the like, and
then applied to various food and drink.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] FIG. 1 on the attached sheet is a graph indicating a
variation of blood glucose level of a normal rat after extracts of
evening primrose seed and starch have been administered to the said
rat.
[0041] FIG. 2 on the attached sheet is a graph indicating a
variation of blood glucose level of a normal rat after extracts of
evening primrose and sucrose have been administered to the said
rat.
(Additional Part)
[0042] FIG. 3 on the attached sheet is an HPLC chart of the extract
in this invention
[0043] FIG. 4 on the attached sheet is a graph indicating a
suppressive effect on the elevation of blood glucose level of the
nondiabetic subject.
[0044] FIG. 5 on the attached sheet is a graph indicating a
suppressive effect on the elevation of blood glucose level of the
mild diabetic subjects.
(End of the Additional Part)
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0045] Embodiments of this invention are as follows.
(Manufacture of the Carbohydrate Absorption Inhibitor)
[0046] Material: Compressed cake obtained in the manufacturing
process of evening primrose oil is used.
[0047] Firstly, the compressed cake was crushed, refluxed by
hexane, and then the defatted substance was obtained by removing
the remaining oil from the said compressed cake. Secondly, the said
defatted substance was fluxed in 70% (v/v) aqueous ethanol, and
then the said ethanol extract was evaporated until carbohydrate
absorption inhibitor (Embodiment 1) was obtained.
(Inhibitory Activity Against .alpha.-Amylase)
[0048] Inhibitory activity (5) of .alpha.-amylase in regard to the
Embodiment 1 (extract of evening primrose seed) was determined by
using an amylase activity measuring kit ("Amylase Test Wako"
manufactured by Wako Pure Chemical Industries, Ltd., Japan), which
is commercially available. Measuring method using human
saliva-derived .alpha.-amylase is as follows.
[0049] After incubating a mixture of the human saliva-derived
.alpha.-amylase solution (0.02 mL) and sample solution (0.01 mL) at
37.degree. C. for 5 min., substrate buffer solution (1.0 mL) was
added to the said mixture and incubated at 37.degree. C. for 60
min. Then the said mixture was incubated in the boiling water for 5
min., and after the reaction stopped, coloring reagent (1.0 mL) was
added and then the absorbance (660 nm) was measured.
[0050] After calculating the enzyme activity (%) based on this
measured value, the inhibitory activity (5) was calculated by the
following formula. The enzyme activity was calculated based on the
absorbance (100%) measured under condition where no sample
coexisted. Inhibitory activity (%)=100-enzyme activity (%)
[0051] Inhibitory activities (%) in regard to other plant-derived
extracts of guava leaf (Comparison 1), banaba leaf (Comparison 2)
and mulberry leaf (Comparison 3) were also calculated by the same
method as shown in the following chart 1. TABLE-US-00001 CHART 1
Concentration Inhibitory Classification Exract (mg/ml) activity (%)
Embodiment 1 Evening 1.0 100 primrose seed Comparison 1 Guava leaf
1.0 0 Comparison 2 Banaba leaf 1.0 80 Comparison 3 Mulberry leaf
1.0 0
[0052] As described in the above chart 1, it is clear that
.alpha.-amylase inhibitory activity against the embodiment 1 is
higher than any of the others.
[0053] Also, after measuring the enzyme activity to the variation
of concentration regarding the embodiment 1 (evening primrose seed
extract) by using the same method, IC.sub.50 (50% inhibition
concentration) against the .alpha.-amylase (derived from human
saliva) was found to be 0.5 mg/mL.
[0054] In connection with the embodiment 1 (evening primrose seed
extract), gallic acid, ellagic acid, catechin, and
pentagalloylglucose, IC.sub.50 (50% inhibition concentration)
against the .alpha.-amylase derived from pancreas of pig was
identified by the same method. The following chart shows the
excellent inhibitory activities. TABLE-US-00002 Chemical compound
IC.sub.50 (mg/ml) Embodiment 1 (evening primrose seed extract) 0.01
Gallic acid 0.4 Ellagic acid >1.0 Catechin 0.8
Pentagalloylglucose 0.02 [.alpha.-glucosidase inhibitory
activity]
[0055] Next, .alpha.-glucosidase inhibitory activity (%) in regard
to the embodiment 1 (evening primrose seed extract) was identified
by the following method. As for the .alpha.-glucosidase for this
measurement, 0.1 mol maleic acid buffer solution (pH6.0) was added
to the acetone powder in the intestinal canal of rat (SIGMA
CHEMICAL CO.) and homogenized in ice by using a glass homogenizer,
and then centrifugalized supernatant was diluted 20 times.
Measuring method is shown below.
[0056] Sample solution (0.01 ml) was added to the enzyme solution
(0.05 ml), then 0.1 M maleic buffer solution (0.64 ml), moreover,
33 mM 4-methylumbelliferyl-.alpha.-D-glucoside (0.3 ml) was added
and then incubated at 37.degree. C. for 30 min.
[0057] After that, the reaction was suspended by adding 3 ml glycin
buffer solution (pH10.3) and the quantity of the isolated
4-methylumbelliferyl was determined by using a fluorometer
(excitation wavelength: 366 nm & fluorescent wavelength: 450
mm). Enzyme activity was calculated based on this determined value
and inhibitory activity (%) was calculated by the following
formula. Also, the enzyme activity was calculated based on the
determined value (100%) of 4-methylumbelliferyl measured under
condition where no sample coexisted. Inhibitory activity
(%)=100-Enzyme activity (%)
[0058] As a comparison, the inhibitory activities (%) in regard to
the plant-derived extracts--guava leaf extract (Comparison 1),
banaba leaf extract (Comparison 2), and mulberry leaf (Comparison
3) were identified by the same method. Result is shown in the
following chart 2. TABLE-US-00003 CHART 2 Concentration Inhibitory
Classification Extract (mg/ml) activity (%) Embodiment 1 Evening
0.1 65 primrose seed Comparison 1 Guava leaf 0.1 77 Comparison 2
Banaba leaf 0.1 76 Comparison 3 Mulberry leaf 0.1 96
[0059] As indicated in Chart 2, although inhibitory activity
against .alpha.-glucosidase of embodiment 1 (evening primrose seed
extract) is less effective than that of guava leaf extract
(Comparison 1), banaba leaf extract (Comparison 2) and mulberry
leaf extract (Comparison 3), it still has excellent inhibitory
activity against .alpha.-glucosidase.
[0060] After measuring the enzyme activities to the variation of
concentration in regard to the embodiment 1 (evening primrose seed
extract), gallic acid, ellagic acid, catechin and
penthagalloylglucose by using the same method, IC.sub.50 (50%
inhibitory concentration) against .alpha.-glucosidase was
identified.
[0061] The following chart shows the excellent inhibitory
activities. TABLE-US-00004 Chemical compound IC.sub.50 (mg/ml)
Embodiment 1 (evening primrose seed extract) 0.1 Gallic acid 0.8
Ellagic acid >0.08 Catechin 0.8 Pentagalloylglucose 0.04
[0062] Those test results indicate that the embodiment 1 (evening
primrose seed extract) comprises the inhibitory activity against
both .alpha.-amylase and .alpha.-glucosidase, and effectively
inhibits the degradation of carbohydrate.
(Carbohydrate Loading Test to Normal Rats)
[0063] In regard to the embodiment 1 (evening primrose seed
extract), carbohydrate absorption inhibitory action in living
animals was tested under the following conditions.
[0064] After breeding 5-week old male wister rats (Clear Japan,
Inc.) for more than one week, then 6 to 8-week old wister rats were
used during the test. Without giving any food to the rats for 24
hours, sample of Embodiment 1 (at the rate of 0.5 g per kg of
weight) was dissolved in distilled water, and carbohydrate (starch
and sucrose: at the rate of 2 g per kg of weight) was dissolved in
distilled water, then both were administered to the stomach
sound.
[0065] To measure a variation of the blood glucose level after
administering the samples to the rats, blood was taken from the
vain of tails before the samples were administered, and at each
stage of 30, 60, 120 and 180 min after the samples were
administered. As a control group, blood was taken from the vain of
the tails of the rats under the same conditions where the sample,
the same amount of distilled water and carbohydrate (starch and
sucrose at the rate of 2 g per kg of weight) were administered to
the rats.
[0066] After centrifuging the blood taken from the rats, the blood
glucose level of the supernatant was measured. For measuring the
blood glucose level, a glucose measuring kit commercially available
was used. ("Glucose B Test Wako" manufactured by Wako Pure Chemical
Industries, Ltd., Japan) The results are shown in FIG. 1 and FIG.
2.
[0067] As shown in FIG. 1 and FIG. 2, in a control group, the blood
glucose level rapidly increased before 30 min passed, on the
contrary, the blood glucose level of the rats of which the
embodiment 1 (evening primrose seed extract) was administered
slowly increased.
(Application to Food and Drink)
[0068] Application to food and drink which are effective for the
prevention of diabetes mellitus and diet are as follows. "Evening
primrose seed extract" shown below is powdered and dried ethanol
extract of evening primrose seed obtained under the same conditions
of the aforementioned embodiment 1. TABLE-US-00005 Composition 1:
Chewing gums Sugar 53.0 wt % Gum base 20.0 Glucose 10.0 Starch
syrup 16.0 Flavoring agent 0.5 Evening primrose seed extract 0.5
100.0 wt % Composition 2: Gummy candies Reduced syrup 40.0 wt %
Granulated sugar 20.0 Glucose 20.0 Gelatin 4.7 Water 9.68 Japanese
apricot (Ume) juice 4.0 Japanese apricot (Ume) flavor 0.6 Coloring
agent 0.02 Evening nrimrose seed extract 1.0 100.0 wt % Composition
3: Candies Sugar 50.0 wt % Starch syrup 33.0 Water 14.4 Organic
acid 2.0 Flavoring agent 0.2 Evening primrose seed extract 0.4
100.0 wt % Composition 4: Soft capsule Rice germ oil 87.0 wt %
Emulsifying agent 12.0 Evening primrose seed extract 1.0 100.0 wt %
Composition 5: Soft drink Fructose and glucose 30.0 wt %
Emulsifying agent 0.5 Evening primrose seed extract 0.05 Flavoring
agent Minute amount Distilled water Rest 100.0 wt % Composition 6:
Tablets Lactose 54.0 wt % Crystallized cellulose 30.0 Starch
degradation product 10.0 Glycerin fatty acid ester 5.0 Evening
primrose seed extract 1.0 100.0 wt % Composition 7: Tablet-shaped
candies Sugar 76.4 wt % Glucose 19.0 Glycerin fatty acid ester 0.2
Evening primrose seed extract 0.6 Distilled water 3.9 100.0 wt
%
[0069] The structure of the extract obtained from the embodiment 1
and similar method contained ellagic acid, gallic acid, catechin,
and pentagalloylglucose.
(Beginning of the Additional Part)
[0070] Analysis in regard to evening primrose seed extract in this
invention is shown in chart 3 below. TABLE-US-00006 CHART 3 Sample
Gallic acid Catechin Ellagic acid PGG*1 Evening 2.7% 1.6% 0.5% 2.3%
primrose extract Lot: R-006 *1Pentagalloylglucose
[0071] Also, HPLC chart is shown in FIG. 3. Considering the above
result, it is recognized that the extract obtained in this
invention contains gallic acid, catechin, ellagic acid and
pentagalloylglucose. It is still impossible to create a sample
excluding the specific component from the evening primrose seed
extract even by the present technology. Therefore, performance test
should be still conducted by using a mixture of various components.
After measuring the effectiveness to inhibit the after-meal
elevated blood glucose level of 16 normal persons female:male=7:9),
the result in FIG. 4 shows that blood glucose level of subjects in
30 minutes after taking evening primrose is controlled. Also, the
rise in blood glucose level of the patient suffering from the mild
diabetes mellitus with the fasting blood glucose level of 110 mg/dl
to 180 mg/dl is more significantly controlled than the rise in
postprandial blood glucose level of the patient in a placebo group.
TABLE-US-00007 CHART 4 Change in the value of insulin when
conducting the food loading test (.mu.U/dl) Before loading test 30
min 60 min 90 min 120 min Control 13.3 .+-. 15.0 28.4 .+-. 23.9
40.0 .+-. 31.1 43.6 .+-. 28.1 50.1 .+-. 30.0 group Evening primrose
12.7 .+-. 9.8 22.4 .+-. 14.5 35.8 .+-. 33.1 43.7 .+-. 35.9 43.7
.+-. 31.4 extract group Significant n.s n.s n.s n.s n.s difference
between groups
[0072] It is apparent that evening primrose comprises an effective
function to control the rapid rise in blood glucose-level after
food loading. Since the rapid rise in blood glucose level is
controlled, the rapid increase in insulin secretion becomes
moderate. This indicates that evening primrose extract is effective
to reduce the burden of insulin secretion of the patient suffering
from insulin deficiency diabetes mellitus.
(End of the Additional Part)
INDUSTRIAL APPLICABILITY
(Beginning of the Additional Part)
[0073] The amount of carbohydrate taken into the human body can be
controlled by inhibiting the digestion of starch and saccharides,
i.e., by inhibiting the activity of a amylase and
.alpha.-glucosidase which are saccharides degrading enzyme inherent
in living body. The risk of type II diabetes mellitus can be
especially controlled by a mechanism which keeps the postprandial
blood glucose level low.
[0074] The said mechanism is significantly safer and harmless than
the direct prevention to control the insulin secretion, and from
the viewpoint of the preventive medicine in the latest mainstream
of alternative medicine, it is considered to be inventive that the
said mechanism can be applied to the function of the evening
primrose leaf extract.
[0075] Also clinical investigation of the diabetes patient
apparently shows that administration of evening primrose does not
directly enhance the insulin secretion, and decrease in the blood
glucose level of human and animals apparently indicates that
evening primrose extract inhibit the absorption of the
saccharides.
(End of the Additional Part)
[0076] As described above, absorption of saccharides can be
effectively controlled in this invention.
[0077] Also this invention can provide the significant
effectiveness to prevent and treat diabetes mellitus and obesity
since the rise in blood glucose level by absorption of saccharides
becomes moderate.
[0078] Furthermore, in this invention, effective component is
extracted from evening primrose seed which is known as an
ingredient of edible oil, therefore the said component is safe and
has no side effect or the like.
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