JP2004256432A - alpha-AMYLASE INHIBITOR - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an α-amylase inhibitor which can safely, surely and sufficiently satisfactorily prevent or treat diseases, even when administered for a long period. <P>SOLUTION: This α-amylase inhibitor is characterized by containing Acanthopanax sieboldianum or its extract. The Acanthopanax sieboldianum is naturally originated and thereby has low toxicity and an α-glucosidase-inhibiting action. Hence, a sugar absorption inhibitor, a blood glucose level elevation or offal fat accumulation inhibitor, or a preventing or treating agent for diabetes, obesity, hyperlipemia or the like which can safely, surely and sufficiently satisfactorily prevent or treat these diseases, even when administered for a long period, and an oral or parenteral composition, food or a medicine containing the agent can be provided. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention is an agent having an α-amylase inhibitory effect, suppressing sugar absorption, suppressing an increase in blood glucose level and accumulation of visceral fat, and effective in preventing and / or treating diabetes, obesity, hyperlipidemia, and the like. And oral or parenteral compositions, foods or medicaments containing them.
[0002]
[Prior art]
In recent years, the number of diabetic patients has been rapidly increasing in Japan, and it is estimated that there are approximately 6 million diabetic patients including potential patients. Also, more than 95% of diabetes is type 2 diabetes, most of which is in an insulin-independent state. Diabetes is also called "quartet of death" and causes complications such as vascular or neurological disorders such as arteriosclerosis, retinopathy and nephropathy, so treating diabetes and preventing complications are important issues. ing. Many type 2 diabetic patients are characterized by postprandial hyperglycemia due to insulin resistance in peripheral tissues and reduced insulin secretion ability relative to pancreatic beta cells, and this treatment is important for the management of diabetes. Is considered important.
[0003]
Among the carbohydrates, starch (starch) is most often taken by the human body, and is said to account for 60% or more of the whole. Starch taken into the human body is hydrolyzed to maltose (maltose), isomaltose (isomaltose), etc. by α-amylase in saliva and pancreatic juice and reaches the small intestine. Disaccharides such as maltose and isomaltose or other oligosaccharides are further hydrolyzed to monosaccharides by the action of α-glucosidase present on the small intestinal mucosal brush border and absorbed by the small intestinal wall.
[0004]
Therefore, by inhibiting the action of α-amylase, an enzyme that digests starch, it suppresses digestion and absorption of carbohydrates, suppresses blood sugar rise, and produces metabolic diseases such as diabetes, obesity, hyperlipidemia, and arteriosclerosis. It is thought that it can be prevented and treated.
From such a viewpoint, in recent years, oligosaccharide-based and peptide-based α-amylase inhibitors have been discovered from microorganisms and cereals, but they have problems in terms of safety and effectiveness, and At present, most have not yet reached the stage of practical use.
[0005]
In addition, tea polyphenols (for example, see Patent Document 1), laurel leaves (for example, see Patent Document 2), peony skin (for example, see Patent Document 3), and A as amylase inhibitors derived from natural products. Herbal medicine, root material of sassafras, rhizome of yellow dock, leaf of medosweet (for example, refer to Patent Document 4), olive leaf and its extracted component (for example, refer to Patent Document 5), and insulina (scientific name: Cissus sicoides) L.) (for example, see Non-Patent Document 1). However, since these natural products have a low α-amylase inhibitory activity, a considerable amount must be added to obtain the required inhibitory activity, which is problematic in terms of cost. In addition, there is a problem in taste quality, and there is a problem in that their use is greatly restricted. Therefore, these natural products have not yet reached the stage of practical use.
[0006]
[Patent Document 1]
Japanese Patent Application Laid-Open No. 3-13928 [Patent Document 2]
JP-A-4-27389 [Patent Document 3]
Japanese Patent Application Laid-Open No. 9-40573 [Patent Document 4]
JP 2000-103742 A [Patent Document 5]
Japanese Patent Application Laid-Open No. 2002-10753 [Non-Patent Document 1]
Takeshi Mori, Yasushi Nishikawa, Yoko Takada, Yoshiko Kashiuchi, Nobuhiro Ishihara, Journal of Japan Society of Nutrition and Food Science, Vol. 54, No. 4, p. 197-203 2001
[Problems to be solved by the invention]
An object of the present invention is to provide a sugar absorption inhibitor which has an α-amylase inhibitory effect, is sufficiently safe even when taken for a long period of time, and is sufficiently satisfactory for performing a reliable treatment, an increase in blood sugar level or accumulation of visceral fat. An object of the present invention is to provide an inhibitor, an agent effective for preventing or treating diabetes, obesity, and hyperlipidemia, and an oral or parenteral composition, food, or medicament containing the agent.
[0008]
[Means for Solving the Problems]
The present inventor has conducted intensive studies to solve the above-mentioned problems, and as a result, it has been found that deciduous shrubs of the Egoceae family, in which the leaves and root bark are dried in Chinese medicine, are nourishing tonics, abdominal pain and pain relief as an analgesic. The present inventors have found that Ukogi used for chills and the like have an α-amylase inhibitory action, and completed the present invention.
[0009]
That is, the present invention
1. Α-amylase inhibitor, characterized by containing ukogi or an extract thereof,
A sugar absorption inhibitor, which comprises the α-amylase inhibitor according to 2.1,
3.1. An inhibitor for increasing blood sugar, comprising the α-amylase inhibitor according to 3.1.
4.1. An agent for preventing and / or treating diabetes, which comprises the α-amylase inhibitor according to 4.1.
5.1. A visceral fat accumulation inhibitor comprising the α-amylase inhibitor according to 5.1.
6.1. An agent for preventing and / or treating obesity, which comprises the α-amylase inhibitor according to 6.1.
7.1. An agent for preventing and / or treating hyperlipidemia, which comprises the α-amylase inhibitor according to 7.1.
An oral or parenteral composition comprising the agent according to any one of 8.1 to 7;
9. The oral composition according to 8, which is a food,
10. The oral or parenteral composition according to 8, which is a medicament,
It is.
[0010]
BEST MODE FOR CARRYING OUT THE INVENTION
Ukogi used in the present invention is a deciduous shrub of the family Egoceae, also known as Himeukogi or Yamaukoukogi, Manshukokogi, in Chinese medicine, dried root bark is called Gokachi, nutrient tonic, abdominal pain as an analgesic, abdominal pain, fatigue It is used for recovery, chills, etc. In the Yonezawa region of Yamagata Prefecture, leaves have been eaten for a long time, and they have been eaten as local dishes such as cut, ukogi rice, soak and tempura.
The ukogi of the present invention may be those normally used for food, and may be from any production place, and are not particularly limited. Is preferred.
[0011]
The ukogi in the present invention can be used in all parts, such as above-ground parts such as leaves, stems, buds, branches, flowers, woody parts, bark parts (bark) and underground parts such as roots and tubers, seeds, fruits and resins. .
Ukogi in the present invention is a dried product obtained by drying Ukogi itself, a pulverized product thereof, a supercritical extract, water or a crude extract with an organic solvent such as alcohol, ether and acetone, and a crude extract. And all the fractions obtained by stepwise purification by various chromatography methods. These may be used alone or in combination of two or more.
For example, an extract obtained by adding 80 L of water to 10 kg of dried leaves of Japanese ukogi and extracting at 90 ° C. for 1 hour may be used as it is, or may be purified by combining various types of chromatography. May be used.
[0012]
The concentration of the ukogi extract in the extracted ukogi extract solution is not particularly limited, but is preferably 15 to 70% by mass, and more preferably about 20 to 60% by mass. If the concentration is less than 15% by mass, it is necessary to evaporate a large amount of a solution such as ethanol or water at the time of drying, and if it exceeds 70% by mass, the viscosity of the solution becomes too high and processing suitability may be deteriorated.
It is a new finding obtained by the present invention that such a dried product or extract of umkogi according to the present invention has an α-amylase inhibitory activity, which has not been known at all.
[0013]
The ukogi according to the present invention have an excellent α-amylase inhibitory action, and are used for preventing or treating glucose absorption inhibitors, inhibitors for increasing blood sugar levels or visceral fat accumulation, diabetes, obesity, hyperlipidemia, etc. It can be used as food or medicine.
That is, α-amylase inhibitors can be used for clinically used increase of blood sugar level or suppression of visceral fat accumulation, and treatment of diabetes, obesity and hyperlipidemia. Inhibition of α-amylase suppresses the production of glucose and fructose (fructose) from food-derived starch, that is, suppresses the absorption of sugar, suppresses blood sugar levels or suppresses visceral fat accumulation, diabetes, obesity, Useful for the treatment of hyperlipidemia.
The ukogi of the present invention can be produced as an α-amylase inhibitor, a sugar absorption inhibitor, an inhibitor of an increase in blood glucose level or an accumulation of visceral fat, a therapeutic agent-containing food or a drug for diabetes, obesity, hyperlipidemia and the like. .
[0014]
The α-amylase inhibitor of the present invention, a sugar absorption inhibitor, an inhibitor of blood glucose elevation or visceral fat accumulation, diabetes, obesity, as a method of applying a drug such as a therapeutic agent for hyperlipidemia, oral administration or Parenteral administration can be employed. Upon administration, the active ingredient can be mixed with a solid or liquid nontoxic pharmaceutical carrier suitable for administration methods such as oral administration, rectal administration and injection, and administered in the form of a conventional pharmaceutical preparation. Such preparations include, for example, solid preparations such as tablets, granules, powders and capsules, liquid preparations such as solutions, suspensions and emulsions, and lyophilized preparations. It can be prepared by conventional means. Examples of the above non-toxic pharmaceutical carriers include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, Examples include albumin, water, and physiological saline. Further, if necessary, conventional additives such as a stabilizer, a wetting agent, an emulsifier, a binder, and a tonicity agent can be appropriately added.
[0015]
As food, as it is, or by adding various nutrients, or contained in food or drink, α-amylase inhibitor, sugar absorption inhibitor, inhibitor of blood glucose elevation or visceral fat accumulation, diabetes, obesity, It is eaten as a health food or food material useful as a therapeutic agent for hyperlipidemia and the like. For example, after adding the above-mentioned appropriate auxiliaries, using conventional means, edible forms, such as granules, granules, tablets, capsules, pastes, etc., may be edible, Various foods, for example, ham, processed meat foods such as sausage, kamaboko, processed marine products such as chikuwa, bread, confectionery, butter, powdered milk, fermented dairy products, or used in addition to water, juice, milk, It may be used by adding to beverages such as tea and soft drinks.
[0016]
The effective dose of the ukogi of the present invention is appropriately selected and determined depending on the age, weight, symptom of the patient, degree of the patient, administration route, administration schedule, formulation form, strength of the inhibitory activity of the material, and the like. In the case of oral administration, it is generally about 10 to 500 mg / kg body weight per day as a dry weight, preferably about 150 to 350 mg / kg body weight per day, and may be administered several times a day.
Ukogi is naturally derived and therefore has low toxicity. For example, even when a hot water extract of Japanese ukogi is orally administered to a rat for a long period of 100 mg / kg daily for 100 days, no deaths are observed. No weight change was observed.
[0017]
【Example】
Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto.
Production Example 1
[Manufacture of Ukogi leaf hot water extract]
80 L of water was added to 10 kg of dried leaves of Ukogi from Yonezawa, Yamagata Prefecture, and the mixture was heated at 90 ° C. for 1 hour to perform extraction, and this extract was filtered using a 60-mesh pass filter. Further, the extract was concentrated at 60 ° C. until the Brix became about 10, then filtered through a 250-mesh pass filter, and sterilized at 130 ° C. for 30 seconds. After spray-drying at an inlet temperature of 140 ° C. and an outlet temperature of 80 ° C., the mixture was sieved with a 30-mesh pass sieve to obtain about 2.2 kg of hot water extract of ukogi leaves.
[0018]
Example 1
[Α-amylase inhibitory activity test]
The α-amylase inhibitory activity test is carried out by a method in which the generated reducing sugar is colored using a DNS (dinitrosalicylic acid) reagent (DT Plummer, translated by Keitaro Hiromi et al., Biochemistry learned from experiments, 245-247, 1981). , Chemical Doujinshi) with some modifications.
That is, production was performed so as to have 50 μl of 0.25 M phosphate buffer (pH 7.0), 50 μl of soluble starch as a substrate (40 mg / ml, manufactured by Wako Pure Chemical Industries), 100 μl of 5 mM calcium acetate solution, and various concentrations. The mixture was mixed with 100 μl of the hot water extract solution of lycopodium leaf obtained in Example 1 and pre-incubated at 37 ° C. for 5 minutes. To this was added 10 μl of α-amylase derived from human saliva (manufactured by Sigma) or α-amylase derived from porcine pancreas (manufactured by Elastin Products) (1 mg / ml) diluted with the same buffer, and added at 37 ° C. for 20 minutes. After the incubation, 2 ml of a DNS reagent and 0.1 ml of distilled water were added, and the mixture was boiled in a boiling water bath for 10 minutes. Thereafter, 4 ml of distilled water was added, and after cooling to room temperature, the amount of generated reducing sugar was measured by absorbance at 535 nm, and the enzyme inhibition rate (%) was calculated by the formula 1 in comparison with the control.
Inhibition rate (%) = 100 − {(AB) / A × 100}
(Here, A represents the absorbance when no inhibitor is contained, and B represents the absorbance when the inhibitor is added.)
Incidentally, IC ₅₀ values of from wheat α- amylase inhibitor as a positive control in this reaction system (manufactured by Wako Pure Chemical Industries, Ltd.) (concentration inhibiting 50% enzyme activity), for the human saliva from α- amylase 11.37 μg / ml, and 5.36 μg / ml for porcine pancreatic α-amylase.
FIG. 1 shows the α-amylase inhibitory activity of the hot water extract of ukogi leaves. As shown in FIG. 1, the hot water extract of ergot leaves of the present invention has an inhibitory effect on α-amylase derived from human saliva and α-amylase derived from pig pancreas in a concentration-dependent manner, and its IC ₅₀ value is 1.98 mg / ml, respectively. , 2.05 mg / ml.
[0019]
The following is a prescription example.
Formulation Example 1
[Manufacture of tablets]
A tablet having the following composition was produced according to a conventional method using the hot water extract of ukogi leaves from Yonezawa, Yamagata Prefecture, obtained in Production Example 1.
(Composition) (Blending: mass%)
Ukogi hot water extract 24
Lactose 63
Corn starch 12
Guar Gum 1
[0020]
Formulation Example 2
[Manufacture of juice]
A juice having the following composition was produced in accordance with a conventional method using the hot water extract of ukogi leaves produced in Yonezawa, Yamagata Prefecture, obtained in Production Example 1.
(Composition) (Blending: mass%)
Frozen concentrated Unshu mandarin orange juice 5.0
Fructose glucose liquid sugar 11.0
Citric acid 0.2
L-ascorbic acid 0.02
Fragrance 0.2
Dye 0.1
Ukogi leaf hot water extract 0.2
Water 83.28
[0021]
【The invention's effect】
Since ukogi or an extract thereof has an α-amylase inhibitory action, α-amylase inhibitor containing these substances may be used as a sugar absorption inhibitor, an inhibitor for increasing blood sugar level or visceral fat accumulation, diabetes, obesity, It is useful as a prophylactic and / or therapeutic agent for lipemia, an oral or parenteral composition, food or medicament containing them. Such a composition is safe even when taken for a long period of time, and can provide a reliable treatment.
[Brief description of the drawings]
FIG. 1 is a view showing the α-amylase inhibitory activity of an extract of hot water of ukogi leaves.

Claims (10)

An α-amylase inhibitor comprising ukogi or an extract thereof. A sugar absorption inhibitor comprising the α-amylase inhibitor according to claim 1. A blood glucose elevation inhibitor comprising the α-amylase inhibitor according to claim 1. An agent for preventing and / or treating diabetes, comprising the α-amylase inhibitor according to claim 1. A visceral fat accumulation inhibitor comprising the α-amylase inhibitor according to claim 1. An agent for preventing and / or treating obesity, comprising the α-amylase inhibitor according to claim 1. An agent for preventing and / or treating hyperlipidemia, comprising the α-amylase inhibitor according to claim 1. An oral or parenteral composition comprising the agent according to claim 1. The oral composition according to claim 8, which is a food. The oral or parenteral composition according to claim 8, which is a medicament.

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