JP2011231095A - Agent for ameliorating type-2 diabetes, and food and beverage containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a technology capable of ameliorating type-2 diabetes satisfactorily by using a natural-product-derived component that has few adverse side effects, whereas, though several attempts to utilize components derived from natural products have been tried for the purpose of ameliorating type-2 diabetes, no effective technology that can achieve a satisfactory effect has not been proposed yet.SOLUTION: It is found that a wax mixture extracted and isolated from Kaoliang has such excellent physiological activity effects that the wax mixture can reduce the blood glucose level and the plasma insulin level more effectively, increase the adiponectin level, and simultaneously reduce the level of resistin, which is one of adipocytokines that have been believed to induce insulin resistance, in a mouse suffering from type-2 diabetes, compared with a wax that is an isolated component originated in a plant other than Kaoliang or an animal or a higher saturated aliphatic alcohol (policosanol) which have been tried to utilize so far.

Description

  The present invention relates to an insulin-independent type 2 diabetes mellitus-improving agent comprising as an active ingredient a wax mixture extracted and separated from a natural product, cuolian, and a food and drink containing the same.

  Diabetes mellitus is a disease in which the ability to return the increased sugar content in blood to a normal level (glucose tolerance) does not sufficiently function, and is roughly classified into type 1 diabetes and type 2 diabetes depending on the mechanism by which this glucose tolerance is reduced.

  Type 1 diabetes, also known as insulin-dependent diabetes, has a strong genetic component, and β-cells in the pancreatic islets of Langerhans secreting insulin, a hormone that lowers blood sugar, are destroyed by immune abnormalities. Is a disease in which the sugar concentration in the blood increases abnormally.

  On the other hand, type 2 diabetes is also referred to as non-insulin dependent diabetes mellitus, and it is mainly caused by cells such as liver and muscle that cause decreased sensitivity to insulin action due to lifestyle-related diseases such as obesity. As a result, the blood insulin concentration and sugar concentration are abnormally increased. This type 2 diabetes is said to account for about 95% or more of all diabetes in Japan.

  A general method for improving type 2 diabetes is to start with diet therapy / exercise therapy, and if the symptoms are not alleviated, treatment with medication is performed. Numerous methods have already been proposed as medications for patients with type 2 diabetes. For example, guanide agents that suppress hepatic gluconeogenesis, thiazolidine-based insulin sensitivity improvers that improve peripheral insulin sensitivity, and insulin secretion stimulating effects. Medication therapies such as sulfonylurea acid are known.

  On the other hand, in recent years, the physiologically active effects of separated components derived from natural products (wax, etc.) without serious side effects have attracted particular attention. To date, methods for collecting active ingredients and attempts to improve diabetes with active ingredients are as follows. As many as disclosed.

(1) Proposal of a method of shaving off the skin part of a sugar cane stem with a razor or a peeler and extracting it under a heated condition using an organic solvent (Patent Documents 1 and 2)
(2) Proposal of a method for efficiently extracting and separating and recovering cane wax contained in sugarcane molasses with lower alcohol (Patent Document 3)
(3) Proposal of application of an extract containing polycosanol obtained from natural products such as sugarcane to the treatment of diabetic peripheral neuropathy (Patent Document 4)
(4) Disclosure of action of hot water extract of corn number hair and cordyceps mycelium to lower blood glucose level of type 1 diabetic rats (Patent Document 5)

Furthermore, the following attempts have been disclosed for improving type 2 diabetes.
(5) Proposal of type 2 diabetes improving agent and type 2 diabetes improving food containing higher saturated fatty alcohol extracted and separated from natural products such as sugarcane as active ingredients (Patent Document 6)
(6) Disclosure of effectiveness of combination of policosanol extracted / separated from natural products such as sugarcane and specific substances known for specific pharmacological action on type 2 diabetes and insulin resistance (Patent Document 7)

  In any of these attempts, sugar or higher saturated aliphatic alcohol (polycosanol), which is a separation / extraction component derived from sugar cane, corn, other plants or animals, is used.

  Moreover, although the said patent documents 1-3 are trying the extraction / separation method of the active ingredient from sugarcane, or antilipidemia and osteoporosis improvement, they do not mention at all about the improvement effect of type 2 diabetes. In addition, Patent Documents 4 and 5 propose physiologically active effects on sugarcane, corn numb hair, and hot water extract of Cordyceps mycelium, but there is no mention of any improvement effect on type 2 diabetes. It has not been.

  On the other hand, Patent Documents 6 and 7 disclose the improvement effect of type 2 diabetes of higher saturated fatty alcohol (polycosanol) extracted and separated from natural products such as sugarcane. There is no mention about.

  Therefore, no attempt has been made so far to focus on colouran among the natural product raw materials, and a wax mixture of a specific composition extracted and separated from colouran has not been able to control blood sugar levels or blood insulin levels in type 2 diabetes. Thus far, no prior art has been found that has an excellent lowering effect and increases adiponectin production.

JP 59-053427 A WO2004 / 105739 JP-A-01-271696 JP 2001-511447 A No. 99/053936 JP 2007-063203 A Special table 2008-509132 gazette

  As described above, although some attempts have been made to use components derived from natural products for improving type 2 diabetes, an effective technique that exhibits a sufficient effect has not yet been proposed. Therefore, an object of the present invention is to provide a technique capable of sufficiently improving type 2 diabetes with a component derived from a natural product with few side effects.

  As a result of intensive studies in view of the above problems, the present inventors have found that a wax mixture extracted and separated from cucumber is a wax or higher-saturation that has been conventionally attempted as a separation component derived from plants or animals other than cucumber. Compared with fatty alcohol (policosanol), this book has found that it has an excellent bioactivity effect that effectively remarkably lowers blood glucose level and plasma insulin concentration of type 2 diabetic mice and increases adiponectin concentration The invention has been completed.

That is, the present invention
(1) a type 2 diabetes mellitus ameliorating agent comprising a wax mixture extracted and separated from cucumber as an active ingredient,
(2) The type 2 diabetes-improving agent according to (1), wherein the wax mixture is mainly composed of octacosanal and triacontanal,
(3) The type 2 diabetes mellitus improving agent according to (1), wherein the sorghum is a sorghum epidermis,
(4) The present invention relates to a type 2 diabetes-improving food or drink containing the type 2 diabetes improving agent according to (1), (2) or (3).

  This specification includes the contents described in the specification and / or drawings of Japanese Patent Applications Nos. 2009-233649 and 2010-089463, which are the basis of the priority of the present application.

  According to the present invention, the condition of type 2 diabetes is sufficiently improved by a component derived from a natural product with few side effects.

The figure which shows the comparison of the fasting plasma insulin density | concentration with a control (standard feed type) and each wax combination type | system | group test feed. (Provided by Dr. Masayuki Watanabe, Showa Women's University, Faculty of Life Sciences) The figure which shows the difference of an Example and a comparative example regarding a blood glucose level transition (mg / dL).

(1) Natural raw material used in the present invention Koryang, which is the raw material of the present invention, has a modern Chinese name of Goryang, Kaorian, and is also called sorghum, cricket, or sorghum, sugarcane, sorghum, depending on the region. It is an annual plant and grain of the genus Sorghum. It is a tropical and subtropical crop that is resistant to drying and grows in areas where rice and wheat do not grow, and is cultivated for food mainly in Africa, Central America and Southeast Asia. The plant height is about 3 meters for wild species, but most of the cultivars are about 1.5 meters. The leaves are more than 1 meter long and about 10 centimeters wide, and the stem is about 3 centimeters thick and has a core.

  There are two types of culang: grain-type cuoliang (grain sorghum) and solgo-type cuoliang (forage sorghum). The grain type is cultivated for the purpose of collecting grains, and the grains are used as a raw material and feed for food and liquor. The Sorgo type has few ears, but the whole stem and leaves are used as feed.

  As the varieties suitable for the present invention, grain-type cuolian is preferable because it contains more octacosanal and triacontananal components that have been found to have a significant improvement effect on type 2 diabetes in the present invention. The content of both components depends greatly on the sampling method from the cucumber stalk, and both the components are particularly present in the epidermis portion of the stem, and also present in extremely high concentrations in the epidermis portion near the stem nodes. Therefore, it has been confirmed that the effect of the present application can be sufficiently exerted even in the solgo type depending on the way of collection. On the other hand, white powdery wax is blown on the surface of the stem buds and leaves as well, but our analysis reveals that the wax is almost free of octacosanal and triacontanal. .

  On the other hand, the sugarcane used in the comparative example in the present application is a plant belonging to the genus Sugaraceae and is also called sweet potato, and is a raw material for sugar (sucrose) along with sugar beet. Widely cultivated in tropical and subtropical regions around the world, the main producing countries and production ratios are Brazil (28.0%), India (21.7%) and China (6.4%). In Japan, it is cultivated mainly in Okinawa Prefecture and Amami Islands.

  In other words, Koryang belongs to the genus Sorghum and is edible, but sugarcane belongs to the genus Saccharomyces and is a raw material of sugar, and both are plants of completely different genera.

(2) Separation and extraction method of the wax mixture of the present invention A typical production method of the wax mixture of the present invention is shown below.

Separation method of the epidermis The wax mixture of the present invention is concentrated and concentrated in the epidermis part of the sorghum stalk, particularly in the vicinity of the nodal part, so that it can be selectively and efficiently recovered using various means. It is desirable. For example, the lined portion of the epidermis and the pis of the internal tissue are mechanically separated by a separation device such as a cane separation system (hereinafter abbreviated as CSS; manufactured by AmClyde, US Pat. No. 3,690,358, FIG. 2). Then, the method of subjecting the skin to extraction, the method of collecting and collecting the wolfberry skin manually using a wire brush, the method of scraping and collecting by hand with a knife, razor, etc., or the automatic peeler Etc. are effective.

How extraction and purification of the wax component then wax component, obtained by solvent extraction using glass Soxhlet extractor or the like from the collected skin portion. That is, the organic solvent such as benzene, isopropanol and hexane was used for extraction by heating in a hot water bath at 70 to 100 ° C. for 2 to 4 hours, and then the residual solvent was evaporated to dryness. To obtain a crude wax. Further, the crude wax is distilled with a thin film distiller, and the high boiling point component is removed as a residue to obtain the purified wax mixture of the present invention.

(3) Components other than the wax mixture that can be used in combination The components other than the wax mixture that can be used in the present invention are not particularly limited as long as they do not interfere with the purpose of the present invention, and can be appropriately selected according to the purpose. The following medicinal ingredients, additives and the like can be mentioned. Examples of the medicinal components include vitamins, blood pressure lowering agents, vasodilators, antiarrhythmic agents, thrombolytic agents, hyperlipidemia agents, and the like. The additive is not particularly limited, and examples thereof include a stabilizer, a surfactant, a solubilizer, a water-soluble polymer, an antioxidant, a pH adjuster, and a dispersant.

(4) Shape of the improving agent of the present invention The type 2 diabetes improving agent of the present invention and the dosage form of food and drink are not particularly limited and can be appropriately selected according to the purpose. For example, powder, fine granules, It may be a solid agent such as a granule or a microcapsule, and may be a tablet or a film coat agent, or may be filled in a capsule. Moreover, it is good also as a solution by making into solution or suspending with the solvent selected suitably.

(5) Food and drink of the present invention Type 2 diabetes-improving food and drink containing the wax mixture of the present invention includes cooking oils, beverages, tablets, granules, dressings, mayonnaises and creams containing these wax mixtures. , Chocolate, potato chips and the like. Such foods and drinks can be produced by adding generally used food materials according to the types of foods and drinks in addition to the wax mixture of the present invention.

(6) Appropriate dosage of the wax mixture of the present invention In the examples of the present invention, about 40 g of mice ingested 7 g / day (0.035 g as a wax mixture) of mixed feed containing 0.5% by weight of the wax mixture. , It has been found that there is an effect of improving type 2 diabetes. Generally, it is said that about 1/50 of the effective amount of 1 kg body weight in rats and mice is an appropriate dose in humans. Therefore, the intake here is 0.875 g / day when converted to a human of 50 kg.
Hereinafter, the present invention will be described in more detail based on examples.

[Production Example 1]
(1) Collection of corn stalk epidermis The production area and varieties of cuolian, which is the raw material of colour wax used in the mouse test, and the method of collecting the epidermis are as follows. Forage sorghum (variety name: Big Sugar Sorgo) from Yasukuni-jima, Okinawa Prefecture, as the raw material for Kouliang, mechanically separated into the epidermis, lined and core by the CSS, the epidermis is collected, and the following solvent extraction It was used for. A sugarcane wax for comparison was also obtained in the same manner as described above.

(2) Extraction and Separation of Wax Component A 2 L glass Soxhlet extractor was used for extraction. A Soxhlet extraction was performed using 150 g of a skin sample and hexane as a solvent. After extraction for 3 hours at a hot water bath temperature of 90 ° C., the residual solvent was evaporated to dryness to obtain about 100 g of crude wax. Next, the crude wax was distilled with a thin film distiller to remove a high boiling point residue as a residue, thereby obtaining 70 g of a purified wax mixture.

(3) Analysis of wax component The composition of the wax mixture was subjected to gas chromatography under the following conditions, and the results shown in Table 1 were obtained.

Gas chromatography condition column: DB-5 ((5% -Phenyl) -Methylpolysiloxane, column length: 30 m,
(ID: 0.25 mm, film thickness: 0.25 μm, manufactured by J & W Scientific)
Temperature rising condition: 150 ° C. → (4 ° C./min)→320° C. (10 min)
Column flow rate: 1.70 mL / min Detector: FID, Detector temperature: 350 ° C.
Carrier gas: N ₂

  According to Table 1, in the raw material cuolian, there are many higher saturated aliphatic aldehyde components that are the sum of octacosanal (C28) and triacontanal (C30), which are the focus of the present invention, compared with sugarcane. It can be seen that the content of C30) is remarkably high, whereas in sugarcane, especially octacosanol (C28) is high, but the higher saturated aliphatic aldehyde component is relatively low.

[Mouse test conditions]
Test mouse type: male, 4 weeks old (“KK-Ay / Ta”, Nippon Claire Co., Ltd., type 2 diabetes model mouse) was used.
-Number of mice per group: 6-Breeding method: After pre-breeding with AIN-93G standard feed for 1 week, each test compound containing the waxes of Example 1 and Comparative Example 1 described below was administered and reared for 8 weeks. .
-Breeding environment: During the breeding period, the test feed and water were freely fed, and the animals were isolated and housed individually in plastic cages at a room temperature of 20 to 25 ° C and a 12 hour light / dark cycle.
-Composition of AIN-93G basic feed (unit: mass%): Casein 20, corn starch 39.8, pregelatinized corn starch 13.2, sucrose 10.0, soybean oil 7.0, cellulose powder 5.0, AIN -93G mineral mix 3.5, AIN-93G vitamin mix 1.0
・ Standard feed: Add 0.5% olive oil to the above basic feed ・ Test feed: Add 0.5% each of the wax mixture to the above basic feed

[Example 1]
(Korean wax-containing test feed) (present invention)
A breeding test was conducted using the purified wax mixture obtained in Production Example 1.
The test feed should be uniformly dissolved in soybean oil used in the basic feed in advance, so that the solid Koulian wax is uniformly dissolved, and then 99.5% by weight of the AIN-93G basic feed and 0.5% by weight of the Kourian wax. What was prepared by mixing was reared under the above conditions as a test diet.

[Comparative Example 1]
(Sugar cane wax combination system test feed)
The test feed was prepared by uniformly dissolving the solid sugarcane wax in soybean oil used in the basic feed in advance, and then uniformly in such a way that the AIN-93G basic feed was 99.5% by mass and the sugarcane wax was 0.5% by mass. What was prepared by mixing was reared under the above conditions as a test meal. Table 2 shows the effect of administration of cucumber wax and sugarcane wax on type 2 diabetes model mice on blood glucose levels and insulin concentrations in fasting plasma.

  From Table 2, administration of a wax-containing test feed to type 2 diabetes model mice significantly reduced the blood glucose level and insulin concentration in the cucumber wax-containing test feed mouse of the present invention compared to the sugar cane wax-containing test feed. ing. Moreover, as shown in FIG. 1, compared with the control (standard feed system), the fasting plasma insulin concentration in the sugar cane wax compounded system is not improved, whereas that in the cucumber wax compounded system is about 50%. % Reduction and a significant improvement effect are recognized.

[Production Example 2]
Next, in order to prove that octacosanal and triacontanal, which are the characteristics of the present invention, are effective as a type 2 diabetes mellitus-improving agent, a case where wax reduction treatment is performed and a case where reduction treatment is not performed A comparative test was conducted.

(1) Collection of the skin of the cucumber stalk The cucumber stalk (variety name: Jongno 5 No. 6A) from Kuroyama Prefecture, Liaoning Province, China was used as the cucumber raw material. First, only the epidermis part of the sorghum stalk was scraped off and collected with a razor or a peeler and subjected to the following solvent extraction.

(2) Extraction and Separation of Wax Component A 2 L glass Soxhlet extractor was used for extraction. A Soxhlet extraction was performed using 150 g of a skin sample and hexane as a solvent. After extraction for 3 hours at a hot water bath temperature of 90 ° C., the residual solvent was evaporated to dryness to obtain about 100 g of crude wax. Next, the crude wax was distilled with a thin-film distiller to remove a high-boiling portion as a residue, thereby obtaining 70 g of a purified wax mixture (hereinafter referred to as “non-reduced coconut wax”).

(3) Reduction treatment of wax The above-mentioned non-reduction treated sorghum wax was subjected to a reduction treatment under the following reaction conditions to obtain a reduced sorghum wax (hereinafter referred to as “reduced sorghum wax”).

<Reduction treatment conditions>
Reaction: 250 mL of chloroform and 10 g of non-reduced coconut wax are placed in a 2 liter round bottom flask equipped with a reflux tube and dissolved by heating in a 60 ° C. hot water bath. After dissolution, add 250 mL isopropanol and shake gently. A NaBH ₄ solution in which 25 g of NaBH ₄ powder is dissolved in 125 mL of 0.1N NaOH aqueous solution is prepared in advance, and this is added to the flask of the wax solution, shaken well, and left in a 60 ° C. hot water bath for 2 hours.
End of reaction: Take the lower layer with a 1 liter separatory funnel and discard the upper layer. Return the lower layer to the flask, add 500 mL of ion-exchanged water heated to 60 ° C., and shake well. Take the lower layer again with a separatory funnel and discard the upper layer. The lower layer was concentrated by heating, and then evaporated to dryness in a vacuum dryer to obtain a reaction product. Yield 85%.
Purification: Distillation was performed with a thin-film distiller at 270 ° C. and 0.2 mmHg. Yield 59%.

(4) Analysis of Wax Component The composition of each wax mixture of the non-reduced sorghum wax and the reduced sorghum wax was measured by gas chromatography under the following conditions, and the results shown in Table 3 were obtained.

Gas chromatography condition column: DB-5 ((5% -Phenyl) -Methylpolysiloxane, column length: 30 m,
(ID: 0.25 mm, film thickness: 0.25 μm, manufactured by J & W Scientific)
Temperature rising condition: 150 ° C. → (4 ° C./min)→320° C. (10 min)
Column flow rate: 1.70 mL / min Detector: FID, Detector temperature: 350 ° C.
Carrier gas: N ₂

  From Table 3, in the non-reduced sorghum wax, among the higher saturated aliphatic aldehydes of interest in the present invention, the contents of octacosanal (C28) and triacontanal (C30) are particularly high. In contrast to the aldehyde component and higher saturated fatty alcohol component, both the components of octacosanal (C28) and triacontanal (C30) are significantly reduced in the reduced coconut wax. At the same time, it can be seen that the contents of the higher saturated aliphatic alcohols octacosanol (C28) and triacontanol (C30) are greatly increased.

[Mouse test conditions]
Test mouse type: male, 4 weeks old (“KK-Ay / Ta”, Nippon Claire Co., Ltd., type 2 diabetes model mouse) was used.
-Number of mice per group: 8-Breeding method: After pre-breeding with AIN-93G standard feed for 1 week, each of the wax-mixed test feeds of Example 2 and Comparative Example 2 below was administered and kept for 8 weeks. .
-Breeding environment: During the breeding period, the test feed and water were freely fed, and the animals were isolated and kept individually in plastic cages at a room temperature of 20 to 25 ° C and a 12 hour light / dark cycle.
-Composition of AIN-93G basic feed (unit: mass%): Casein 20, corn starch 39.8, pregelatinized corn starch 13.2, sucrose 10.0, soybean oil 7.0, cellulose powder 5.0, AIN -93G mineral mix 3.5, AIN-93G vitamin mix 1.0
・ Standard feed: Add 0.5% olive oil to the above basic feed ・ Test feed: Add 0.5% each of the wax mixture to the above basic feed

[Example 2]
(Non-reduced cucumber wax-containing test feed) (Invention)
A breeding test was performed using the non-reducing treated sorghum wax of Production Example 1.
The test feed was prepared by uniformly dissolving solid non-reduced cucumber wax in soybean oil used in advance for the basic feed, and then AIN-93G basic feed 99.5% by mass, non-reduced cucumber wax 0.5% by mass In this way, the mixture prepared by uniformly mixing was reared under the above conditions as a test diet.

[Comparative Example 2]
(Reduction-treated cucumber wax compounded test feed)
A breeding test was conducted using the reduction-treated kuryan wax of Production Example 2.
The test feed is prepared by uniformly dissolving the solid reduced cucumber wax in soybean oil used in advance for the basic feed, and then AIN-93G basic feed 99.5% by mass and reduced cucumber wax 0.5% by mass. In addition, a sample prepared by mixing uniformly was bred under the above conditions as a test food.

After the breeding, about 1 mL of blood was collected from the mouse under ether anesthesia. About 1 mL was centrifuged at 3000 rpm for 10 minutes, and the supernatant was used as a serum sample, which was used for measurement of each concentration of insulin, adiponectin and resistin.
・ Insulin concentration: Morinaga ultrasensitive mouse insulin measurement kit (manufactured by Morinaga Life Science Institute)
・ Adiponectin concentration: QuantikineAdiponectin / Acrp30 Immunoassay kit (R & D SYSTEMS)
-Resistin concentration: Resistin, ELISA Kit, Quantikine (R & D SYSTEM)

  Table 4 shows the effects of administration of non-reduced cucumber wax and reduced cucumber wax on blood glucose levels, fasting plasma insulin, adiponectin and resistin concentrations.

  From Table 4, blood glucose level and insulin in mice using the non-reduced cucurian wax compounded test diet of the present invention compared to the reduced treated cucurian wax compounded system when the type 2 diabetes model mouse was administered with the cucurian wax compounded test diet The concentration is decreasing and the adiponectin concentration is increasing. On the other hand, the resistin concentration, which is a kind of adipocytokine that is believed to cause insulin resistance, is significantly lower in mice using the non-reduced cucumber wax-blended test feed of the present invention than in the reduced-treated cucumber wax-blended system. ing.

  That is, it was found that octacosanal (C28) and triacontanal (C30) are effective in improving type 2 diabetes.

[Example 3]
A human intervention test was conducted with a 70-year-old male as a test subject. The day before the inspection, avoid excessive exercise, and drink SB food frozen foods “Scallop miscellaneous cooking”, “Kani miscellaneous cooking” and “Tori miscellaneous cooking” with one meal (180-210 kcal) in the morning, noon, and evening It was not fast, and it was fasted after 19:00.

  After fasting for 12 hours from the previous day, 30 mg of non-reduced mulberry wax was added to 30 cc of milk and dispersed and drunk. Thirty minutes later, the fasting blood glucose level was measured using a blood glucose level measuring device for self-test (ARKRAY Co., Ltd. gluco card meter set).

  Immediately thereafter, 14 g of glucose was ingested with 100 cc of water. Autologous blood glucose was measured over time from 30, 60, 120, 150, 180 and 210 minutes after the start of ingestion.

[Comparative Example 3]
On another day, self blood glucose measurement was performed in the same manner as in the example except that the non-reduced sorghum wax was not taken.

  FIG. 2 shows a graph of the blood glucose levels of Example 3 and Comparative Example 3. From FIG. 2, it was clearly recognized that the increase in blood glucose level was smaller when the non-reduced sorghum wax was taken.

  From the results of the above Examples and Comparative Examples, the quorian wax mixture of the present invention mainly composed of higher saturated aliphatic aldehydes of octacosanal and triacontanar can extremely effectively improve insulin-independent type 2 diabetes. I understood.

  According to the present invention, a wax mixture having a specific composition derived from Koryan, which can be easily produced at low cost, is effective in improving type 2 diabetes caused by lifestyle-related diseases, and is highly safe and can be used, is used as an active ingredient. Type-diabetes-improving agent, and foods and drinks suitable for them as hospital foods and drinks, health drinks or foods, feed supplements and the like can be provided.

Claims (4)

  A type 2 diabetes mellitus-improving agent comprising a wax mixture extracted and separated from cuolian as an active ingredient.   The type 2 diabetes mellitus ameliorating agent according to claim 1, wherein the wax mixture contains octacosanal and triacontanal as main components.   The type 2 diabetes mellitus ameliorating agent according to claim 1, wherein the wolfberry is a frog skin.   A type 2 diabetes improving food or drink containing the type 2 diabetes improving agent according to claim 1, 2 or 3.

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