JP2009108025A - Therapeutic agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a therapeutic agent containing an extract of the leaf portions of a plant belonging to genus Ficus as an active ingredient, since, while the extract of the Ficus carica is known to have functions such as a lipolysis-promoting action, a constipation-eliminating action, and a melanin production-promoting action, the leaf portions of a plant belonging to genus Ficus has especially remarkable effects for various other diseases. <P>SOLUTION: A hyperuricemia-preventing or improving agent, an anti-osteoporosis agent, an antidepressant-antistress agent, an adiponectin production-promoting agent, a hypocholesterolemic agent, a hypotensive agent, a hangover-preventing or improving agent, an external preparation for skin, an antidiabetic agent, or a rheumatic medicine, contains the extract of the leaf portions of the plant belonging to genus Ficus as the active ingredient. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a therapeutic agent useful for various diseases comprising an extract of leaves of plants belonging to the genus Fig as an active ingredient.

Fig extract is known to have functions such as a lipolysis promoting action (Patent Document 1), a constipation relieving action (Patent Document 2), and a melanin production promoting action (Patent Document 3).
However, there is no view that the leaf extract of a plant belonging to the genus Fig is effective with remarkable effects on various diseases applied in the present invention described below.
Japanese Patent Laid-Open No. 2005-60366 JP 2003-88328 A JP 2002-47130 A

  An object of the present invention is to provide various therapeutic agents that are effective with a particularly remarkable effect on various diseases applied in the present invention described below.

The invention according to claim 1 is a preventive or ameliorating agent for hyperuricemia comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.
Invention of Claim 2 is an anti-osteoporosis agent which uses the extract of the leaf part of the plant which belongs to the genus Fig as an active ingredient.
The invention according to claim 3 is an anti-depressant / anti-stress agent comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.
Invention of Claim 4 is an adiponectin production promoter which uses the extract of the leaf part of the plant which belongs to the genus Fig as an active ingredient.
The invention according to claim 5 is a cholesterol-lowering agent comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.
The invention according to claim 6 is an antihypertensive agent comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.
The invention according to claim 7 is an agent for preventing or improving hangover comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.
The invention according to claim 8 is an external preparation for skin comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.
The invention according to claim 9 is an antidiabetic agent characterized by comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.
The invention according to claim 10 is a therapeutic agent for rheumatism comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.

  According to the present invention, there are provided various therapeutic agents that are particularly effective for various diseases applied in the present invention described below with remarkable effects.

  Hereinafter, the present invention will be described in more detail.

  The leaf part of the plant belonging to the genus Ficus used in the present invention is not particularly limited as long as it is a leaf part of a plant belonging to the genus Figaceae, but preferably fig (F. carica L.), Inubiwa ((F. erecta Thumb.), Itabikazura ((F. sarmentosa Roxb. var. nipponica Corner)) and the like.

A method for preparing the leaf extract of a plant belonging to the genus Fig will be described.
As a pre-stage for preparing a leaf extract of a plant belonging to the genus Ficus, the leaf portion of the plant belonging to the genus Ficus is preferably dried and pulverized.
Subsequently, the leaves of the plant belonging to the genus Fig are contacted with a solvent to obtain an extract.

  As a solvent to be used, for example, water, an organic solvent, a mixed solution of water and an organic solvent, or the like can be used. Examples of the organic solvent include lower alcohols represented by ethanol, methanol, propanol and butanol, ethers represented by dimethyl ether and diethyl ether, halogenated hydrocarbons represented by chloroform, carbon tetrachloride, acetonitrile, and the like. Examples include ethyl acetate and acetone. Of these, water, an aqueous ethanol solution, butanol, and ethyl acetate are preferable.

  The obtained extract can be used as it is, but may be subjected to dilution, concentration, lyophilization and the like. It can also be purified. Examples of the purification method include known means for removing inert impurities from the extract by a separation technique such as chromatographic liquid-liquid partition.

  The extraction time may be a time for sufficiently extracting soluble components from the extraction raw material, and may be set as appropriate according to the extraction temperature and the like. Preferably, it is 30 minutes to 48 hours. For example, when the extraction temperature is less than 50 ° C., 6 to 48 hours is appropriate, and when it is 50 ° C. or more, 30 minutes to 24 hours are appropriate. .

Apart from the above, a supercritical fluid extraction method can be mentioned as a method for obtaining an extract from the leaf part of a plant belonging to the genus Fig.
The supercritical fluid extraction method is a method of performing extraction using a supercritical fluid that is a fluid that exceeds the critical point (critical temperature, critical pressure) of a gas-liquid substance. As the supercritical fluid, carbon dioxide, ethylene, propane, nitrous oxide (laughing gas) or the like is used, and carbon dioxide is preferable.

  The supercritical fluid extraction method includes an extraction step of extracting a target component with a supercritical fluid and a separation step of separating the target component and the supercritical fluid. In the separation step, any one of extraction separation by pressure change, extraction separation by temperature change, or extraction separation using an adsorbent and an absorbent may be performed.

  The dosage of the leaf extract of a plant belonging to the genus Fig varies depending on the age, weight, indication symptoms, etc. of the patient. ˜1 g, preferably about 3 mg to 300 mg should be administered.

  Moreover, when using the extract of the leaf part of the plant which belongs to a fig genus as a skin external preparation, it is preferable to contain in the ratio of 0.0001-10 mass% as lyophilized powder in an external skin solvent.

  The therapeutic agent of the present invention can be appropriately prepared by a known method in the form of a solid or solution (hereinafter, also referred to as a preparation) such as a tablet, pill, capsule, granule, powder, powder, or liquid. That is, the solid preparation or liquid preparation useful in the present invention is produced by using a well-known preparation method that has been well established. Examples of additives include excipients, pH adjusting agents, cooling agents, suspending agents, diluents, antifoaming agents, thickeners, solubilizers, disintegrating agents, binders, lubricants, antioxidants. Agents, coating agents, coloring agents, flavoring agents, surfactants, plasticizers or fragrances.

  The therapeutic agent of the present invention can be taken as various health foods and functional foods. Examples of these include various products, but for the production of health foods and functional foods, in addition to commonly used food materials and food additives, excipients, extenders, binders, It can be used in the form of food and drink preparations using adjuvants such as disintegrants, lubricants, dispersants, preservatives, wetting agents, solubilizers, preservatives, stabilizers, capsule bases and the like. Specific examples of the adjuvant include lactose, fructose, glucose, starch, gelatin, magnesium carbonate, synthetic magnesium silicate, talc, magnesium stearate, calcium carbonate, methylcellulose, carboxymethylcellulose, or a salt thereof, gum arabic , Polyethylene glycol, syrup, petrolatum, glycerin, ethanol, propylene glycol, citric acid, sodium chloride, sodium sulfite, sodium phosphate, pullulan, carrageenan, dextrin, reduced palatinose, sorbitol, xylitol, stevia, synthetic sweetener, citric acid Ascorbic acid, acidulant, baking soda, sucrose ester, hardened vegetable oil, potassium chloride, safflower oil, beeswax, soybean lecithin, flavor, and the like can be blended. Regarding the production of such health foods and functional foods, reference books for pharmaceutical preparations such as “Japanese Pharmacopoeia Manual (General Rules for Preparations)” (Yodogawa Shoten) can be referred to.

  In addition to the above, the therapeutic agent of the present invention can be taken as a food or drink. Specifically, natto, thick fried, tofu, konjac, dumplings, pickles, boiled, croquettes, sandwiches, pizzas, hamburgers, dumplings, shumai, salads, etc., various powders (beef, pork, chicken and other livestock products) Marine products such as shrimp, scallops, sea bream, kelp, vegetables / fruits, plants, yeast, algae, etc.), pudding, cookies, crackers, bread, cakes, chocolate, potato chips, biscuits, donuts, jellies and other confectionery, Japanese rice crackers such as rice crackers, sheep crab, daifuku, ohagi, other buns, Japanese confectionery such as castella, frozen confectionery (rice cake etc.), bread and confectionery such as chewing gum, noodles such as udon, buckwheat and kishimen, kamaboko, ham, fish sausage, etc. Fish paste products, meat products such as ham, sausage, hamburger, corn beef, salt, pepper, miso, soy sauce, sauce, dressy Seasonings such as gyu, mayonnaise, ketchup, sweeteners, spices, teppanyaki foods such as Akashi-yaki, takoyaki, monja-yaki, okonomiyaki, yakisoba, fried udon, dairy products such as cheese, hard-type yogurt, and fats and oils Various foods such as powdered solids of flavors and fragrances (vanilla, citrus fruits, bonito etc.) and powdered foods and drinks (instant coffee, instant tea, instant milk, instant soup, miso soup, etc.) These are not particularly limited.

  Furthermore, in the present invention, for example, royal jelly, propolis, vitamins (A, C, D, E, K, folic acid, pantothenic acid, biotin, derivatives thereof, etc.), minerals (iron, magnesium, calcium, zinc, etc.), Selenium, lecithin, carotenoids (lycopene, astaxanthin, zeaxanthin, lutein, etc.), saponins (gymnemic acid, soybean saponin, ginseng saponins, etc.), fatty acids, proteins (collagen, elastin, etc.), oligosaccharides (isomalto-oligosaccharides, cyclic oligosaccharides, etc.) ), Phospholipids and derivatives thereof (phosphatidylcholine, sphingomyelin, ceramide, etc.), sulfur-containing compounds (eg, alliin, sepaene, taurine, glutathione, methylsulfonylmethane), sugar alcohols, lignans (sesamin, etc.), Contains animal and plant extracts Root vegetables (turmeric, ginger, etc.), may be used in combination and the like.

In addition, when an extract of a leaf part of a plant belonging to the genus Fig is used as an external preparation for skin, known materials usually used as an external preparation for skin, such as pigments, fragrances, preservatives, surfactants, pigments, antioxidant An agent, a humectant, an ultraviolet absorber and the like can be appropriately blended.
The external preparation for skin of the present invention can be used in a known form such as cream, milky lotion, lotion, pack and the like.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not limited to these. The therapeutic agent of the present invention is a preventive or ameliorating agent for hyperuricemia, an anti-osteoporosis agent, an antidepressant / anti-stress agent, an adiponectin production promoter, a cholesterol-lowering agent, a blood pressure-lowering agent, a hangover preventing or improving agent, an anti-diabetic agent It is extremely useful as a therapeutic agent for rheumatism. The external preparation for skin of the present invention is extremely useful as a wrinkle formation inhibitor and an acne treatment agent. Hereinafter, the various medicinal effects will be described with examples.

Example 1 (improvement effect of hyperuricemia)
Crush 1 kg of dried fig (F. carica L.) leaves, add about 10 times the amount of 60% aqueous ethanol solution (10 liters), extract under heating and reflux for 5 hours, filter, and collect the filtrate did. The filtrate was concentrated and further freeze-dried to obtain a freeze-dried powder 1 of the leaf extract of a plant belonging to the genus Fig.

Experimental Method As test animals, Wistar rats (8 weeks old, body weight of about 180 g) were used in groups of 6 animals.
Adenine was added to the test feed at a concentration of 0.75% and fed to rats to cause inhibition of uric acid excretion into the urine from the kidney, thereby giving a model animal of hyperuricemia.
The control group was the above 0.75% adenine feed only, and the drug administration group was a feed containing 0.75% adenine and the above powder 1. Although the feed was freely consumed, the concentration of the powder 1 in the test diet of the drug administration group was adjusted so that the intake amount was 1 mg / kg body weight. The uric acid level in the blood was measured on the test start day and 24th day.
As a result, the blood uric acid concentration on the test start day of the control group was 0.57 mg / ml, and it was 2.33 mg / ml on the 24th day, whereas the blood uric acid concentration on the 24th day of the drug administration group was The uric acid concentration was 0.82 mg / ml.
As is clear from this result, the blood uric acid concentration in the control group was significantly increased, whereas in the drug administration group, the concentration was not increased. Therefore, it was shown that the leaf extract of a plant belonging to the genus Fig is useful as an agent for preventing or improving hyperuricemia.

Example 2 (Anti-osteoporosis effect)
Osteoporosis Improvement Effect Test SD rat (22 weeks old) Female ovaries were surgically removed to create osteoporosis model rats. Ovariectomized rats were divided into 6 groups of 7 animals, and physiological saline so that the intake of powder 1 of Example 1 was 1 mg / kg every other day (total 17 times) during the 35-day test period. 2 ml of water-dissolved liquid was orally administered. The feed was the solid feed CRF-1 for mice, rats and hamsters from Oriental Yeast Co., Ltd. There was no difference in food intake between groups during the study period. On the 35th day after the start of the test, the weight of the rat was measured, and then the femur was removed. The femur was used for analysis with the adhesive tissue and muscle removed. After measuring the volume of the femur, it was washed three times with ethanol, then washed three times with acetone, dried overnight, and then weighed to determine the dry weight of the femur. From the volume and dry weight, the bone density (dry weight g / volume mm ³ ) was measured. As a control experiment, Table 1 shows the results together with an example (comparative example) in which the above experiment was repeated except that physiological saline not containing the powder 1 was administered to rats.

  When Example 2 and the comparative example were compared, Example 2 showed a significant difference at a risk rate of p <0.05.

Example 3 (Antidepressant / Anti-stress effect)
The therapeutic effect of the powder 1 of Example 1 was examined.
Evaluation of tranquilizing effect by forced mouse swimming test The therapeutic agent of the present invention was evaluated by the forced mouse swimming test developed by Porsolt in 1977. This is one of the most frequently used animal model experiments for depression. In this test, the mouse is forced to swim in a limited space to cause “immobility”. This immobility state is thought to reflect a kind of “despair state” in which stressed animals abandon their escape from water, and is associated with depression and stress in humans. In fact, antidepressants have been found to specifically reduce the duration of immobility in this situation, and this shortening has been found to have a significant correlation with clinical titer.

The test method is as follows.
Mice are forced to swim in a plastic cylinder containing 25 ° C. water to a depth of 15 cm. After forced swimming for 5 minutes, dry in a dryer at 30 ° C. for 15 minutes and return to the home cage. On the next day, the test sample is intraperitoneally administered to the mouse, one hour later, forced swimming for 5 minutes is imposed again, and the duration of the immobility that appears is measured using a stopwatch. A state in which the mouse floats on the water and is stationary is determined as an immobile state. For the duration of stationary state, a significant difference test is performed, and a statistically significant difference is tested. For the experiment, male ddY mice are used, and there are 6 mice per group. All tests are conducted between 1pm and 6pm. A test using imipramine, an antidepressant, as a positive control will also be conducted.

  As a result, the duration of immobility of the mouse administered with Powder 1 at 30 mg / kg was 170.0 ± 1.6 seconds. The control (saline only) was 220.0 ± 2.2 seconds. The duration of immobility in positive control mice (30 mg / kg dose) was 176.5 ± 4.0 seconds. The duration of immobility in this example and the positive control is significantly different at a risk rate of 1%. In addition, even if it used 2-3 times amount of the powder 1, the same result was obtained.

Example 4
Adiponectin production increase confirmation test Normal human preadipocytes were used and seeded in a 96-well microplate at 1.0 × 10 ⁴ cells. Human preadipocyte basal medium was used as the seeding medium. After 24 hours, the medium was replaced with a growth medium to which the differentiation-inducing additive and the powder 1 of Example 1 were added, and further cultured for 1 week. Thereafter, the amount of adiponectin produced in the culture supernatant was quantified by ELISA. The evaluation results of each sample are shown below as relative values when the amount of adiponectin in the blank (sample not added) is 100. The added powder 1 concentration was 10 μg / ml.

  Test result: relative value = 369. This value has a significant difference at a risk rate of 1%.

Example 5 (cholesterol lowering action)
ICR male mice weighing about 20 g (5 per group) were given a high cholesterol-cholate diet (71.9% standard diet, 15% sucrose, 2% salt, 10% coconut oil, 0.6% cholesterol, 0.2% cholic acid, 0.3% choline chloride) was fed (free intake) from the first day to the seventh day of the test. On the 6th and 7th day of the test, 5 mg of the powder 1 of Example 1 was dissolved in distilled water and orally administered. Thereafter, fasting was performed for 24 hours, and blood was collected from the mice on the 8th day of the test, and the serum was separated.

  In addition, heparin was added to a portion of the collected serum and precipitated to obtain heparin-precipitated lipoprotein as low density lipoprotein (LDL). The total cholesterol level in serum and the cholesterol level in LDL were reported by C. C. Allain et al. (Clinical Chemistry, 1974, 20, 470-475). ) And measured.

  The value obtained by subtracting the LDL cholesterol value from the total cholesterol value in the serum was calculated as a high density lipoprotein (HDL) cholesterol value. The control group is a group not administered with the powder 1.

  The results are shown in Table 2. As is apparent from Table 2, an obvious effect of lowering serum total cholesterol was observed.

Example 6 (blood pressure lowering effect)
Powder 1 of Example 1 was added to a general commercial feed (Funabashi Farm, Funabashi SP), and the changes in the maximum blood pressure value and body weight were compared using stroke-prone spontaneously hypertensive rats (SHR-SP). As a control group, a general sample to which powder 1 was not added was used. The A group is the control group and the B group is the present invention group, and each group of 6-week-old male SHR-SPs is bred for 7 weeks, and changes in blood pressure and body weight when they reach 12 weeks of age. Investigated about. As shown in Table 3, in the change of blood pressure, significant suppression of blood pressure increase was observed in the present invention group. In the present invention group, the concentration of the powder 1 in the feed was adjusted so that the intake amount of the powder 1 per day of the powder 1 was 50 mg / kg body weight.

Reference example 1
〔Animal experimentation〕
Four-week-old Fischer 344 male rats (Nippon Claire Co., Ltd.) were preliminarily raised on a standard diet for 6 days, then divided into 2 groups of 25 rats per group, and fed with experimental diets as shown in Table 4. Raised for 6 months. The feed was freely consumed. The carcinogen (1,2-dimethylhydrazine) was administered into the abdominal cavity of the rats so that the body weight was 20 mg / kg body weight 20 times from the first week to the 20th week after the start of the test. The presence or absence of colorectal cancer was examined by dissecting rats and removing the large intestine. Table 4 shows the composition of the feed used in the animal experiments, and Table 5 shows the frequency of colorectal cancer. In the present invention group, the concentration of Powder 1 in the feed was adjusted so that the daily intake of Rat 1 of Powder 1 of Example 1 was 50 mg / kg body weight.

Example 7 (Hangover prevention or improvement effect)
Wister male rats (7-8 weeks old), 6 animals in a group, fasted overnight, then orally administered the powder 1 of Example 1 (10 ml / kg) the next morning, 15 minutes later (W / V) An aqueous ethanol solution 20 ml / kg was orally administered. After administration of the aqueous ethanol solution, blood was collected from the tip of the tail after 1, 3, and 5 hours, and the blood alcohol concentration was measured using a blood alcohol measurement kit (manufactured by Sigma).

  As a result, the blood alcohol concentration in rats was 150 mg / dl immediately after administration of the ethanol aqueous solution, whereas it was 105 mg / dl after 1 hour, 80 mg / dl after 3 hours, and 33 mg / dl after 5 hours. Yes (average). In contrast, the control group to which no powder 1 was administered was 150 mg / dl immediately after ethanol aqueous solution administration, whereas 140 mg / dl after 1 hour, 107 mg / dl after 3 hours, and 88 mg / dl after 5 hours. dl.

Example 8
Juice was prepared according to the following formulation.
Frozen concentrated orange juice 5.0 parts by weight Fructose glucose liquid sugar 1.0 part by weight Citric acid 0.10 parts by weight L-ascorbic acid 0.09 parts by weight Powder 1 of Example 1 0.05 parts by weight

  A panel of 5 healthy individuals (aged 25-32 years old, 3 men, 2 women) who were determined to be aldehyde dehydrogenase deficient by the ethanol patch test. Was used. The amount of powder 1 in the juice was set to 150 mg in the following test.

Twenty minutes after taking the juice and control juice, 135 ml of beer (alcohol concentration of about 5.5%) was drunk, and subjective symptoms 20 minutes after drinking were answered in a questionnaire.
The panel test was conducted blindly considering the order effect, and the day was changed at the same time zone.
The subjective symptom was evaluated in 1 to 5 (1: no symptom, 2: somewhat symptomatic, 3: symptomatic, 4: slightly terrible, 5: terrible), and the significant difference was tested by Paired-t test. .

  The results are shown below. The juice of Example 8 was found to improve the degree of sickness and hot flashes at a risk rate of 5%, and prevent sickness.

Anti-drunkenness effect of juice and control juice (average value)
Juice of Example 8:
The degree of sickness 2.3 *
Hot flash 2.1 *
Heartbeat 2.5
Degree of sleepiness 3.3
Control juice:
Sickness 3.5
Hot flashes of face 3.7
Heartbeat 3.3
Degree of sleepiness 3.4
*: Significantly different from control juice (P <0.05)

Example 9 (wrinkle formation inhibitory effect)
A wrinkle formation model was prepared by irradiating UVB (long wavelength ultraviolet rays) for 10 weeks on the back of two groups of hairless mice, each of 5 mice. Thereafter, a liquid obtained by dissolving the powder 1 prepared in Example 1 in a ratio of 0.5% by mass in a 10% aqueous ethanol solution (Example 9) is included in one group of the wrinkle formation model, and 10% is included in the other group. % Ethanol aqueous solution alone (Comparative Example) was continuously applied to the back where wrinkles were formed once a day, at a rate of 5 days per week for 4 weeks. After the application period of 4 weeks, replicas were collected from the back of each model, and wrinkle scores were assigned to each of the obtained replicas according to the following criteria.
(Wrinkle score standard)
0: Directional structure is not recognized.
1: A fibrous thin structure is recognized with directionality.
2: A thick rod-like structure is recognized together with a fibrous thin structure having directionality.
3: A thick rod-like structure with directionality is observed.

  The evaluation using the wrinkle score is an evaluation by defining a linear structure with directionality on a replica as a wrinkle. Therefore, according to the wrinkle score standard, the higher the score, the better the skin state where wrinkle formation has progressed. When the average value of each group was computed about the wrinkle score obtained above, Example 0 was 0 and the comparative example was 1.0. When the wrinkle score of both groups was subjected to a significant difference test by Mann-Whitney test, the wrinkle score of Example 9 was significantly smaller than the wrinkle score of the comparative example at a risk rate of 0.05 or less.

Example 10
A cream having the following composition containing the powder 1 obtained in Example 1 was prepared by a conventional method.
Powder 1 10 parts by weight Glycerol sorbitan fatty acid ester 60 parts by weight Microcrystalline wax 10 parts by weight Olive oil 30 parts by weight Liquid paraffin 180 parts by weight Magnesium stearate 10 parts by weight Propylene glycol 37 parts by weight Magnesium sulfate 7 parts by weight Purified water 655 parts by weight

Example 11
About the cream of the said Example 10, the wrinkle formation inhibitory effect was investigated. That is, using a paneler worried about wrinkles, the cream of Example 10 was applied to the right side of the face twice a day in the morning and evening for 1 month every day, and the improvement of the right side wrinkles with respect to the left side was improved. +: Obviously improved, +-: slightly improved,-: not improved. As a result, all the panelists evaluated it as very improved.

Example 12 (Acne treatment effect)
Milk liquid:
An emulsion was prepared by the following composition and the following production method, and the acne prevention and improvement effects were examined.

(Production method)
A. Components (1) to (6) are heated and mixed and kept at 70 ° C.
B. A part of components (9) and (11) are heated and mixed and kept at 70 ° C.
C. Add A to B, mix, and uniformly emulsify.
(7), (8), (12) and (13) dissolved in the remainder of (11) after cooling D. C were added and mixed uniformly to obtain an emulsion.

(Test method)
A panel of 15 females aged 22 to 40 years per test milk was applied to the face with an appropriate amount of test milk after washing the face twice daily in the morning and night. The coating was carried out for 12 weeks, and the effectiveness of the acne improving effect by the coating was judged by the following three ranks, and evaluated according to the following evaluation criteria.

(Effectiveness rank)
Effective: Acne is difficult to make. Acne disappeared.
Slightly effective: Acne is a little difficult to do. Acne is less noticeable.
Invalid: No change before use.

  As a result, all panelists evaluated it as “effective”.

Example 13 (Anti-diabetic effect)
Diabetes was induced by administering streptozotocin once to the tail vein of 6-week-old male SD rats (6 rats per group).
The dose of powder 1 of Example 1 was 500 μg / kg, and was orally administered 1 hour before administration of streptozotocin (STZ), and orally administered once a day for 13 days from the next day. The day after the final administration, 50% glucose aqueous solution (10 ml / kg) was orally administered, and blood glucose level (mg / dl) was measured over time (o-toluidine / boric acid).

  In addition, as a normal control group, a group in which only sterile water was administered without administering STZ, a group in which STZ was administered and sterilized water was administered as a disease state control group, and STZ was administered as a positive control group and nicotinamide ( 50 mg / kg) was provided. Nicotinamide has been reported to be effective against STZ diabetes models (Animal utilization for new drug development, 419-422, R & D planning, 1985).

  Diabetes is a disease in which the ability to metabolize glucose is reduced and hyperglycemia occurs. In this example, a peak of blood glucose level was observed 1 hour after glucose administration, but the maximum blood glucose level was 360 mg / dl in the pathological condition control group, and the maximum blood glucose level was 164 mg / dl in the normal control group. The maximum blood glucose level of the pathological condition control group was about twice that of the normal control group, and a decrease in glucose metabolism ability was observed in the pathological condition control group.

  The activity of the powder 1 was calculated by the suppression rate (%) with respect to the blood glucose level of the pathological condition control group according to the formula 1.

(Formula 1)
Suppression rate (%) = [1- (highest blood glucose level of powder 1 administration group or positive control group−highest blood glucose level of normal control group) / (highest blood glucose level of disease state control group−highest blood glucose level of normal control group)] × 100

  As a result, the suppression rate of the powder 1 administration group was 60.3%. The suppression rate of the positive control group was 43.0%. Therefore, in the extract 1 administration group, an excellent decrease in blood glucose level was observed and the ability to metabolize sugar was improved as compared with the pathological condition control group.

Example 14 (anti-rheumatic effect)
DSEK cells, a fibroblast cell line established from the synovium of a patient with chronic rheumatoid arthritis, were treated with 5% CO in Iscov-MEM medium (IMDM: Gibco BRL) containing 10% FBS (manufactured by BioWitacker). _{In the} presence of ₂ cells, the cells are cultured at 37 ° C. until saturation in the incubator, and the cells are suspended in the above medium with a trypsin-EDTA solution (manufactured by BioWitacker) to 3 × 10 ⁴ cells / ml 200 μl was dispensed into each well of a 96-well microtiter plate (manufactured by FALCON). After 5 to 7 days of culture, when the cells were almost 80% saturated, the medium was changed, and 200 μl of the above medium in which the powder concentration of the powder 1 of Example 1 was 500 μg / ml was added.
After 24 hours and 72 hours, 10 μl of premix WST-1 (Takara Shuzo Co., Ltd., MK400) was added and reacted at 37 ° C. for 3.5 hours, and the absorbance at 450 nm (A ₄₅₀ ) to absorbance at 650 nm (A ₆₅₀ ) The subtracted value was defined as the degree of cell proliferation. As a result, the cell proliferation degree after 24 hours was 0.79, and after 72 hours it was 0.36, and antirheumatic activity was observed. In the control group to which the powder 1 was not added, the cell proliferation degree after 24 hours and 72 hours was 3.90.

In each of the above examples, when the powder 1 of Example 1 was prepared, the same result as above was obtained even when the extract was prepared using hot water without using the ethanol aqueous solution. In addition, in the preparation of the powder 1 of Example 1, as a raw material, plants belonging to other fig genus, for example, Inobiwa ((F. erecta Thumb.), Itabikazura ((F. sarmentosa Roxb. Var. Nipponica Corner), etc.) Is mentioned.
The same results as described above were obtained when the leaves were used. The therapeutic agent of the present invention is also useful as a feed form.

Claims (10)

  A preventive or ameliorating agent for hyperuricemia comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.   An anti-osteoporosis agent comprising, as an active ingredient, an extract of a leaf part of a plant belonging to the genus Fig.   An anti-depressant / anti-stress agent containing as an active ingredient an extract from the leaves of plants belonging to the genus Fig.   An adiponectin production promoter comprising, as an active ingredient, an extract of a leaf part of a plant belonging to the genus Ficus.   A cholesterol-lowering agent comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.   An antihypertensive agent comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.   An agent for preventing or improving hangover, comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.   An external preparation for skin containing as an active ingredient an extract of the leaves of plants belonging to the genus Fig.   An anti-diabetic agent comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.   A therapeutic agent for rheumatism, comprising an extract of a leaf part of a plant belonging to the genus Fig as an active ingredient.