TW201300123A - Ginger extract for inhibiting fat cell storing oil and a combination comprising the ginger extract - Google Patents

Abstract

The present invention disclose a ginger extract for inhibiting fat cell storing oil, as well as the combination comprising the ginger extract. The ginger extract is extracted from Alpinia galanga and Zingiber zerumbet.

Description

Ginger extract for inhibiting accumulation of oil droplets in fat cells and pharmaceutical composition containing the same

The present invention relates to a ginger extract for inhibiting accumulation of oil droplets in fat cells, and a pharmaceutical composition comprising the ginger extract.

Adipose cells are cells that contain fatty oil droplets in the cytoplasm. They can be classified into metabotropic multi-aparticular fat cells (brown fat cells) and storage-type single-atrial fat cells (also known as white fat cells).

Brown fat cell line is used to store medium or small fat oil droplets. The inside contains a large number of mitochondria to provide heat, mostly in the head and neck; white fat cell is used to store large fat oil droplets. Its nucleus and mitochondria are pressed to the edge of fat cells with low metabolism.

In addition to storing too much triglyceride, fat cells can also be used to regulate energy and blood sugar. Fat cells accumulate on the periphery of various organs to reduce the vibration of organs and the friction between organs to protect organs. The function. However, once too much calories are taken, fat cells are stored in large amounts of fatty oil droplets, which can easily cause obesity.

In general, there are an average of 30 billion white fat cells in adults, which are mainly used to store triglycerides. Under normal physiological conditions, the number of fat cells in the body will no longer increase or decrease after puberty. Therefore, for an adult individual, "obesity" refers to a situation in which fat cells in an individual accumulate oil droplets, thereby causing an increase in fat cells.

At present, the commonly used weight-loss medicines on the market include Meridia (Sibutramine), Xenical (Orlistat), chitin or laxative (magnesium oxide).

1. Nuometing mainly makes the pro-adrenalin and serum-promoting hormones in the brain prolong the action time, and increases the metabolic rate of the organism to accelerate the consumption of fat and achieve the effect of losing weight.

2, Roche fresh system on the small intestine, used to inhibit the activity of lipolytic enzymes, reduce the amount of fat decomposed into fatty acids by the lipolytic enzymes, so that the small intestine can not absorb fat, thereby reducing the body's intake of excess fat.

3, chitin is mainly to increase the satiety of the user, and has the effect of absorbing a small amount of fat.

4, the use of laxatives, such as magnesium oxide, mainly in the post-meal after the mandatory excretion of all food, is a more intense form of early weight loss, because of this way the body is not recommended, it is not recommended.

However, the conventional use of weight loss medicines is accompanied by many side effects that make the user uncomfortable, and the user is reluctant to continue using the conventional weight loss medicine. For example, long-term use of Nome Ting is prone to side effects such as dry mouth, insomnia, headache or constipation, which affects the daily routine of the user and is unwilling to continue to use it. Roche's action mechanism prevents the small intestine from absorbing fat. The user often discharges a large amount of oil during the release of the stool, and even inadvertently leaks when venting, thus causing great inconvenience to the daily routine of the user. Although chitin can increase the satiety of the user in advance, so that the user does not eat too much food to reduce fat absorption, however, the weight loss effect of chitin is not as good as the other three.

Therefore, it is possible to provide a pharmaceutical composition comprising an active ingredient derived from a natural herb, and the active ingredient is capable of directly inhibiting the accumulation of oil droplets in the fat cells of the living body, thereby achieving the purpose of reliably controlling body weight and slowing the occurrence of obesity. It also enables users to endure the side effects associated with the use of weight loss medicines, which is a great boon for patients who lose weight.

The main object of the present invention is to provide a ginger extract which inhibits the accumulation of oil droplets in fat cells by inhibiting the accumulation of oil droplets by fat cells in the living body, thereby slowing the occurrence of obesity in the individual.

A second object of the present invention is to provide a pharmaceutical composition comprising a ginger extract comprising a ginger extract extracted from a natural herb.

In order to achieve the foregoing object, the technical content of the present invention comprises: a ginger extract for inhibiting accumulation of oil droplets in fat cells, which is obtained by the following steps: a drying step, a ginger and red ball ginger Drying the roots or stems to reduce the water content of the roots or stems of the southern ginger and red ball ginger to less than 10%, to obtain a dried dried ginger and a dried red chrysanthemum; an extraction step, The dried ginger mixture of 25~75% by weight and the dried red chrysanthemum of 25~75% by weight are mixed into a dry mixture of ginger, and the dried mixture of the ginger is extracted with a solvent to obtain a ginger extract; In a concentration step, the ginger extract is concentrated to obtain a ginger extract having an oil droplet inhibiting accumulation of fat cells.

In the ginger extract of the present invention for inhibiting the accumulation of oil droplets in the fat cells, the solvent of the extraction step may be selected from water, methanol, ethanol, acetone, ethane, propane, butane or hexane.

In the ginger extract of the present invention for inhibiting the accumulation of oil droplets in the fat cells, the weight ratio of the ginger dry mixture to the solvent is preferably from 1:8 to 1:12.

In the ginger extract of the present invention for inhibiting the accumulation of oil droplets in the fat cells, the extraction step is preferably performed by ultrasonic vibration.

In the ginger extract of the present invention for inhibiting the accumulation of oil droplets by the fat cells, the drying step may be selected as a freeze drying treatment, a spray drying treatment, an evaporation treatment or a heat drying treatment.

In the ginger extract for inhibiting the accumulation of oil droplets in the fat cells of the present invention, the concentration step may be selected as a vacuum concentration treatment, an evaporation treatment or a heat drying treatment.

A pharmaceutical composition comprising a ginger extract comprising: a ginger extract as described above; and a pharmaceutically acceptable carrier or excipient for shaping the ginger extract into the pharmaceutical composition.

In the pharmaceutical composition of the present invention containing ginger extract, the pharmaceutical composition is preferably administered orally to an individual.

In the pharmaceutical composition containing the ginger extract of the present invention, the pharmaceutical composition may be selected from a tablet, a capsule, a powder, a granule or a liquid.

In the pharmaceutical composition containing the ginger extract of the present invention, the pharmaceutical composition preferably comprises 300 to 600 mg of ginger extract per kg body weight of the individual.

The above and other objects, features, and advantages of the present invention will become more apparent from the aspects of the appended claims. The ginger extract of the present invention for inhibiting the accumulation of oil droplets in the fat cells is prepared by the following method. The preparation method of the ginger extract comprises a drying step S1, an extraction step S2 and a concentration step S3.

The drying step S1 is to dry the root or stem of the ginger and the red ball ginger, so that the water content of the root or stem of the southern ginger and the red ball ginger is reduced to less than 10%, and a dried ginger and a dried ginger are obtained. Red ball ginger dry matter. More specifically, the drying step S1 may be selected but not limited to drying by a freeze drying treatment, a spray drying treatment, an evaporation treatment or a heat drying treatment. The genus Alpinia galanga , also known as galangal, reed ginger or scented ginger, has sweet taste, bitterness and warmth, and enters the spleen and stomach, and has the functions of antibacterial, improving indigestion and anti-allergy; Zingiber zerumbet , also known as ball ginger, has a spicy and warm taste and has the function of inhibiting cancer cell proliferation and improving allergies. In this embodiment, the dried ginger and red ball ginger are freeze-dried to obtain the dried dried ginger and the dried red ginger. Thereby, the active ingredients in the southern ginger and red ball ginger are concentrated to enhance the extraction efficiency of the extraction step S2.

The extraction step S2 is to mix 25~75% by weight of dried ginger and 25 to 75% by weight of dried red ginger to form a ginger dry mixture, and extract the ginger dry mixture with a solvent. A ginger extract is obtained. For example, the solvent may be selected from, but not limited to, water, methanol, ethanol, acetone, ethane, propane, butane or hexane, etc., wherein the weight ratio of the ginger dry mixture to the solvent is preferably 1:8. To 1:12. In this embodiment, the ginger dry mixture is extracted by using 95% ethanol as a solvent, and the active ingredient of the ginger dry mixture is extracted by ultrasonic vibration, and the extraction time is 8 hours, and the raffinate of the southern ginger and the red ball ginger is removed. After that, the ginger extract was obtained. Thereby, the active ingredients of the ginger and the red ball ginger can be extracted into the ginger extract to prepare the ginger extract into a pharmaceutical composition having an oil droplet inhibiting accumulation of fat cells.

In the concentration step S3, the ginger extract is concentrated to obtain a ginger extract having an oil droplet which inhibits accumulation of fat cells. For example, the concentration step S3 is selectable but not limited to concentration by a reduced pressure concentration treatment, an evaporation treatment or a heat drying treatment. In this embodiment, the solvent of the ginger extract is removed by a concentration treatment under reduced pressure to obtain the ginger extract. Thereby, the ginger extract has a higher concentration of the active ingredient, and the effect of the ginger extract of the present invention on inhibiting accumulation of oil droplets by the fat cells is enhanced.

In order to confirm that the ginger extract of the present invention has the effect of inhibiting the accumulation of oil droplets in the fat cells, the following tests were carried out to prepare different weight percentages of the ginger extract of Nanjiang and Red Ginger, and the following test was carried out to demonstrate that the ginger extract inhibits accumulation of fat cells. The role of oil droplets.

"Preparation of ginger extract containing different weight percentages of South Ginger and Red Ginger"

The ginger extracts of the present examples were each obtained by extracting the weight percentage of dried dried ginger and dried red ginger as shown in Table 1. More specifically, the ginger dry mixture is a mixture of the dried dried ginger and the dried ginger. The present embodiment is a dry mixture of ginger having a total weight of 6 kg and a ratio of 60 to 65 liters. % alcohol is extracted. Referring to Table 1, the ginger dry mixture of the first group is dried red ginger, the dry mixture of the ginger of the second group is dried ginger, and the dry mixture of the third group contains 50% by weight. Ginger dry matter, and 50% by weight of dried red ginger powder; Group 4 ginger dry mixture contains 66.7% by weight of dried ginger, and 33.3% by weight of dried red ginger; The group 5 ginger dry mixture contained 75.0% by weight of dried ginger, and 25.0% by weight of red ball ginger dried; the group 6 ginger dry mixture contained 33.3% by weight of dried ginger. And the dry weight of 66.7% of the dried red ginger; the dry mixture of the seventh group of ginger contains 25.0% by weight of dried ginger, and 75.0% by weight of dried red milk ginger. After extracting and concentrating in the ratios indicated by the above respective groups, the ginger extract was obtained, and (A) cell viability test and (B) oil red staining test were carried out with different doses of ginger extracts of groups 1 to 7.

(A) Cell viability

To confirm that the ginger extract of the present invention does not have a cytotoxic effect on cells, this example measures cell viability by MTT cell activity staining (MTT assay). This example utilizes succinate dehydrogenase (Dehydrogenase) in living cell mitochondria to metabolize yellow MTT [3-(4,5-cimethylthiazol-2-yl)-2,5 in culture medium for a certain reaction time. -diphenyl tetrazolium bromide (MTT for short), the tetrazolium in MTT was converted into a blue formazan, and the formazan was dissolved in 0.1% DMSO, and the absorbance of formazan at a wavelength of 550 nm was measured by a spectrophotometer. The more the number of cells (the more vigorous the mitochondrial respiration), the higher the activity of succinate dehydrogenase. The higher the amount of MTT metabolized into formazan, the higher the absorbance at 550 nm, so the absorbance at 550 nm can be measured. The cell viability was estimated to confirm that the ginger extract of the present invention is not cytotoxic.

Please refer to the second table. In this example, the cell viability test was carried out with a pre-adipocyte cell line 3T3-L1. The pre-adipocyte cell line 3T3-L1 was purchased from the Taiwan Hsinchu Food Industry Development Research Institute. The number is BCRC 60159. In this example, 42 groups of pre-adipocytes 3T3-L1 (the number of cells in each group is 1×10 ⁴ cells/ml) were co-cultured for 24 hours under the conditions of temperature 37 ° C and 5% carbon dioxide gas, respectively, and then added as in Table 2, respectively. Show different ratios of South Ginger to Red Ginger (according to Table 1), and different doses (0, 31.25, 62.5, 125, 250, and 500 μg/ml) of ginger extract, for a total of 42 groups of fat cells. After adding the ginger extract shown in Table 2 to the 42 groups of fat cells, each group of fat cells was further cultured at 37 ° C and 5% carbon dioxide gas for 24 hours, and then subjected to MTT assay and measuring the absorbance at 550 nm. Cell viability in each group.

Please refer to Table 3 for the cell viability of each group. Each of the groups A1 to A7 was based on the absorbance values measured by the group without added ginger extract (ie, group A1-0, group A2-0, group A3-0, group A4-0, The cell viability of the A5-0 group, the A6-0 group, and the A7-0 group was 100% of each group, and the remaining group of ginger extracts (Groups A1-1 to A1-5, Groups A2-1 to A2-5, Groups A3-1 to A3-5, Groups A4-1 to A4-5, Groups A5-1 to A5-5, Groups A6-1 to A6-5 and The cell viability of group A7-1 to group A7-5 was higher than 90% of the baseline of each group, and there was no significant difference ( p < 0.05). Therefore, the ginger extract of the present invention showed no cytotoxic effect by the cell-active staining method of this example.

(B) Oil red staining test

In order to confirm that the ginger extract of the present invention can inhibit the accumulation of oil droplets in the fat cells, in this example, a group of pre-differentiated fat cells 3T3-L1 is taken as a control group, and 42 groups of cells which have differentiated into adipocytes are 3T3-L1. As an experimental group, Oil-red O stain was performed.

Please refer to the fourth table. In this example, the pre-adipocyte cell line 3T3-L1 is cultured in DMEM medium containing 10% bovine serum, and the cells are self-cultivated with a desorbent (Trypsin-EDTA). After desorption, add an appropriate amount of differentiation medium I to uniformly suspend the cells. After cell counting, take 1×10 ⁶ cells/ml of pre-adipocytes into a 6-well flat-bottom cell culture dish and incubate at 37 ° C, 5 In the condition of % carbon dioxide gas, after 2 days of culture, the differentiation medium I was replaced with differentiation medium II, and after 3 days of continuous culture, the culture medium III was cultured for 7 to 15 days, during which time fresh differentiation medium was replaced every 2 days. III. At least 70% of the cells in each group showed oil droplets, indicating that the adipocyte differentiation was completed.

In this example, the pre-differentiated fat cells 3T3-L1 (control group) and the 42 cell lines (experimental group) which have been differentiated into adipocytes were co-cultured at a temperature of 37 ° C and 5% carbon dioxide gas, each group. The number of initial cultured cells was 1×10 ⁴ cells/ml, and after 24 hours of culture, the 42 groups of cell lines were respectively added to different groups as shown in Table 5 (groups 1 to 7 according to Table 1), Different doses (0, 31.25, 62.5, 125, 250 and 500 μg/ml) of ginger extract, the 42 groups of fat cells were incubated at 37 ° C, 5% carbon dioxide gas for 24 hours, the control group and the experimental group were carried out. Oil red staining test.

The operation procedure of the oil red staining test of the present embodiment is as follows: after the culture medium of each group of fat cells is aspirated, the fat cells are washed with a PBS buffer solution, and 2 ml of a fixing solution (PBS containing 10% formalin) is added and allowed to stand 1 The fat cells were fixed in an hour, and after removing the fixing solution, 0.2 ml of oil red dye (50 mg of oil red dissolved in 10 ml of isopropanol) was added and allowed to stand for 1 hour, using an oil red dye to the fat cells. Fat dyeing, after removing excess red dye, and measuring the absorbance at 510nm, B1-0, B2-0, B3-0, B4-0, B5-0, B6-0 in each group The B7-0 group was used as a control group (the percentage of oil droplets was 100%), and the experimental group of each group was compared with the control group to compare the percentage of oil droplets contained in the fat cells.

The undifferentiated preadipocyte 3T3-L1 of the present example has an oil droplet accumulation rate of only 5.26±0.18% of those differentiated into adipocytes, thereby confirming that the adipocyte differentiation of the present embodiment is successful, and indeed has accumulated oil droplets. The function.

Please refer to Table 6, which is the oil droplet accumulation rate of each group in this example. Each of the groups B1 to B7 is based on the absorbance value measured by the group without added ginger extract (ie, the B1-0 group, the B2-0 group, the B3-0 group, the B4-0 group, The oil accumulation rate of Group B5-0, Group B6-0 and Group B7-0 is 100% of each group respectively. The oil accumulation rate of this example is the lowest in Group B7-0, followed by The order is B6-0, B5-0, B4-0, B3-0, B2-0 and B1-0, in which the oil accumulation rate in each group is The dose of ginger extract in each group was inversely proportional.

From the above, the ginger extract of the present invention has the effect of inhibiting the accumulation of oil droplets by the fat cells, and the South ginger extract and the 75% by weight of the red ball ginger extract having a weight percentage of 25% have a preferable inhibitory effect.

(C) Foodborne obese animal model

This example was tested by Wistar male rats (8 weeks old, weighing about 200-250 g) purchased from the National Laboratory Animal Breeding and Research Center. The rats were housed at a temperature (25 ± 1 ° C). The light (12 hours of sunshine time) was maintained in a normal range environment, allowing rats to eat and drink freely. The feed of the rats was fed with high fat (60 kcal% fat diet, TestDiet). Formula 58Y1), after 4 weeks of feeding, the weight gain is selected to be 40% or more of the initial body weight, and is used as the high-fat diet-induced obesity rat (HD rat) of the present embodiment. The ginger extract of the present invention lasts for 12 weeks to observe that the HD rat can achieve the effect of inhibiting the accumulation of oil droplets of the fat cells by the ginger extract of the present invention, and the ginger extract of the present invention can control the body weight of the HD rat Will not continue to rise due to high fat diet.

Please refer to the seventh table. In this example, the ginger extract of the seventh group (the weight percentage of the dried dried ginger and the dried red ginger) is 25.0% and 75.0%, respectively, and the daily administration tube is used. Different doses (150, 300 and 600 mg/kg body weight/day) of ginger extract were administered to HD rats of groups D1, D2 and D3, and the body weight of the HD rats was measured during the feeding period, and after the 12th week. The HD rats of each group were sacrificed, and the white fat cells next to the parasitoids were taken to make tissue sections to observe the accumulation of oil droplets in the fat cells of HD rats.

Referring to Table 8, the D0 to D0-4 groups were HD rats which were not fed the ginger extract of the present invention, and the weight of the HD rats of the D0 group was increased after the 12th week of feeding. 116% of the 0 weeks, while the D1, D2, and D3 groups were fed 150, 300, and 600 mg/kg body weight/day of ginger extract, respectively, in which the D2 and D3 HD rats were raised to the 12th. After week, the body weight of the HD rats in the D2-4 group was 96.5% at week 0, and the weight loss of the HD rats in the D3-4 group was 94.2% at week 0; thus, it was confirmed that each kilogram was given per day. The individual feeds 300 to 600 mg of the ginger extract of the present invention, and has the effect of inhibiting the body weight gain of the organism due to the intake of high fat food.

Please refer to Figures 2 to 5 for the HE staining of the white rat adipocytes adjacent to the D0-4, D1-4, D2-4 and D3-4 groups (magnification: 200 × ). In this example, the white fat cells of the parasitoid of the HD rats were taken out, fixed with 10% neutral formalin solution, embedded in paraffin, sliced, and stained with hematoxylin and eosin (Hematoxylin and Eosin stain) Cell staining for microscopic examination.

Compared with Figure 2, the number of fat cells per unit area is larger in Figures 3 to 5, and the cell volume is smaller. Among them, the number of cells in group D3-4 is larger than that in group D2-4; more specifically Please refer to the table 9 to count the number of fat cells per unit area in the experimental group (Group D3) which took the ginger extract of the present invention for 12 weeks, and the D3, 2, D3-3 and D3- All 4 groups were less than the D3-1 group and had significant differences ( p < 0.05). From this, it was confirmed that the ginger extract of the present invention does have the effect of inhibiting the accumulation of oil droplets by the fat cells, and the fat cells are inhibited from accumulating oil droplets by taking the ginger extract of the present invention, and the body weight of the HD rats is also controlled without ingestion. High fat diet and continuous weight gain.

The ginger extract of the present invention can inhibit the accumulation of fat cells by inhibiting the adipocyte differentiation (hyperplasi), thereby inhibiting the accumulation of oil droplets by the fat cells, thereby achieving the effect of controlling the body weight of the organism, especially an effective dose. Ginger extract is used for preparing a medicament or health food for inhibiting accumulation of oil droplets of fat cells, and the ginger extract is combined with a pharmaceutically acceptable carrier or excipient to form a pharmaceutical composition, wherein the ginger extract can be Prepared into any convenient form, such as tablets, capsules, powders, granules or liquids, or combined with other foods or beverages, in an edible form for the organism to be taken orally. Take it. In the pharmaceutical composition, the dose of the ginger extract is preferably 300-600 mg/kg body weight per unit body weight, and the weight percentage of the south ginger extract in the ginger extract is preferably 25-75. The weight percentage of %, and red ball ginger extract is preferably 25-75%, and the application time can last for 12 weeks to achieve the effect of controlling the weight of the individual.

The present invention provides a ginger extract for inhibiting accumulation of oil droplets in fat cells, which is capable of reducing the body's obesity by inhibiting the accumulation of oil droplets by fat cells in the living body, and has the effect of helping the individual to control body weight.

The invention provides a pharmaceutical composition containing ginger extract, which comprises a ginger extract extracted from a natural herb, Nanjiang and Red Ginger, so that the user does not have to endure the side effects accompanying the use of the weight-loss medicine. The user continues to use the efficacy of the pharmaceutical composition.

While the invention has been described in connection with the preferred embodiments described above, it is not intended to limit the scope of the invention. The technical scope of the invention is protected, and therefore the scope of the invention is defined by the scope of the appended claims.

S1. . . Drying step

S2. . . Extraction step

S3. . . Concentration step

Fig. 1 is a block diagram showing the preparation steps of the ginger extract for inhibiting accumulation of oil droplets in the fat cells of the present invention.

Fig. 2 is a HE staining section of the para-sacral white fat cells of the D0-4 group HD rats of the present Example.

Fig. 3 is a HE staining section of the para-sacral white fat cells of the D1-4 group HD rats of the present Example.

Fig. 4 is a HE staining section of the para-sacral white adipose cells of the D-group HD rats of the present Example.

Fig. 5 is a HE staining section of the para-negative white fat cells of the D3-4 group HD rats of the present Example.

S1. . . Drying step

S2. . . Extraction step

S3. . . Concentration step

Claims (10)

A ginger extract for inhibiting accumulation of oil droplets in fat cells is obtained by the following steps: drying a root or stem of a ginger and red ball ginger in a drying step to make the ginger and red ginger The water content of the root or stem is reduced to less than 10%, and a dried ginger and a dried red ginger are obtained; an extraction step is to dry the dried ginger with a weight percentage of 25 to 75%, and the weight is a dried red chrysanthemum with a percentage of 25 to 75%, mixed into a dry mixture of ginger, and the dried mixture of the ginger is extracted with a solvent to obtain a ginger extract; and a concentration step is carried out to concentrate the ginger extract to obtain A ginger extract that inhibits the accumulation of oil droplets in fat cells. The ginger extract for inhibiting the accumulation of oil droplets of the fat cells according to the first aspect of the invention, wherein the solvent of the extraction step is water, methanol, ethanol, acetone, ethane, propane, butane or hexane. The ginger extract for inhibiting the accumulation of oil droplets of the fat cells according to the first aspect of the patent application, wherein the weight ratio of the ginger dry mixture to the solvent is 1:8 to 1:12 The ginger extract for inhibiting accumulation of oil droplets in the fat cells according to the first aspect of the patent application, wherein the extraction step is performed by ultrasonic vibration. The ginger extract for inhibiting accumulation of oil droplets of the fat cells according to the first aspect of the invention, wherein the drying step is a freeze drying treatment, a spray drying treatment, an evaporation treatment or a heat drying treatment. The ginger extract for inhibiting the accumulation of oil droplets of the fat cells according to the first aspect of the invention, wherein the concentration step is a vacuum concentration treatment, an evaporation treatment or a heat drying treatment. A pharmaceutical composition for inhibiting accumulation of oil droplets in an adipose cell, comprising: a ginger extract as described in claim 1; and a pharmaceutically acceptable carrier or excipient for shaping the ginger extract It is the pharmaceutical composition. The pharmaceutical composition for inhibiting the accumulation of oil droplets of the fat cells according to the seventh aspect of the invention, wherein the pharmaceutical composition is administered orally to the individual. A pharmaceutical composition for inhibiting accumulation of oil droplets in an adipose cell according to claim 7, wherein the pharmaceutical composition is a tablet, a capsule, a powder, a granule or a liquid. A pharmaceutical composition for inhibiting the accumulation of oil droplets of adipose cells according to claim 7, wherein the pharmaceutical composition is administered with 300 to 600 mg of ginger extract per kilogram of body weight.