KR20080090169A - Active extracts, containing scoparone, isolated from mugwort or chestnut peel having inhibitory effects on obesity - Google Patents

Abstract

A weight-control composition containing a mugwort or chestnut-peel extract or scoparone isolated from it is provided to enable one to take the weight-control composition in various methods such as oral administration or injection, and to inhibit one's appetite. A weight-control composition containing a mugwort or chestnut-peel extract or scoparone isolated from it comprises a pharmaceutically acceptable supplement such as a solvent, a disintegrant, a sweetening agent, a binder, a coating agent, a bulking agent, a lubricant, or a flavoring agent. The weight-control composition further comprises a pharmaceutically acceptable carrier selected from a saline solution, sterile water, Ringer's solution, a buffered saline solution, a dextrose solution, a maltodextrin solution, glycerol, ethanol, or their mixture. The weigh-control composition is prepared in the form of an injection such as an aqueous solution, a suspension or an emulsion, pills, capsules, granules, or tablets.

Description

Mugwort or Yulpi extract or weight-controlling composition containing scoparon separated from it {ACTIVE EXTRACTS, CONTAINING SCOPARONE, ISOLATED FROM MUGWORT OR CHESTNUT PEEL HAVING INHIBITORY EFFECTS ON OBESITY}

1 is a graph showing the change in food intake after injecting the composition of the present invention in C57 / BL6 mice,

2 is a graph showing the change in food intake after oral administration of a feed containing the composition of the present invention in ApoE-/-mice,

3 is a graph showing the change in body weight after oral administration of a feed containing the composition of the present invention in ApoE-/-mice,

4 is a graph showing the amount of weight change according to FIG.

5 is a graph showing the change in body weight after oral administration of a feed containing the composition of the present invention in C57 / BL6 mice,

6 is a graph showing the amount of weight change according to FIG. 5,

7 is a graph showing changes in blood triglyceride (TG) concentration after administration of the composition of the present invention to C57 / BL6 mice.

8 is a graph showing changes in food intake after injection of the composition of the present invention into a catheter inserted into the brain of an SD rat.

The present invention relates to a weight control composition for the treatment and prevention of obesity comprising a mugwort or yulpi extract or scoparon isolated from it as an active ingredient.

Obesity is defined as an excessive increase in body fat and is caused by a combination of genetic predisposition and environmental factors. Obesity not only increases the risk of diabetes or cardiovascular disease, but also acts as a risk factor for various chronic diseases such as heart failure, high blood pressure, osteoarthritis, sleep apnea, and some cancers. Therefore, effective treatment and prevention of obesity is very important not only to improve public health but also to reduce health care costs.

Obesity is already a common medical problem, especially in the United States. According to the NHANES results published in 2002, the prevalence of obesity and overweight in Americans between 1999 and 2000 was 30.5% and 64.5%, respectively. There was a statistically significant increase over 22.9% and 55.9% of the results of NHANES III between 1994, and since the start of the 1960 survey, the trend has continued to increase (Flegal KM, Carroll MD, Ogden CL, Johnson). CL: Prevalance and Trends in Obesity Among US Adults, 1999-2000. JAMA 2002; 288: 1723-1727).

In Korea, the results of continuous follow-up have not been reported yet, but as the lifestyle is westernized, daily physical activity decreases and energy consumption decreases, while high-fat diet, high-energy diet, and the increase of instant cooking industry increase energy. Given the increased intake, it is thought to have similar results. Since daily changes in energy consumption remain relatively constant at around 2%, energy intakes show significant fluidity of ± 23% in daily changes, so controlling food intake is considered the most important determinant to maintain energy homeostasis. . As a result, dietary supplements and medicines have been developed to achieve weight loss, but the diet products developed so far are only a combination of ingredients that induce temporary releasing of the body rather than improving the underlying metabolism. Therefore, the effect is insignificant and even if the weight loss occurs temporarily, it is often returned to the original weight. In addition, most of the components contained in the existing diet products are rarely studied for possible side effects on the human body is likely to be accompanied by serious toxicity upon long-term administration.

It is an object of the present invention to provide a composition for treating and preventing obesity that can control weight by inhibiting appetite by using an active ingredient of mugwort or yulpi extract.

The present invention provides a weight control composition comprising the mugwort or yulpi extract. In another aspect, the present invention provides a composition for weight control comprising scoparon which is an active ingredient of the extract.

Conventionally, extracts such as mugwort and yulpi have been known to be effective in liver diseases. In particular, scoparon is potent immunosuppressive, vascular relaxant and lipid lowering properties {Huang HC, Chu SH, Chao PD, Eur. J. Pharmacol., 198 , 211-213 (1991); Huang HC, Huang YL, Chang JH, Chen CC, Lee YT, Eur. J. Pharmacol., 217 , 143-48 (1992); Huang HC, Lee CR, Weng YI, Lee MC, Lee YT, Eur. J. Pharmacol., 218 , 123-28 (1992) .; And Huang HC, Weng YI, Lee CR, Jan TR, Chen YL, Lee YT, Br. J. Pharmacol., 110 , 1508-514 (1993)}, but it is not yet known that wormwood or bark extract and its ingredients, scofarone, can regulate appetite.

The present inventors have completed the present invention by discovering the effect of weight loss and the reduction of triglyceride (TG) in the blood when wormwood or yulpi extract or scoparon is continuously administered for a predetermined period of time.

As a result of the oral and intraperitoneal administration (IP) of the composition of the present invention comprising the mugwort or yulpi extract or scoparon to induce the mechanism of inducing weight loss and reduction of TG in the body, these substances suppress appetite It was confirmed that the function (Figs. 1 to 7). In addition, the appetite suppression mechanism of the present invention is not clearly identified, but through the internal cerebral artery ventricular injection experiment (ICV) these substances were confirmed to act on the appetite center of the brain (hypothalamus) (Fig. 8).

The composition of the present invention includes mugwort extract, yulpi extract or scoparon as an active ingredient, and may include a pharmaceutically acceptable adjuvant, and the adjuvant may include a solvent, a disintegrant, a sweetener, a binder, a coating agent, an expanding agent, Solubilizers such as lubricants, lubricants or flavoring agents.

In addition, the compositions of the present invention may comprise one or more pharmaceutically acceptable carriers for administration. The pharmaceutically acceptable carrier may be used in combination with saline solution, sterile water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, antioxidants, buffers And other conventional additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.

Formulation forms of the compositions of the present invention may be granules, powders, coated tablets, tablets, capsules, suppositories, syrups, juices, suspensions, emulsions, drops or injectable solutions and sustained release formulations of the active compounds, and the like. have. The compositions of the present invention can be administered in a conventional manner via the intravenous, intraarterial, intraperitoneal, sternum, transdermal, nasal, inhalation, topical, rectal, oral, intraocular or intradermal routes.

The dosage of the composition of the present invention may vary depending on the age, sex and weight of the patient.

Hereinafter, the present invention will be described in more detail by Examples and Examples, but the scope of the present invention is not limited by the following Examples.

Production Example  1: Preparation of the composition of the present invention

Scofarone and DMSO were mixed to prepare as an injectable composition. In this case, in order to confirm the effect according to the amount of scoparon, 10 mg / kg, 50 mg / kg, and 100 mg / kg of scofaron were respectively mixed in 50ul of DMSO to prepare an intraperitoneal injection (IP) composition.

Example  1: by intraperitoneal injection of the composition of the present invention C57 Of BL6  Change in food intake of rats (FIG. 1)

 Rats fasted overnight were randomly divided into four groups to include five animals in each group, DMSO in the first group, 10 mg / kg scoparon in the second group, and 50 mg / kg in the Sco group. Paron, the fourth group, were injected into the abdominal cavity, respectively, the composition of the present invention prepared according to Preparation Example 1 containing 100 mg / kg of scoparon. Changes in the food intake of rats in each group were observed for 24 hours after injection, and the results are shown in FIG. 1.

As shown in Figure 1, there was no difference in food intake in all groups before administration of each composition. However, after administration of each composition, the food intake began to decrease from the scoparon concentration of 10 mg / kg, and the food intake was significantly decreased in the group administered the composition containing 50 mg / kg or more of scoparon.

Production Example  2: Preparation of feed for oral administration of the composition of the present invention

Scofarone was mixed with the feed so as to contain 10 mg or 100 mg of scoparone per kg of the feed intake of the rat, thereby preparing a feed containing the composition of the present invention to be orally administered to the rat.

Example  2: ApoE  -/-Change in food intake of rats (Figure 2)

Groups of ApoE-/-mice were randomly divided to include 5 animals in each group, followed by feed containing high fat (20%) and high cholesterol (0.2%) in the first group, and high fat (20%) and high in the second group. Feed containing scoparon (100 mg / kg) with cholesterol (0.2%) was fed. At this time, the food intake restriction group was prepared separately and raised.

During the two-week oral administration period from two days before the experiment, the weight and food intake of the rats belonging to each group were measured daily, and the results are shown in FIG. 2.

Prior to the administration of each composition, there was no difference in food intake between the control group and the group administered the composition of the present invention prior to drug administration (control: 4 ± 0.2g; scofaron-containing feed group: 3.97 ± 0.2) g NS). However, as shown in FIG. 2, in the chronically orally administered group of the present invention, the food intake began to decrease significantly from the second day of administration (control: 4.4 ± 0.16g; scofaron-containing feed group: 3.3 ± 0.4). g), this decrease in food intake lasted two weeks during the administration of the composition of the present invention.

Example  4: 8 weeks old Apo  Change in body weight of E-/-mice (Figures 3 and 4)

As experimental animals, male rats (Apo E-/-), weighing 24 ± 0.89 g and 8 weeks old, were selected. The mice used in the experiment were kept in an environment in which the temperature was maintained at 22 ± 2 ° C. until the end of the experiment and the contrast cycle was controlled every 12 hours.

The rats were randomly divided to include 5 rats in each group, and the control group 1 was fed a normal feed, the second group was fed a high fat (20%) and a high cholesterol (0.2%) (HFD). The group had a diet containing scoparon (10 mg / kg) with high fat (20%) and high cholesterol (0.2%) (HFD + Sco 10mg / kg), and the fourth group had a high fat (20%) and high cholesterol ( 0.2%) and feed containing scoparon (100 mg / kg) (HFD + Sco 100 mg / kg).

There was no weight difference between groups before administration of each composition (control: 25.73 ± 0.39; HFD group: 26.77 ± 0.5g; HFD + Sco 10mg / kg group: 24.49 ± 0.2g; HFD + Sco 100mg / kg group: 24.3 ± 0.8 g NS).

However, as shown in FIG. 3, the group chronically orally administered the composition of the present invention showed statistically significant weight loss than the control group at 14 days (2 weeks after administration) (control group: 26.87 ± 0.98 g; HFD group: 28.35 ± 1.2g; HFD + Sco 10mg / kg group: 26.28 ± 1g; HFD + Sco 100mg / kg group: 25.6 ± 0.8g NS).

As a result, the weight change was the highest for the second group, that is, the HFD group, and the lowest for the fourth group, the HFD + Sco 100 mg / kg group (FIG. 4).

Example  5: C57 Of BL6  Change in body weight of rats (FIGS. 5 and 6)

As the experimental animals, male rats (C57 / BL6) weighing 23.31 ± 0.30g were selected. The mice used in the experiment were kept in an environment in which the temperature was maintained at 22 ± 2 ° C. until the end of the experiment and the contrast cycle was controlled every 12 hours.

The rats were randomly divided to include 5 rats in each group, and then the control group 1 was fed a general diet, the second group was fed a diet containing high fat (20%) and high cholesterol (0.2%), Group 3 contains feed (HFD + Sco 10mg / kg) containing scoparone (10mg / kg) with high fat (20%) and high cholesterol (0.2%); group 4 contains high fat (20%) and high cholesterol Feed (HFD + Sco 100 mg / kg) containing scoparon (100 mg / kg) was fed with (0.2%).

There was no weight difference between groups before administration of each composition (control: 23.55 ± 0.99g; HFD group: 23.06 ± 0.6g; HFD + Sco 10mg / kg group: 23.16 ± 0.5g; HFD + Sco 100mg / kg group: 23.73 ± 0.6g NS)

However, as shown in Figure 5, the group chronically orally administered the composition of the present invention showed a statistically significant weight loss than the control group at 8 weeks after administration (control: 29.04 ± 0.93 g; HFD group: 29.24 ± 0.63) g; HFD + Sco 10 mg / kg group: 28.68 ± 0.36 g; HFD + Sco 100 mg / kg group: 28.47 ± 0.64 g NS).

That is, as a result, the weight change was the highest in the second group, that is, the HFD group, the lowest in the fourth group, HFD + Sco 100mg / kg group (Fig. 6).

Example  6: C57 Of BL6 Rat  Blood Triglycerides ( TG ) Change in concentration (FIG. 7)

As the experimental animals, male rats (C57 / BL6) weighing 23.31 ± 0.30g were selected. The mice used in the experiment were kept in an environment in which the temperature was maintained at 22 ± 2 ° C. until the end of the experiment and the contrast cycle was controlled every 12 hours.

The rats were randomly divided to include 5 rats in each group, and then the control group 1 was fed a general diet, the second group was fed a diet containing high fat (20%) and high cholesterol (0.2%), Group 3 contains feed (HFD + Sco 10mg / kg) containing scoparone (10mg / kg) with high fat (20%) and high cholesterol (0.2%); group 4 contains high fat (20%) and high cholesterol Feed (HFD + Sco 100 mg / kg) containing scoparon (100 mg / kg) was fed with (0.2%).

After administration of each composition, the blood was collected and the blood triglyceride (TG) concentration was measured using a body fluid analyzer.

As shown in FIG. 7, the group chronically orally administered the composition of the present invention showed a statistically significant decrease in TG concentration at 8 weeks after the administration (control: 53 ± 0.78 mg / L; HFD group: 79.8). ± 0.58 mg / L; HFD + Sco 10 mg / kg group: 69 ± 0.55 mg / L; HFD + Sco 100 mg / kg group: 62.33 ± 0.69 g NS).

Example  7: SD  Change in food intake of rats (FIG. 8)

Catheter was inserted into the intracerebral ventricle of each mouse. After stabilizing the mice for a week after the procedure, 2 μg, 10 μg, and 20 μg of scoparon were dissolved in 50 μl of DMSO and injected into the catheter. Changes in the food intake of rats in each group were observed for 24 hours after injection, and the results are shown in FIG. 8.

After the administration of each composition, the food intake was significantly decreased in the group to which the composition of the present invention containing 2 μg, 10 μg, 20 μg or more of scoparon was administered.

The composition of the present invention can be administered by a variety of methods, such as oral administration or injection, and by continuously administering the composition of the present invention, the amount of food intake is reduced to control the weight and lower the blood triglyceride concentration.

Claims (4)

Weight control composition comprising mugwort extract or yulpi extract as an active ingredient. Weight control composition comprising scoparon as an active ingredient. The composition of claim 1 or 2 for oral administration. The composition of claim 1 or 2 for injection.

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