KR100718161B1 - Lipase Inhibitor for Anti-obesity and Use - Google Patents

Abstract

The present invention relates to an anti-obesity lipase inhibitor capable of preventing obesity by inhibiting the action of lipase, a digestive enzyme, to inhibit the absorption of fat in the body. More specifically, in the search for the high inhibitory activity of lipase in cereals and / or herbs, soybean and rice eye extracts were added at 1.0wt% or more, green tea and rooibos extracts were added at 0.25wt%, and cinnamic acid and catechins were 0.1 Addition of wt% or more inhibited lipase activity.

Among these extracts, the grains were ground to 40 mesh, purified water was mixed at a ratio of 1: 5, extracted with stirring at 120 rpm for 24 hours at room temperature, and the supernatant obtained by centrifugation at 10,000 rpm at 4 ° C was lyophilized to -20 ° C. Get The tea is added with purified water at a ratio of 1:20 and extracted at room temperature with stirring at 120 rpm for 24 hours. The extract is filtered through a 5 μm filter, concentrated under reduced pressure, and the concentrate is dried to obtain a powder. If the lipase inhibitor powder obtained as described above is supplied as a food or medicine by capsules, pills or tablets, it can lower obesity while eating a normal meal.

Description

Lipase Inhibitor for Anti-obesity and Use}             

Figure 1 shows the lipase inhibitory effect of green tea extract.

Figure 2 shows the weight change upon administration of a lipase inhibitor to mice.

The present invention relates to an anti-obesity lipase inhibitor for preventing obesity by the principle of inhibiting the action of lipase, a lipolytic enzyme, to inhibit the absorption of fat in the body. More specifically, the present invention relates to an anti-obesity lipase inhibitor comprising any one or more extracts extracted from soybeans, rice eyes, green tea, rooibos tea, and cinnamon having high lipase inhibitory activity in cereals and / or herbs.

Obesity is a risk of 5D (disfigurement, discomfort, disability, disease, death), causing various complications and eventually cause death, and should be prevented and treated if possible.

Obesity suffers from low productivity and inconvenient conditions due to various symptoms, which adversely affects the quality of life and is not beneficial in terms of cost / effectiveness. According to the National Nutrition Survey, 27.3% of Koreans are judged to be obese people with a BMI of 25 or more and are expected to increase to 40% within the next five years.

Obesity is a problem in itself, but because it causes various complications that lead to adult diseases such as diabetes, hyperlipidemia, and vascular disease, the Korean Medical Association specifies that obesity is a disease and should be treated. . Obesity is more affluent than the rich and developed countries, and since most of the world's human problems, developed countries around the world have been leading the way in the development of medicines for the treatment of this disease. As a result, Xenical and Reductil have recently been developed and sold. Currently, the global obesity drug market is estimated at $ 1.3 billion, and is expected to expand to $ 8 billion in the next 10 years.

On the other hand, obese people feel social prejudice and inequality in their bodies, and some women feel embarrassed, so they may show anxiety, depression, adaptation disorder, personality disorder and hysteria. They feel socially inferior and feel guilty about their lack of control over weight loss. In other words, in the current trend that emphasizes appearance, the scale of related industries is rapidly increasing as obesity suppression or weight loss has become one of the appearance management industries, reflecting the needs of people who want to become thinner.

In view of the seriousness of the problem of obesity, a lot of research expenses, research personnel and time have been invested in the world so far, various proposals have been proposed based on diet, exercise, and behavioral therapy, but the failure rate is 95%. There is no quick solution. Therefore, new research is needed to improve existing research or to suggest new solutions. If a new solution is proposed, either locally or fundamentally, to solve the problem of obesity, it is expected to have a significant industrial and social impact as well as improving the quality of life of the individual.

Obesity is caused by a combination of genetic, metabolic, mental, environmental, and socioeconomic factors, but the physical energy consumed is greater than the energy consumed, resulting in the accumulation of the rest in the body. This is called primary obesity or simplicity obesity. On the other hand, secondary obesity, called symptomatic obesity, is caused by hereditary obesity (congenital hyperplastic syndrome), endocrine obesity, hypothalamic obesity, and obesity due to drugs, which is obviously different from primary obesity. All of this results in an increase in weight. Obesity is a condition in which the body's fat tissue is excessively accumulated, rather than simply being overweight. In other words, obesity has a variety of causes, and there are various treatments or measures to cope with it. Currently, drugs capable of treating primary obesity are Xenical ^® developed by Hoffman La Roche, Switzerland, and Reductil ^® developed by Knoll AG, Germany. The market for obesity medicines, which recently launched, is estimated at around $ 1.3 billion worldwide and is expected to increase to $ 8 billion in the next decade. In view of the seriousness of the problem of obesity, this is not a large scale because the drug is obviously effective but slow. This is contrary to the common knowledge that the efficacy of the drug will appear quickly, but if obesity is rapidly treated to lose weight rapidly, various side effects caused by malnutrition, as well as other problems such as arthritis, hair loss. As a result, there is a limit that the drug can only be slow in order to be a safe product without various side effects associated with weight loss. Xenical, the developer with the largest market share for obesity, also reported a 30-lb weight loss in a year, according to Roche, a developer.

On the other hand, Xenical's principle of action is to inhibit the action of lipase, one of the digestive enzymes, to inhibit the breakdown of fat, which eventually inhibits the absorption of fat by 30%. However, even if the enzyme of the same type is slightly different in amino acid sequence (sequence) the structure of the enzyme inhibitor does not work the same, there is a problem that can not guarantee that the lipase inhibitor of Westerners as it inhibits the lipase of Asians. Moreover, Western diets are high-fat diets, which reduce fat digestibility and inhibit fat absorption, which can have a significant effect on weight loss.However, Koreans have an average balance of carbohydrates, fats, and proteins, Obesity is inevitable in preventing obesity. Therefore, the present invention first aims to solve the problem of obese people in Korea, and to use the principle of suppressing the absorption of carbohydrates and fat. The present invention searches for and digests digestive enzyme inhibitors in a way to lower the digestibility of foods, studies the mode of action on the inhibitors, which may appear as a side effect of digestion suppression, that is, the treatment of inhibitors that can minimize indigestion This is the result of research to determine the concentration.

On the other hand, the prior art related to the present invention is Japanese Patent Laid-Open No. 7-25779 (Delipase-derived lipase inhibitor) is a hot water extraction from embryos that separate fat from rice, and Korean Patent Publication No. 2001-79635 (containing a lipase inhibitor) The pharmaceutical composition) relates to a composition in which a lipase inhibitor (oristat or tetrahydrolipstatin), a gum, an emulsifier, etc. are mixed, and Korean Patent Publication No. 2004-12110 (lipase inhibitor and a functional food for preventing obesity) It relates to a lipase inhibitor (diosin or derivatives thereof) derived from the present invention is different from the present invention.

An object of the present invention is to provide an anti-obesity lipase inhibitor that can prevent obesity by the principle of reducing the body's absorption of fat by inhibiting the activity of lipase which is a fat digestive enzyme for the prevention of obesity mentioned above.

The anti-obesity lipase inhibitor of the present invention can satisfy the appetite for the purpose of simple obesity treatment, but by suppressing the action of digestive enzymes to reduce the absorption of excess nutrients into the body can suppress obesity.

Anti-obesity lipase inhibitor of the present invention for achieving the above-mentioned object includes any one or more selected from grain extracts, herbal extracts.

In the present invention, the activity for lipase inhibition was measured for various grains. As grains that can inhibit lipase activity, an object of the present invention may be soybean or rice bran.

In the present invention, the activity for lipase inhibition was measured for various herbs, and herbs that can inhibit lipase activity, which is an object of the present invention, may be used for green tea, rooibos tea, or cinnamon.

Cereal extract or herb extract in the present invention can be obtained by using the conventional extraction method using water or an organic solvent and there is no particular limitation when extracting them. As an example of the method of extracting cereals or herbs in the present invention, 1: 5 to 20 parts by weight of purified water or ethanol is added to cereals or herbs, followed by extraction at 4 ° C. to 50 ° C. for 24 to 48 hours, followed by filtration and concentration under reduced pressure. Can be obtained.

Meanwhile, the grain extract or herb extract of the present invention may be dried and powdered. At this time, the drying method of the cereal extract or herb extract may be dried using a general drying method such as conventional natural drying, hot air drying, far-infrared drying and freeze drying.

In the anti-obesity lipase inhibitor of the present invention, the content of any one or more extracts selected from cereal extracts and herbal extracts as essential components may be included 0.1 to 10wt%. In the anti-obesity lipase inhibitor of the present invention, if the content of any one or more extracts selected from cereal extracts and herbal extracts is less than 0.1wt%, the inhibition of lipase activity is minimal, and the extract of any one or more selected from cereal extracts and herbal extracts If the content is more than 10wt%, there is no increase in the apparent effect on the inhibition of lipase activity. Therefore, in the anti-obesity lipase inhibitor of the present invention, the content of one or more extracts selected from cereal extracts and herbal extracts is preferably included in an amount of 0.1 to 10 wt%.

Meanwhile, the present invention includes an anti-obesity food or an anti-obesity drug including an anti-obesity lipase inhibitor.

The anti-obesity food or the anti-obesity drug of the present invention may be provided as an anti-obesity food or an anti-obesity drug by adding an ingredient containing an anti-obesity lipase inhibitor as an essential component and other excipients. . At this time, any subsidiary material containing an excipient may be used as long as it is food or pharmaceutically acceptable. As an example of such an excipient in the present invention, any one or more selected from lactose, glucomannan, and polysaccharide may be used to provide an anti-obesity lipase inhibitor as an anti-obesity food or an anti-obesity drug. The anti-obesity foods or anti-obesity medicines can be formulated as pills, tablets or capsules.

Hereinafter, the present invention will be described by the following examples, test examples, and application examples. However, these are not limited to the scope of the present invention by them as an embodiment of the present invention.

Example 1 Lipase Inhibitor Extraction of Samples (for Inhibitory Activity)

As a sample for measuring the enzyme activity inhibition rate, 10 kinds of flour, barley rice, buckwheat flour, rye flour, kidney bean, raw soy flour, rice snow powder, bokbunja, rooibos tea and green tea were purchased. Among them, barley rice and kidney beans were purchased in the form of grains, crushed by a grinder, and used as a sample by hitting with a 40 mesh sieve. Extraction method is a mixture of each sample and water in a ratio of 1: 5, then extracted with stirring for 24 hours at a speed of 120 rpm at room temperature, centrifuged at 10,000 rpm at 4 ℃ to take the supernatant until analysis- Store at 20 ° C.

Example 2 Screening of Lipase Inhibitors from Grains and Teas

3.0 g of Tris (hydroxymethyl) -aminomethane and 6.0 g of sodium deoxycholate were dissolved in purified water and adjusted to pH 7.7 with concentrated hydrochloric acid (c-HCL). 1 g of olive oil was dissolved in 100 ml of ethanol, stirred well, and 4 ml of the solution was slowly added to a stirred 100 ml of buffer (Tris-deoxycholate pH 7.7) to prepare an emulsion. When using a spectrophotometer, the substrate should be within the range where the absorbance can be analyzed at 340 nm, and it is good to determine if the absorbance is about 1.0.

1 ml of substrate emulsion was added to Cuvet, 1 ml of lipase solution was added, and the cuvet was immediately shaken and mixed, and the absorbance was recorded at 340 nm for 1 minute using a spectrophotometer.

Inhibitor activity was expressed as a relative value of the enzyme activity in the presence of the inhibitor with an enzyme activity of 100 when no inhibitor was added. Lipase inhibitory activity of each plant extract was analyzed in two enzymes from animals and humans. In Table 1, the enzyme-derived enzyme activity measured without adding an extract was determined as a reference (100%), and the activity of the enzyme was relatively indicated when the extract was added. Wheat flour extract did not show lipase inhibitory activity, and buckwheat inhibited lipase only when the addition amount was low. The addition of green tea, soybean, rice bran, and rooibos tea extracts showed that the lipase activity was dependent on the added amount, so they were clearly considered to contain lipase inhibitors. In particular, green tea and rooibos tea were found to be highly valuable as inhibitors of digestive enzymes for weight loss because the lipase activity was almost completely inhibited even when 0.25% was added.

Table 1. Effect of Cereal and Tea Extracts on Lipase Activity

extract % Remaining activity 0.25% 0.5% 1.0% Wheat flour 136.8 140.8 146.2 Buckwheat 241.7 80.8 24.1 Green tea 2.3 0.0

Soybean 22.3 7.2 0.5 Rice germ 70.5 26.3 2.9 Rooibos tea

On the other hand, the results of analyzing the effect of the same extract on the lipase activity derived from the human body (pancreas) was shown in Table 2. In the inhibition experiment of human-derived lipase, there was a limitation in analyzing by concentration due to the price of a commercial enzyme, and the inhibitory activity was analyzed by adding a sample at the concentration of 1%, which was the highest inhibitory activity in the pig-derived enzyme experiment. All of the selected samples showed lipase inhibitory activity, and similarly to lipases derived from pigs, green tea, soybean, rice snow, and rooibos tea also all completely inhibited lipases derived from humans. Green tea, soybean, rice bran, and rooibos were found to be able to regulate the digestion and absorption of fat in the food consumed by humans by completely inhibiting the action of fat hydrolase in the human digestive system.

Table 2. Effect of Cereal and Tea Extracts on Lipase Activity

extract % Remaining activity Wheat flour 30.2 Buckwheat 14.4 Green tea

Soybean 0.4 Rice germ 0.4 Rooibos tea

IC ₅₀ value calculated by analyzing lipase inhibitory activity for each concentration of green tea was 0.02% (see Table 3, Figure 1). Some teas have been reported to be effective in weight loss because the tea component is said to release body fat as energy. In the present invention, the tea extract has shown the possibility of inhibiting fat digestion and consequently inhibiting the absorption of fat, thereby inhibiting weight gain and inducing weight loss. It is considered a new discovery in terms of suppression of absorption.

Table 3. Effect of Green Tea Extract on Lipase Activity

Green Tea Extract (%) % Remaining activity 0.001 84.7 0.01 75.4 0.1 16.5 0.5 5.0 1.0 0.73

As a result of analyzing lipase inhibitors in plants, the inhibitory effect of cinnamon or green tea extract was high, and representative representative substances contained in these plants were selected to analyze the lipase inhibitory effects of pigs (Table 4) and human origin (Table 5). Tables 4 and 5 show. Cinnamic acid, although not potent, had inhibitory effects on lipase derived from pigs, while phytic acid and catechin almost completely inhibited lipase activity. On the other hand, when the same substance was treated with lipase derived from the human body at 0.5% concentration, phytic acid acted as an activator to increase enzyme activity, and cinnamic acid and catechin showed lipase inhibitory effect. When developing foods, plant extracts could change their ingredients according to the place of origin, climate, and timing, making it difficult to maintain standards and standards, making it difficult to standardize quality uniformity or function. However, finding the functional ingredient can solve this problem, and it is considered that the present invention reveals two kinds of inhibitors of phytic acid and catechin.

Table 4. Effect of Cinnamic Acid, Phytic Acid, and Catechin on Lipase Activity

matter 0.005% 0.05% 0.1% One% Cinnamon 102.3 ¹⁾ 56.2 - - Phytic acid - 48.2 0.54 8.1 Catechin - 97.9 0.5 1.4

^{1) In} case of Cinnamic acid, the solubility was low so that it was 0.005% and 0.05%.

Table 5. Effects of Cinnamic Acid, Phytic Acid, and Catechin on Lipase Activity

matter % Remaining activity Cinnamon 66.7 Phytic acid 188.7 Catechin 54.7

Example 3 Extraction of Lipase Inhibitor

As found through the above search process, grain extracts may contain interference factors in measuring lipase inhibition, so herbs rather than grains can be used to obtain more accurate data in animal and human experiments. The extracts were obtained from green tea and rooibos tea among herbs, which were found to be advantageous for setting as an indicator of management.

① Add 1,200L of drinking water to 60kg of green tea and rooibos tea, extract it for 24 hours with stirring at 120rpm at room temperature, and separate green tea leaves with gauze.

② Filter through a filter with a pore size of 5㎛ to obtain a clarified filtrate.

③ Concentrate and dry the 900L extract under reduced pressure to obtain powder.

Test Example 1 Safety Test of Lipase Inhibitor

In general, unlike food intake, when manufacturing a food that exhibits health functionalities from a particular material, the process usually involves concentration of useful ingredients. At this time, even if the raw material is proven safe, the concentrate is different from the common sense (常食), so it is necessary to confirm the safety. To confirm the safety of the green tea concentrates selected as lipase inhibitors, lyophilized green tea extract was used as dry weight to produce 2.5% (G2.5), 5.0% G5) and 10% Green tea extract was added to the G10) level and then provided to the SD rat.

When the feed is freely ingested, the weight change and the feed intake were calculated while breeding for 10 days and shown in FIG. 2 and Table 6, respectively.

As shown in FIG. 2, SD rats ingesting a feed containing a large amount of green tea extract showed more weight loss than the control group ingesting a feed containing no green tea extract.

In addition, as shown in Table 6, the daily feed intake of the control group was 15.39 g, which was similar to that of a normal rat, but the feed intake of the green tea group was 11.26 to 4.54 g. Decreased in proportion to feed intake. In other words, rats exhibited a phenomenon of refusing the feed containing the green tea extract. Therefore, it was impossible to test the safety of the green tea extract by the free feeding method. For reference, the stools were collected from 3 days before the end of breeding to analyze the moisture and fat content. Moisture was higher than the control group, especially, the higher the green tea content of the feed tended to increase the moisture of the stool, which is thought to be caused by eating a lot of water intake of the feed. Fats were generally low in the treatment group, but the interpretation of the results seems meaningless because the intake of the feed was abnormal.

Table 6. Effect of Oral Administration of Lipase Inhibitors (Green Tea)

Green tea extract Feed benefit (g / day) Weight gain (g / 10 days) Dietary Efficiency (FER) Control 15.39 ± 2.01 ^c -1.41 ± 36.24 ^a -0.04 ± 0.29 ^a G2.5 11.26 ± 4.22 ^b -24.23 ± 39.96 ^ab -0.35 ± 0.58 ^a G5 8.49 ± 2.63 ^b -42.41 ± 27.76 ^bc -0.66 ± 0.64 ^a G10 4.54 ± 1.42 ^a -76.01 ± 22.51 ^c -1.94 ± 1.03 ^b

Green tea extracts mixed with feed tend not to be consumed by rats, so in the second experiment using experimental animals, green tea and cinnamon extracts were dissolved in water and orally administered. The green tea extract dose was set to 500mg / kgBW, 1,000mg / kgBW, 1,500mg / kgBW, and these treatment groups were abbreviated GT500, GT1000, and GT1500, respectively.

The green tea extract was dissolved in distilled water, administered 2ml once a day and raised for 14 days, and the results of calculating feed intake, weight change, and dietary efficiency (FER) are shown in Table 7.

The average diet intake was 13.2-13.9g, body weight decreased 4.1-4.5g, and the feed efficiency ratio (FER) varied from 0.31 to 0.39. There is no significant difference between the control group and each treatment group, so once the green tea concentrate administration does not seem to show any adverse effects on the physiology of rats. However, 9-week-old rats generally gained weight. The reason why the control group also lost weight was thought to be due to stress caused by oral administration and stress from the bottom of the metabolic cage when sampling. .

Table 7. Effect of Oral Administration of Lipase Inhibitor (Green Tea Extract)

Green tea extract Weight (g) Weight gain (14 days) Feed Intake (g / day) FER Control 340.95 ± 20.76 ^a -4.14 ± 2.94 ^a 13.52 ± 3.98 ^a -0.39 ± 0.35 ^a GT 500 336.32 ± 24.56 ^a -4.17 ± 1.68 ^a 13.79 ± 1.86 ^a -0.32 ± 0.15 ^a GT1000 337.71 ± 20.13 ^a -4.52 ± 2.56 ^a 13.17 ± 2.48 ^a -0.36 ± 0.22 ^a GT1500 336.57 ± 18.10 ^a -4.13 ± 2.09 ^`a 13.87 ± 1.85 ^a -0.31 ± 0.18 ^a

Various factors related to side effects or safety of green tea extract were analyzed. Table 8 shows the liver weights of rats treated with green tea extract. The mean liver weight of the control group was 2.43g per 100g body weight, and the treatment group was 2.59∼2.71g, which was significantly higher than the control group. The weight of the liver is increased by the accumulation of fat or glycogen, and the intake of the feed in this experiment was almost the same. There was no. However, it was judged that the increase in liver weight did not mean much because the range did not deviate much from the average.

The total cholesterol (TC) and total triglyceride (TG) contents contained in the liver are shown in Table 9. The GT500 group had significantly lower TC than the control group, but the other treatment groups did not differ from the control group. The liver TG was significantly lower in the GT500 and GT1000 groups than in the control, but the GT1500 group did not show a constant tendency because it was not different from the control group.

Table 8. Effect of lipase inhibitor oral administration on liver weight in rats (green tea extract)

Green tea extract Liver weight (g) ^* Control 2.42 ± 0.11 ^a GT500 2.59 ± 0.18 ^b GT1000 2.63 ± 0.18 ^b GT1500 2.71 ± 0.14 ^b

* Weight per 100 g of BW

Table 9. Effects of Oral Administration of Lipase Inhibitor on Liver Markers in Rats (Green Tea Extract)

Green Tea Extract TC (mg / g liver) TG (mg / g liver) Control 2.23 ± 0.17 ^bc 7.76 ± 1.82 ^c GT500 1.95 ± 0.24 ^a 5.58 ± 0.96 ^a GT1000 2.07 ± 0.15 ^ab 5.86 ± 1.55 ^ab GT1500 2.29 ± 0.15 ^c 7.09 ± 1.23 ^bc

The blood samples of rats were analyzed for hematocrit (HCT) and hemoglobin (Hemoglobin, Hb) contents. The HCT of the control group was 49.55% and the treatment group ranged from 49.22% to 49.78%. There was no difference between the control group and the treatment group. Hb in blood was 15.21-15.86 in all experimental groups, and there was no difference between control, treatment and treatment groups. Judging from the HCT and Hb levels of whole blood, all of them fall within the normal range.

Table 10. Effect of Oral Administration of Lipase Inhibitor on Blood Index in Rats (Green Tea Extract)

Green tea extract HCT (%) Hb (g / dL) Control 49.50 ± 1.93 ^a 15.86 ± 0.67 ^a GT500 49.78 ± 2.54 ^a 15.64 ± 0.58 ^a GT1000 50.57 ± 1.81 ^a 15.73 ± 0.51 ^a GT1500 49.22 ± 2.59 ^a 15.21 ± 0.78 ^a

Serum TC, TG, high-density lipoprotein (HDL-C) and free fatty acid (FFA) content was analyzed and shown in Table 11. TC did not differ between the control and GT500 groups, but the control and GT500 groups showed significant differences between the GT1000 and GT1500 groups. TG did not differ between the treatment groups, but the control content was significantly higher than the treatment groups. HDL-C showed the same trend as TC. The high HDL-C levels in the treatments were positive results for cardiovascular disease, but were not related to the action of lipase inhibitors. FFA was not different between the control, GT500, and GT1000 groups, but significantly different between the three treatment groups and the GT1500 group.

Table 11. Effect of Oral Administration of Lipase Inhibitor on Serum Levels in Rats (Green Tea Extract)

Green tea extract TC (mg / dL) TG (mg / dL) HDL-C (mg / dL) FFA (meq / L) Control 73.00 ± 17.05 ^a 29.14 ± 2.12 ^b 21.80 ± 5.07 ^a 390.38 ± 103.42 ^a GT500 83.67 ± 13.11 ^ab 24.63 ± 2.67 ^a 27.13 ± 3.52 ^ab 398.33 ± 88.17 ^a GT1000 100.17 ± 18.41 ^b 22.00 ± 3.87 ^a 30.50 ± 7.23 ^b 398.29 ± 79.12 ^a GT1500 100.44 ± 20.86 ^b 25.20 ± 2.59 ^a 32.56 ± 7.40 ^b 574.00 ± 106.82 ^b

SGOT, SGPT levels and glucose and uric acid contents, which are indicators of liver function in serum, were analyzed and shown in Table 12. SGOT was significantly different from GT1000 and GT1500 groups in the control and GT500 groups. SGPT was higher in the green tea extract treatment group than the control group, but there was no significant difference among all experimental groups. Glucose was the highest in the control group and GT500 group and the lowest in the GT1500 group, but did not show a constant trend in proportion to the green tea extract dose. Uric acid was the lowest in the control group at 1.77 mg / dL, but there was no significant difference among all experimental groups.

Table 12. Effect of lipase inhibitor oral administration on liver function index of rats (green tea extract)

Green tea extract SGOT (U / L) SGPT (U / L) Glucose (mg / dL) Uric acid (mg / dL) Control 88.38 ± 15.56 ^a 38.13 ± 7.10 ^a 141.75 ± 24.61 ^ab 1.77 ± 0.21 ^a GT500 101.67 ± 40.75 ^ab 42.89 ± 19.86 ^a 166.22 ± 21.64 ^b 2.13 ± 0.37 ^a GT1000 120.71 ± 17.97 ^bc 47.14 ± 10.40 ^a 130.57 ± 28.88 ^a 2.00 ± 0.42 ^a GT1500 131.78 ± 26.53 ^c 47.11 ± 11.58 ^a 116.56 ± 27.67 ^a 2.04 ± 0.40 ^a

Meanwhile, the results of analyzing the fat, protein, and ash after collecting and drying the stool from 3 days before the end of the experiment to the end date are shown in Table 13. Protein content did not differ between all experimental groups. Fat was highest in GT1000 group at 1.86% and lowest in control group at 0.99%.

The ash content was the highest in the control group, followed by the GT1000 group, and relatively low in the GT500 and GT1500 groups. Based on the components of the stool, there was a possibility that the fat absorption rate was lowered due to the inhibition of lipase activity due to the high fat content of the treated group, but it was judged that 14 days of the experiment period was not sufficient for the inhibitory effect. In general, it is known that digestive enzyme inhibitors are effective and require long adaptation time to inhibit the absorption of nutrients.

In addition, changes in body weight (Table 14), weight gain (Table 15), dietary changes (Table 16) and changes in FER (Table 17) are shown in the following table to confirm the safety of rat lipase inhibitors for two weeks. Indicated.

Table 13. Effects of Oral Administration of Lipase Inhibitor on Fecal Components in Rats (Green Tea Extract)

Green tea extract Fat(%) protein(%) Ash content (%) Control 0.99 ± 0.15 ^a 19.61 ± 1.37 ^a 21.37 ± 0.56 ^c GT500 1.45 ± 0.31 ^ab 19.46 ± 0.79 ^a 18.13 ± 1.26 ^a GT1000 1.86 ± 0.59 ^c 20.87 ± 2.17 ^a 19.36 ± 0.34 ^b GT1500 1.38 ± 0.18 ^ab 19.97 ± 2.30 ^a 18.16 ± 1.02 ^a

Table 14. Effect of Oral Administration of Lipase Inhibitor on Body Weight of Rats (Green Tea Extract)

weight 0 days 7 days 9 days 14 days Control 340.95 ± 20.76 ^a 327.65 ± 40.13 ^a 317.01 ± 43.50 ^a 291.24 ± 44.27 ^a GT 500 336.32 ± 24.56 ^a 323.13 ± 27.83 ^a 318.76 ± 31.48 ^a 286.25 ± 26.09 ^a GT1000 337.71 ± 20.13 ^a 315.45 ± 42.45 ^a 313.60 ± 39.75 ^a 283.52 ± 36.95 ^a GT1500 336.57 ± 18.10 ^a 312.94 ± 29.95 ^a 316.00 ± 27.55 ^a 287.03 ± 25.24 ^a

Table 15. Changes in weight gain in rats administered orally with lipase inhibitors (green tea extract)

Weight gain 0-7 days 7-9 days 9-12 days 0-14 days Control -1.90 ± 3.85 ^a -5.32 ± 5.76 ^a -8.59 ± 4.80 ^a -4.14 ± 2.94 ^a GT 500 -1.88 ± 3.32 ^a -2.19 ± 5.59 ^a -10.83 ± 5.88 ^a -4.17 ± 1.68 ^a GT1000 -3.18 ± 4.01 ^a -0.93 ± 10.05 ^a -10.03 ± 7.02 ^a -4.52 ± 2.56 ^a GT1500 -3.38 ± 2.96 ^a 1.53 ± 6.89 ^a -9.66 ± 9.44 ^a -4.13 ± 2.09 ^a

Table 16. Changes in Feed Intake of Rats Under Oral Administration of Lipase Inhibitor (Green Tea Extract)

Feed intake 0-7 days 7-9 days 9-12 days 0-14 days Control 16.04 ± 4.37 ^a 11.65 ± 5.69 ^a 8.30 ± 5.48 ^a 13.52 ± 3.98 ^a GT500 15.82 ± 1.93 ^a 13.29 ± 4.35 ^ab 9.19 ± 5.15 ^a 13.79 ± 1.86 ^a GT1000 15.14 ± 3.64 ^a 12.28 ± 3.79 ^a 9.17 ± 4.55 ^a 13.17 ± 2.48 ^a GT1500 13.71 ± 3.55 ^a 17.69 ± 3.58 ^b 11.77 ± 6.67 ^a 13.87 ± 1.85 ^a

Table 17. Changes in dietary efficiency (FER) during oral administration of lipase inhibitors (green tea extract)

 FER Green tea extract 0-7 days 7-9 days 9-12 days 0-14 days Control -0.18 ± 0.30 ^a -0.84 ± 0.99 ^a -3.83 ± 7.85 ^a -0.39 ± 0.35 ^a GT 500 -0.14 ± 0.21 ^a -0.35 ± 0.88 ^a -2.65 ± 3.85 ^a -0.32 ± 0.15 ^a GT1000 -0.28 ± 0.37 ^a 0.00 ± 1.18 ^a -3.05 ± 5.20 ^a -0.36 ± 0.22 ^a GT1500 -0.30 ± 0.27 ^a 0.05 ± 0.40 ^a -1.62 ± 1.74 ^a -0.31 ± 0.18 ^a

* GT500: 500mg / kgBW, GT1000: 1000mg / kgBW, GT1500: 1500mg / kgBW

Test Example 2 Animal Safety Breeding Test

end. Feed preparation

Based on the results of the in vitro experiment, the selected green tea and cinnamon extract powder was added to the general solid feed to 2.5%, 5%, and 10%, respectively.

I. Conditions such as breeding

In the first experiment using experimental animals, 32 male Sprague-Dawley rats of 9-week-old were purchased and preliminarily bred for 1 week with solid blended feed (Samyang Yuji Feed). n = 8). That is, the first experiment was classified into a control group, green tea 2.5% added group, green tea 5% added group, green tea 10% added group and raised for 10 days. Green tea or cinnamon extract supplement feed and drinking water were supplied freely, and the environment of the animal feeding room was maintained at a temperature of 23 ° C ± 1 ° C, a humidity of 50 ± 5%, and a 12-hour light-dark cycle.

In the second experiment using experimental animals, green tea and cinnamon extracts were dissolved in water and orally administered, which was different from the first experiment. The green tea or cinnamon extract doses were 500mg / kg, 1,000mg / kg, 1,500mg / kg body weight and were bred for 14 days. Fasting 12 hours before organ extraction or blood collection.

All. analysis

Changes in body weight were measured before and after the experiment. Three to four days before the end of the experiment, they were transferred to a metabolic cage to collect stools, dried, and excreted in carbohydrates, fats, and proteins. Was determined. Serum glucose, total cholesterol, triglycerides, high density and low density lipoproteins, free fatty acids, insulin, hemoglobin, hematocrit, SGOT, SGPT, etc. Each was analyzed using.

Based on the above results, green tea and rooibos tea showed high inhibitory activity on lipase. The fact that they show inhibitory activity in the digestive enzymes of the human body is a new fact, and it was judged that it is useful as a weight loss material. However, these are mainly known substances consisting of proteins, there is a problem that can not secure the monopoly of the utilization. The IC ₅₀ value of green tea against lipase derived from the human body was 0.02%. As plant extracts have no indicators of quality control, the representative substances contained in plants were analyzed for the effects of tannin and catechin on enzyme activity. Could.

On the other hand, to evaluate the safety of green tea and cinnamon concentrates selected as raw materials for digestive enzyme inhibitors, 500mg, 1,000mg, and 1,500mg were administered orally for each kg of SD rat body weight. Analyzed. Body weight and liver weight were in the normal range and whole blood HCT and Hb were normal. Serum TC, TG, HDL-C, and FFA showed some significant differences between the control and treatment groups, but did not show adverse effects overall. Serum SGOT, SGPT and uric acid uric acid, which are indicators of liver function, also did not differ between the control and treatment groups. .

<Application Examples 1 to 6>

From the above results, 0.1wt% to 10wt% of any one component selected from soybean, rice snow, green tea, rooibos extract, cinnamic acid and catechin, and 99.9wt% to 90wt% of any one component selected from lactose, glucomannan and polysaccharide as excipients The mixture was prepared into tablets and capsules that are easy to carry and take as shown in Table 18 according to a known method.

Table 18. Application Examples of Extracts

division Extract amount added (wt%) ① ② ③ ④ ⑤ ⑥ Application example 1 (soybean) 1.0 2.0 4.0 6.0 8.0 10 Application example 2 (rice snow) 0.5 1.0 3.0 5.0 7.0 9.0 Application example 3 (green tea) 0.5 0.75 1.0 3.0 5.0 7.0 Application example 4 (rooibos tea) 0.25 0.5 0.75 1.0 3.0 5.0 Application Example 5 (Cinnamon) 0.1 0.2 0.3 0.4 0.5 0.6 Application Example 6 (Catechin) 0.1 0.2 0.3 0.4 0.5 0.6

Application Examples 1 and 2 were prepared as tablets using lactose as an excipient, Application Examples 3 and 4 were prepared as capsules using glucomannan as excipients, and Application Examples 5 and 6 were used as capsules using polysaccharides. Prepared.

In Table 18, the values of ① to ⑥ for each application example are the inhibitor extract content contained in each application example, and the remaining content represents the content of the excipient (for example, ① in Application Example 2 is 0.5% by weight of rice eye extract, Tablets containing 95.5% by weight of lactose as excipient).

     According to the present invention, a lipase inhibitor derived from the human body was found that when 0.1 wt% of cinnamic acid and catechin are added, 0.25 wt% of green tea and rooibos is added, and 1.0 wt% of soybean and rice snow are added to inhibit lipase activity. It became. The use of each or two or more of these ingredients as a food or drug is effective in preventing obesity.

Claims (7)

An anti-obesity lipase inhibitor comprising cinnamic acid or phytic acid. delete delete delete delete delete delete

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