TW200528123A - Lipase inhibitor - Google Patents

Abstract

It is intended to provide a lipase inhibitor which has a high safety and an excellent lipase inhibitory activity. A lipase inhibitor comprising, as the active ingredient, at least one plant selected from the group consisting of avocado, Flacourtia inermis, Pouteria campechiana, Eugenia jambolana, Syzyginum jambos and Syzygium samarangense, or an extract thereof.

Description

200528123 IX. Description of the invention: [Technical field to which the invention belongs] The present invention relates to an effective and highly safe lipase inhibitor, which Ab /, dagger effectively block the pancreatic lipase in vivo responsible for lipid digestion and absorption, and can Inhibit and prevent obesity and high fat. [Prior art] Obesity and abnormally high serum lipid-associated hyperlipidemia accompanying increased body fat are closely related to the onset of various lifestyle diseases such as hypertension, arteriosclerosis, and diabetes. Obesity is due to physical factors, dietary factors, mental factors, central factors, metabolic factors, insufficient exercise, etc., and the calorie intake exceeds the result of calorie consumption, resulting in fat accumulation. Among the lipids in the diet, triglycerides account for most of the lipids. They are decomposed into mono-glycerol and free fatty acids by the month of the pancreatic juice and absorbed in the small intestine. Therefore, it is thought that by inhibiting the action of this lipase, it is possible to suppress the absorption of lipids from the diet, thereby suppressing obesity and hyperlipidemia. In view of the foregoing, active search for an excellent lipase-inhibiting active ingredient ', that is, a lipid-absorption-inhibiting active ingredient is derived from a natural ingredient. So far, there have been raw coriander, eucommia ulmoides tea, white tea, green tea, black tea, oolong tea, phospholipid test, soy protein, tannin, peony root, yellow lotus, cork, peony peel, black grass, tea, bitter pepper, sweet pepper , Pumpkin, shimeji mushroom, maitake mushroom, rattan, poisonous (Radix Angelicae Pubespeneis), ginger, betel nut, Yangmeipi, Cassia, etc. have been reported to have lipase inhibitory activity (Patent Documents 1, 2). However, sufficient results were not obtained. [Patent Literature 1] Japanese Patent Laid-Open No. 2002-179586 98334.doc 200528123 [Patent Literature 2] Japanese Patent Laid-Open No. 2002-275077 [Summary of the Invention] Therefore, the present invention aims to provide an excellent lipase inhibitory activity and to be safe Sexual lipase inhibitor. It is another object of the present invention to provide a lipid absorption inhibitor, an anti-obesity agent, and a hyperlipidemia improving agent. The present inventors have conducted research on a variety of lipid blocking effects from natural plants and found that specific plants or their extracts have excellent lipase blocking effects and lipid absorption blocking effects and have high safety, and thus completed the present invention . That is, the present invention is provided by Persea Americana Mill ·, Flacurtia inermis Roxb., Pouteria campechiana Baehni, Eugenia jambolana Lam., And Syzygium jambos (Linn.) Alston) and lotus mist (Szygium samarangense Merr & Perry) selected more than one plant or its extract as an active ingredient lipase inhibitor. Furthermore, the present invention provides a lipid absorption inhibitor, an anti-obesity agent, and a hyperlipidemia improving agent using these plants or their extracts as effective ingredients. In addition, the present invention provides the use of these plants or their extracts, and is used for the production of lipid absorption inhibitors, anti-obesity agents, and hyperlipidemia improvers. In addition, the present invention provides a method for inhibiting lipid absorption, a method for preventing obesity, and a method for improving hyperlipidemia by administering an effective amount of these plants or their extracts. The specific plant or its extract used in the present invention has a lipid-blocking activity system which has not been known so far. This is the first invention obtained by the present invention. Therefore, these 98334.doc 200528123 Dougian plants or their extracts have excellent lipase inhibitory activity and can be used as lipase inhibitors, as well as lipid absorption inhibitors, anti-obesity agents, and hyperlipidemia improvers. it works. In addition, these specific plants or their extracts can also be used as food and drink and cosmetics to suppress obesity and hyperlipidemia. In addition, since these specific plants or their extracts are derived from natural sources, they can provide lipid-absorption inhibitors, anti-obesity agents, and hyperlipidemia improvers for safety.实施 [Embodiment] The plants used in the present invention include avocado (persea Americana Mill, Camphoraceae), purple plum (Flacourtia inermis Roxb), egg yolk fruit (P 〇uteria campechiana Baehni (Shanxi Branch), Eugenia jambolana Lam., Szygium jambos (Linn ·) Alston, Syzygium samarangense Merr & Perry). These plant extracts can also be obtained by performing extraction operations from plants as described below, in addition to commercially available ones. In the above-mentioned plant system used in the present invention, the above-ground parts of the leaves, stems, buds, it *, xylem, veneer (bark), etc. of the plant; the roots, tubers, etc., seeds, fruits, resin, etc. Parts. The above plants or their extracts include the original plants, pulverized products (fresh or dried), juice extracts, crude extracts, and purified products of crude extracts. These may be used singly 'or in combination of two or more kinds. Examples of the extraction solvent obtained from the above-mentioned plants include low-carbon alcohols such as methanol, ethanol, propanol, and butanol; esters such as ethyl acetate; 98334.doc 200528123 ethylene glycol, butanediol, and propylene -Battle — Polyols such as Uchiichi, L3-butanediol, glycerol; ethers such as diethyl ether and petroleum ether; polar solvents such as acetone and acetic acid; hydrocarbon solvents such as benzine, hexane and xylene ; Physiological saline and water. As the extraction solvent, water or alcohol is preferred, and water is particularly preferred. These extractive dissolving systems may be used singly or in combination of two or more. For the extraction method, a general method can be used, for example, a method of immersing a dried substance or dried powder in a solvent, and a method of adding a warmer in a temperature range from normal temperature to the melting point. The obtained extract can be used directly after removing the solid matter by dehydration or ionization, or used directly, or the solvent can be concentrated or used after drying. The present invention is best performed by drying the solvent extract under reduced pressure. Then, the solvent is removed by means of vacuum drying, and then dried to be used as a crude dried product of the plant extract. The purification of the crude extract can be carried out using the method described in the application, such as: using active branches, silicone, polymerization Methods such as muscle column chromatography, liquid / night extraction, fractional precipitation, etc. of the carrier, etc. The specific plant of the present invention or the extract thereof obtained as described above may have excellent lipase inhibitory activity as described below. Effectively used as a lipase inhibitor, an anti-obesity agent, an anti-obesity agent, and a hyperlipidemia remedy. The lipase inhibitor of the present invention is used as an anti-obesity agent for anti-obesity and anti-obesity Medicines and lipemia improvement agents, etc. can be used daily, can be used either orally or parenterally, it can be made, plate, spinner, granules, powder, capsules , Solution, suspension 1 、 Emulsion system 1 ... Cold, Dong desiccant, etc. These clothing systems can be prepared according to the usual methods in preparation. In addition, π week clothing such as the above-mentioned various agents 98334.doc 200528123 type pharmaceutical preparations can be added with other desired Pharmaceutically acceptable carriers. For example ... glucose, lactose, sugar, gluten powder, mannitol, dextrin, fatty acid glycerides, polyethylene glycol, #ethyl starch, ethylene glycol, polyoxyethylene sorbitan In addition to sugar alcohol anhydride fatty acid esters, amino acids, gelatin, albumin, water, physiological saline, etc., appropriate stabilizers, wetting agents, emulsifiers, binding agents, isotonic agents, etc. may be added as necessary. Idiomatic

The plant or the extract thereof can also be used in combination with food and beverage. Here, the so-called food and beverage line directly adds the above plants or their extracts or adds various nutrients into the knife. "I contain these substances in the mouth of I Rengen, and it can be used as a health care for the treatment and prevention of obesity and hyperlipidemia." Food or food material. Examples of these types of stigma include: granules, granules, bonding agents, capsules, pastes and the like in which conventional additives are added to the active ingredients. In addition, it can also be used in processed meats such as ham and sausages; aquatic processed foods such as fish plates and fish rolls; foods such as bread, cakes, cream, milk powder, fermented dairy products, or water 'juices, milk, refreshing drinks, etc. Used in beverages.

The effective dosage + amount of the plant or its extract of the present invention is appropriately determined according to the patient's age, weight, symptoms, patient condition, route of administration, administration cycle, formulation type, intensity of material blocking activity, etc., such as 2. When the extract is administered orally, 'based on dry weight conversion ... Generally, it is better to ask Bokamoke's weight per day. For Syzygium samarangense Merr &

Peiry) hot water extract, in terms of dry weight, especially 5 ~ 300 mg / kg body weight per day. In addition, the plant or its extract of the present invention can also be used as a cosmetic or cosmetic product containing a lipase inhibitor. For example, the dried κ of the plant of the present invention is added to wheat 98334.doc -10- 200528123 germ oil or olive oil to become a composition containing a lipase inhibitor, which is then used as a makeup ::: material. The y, y, y, y, y, y of phytocarp or its extract according to the present invention are not particularly limited, but, for example, relative to wheat germ oil or sandalwood oil, the dry weight ρ is preferably 0.1 to 60% by weight, It is particularly preferably from 0.5 to 50% by weight. 2. Use the above lipase inhibitor-containing composition as a cosmetic product. When making cosmetic products, you can use various types, such as: lotion, liquid, cream, hand cream, lotion, essence, wash Hair fine, moisturizing, etc. The above-mentioned cosmetic products can be manufactured according to a conventional method. Alternatively, the cosmetics j may be used in any combination with commonly used auxiliaries. The added amount of the plant or the extract thereof according to the present invention is calculated on a dry weight basis, preferably 0.01 to 20% by weight based on the total weight of the cosmetic product. The plant used in the present invention has low toxicity because it is derived from nature. For example, even if a rat is administered orally with a hot water extract of lotus fog (Syzygi samarangense Merr & Peiry), it is 100% daily. 〇mg / kg over a long period of 100 days, no deaths were confirmed and no change in body weight was observed. Examples The following series of examples illustrate the present invention in more detail, but the present invention is not limited to these examples. Example 1 (1) Extraction of plants: 10 grams each of Pear (Persea Americana Mill.), Purple Plum (Flacourtia inermis Roxb.), And Yolk Fruit (Pouteria campechiana 98334.doc -11- 200528123)

Baehm), Eugenia jambiana Lam, Szygmm jambos (Lmn.) Alston, and lotus mist (Samarangense Merr & Perry, Myrtle) The milliliter of distilled water was boiled at 100 ° C for 30 minutes, and then freeze-dried to obtain each hot-water extracted dried product. (2) Lipase inhibitory activity test The lipase inhibitory activity was measured using porcine pancreatic lipase (manufactured by Sigma) and "lipase kit S" manufactured by Daiichi Pharmaceutical. The measurement method was performed by partially changing the manufacturer's instructions. That is, 150 microliters of the extract-containing reagent sample was added with 40 microliters of an enzyme solution (0.05 mg / ml porcine lipase, 125 millimoles per liter of Tds hydrochloric acid (pH 7.5)), and 500 microliters of Color solution (buffer containing 0.5 mg / ml 5,5'-dithiobis (2-nitrobenzoic acid)), after mixing, preheat at 5 ° C for 5 minutes, and add 50 microliters of matrix solution (6.69 mg / ml tributyric acid disulfide + 5.73 mg / ml sodium dodecyl sulfate), after mixing, react at 30 C for 30 minutes under light. Thereafter, 1 ml of a reaction stop solution was added to stop the reaction. The blank group was added with a reagent sample solution, an enzyme solution, and a coloring solution 'and heated at 30 ° C for 5 minutes, and heated at 30 ° C for 30 minutes under light, and the reaction solution was added with a matrix solution. The absorbance of each sample was measured at a wavelength of 412 nm. The lipase inhibitory activity was calculated using the following formula. (Mathematical formula 1) Lipase inhibitory activity = 100- (AT-ABT) / (AC-ABC) x100 (〇 / 〇) AT: absorbance of reagent sample ABT: absorbance of blank group of reagent sample AC: of blind sample Absorbance 98334.doc 200528123 ABC: Comparative Example of Absorptivity of the Blank Group of the Sample for Blind Examination 1 Pair of lavender (banaba), rosemary (guava), guava (lafuma), rooibos (rooibos) , Betel nut, allspice, xiaolianmei, cassia cassia, pepper, sagebrush, eucommia ulmoides, acanthopanax senticosus, hawthorn, ginseng, hypericum perforatum, lemongrass, cat's claw, jasmine, ginger , Hop (hop), dogwood, mangosteen, American ginseng, wheat, lycorrhiza, coix seed, cassia seed, apple, pumpkin, snow lotus (yacon), peony root, bitter tincture, spoon vine, ginseng fruit test. Table Uf shows the results of lipase inhibitory activity of each hot water extract. Each of the present invention's complex, samura, plum, egg fruit, Kennedy rose apple, fragrant fruit, and lotus mist each has a high lipase inhibitory activity.

98334.doc 13- 200528123 [Table i] Plant extract lipase inhibitory activity (IC5G mg / ml) Example 1 Lotus mist 0.13 Bergamot 0.15 Kent's rose apple 0.26 Yolk fruit 0.31 Purple plum 0.33 Avocado 0.38 Comparative example 1 large Flower Lagerstroemia 0.56 Rosemary 0.57 Guava 0.69 Apocynum 0.71 Ruyi Persian 0.84 Betel Nut 0.98 Sweet Pepper 1.03 Xiaolian Zhao 1.04 Bean Tea Cassia 1.26 Japanese Pepper 1.30 Spoon Vine > 1.43 Eucommia ulmoides > 1.43 Acanthopanax sentifolium > 1.43 Hawthorn > 1.43 Ginseng > 1.43 St. John's wort, > 1.43 Lemongrass > 1.43 Cat's claw, > 1.43 Jasmine > 1.43 Ginger > 1.43 Hopper > 1.43 Dogwood > 1.43 Mountain Flat > 1.43 Western Ginseng > 1.43 Wheat > 1.43 Stone Test > 1.43 Coix Seeds > 1.43 Cassia Seeds > 1.43 Apple > 1.43 Pumpkin > 1.43 Snow Lotus > 1.43 Peony Root > 1.43 Melia > 1.43 Spoon Ginseng > 1.43 Ginseng Fruit > 1.43 98334.doc -14- 200528123 Example 2 (1) Extraction of plants According to the same method as in the example, 10 grams of egg yolk fruit (Potauteda campechiana Baehni), EUgenia jamaiana Lam., and Syzygium samarangense Meir & Perry) to obtain dried extracts of each hot water. (2) Lipid absorption hindering activity test

ICR mice (male, 6 to 7 weeks old) who had been fasted for 24 hours were forcibly given 200 microliters of olive oil as a control group. On the other hand, the collapse group was mixed with hot water to extract dried matter at a concentration of 100 mg / ml, and each mouse was forcibly administered with 200 microliters in the stomach. Blood was collected from the tail vein before compulsory administration and at 1, 2, 3, and 6 hours after administration, and the serum was centrifuged. The "giyceride G Test Wako" of Wako Pure Chemicals was used to measure triglycerides in serum. Taking time as the horizontal axis and serum triglycerol production as the vertical axis as B, the area under the curve was obtained from the obtained curve as an indicator of lipid absorption inhibiting activity. The lipid-blocking activity is the curve of the control group; 7. Becha is 100, and the relative value of the area under the curve of each test group is compared. Comparative Example 2 The same test was performed on Lagerstroemia indica and green tea. Table 2 shows the measurement results of lipid absorption inhibiting activity of each hot water extract. The yolk fruit, lotus mist, and absorption inhibiting activity of the present invention are shown. The extracts of K. rosemary have high lipids. 98334.doc -15-200528123 [Table 2] The ratio of plant extracts to the control group. Example 2 Yolk fruit 51 Lotus mist 52 K. rosemary 76 Comparative example 2 Large flowers Lagerstroemia indica 88 green tea 89 --__ * The area under the curve of the control group is 100. Prescription Example 1 The ingredients are mixed according to the following prescription, granulated, dried and granulated, and then tableted to make a tablet. (Recipe) Kent's Rosehip Extract (Example 1) 40 mg of microcrystalline cellulose 100 lactose 80 magnesium stearate 0.5 methyl cellulose 12 Formulation Example 2 Obtained by formulating the ingredients according to the general method below Homogeneous 'Month / Drink'. The resulting clear >: After the beverage was filled in brown guanzi, the bottle was capped with Shaoyu and subjected to heat treatment. These beverages have good appearance and flavor. (Prescription) Lotus mist extract (Example 1) 0.8 g 98334.doc 16- 200528123 Flavor 0.8 Water 100 Reduced starch saccharification 24 Fructose 18 Formulation Example 3 According to the following formulation, each component is obtained by the general method. A homogenized cream. (Prescription) isopropyl stearate 8.0% by weight jojoba oil 6.0 sterol 8.0 stearyl alcohol 2.0 polyoxyethylene lauryl ether 1.5 propylene glycol 6.0 sorbitol 1.0 parabens 0.4 fragrant fruit extract (Example 1) 0.5 Vitamin E 0.5 Fragrance 0.1 Water 66.0

98334.doc 17

Claims (1)

200528123 10. Scope of patent application: L-lipase inhibitor, which is selected from the group consisting of road pear, purple plum, egg yolk fruit, Kennedy rose apple, fragrant fruit and lotus mist-more than one kind of plant Or its extract as an active ingredient. 2. · A lipid absorption inhibiting agent, which uses one or more plants or extracts thereof selected from the group consisting of avocado, purple plum, egg yolk fruit, Kennedy rose apple, fragrant fruit, and lotus mist as an active ingredient . 3. · Use of one or more plants or extracts thereof from the group consisting of avocado, purple plum, egg yolk fruit, Kennedy rose apple, fragrant fruit, and lotus mist, which are used to produce lipid absorption inhibitors . 4. A method for impeding the absorption of lipids by administering an effective amount of one or more selected plants or extracts thereof from the group consisting of avocado, purple plum steamed fruit, Kennedy rose apple, fragrant fruit and lotus mist . 5. An anti-obesity agent, which uses as active ingredient one or more plants or extracts thereof selected from the group consisting of avocado, purple plum, egg yolk fruit, Kennedy rose apple, fragrant fruit and lotus mist. 6. The use of one or more plants or extracts thereof selected from the group consisting of avocado, purple plum, egg yolk fruit, Kennedy rose apple, fragrant fruit and lotus mist, and is used for the manufacture of anti-obesity agents. 7. A method for preventing obesity, which comprises administering an effective amount of one or more plants or extracts thereof selected from the group consisting of Luo pear, purple plum, egg yolk fruit, Kennedy rose apple, fragrant fruit and lotus mist. 8 · A hyperlipidemia improving agent, which is one or more selected from the group consisting of avocado, purple plum, mayonnaise, Ken > peach, fragrant fruit and lotus mist 98334.doc 200528123 Or its extract as an active ingredient. 9. Use of one or more plants or extracts thereof selected from the group consisting of butternut, purple plum, egg yolk, kennel rose apple, fragrant fruit, and lotus mist, used for the manufacture of hyperlipidemia Disease improver. A method for improving lipemia by administering an effective amount of one or more plants or extracts thereof selected from the group consisting of avocado, purple plum, egg yolk fruit, Kennel rose apple, fragrant fruit and lotus mist . 98334.doc 200528123 VII. Designated representative map: (1) The designated representative map of this case is: (none) (II) Brief description of the component symbols of this representative map: 8. If there is a chemical formula in this case, please disclose the one that best shows the characteristics of the invention Chemical formula: (none) 98334.doc