KR101170801B1 - Appetite suppressant composition - Google Patents

Abstract

The present invention relates to an appetite suppressant composition comprising an extract of ginger as an active ingredient.

Description

Appetite suppressant composition

The present invention relates to an appetite suppressant composition comprising a spice extract of a plant material as an active ingredient.

As the society develops and Western food culture flows in, various adult diseases are occurring as vegetarian-oriented traditional food culture disappears. Adult diseases such as diabetes, hypertension, obesity and heart disease can be prevented by controlling the amount of calories and fat, and the importance of controlling the amount of meal is gradually emphasized to lead a healthy life.

Psychologically, you may feel hungry or screaming, but the biggest determinant of how much food you eat is hunger and satiety, which depends on various hormones and biological responses in your body.

Meal therapy to reduce the amount of food among the methods for controlling the amount of food has a lot of problems to be administered for a long time due to side effects such as electrolyte abnormalities or fasting, in particular fasting is the biggest cause for not performing long-term meal therapy. In order to fill this fasting feeling, a method of extending gastric hunger by inflation of the gastrointestinal tract using insoluble carbohydrates and delaying food movement time, for example, a gel-type food without calories has been developed and used. However, this kind of food not only tastes bad, but also makes the stomach bloated after eating, and does not properly solve the feelings of hunger or emptiness. There is a problem.

 As another method for controlling the amount of meal, research on the mechanism of suppressing hunger by increasing satiety has been emphasized. Short-term satiety during food intake is mainly due to mechanical satiety caused by the expansion of the gastrointestinal tract due to food intake and chemical satiety in response to cholecystokinin, a peptide released from the stomach after eating. Divided into Cholecystokinin is a hormone secreted by the small intestine to help digest fats and proteins. During normal digestion, cholecystokinin enters the blood and acts on the stomach as it fills the stomach. Suppress and induce satiety. Based on the above study, appetite suppression by stimulating secretion of the satiety center of the hypothalamus hypothalamus (VMH), more specifically, cholecystokinin (CCK, Cholecystokinin) has been widely used as a method for controlling the amount of meal. In this regard, the United States patent discloses oral administration of trypsin inhibitors that increase satiety by stimulating the release of cholecystokinin (CCK), and for nutritionally interfering compositions for promoting and prolonging the state of satiety by stimulating the release of CCK. It is starting. However, the weight management mechanism of the composition relates to limiting calorie intake by simply giving satiety without considering overall nutritional requirements.

Most other methods of suppressing appetite mainly cause appetite suppression by increasing the utility of norepinephrine, serotonin, and dopamine, which are the brain's appetite-regulating neuroconductors. As a substance that suppresses appetite, the first is a noradrenaline-based drug that suppresses noradrenaline reuptake and keeps neurochemicals acting on the nerve cell junctions for a long time, thereby enhancing adrenergic stimulation and inhibiting appetite. However, it has side effects such as excitement, sleep disorders, nervousness, headache, dry mouth, tachycardia, and high blood pressure. Second, serotonin-based drugs increase serotonin secretion, inhibit resorption, and are currently marketed as antidepressants and binge eating disorders. Third, a combination of noradrenaline-based and serotonin-based drugs is sibutramine (sibutramine trade name), which suppresses norepinephrine and serotonin reuptake secreted by neuronal junctions and partially inhibits dopamine reuptake. In the hypothalamus But increasing the concentration to increase the feeling of fullness after a meal the drug to suppress the appetite, a problem was serious, such as the side effects such as elevated blood pressure, increased heart rate, dry mouth and constipation, insomnia, loss of appetite hypertension, nausea may appear.

The present invention is an appetite suppression composition, appetite suppression pharmaceutical composition, appetite suppression health functional food comprising a spice extract that can feel psychological stability due to satiety after ingestion by using a spice of plant material that causes satiety as an active ingredient Or to provide an appetite suppressant health drink.

The present invention is to provide an extract having an appetite suppressing activity extracted from ginger.

The present invention is to provide an appetite suppressing composition comprising an extract of ginger as an active ingredient.

In addition, to provide an appetite suppressant composition exhibiting an excellent effect by further mixing the ginseng extract in the extract.

The present invention is to provide an appetite suppression pharmaceutical composition, appetite suppression functional food or appetite suppression health drink containing the extract showing the appetite suppression effect as an active ingredient.

 As described above, the present invention using the spices of the natural material is stable without side effects, can obtain the material at a low price economical, can feel the satiety when ingestion can suppress the appetite without psychological pain due to fasting It provides a composition for preventing and treating appetite suppression.

Figure 1 shows the number of cells responding to the distribution rate of TRPA1 and TRPV1 receptors in neurons responding to cholecystokinin.
Figure 2 shows the presence and reaction of the presence of the TRPV1 receptor in response to capsaicin (capsaicin) of the red pepper and TRPA1 receptor in response to AITC, the main component of mustard oil.
Figure 3 shows the inward currents caused by the vagus nerve for capsaicin, red pepper powder, cheongyang pepper and red pepper, the following traces show the effect of water extract on the finely separated vagus nerve. A represents the mean ± SEM value of the induced currents, and B represents the response rate of neurons that respond sensitively.
Figure 4 is the current response to the extract was measured against the voltage clamp (Voltage clamp) Vagus nerve at -50 mM. Traces obtained in the presence of Ruthenium red from the same cells are shown.
Figure 5 shows the inward currents induced in the vagus nerve by TRTC1 agonists AITC and other spice water extracts. All traces were recorded at VH -50mV. A represents the mean ± SEM value of the induced currents, and B represents the response rate of neurons that respond sensitively.
Figure 6 shows the change in activity of the vagus nerve of AITC, P. kochu extract by long-term low temperature storage.
Figure 7 shows the responsiveness of the isolated vagus nerve to the mixture of Pangol pepper water extract (GP) and ginseng water extract (GIN).

Hereinafter, the present invention will be described in detail.

The present inventors have inversely correlated the activity of vagus nerve with the delivery of satiety and the reduction of food intake, and the induction of satiety and no significant reduction of food intake do not occur without vagus nerve activity. Stimulation of pepper and TRPA1 receptors based on capsaicin, a stimulant of TRPV1 receptors, while trying to develop a spice of natural substance that directly acts on the vagus nerve that delivers the activity and satiety of the internal organs Spices other than peppers, such as garlic and mustard, were found, and the presence or absence of irritation of the vagus nerve by these substances was determined through the inward currents that excite the nerve cells and the response rate of the nerve cells to each spice. Spices act on TRP (transient receptor potential) receptors expressed in vagus nerve cells The present invention was completed by increasing the activity of hard cells, and also by mixing ginseng with the spice, the present invention was completed by confirming that satiety can be induced by further increasing the excitatory response to the vagus nerve.

In the present invention, 'water extract' refers to the result of extracting water using a solvent, preferably distilled water, as a solvent in making a spice extract of a plant material.

In the present invention, 'ginger' contains a lot of moisture, minerals (Ca, Fe) and vitamins (A, B1, B2, C, NiaciN), gingerol (Gingerol), gingerology (Gingerone) It is used as a spice with its unique aroma and spicy taste by the sour ingredient of Shogaol. The harvested root is called ginger, and the root of ginger is steamed or boiled and dried. Roasted fire and dried is called black river.

In the present invention, the vagus nerve is the tenth cranial nerve derived from the soft tissues, and includes two fibers of the parasympathetic nerve and afferent perception and is distributed in most of the intestines.

The transient receptor potential (TRP) family of ion channels includes more than 30 cation channels and can be divided into seven major subfamilies: TRPC, TRPV, TRPM, TRPP, TRPML, TRPA, and TRPN. . Of these, the transient receptor potential vanilloid 1 receptor (TRPV1) is a ligand mediated cation channel that is selectively expressed on small non-myelinated peripheral nerve fibers (skin nociceptors) and responds to capsaicin. See Caterina and Julius, 2001, "The Vanilloid Receptor: A Molecular Gateway to the Pain Pathway," Annu Rev Neurosci, 24: 487-517; and Montell et al., 2002, "A unified nomenclature for the superfamily of TRP cation channels" Mol Cell, 9: 229-31. When TRPV1 is activated by agents such as capsaicin and other factors such as heat or hydrogen ions, calcium enters the cell and triggers a pain signal. Another ion channel, the transient receptor potential channel ankyrin-repeat 1 (TRPA1), also called ankyrin-like protein 1 (ANKTM1) receptor, is a nociceptive receptor marker such as TRPV1, a calcitonin gene related peptide. (CGRP) and subpopulations of somatosensory neurons expressing substance P (Story et al. (2003) Cell 112: 819-829), which have also been reported to be expressed in the vagus nerve but in the vagus nerve There is no definitive data on the distribution of.

In the present invention, to provide an extract having an appetite suppressing activity extracted from ginger.

In the present invention to provide an appetite suppressing composition comprising an extract of ginger as an active ingredient.

The present invention is to extract the spice, it may be an extract of ginger and the extraction method and the extraction solvent is irrelevant to be extracted by a method commonly used in the art, preferably the extract is a water extract extracted with water as a solvent More preferably, the extract may be a water extract obtained by heat extraction or cold extraction with water as a solvent. The water used as the solvent is not limited to the type of water, but may be preferably extracted using distilled water as a solvent.

In the present invention, it is possible to use a heat-extracted water extraction method, and as an example of the present invention, any one selected from the plant material is powdered by hot air drying at 30 to 70 ℃, preferably 40 to 60 ℃, the powder of 0.1 L to 10 L of distilled water, preferably 3 L to 5 L of distilled water per 100 g of weight, and then reflux cooler at 80 to 120 ° C., preferably at 90 to 110 ° C. for 70 to 120 minutes, preferably 80 to 100 It can be prepared by the process of extraction for a minute. Further, after cooling to room temperature after the extraction, Whatman Grade No. 1 can be filtered under reduced pressure using a filter paper, and the obtained residue is mixed with 0.1L to 3L of distilled water, preferably 0.5 to 2L of distilled water, and then 80 to 120 ° C, preferably 90 to 110 ° C for 70 to 120 minutes. , Preferably 80 to 100 minutes and then cooled to room temperature, Whatman Grade No. It can extract by the method of filtration under reduced pressure using 1 filter paper, and the scope of the present invention is not limited to the said example.

In addition, in the spice extract sample, garlic and onion containing allyl (ally) -based compounds suspected of thermal decomposition of the active ingredient due to extraction at 80 to 120 ℃, preferably 90 to 110 ℃ separately at a low temperature Cold extraction can be performed to obtain a sample.

In the present invention, it is possible to use a cold extraction water extraction method, as an example of the present invention, any one selected from the plant material suspected of pyrolysis is powdered by hot air drying at 30 to 70 ℃, preferably 40 to 60 ℃ , 12L to 48 hours at 0.1L to 10L of distilled water, preferably 3L to 5L of distilled water per 100 g of the weight of the powder, and then at 0 to 10 ° C, preferably 2 to 6 ° C, more preferably 4 ° C. , Preferably 18 hours to 30 hours, more preferably 24 hours, extracted and allowed to cool at room temperature after extraction, and filtered under reduced pressure using Whatman Grade No. 1 filter paper, the residue obtained at this time 0.1L to 3L Of distilled water, preferably 0.5 to 2 L of distilled water, followed by 0 to 10 ° C, preferably 2 to 6 ° C, more preferably 4 ° C, 12 to 48 hours, preferably 18 to 30 hours. Liver, was extracted and more preferably from 24 hours to extract a method of filtration under reduced pressure using a Whatman Grade No.1 filter paper, and the scope of the present invention is not limited to the above example.

The present invention is to provide an appetite suppressant composition comprising as an active ingredient selected from the group consisting of the extract.

In addition, the present invention is to provide an appetite suppressant composition comprising an extract of ginger as an active ingredient.

The extract may be a mixture of ginseng extract, preferably, the mixing ratio of the extract and ginseng extract is 2 to 5: 1 (w / w), more preferably 2.5 to 3.5: 1 (w /) based on the weight. It may be extracted as w).

At this time, the spice extract and ginseng extract is not particularly limited to the extraction method or the solvent, preferably may be a water extract extracted with water as a solvent, more preferably the extract is heat-extracted or cold-extracted with water as a solvent Water extract. In this case, the water used as the solvent is not limited to a specific water type, but is preferably extracted with distilled water as a solvent.

The present invention provides an appetite suppressing pharmaceutical composition comprising the spice extract as an active ingredient.

The composition comprising the extract of the present invention may be a pharmaceutical composition further comprising a suitable carrier, excipient and diluent according to conventional methods.

Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.

Pharmaceutical compositions comprising extracts according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Suitable formulations known in the art are preferably used as disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents that can be included in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may include at least one excipient such as starch, calcium carbonate and sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the preferred effect, the extract of the present invention is preferably administered at 0.0001 to 10000 mg / kg, preferably 0.001 to 1000 mg / kg, more preferably 1 to 500 mg / kg per day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

The extract of the present invention can be administered to mammals such as rats, mice, livestock, humans and the like in various routes. It consists of all the modes of administration commonly used in all parts of the body that require administration for appetite suppression, for example, can be administered by injection orally, rectal or muscle, subcutaneous and the like.

The present invention provides an appetite suppressing health functional food comprising the spice extract as an active ingredient.

Examples of the food to which the extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods. It may also be added to food or beverages for the purpose of preventing and improving appetite suppression. At this time, the amount of the extract in the food or beverage may be added to 0.01 to 25% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 10 g, preferably 0.3 to 5g based on 100 ml. have.

The health functional beverage composition of the present invention has no particular limitation on the other ingredients other than the above-mentioned extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above, the extract of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extracts of the present invention may contain flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These ingredients may be used independently or in combination, and the proportion of such additives is not so critical but may generally be selected in the range of 0.001 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples, Experimental Examples, and Production Examples. However, the following Examples, Experimental Examples and Preparation Examples are for exemplifying the present invention, and the content of the present invention is not limited to the following Examples, Experimental Examples, and Preparation Examples or the scope of the present invention is limited.

< Example >

Example  1: Preparation of water extracts and purchase of pharmaceuticals

Example  1-1: Preparation of Water Extract

Freshly prepared spices, mustard leaf, mustard leaf, red pepper powder, green onion, garlic, buttercup, leek, Japanese pepper, ginger, garland chrysanthemum, scallion, onion, cheongyang pepper, parsley The hot air was dried at, and powdered and used as an extract sample. 100 g each of the powder was added to 4 L of distilled water, and extracted using a reflux condenser for 90 minutes at 100 ° C. After extraction, the mixture was allowed to cool at room temperature and filtered under reduced pressure using Whatman Grade No. 1 filter paper. Each residue was mixed with 1 L of distilled water and then extracted at 100 ° C. for 90 minutes and filtered under reduced pressure using Whatman Grade No. 1 filter paper. Efficacy evaluation was carried out using the solids obtained by lyophilization of the filtrate obtained from the two extraction processes, which are shown in Table 1.

Of the extract samples, garlic and onions containing ally-based compounds suspected of pyrolysis of the active ingredient due to extraction at 100 ℃ purchased after commercially washed, dried at 50 ℃ hot air, powdered and extracted Used as a sample. 100 g of each powder was added to 4 L of distilled water, extracted at 4 ° C. for 24 hours, cooled to room temperature after extraction, and filtered under reduced pressure using Whatman Grade No. 1 filter paper. Each residue was mixed with 1 L of distilled water and then extracted at 4 ° C. for 24 hours and filtered under reduced pressure using Whatman Grade No. 1 filter paper. Efficacy evaluation was carried out using the solids obtained by lyophilization of the filtrate obtained from the two extraction processes, which are shown in Table 2.

Yield of water extract of 16 spices at 100 ° C. Item Species % lampshade Brassica juncea var . juncea 37.6 ± 0.8 Sesame Perilla frutescens var . japonica 27.3 ± 1.1 Mustard leaf Brassica juncea 37.0 ± 1.5 chili powder Capsicum annuum 43.7 ± 0.9 Green onion Allium fistulosum 40.2 ± 1.2 garlic Allium scorodorpasum var . viviparum Regel 63.5 ± 1.8 Buttercup Oenanthe javanica 17.2 ± 0.3 chives Allium tuberosum 32.8 ± 0.8 Sancho Zanthoxylum piperitum De Candolle 13.0 ± 1.1 ginger Zingiber officinale 19.5 ± 0.4 Garland chrysanthemum Chrysanthemum coronarium var . spatiosum 33.3 ± 1.2 Silpa Allium fistulosum 47.1 ± 1.4 onion Allium cepa 71.3 ± 3.1 Cheongyang Pepper Capsicum annuum  ( chungyang - kochu ) 41.9 ± 2.2 parsley Petroselinum crispum 36.4 ± 1.3 Chilli pepper Capsicum annuum  ( Kwari - kochu ) 37.1 ± 1.7

As shown in Table 1, the yield of water extracts for fresh, sesame leaf, mustard leaf, red pepper powder, green onion, garlic, buttercup, leek, Japanese pepper, ginger, garland chrysanthemum, green onion, onion, green pepper, parsley and green pepper Could.

Yield of water extract of garlic and onion at 4 ° C. Item Species % garlic Allium scorodorpasum var . viviparum Regel 54.1 ± 2.3 onion Allium cepa 60.8 ± 4.3

As shown in Table 2, the yield of cold extracts of garlic and leeks was obtained.

Example  1-2: purchase of drugs

Capsacin and TRPA1 selective antagonist HC-030031 [2- (1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl) -N -(4-isopropylphenyl) acetamide] and cholecystokinin-octapeptide sulfated were purchased from Tocris Cookson (Ballwin, Mo.). Prior to dilution using an external solution, capsacin was dissolved in 1 mM ethanol with a maximum ethanol concentration of 0.02% and a concentration of 200 nM used in the following experiment. Aryl isothiocyanate (AITC), a selective agonist of the TRPA1 receptor as a major component of mustard oil, was purchased from Sigma-Aldrich (St. Louis, MO).

Example  2: Isolation of the vagus nerve

Cell bodies of the vagus nerve of Sprague-Dawley rats aged 4 to 11 days were treated with type II-S trypsin (4-5 mg / ml at 1310 units / mg; Sigma-Aldrich., St. Louis, MO) in the nodose ganglion. After enzymatic treatment at 31 ° C. for 28-40 minutes, fire-polish Pasteur pipettes were used by mechanical separation.

Example  3: measurement of current and response rate

Current through the TRP receptor was measured by means of voltage fixation using an EPC 9 (HEKA, Lambrecht, Germany) ammeter and pClamp 9 software (Molecular Devices, Sunnyvale, California). Electrical measurements were performed using a modified perforated (nystatin) patch method (Akaike and Harata, 1994; Horn and Marty, 1988), and the voltage used in this experiment was -50 mV. 0.1 g of each natural water extract was dissolved in 50 ml of cerebrospinal fluid (extracellular fluid), and the average amount of current generated when testing the cell body of the acutely isolated vagus nerve after enzyme treatment was shown. 150 mM NaCl, 5 mM KCl, 1 mM MgCl ₂ , 2 mM CaCl ₂ , 10 mM HEPES and 10 mM glucose. The pH was adjusted to 7.4 by Tris-base. Intracellular fluids were 50 mM KCl, 100 mM K gluconate, and 10 mM HEPES, and pH was adjusted to 7.2 by Tris-base. The reaction rate was determined by the occurrence of a significant reaction when each sample was continuously treated for 5 minutes. Therefore, the number of reactions for each sample was expressed as a percentage after dividing by the total number. All data are expressed as standard deviation of mean and ± mean values and p <0.05 is considered to be statistically significant.

< Experimental Example >

Experimental Example  One

Experimental Example  1-1: Confirmation of the Vagus Nerves

The vagus nerves separated by the method of Example 2 were secreted from the stomach after meal, and the current and reaction rate according to Example 3 were measured using cholecystokinin-octapeptide-sulpate (cholecystokinin), an activator of 50 nM of cholecystokinin (CCK).

* As a result of this experiment, 11 neurons, 25% of the total 43 cells, responded to cholescystokinin secreted by 50 nM of cholecystokinin after a meal, and a current of 99 ± 29.8 pA was generated in the neurons. Therefore, the criteria for selecting spices for plant materials that cause satiety are based on 99 ± 29.8 pA.

Experimental Example  1-2: for the vagus nerve that conveys a feeling of satiety Capsaicin AITC Reaction rate

In Example 2 and Example 3, whether or not vagus nerve cells identified in response to cholecystokinin in response to the reaction of capsaicin and AITC generated from red pepper and mustard oil generate excitatory currents. According to the reaction rate.

As shown in FIG. 1, all cholecystokinin-responsive cells have TRPV1 receptors in response to capsaicin, and 27% of the neurons responding to cholecystokinin are TRPA1 simultaneously with TRPV1. It also had a receptor. In other words, capsaicin can excite nerve cells that deliver all satiety, and mustard oil can also excite the vagus nerve, which delivers about 27% satiety, using spices that contain antifungal drugs as the main component of TRPA1 and TRPV1 receptors. It was confirmed that it can cause satiety.

Experimental Example  2

The water extract of Example 1 is a spice other than red peppers such as garlic and mustard, which contains red peppers mainly containing capsaicin, which is a stimulating substance of TRPV1 receptor, and a substance acting on TRPA1 receptor, depending on the main containing substance. The experiment was divided into two groups.

Experimental Example 2-1: Capsaicin AITC 's response to the vagus nerve

For the capsinecin and AITC obtained in Example 1-2, the present invention, in the present experiment, the presence of TRPV1 receptor in response to capsaicin, which is the main component of red pepper, and TRPA1 receptor in response to AITC, the main component of mustard oil, in the vagus nerve Experiments confirming the reaction with and were carried out in accordance with Example 2 and Example 3. For this purpose, the size and reactivity of the reaction by 200 nM capsaicin (capsaicin) and 0.2 mM AITC were tested using the rapidly isolated vagus nerve.

Type of sample evoked currents (pA) response rate (%) AITC 29.4 ± 6.4 27.6 Capsaicin 94.0 ± 22.8 43.5

As shown in Figure 2 and Table 3, 200nM capsaicin and 0.2 mM AITC generated 94.0 ± 22.8 and 29.4 ± 6.4 pA inward current, respectively. At this time, 27.6% of the neurons responded to AITC and 43.5% to capsaicin. Thus, it can be seen that 27.6% and 43.5% of the vagus nerves express TRPA1 or TRPV1 receptors.

Experimental Example 2-2: Reaction of Capsaicin- Containing Red Pepper Powder, Cheongyang Pepper, and Red Pepper in the Vagus Nerve at 200nM Capsaicin

The spices were extracted with water by the method described in Example 1, and the red pepper powder, Cheongyang pepper and red pepper peppers for the voltage clamp (Voltage clamp) of the vagus nerve were fixed to -50 mM by the method described in Examples 2 and 3. The effect of water extract and capsaicin at 200nM concentration was determined by the inward current incidence and the rate of vagus nerve responding to each sample (number of neurons responding / total number of neurons tested). Measured.

Caused currents and response rate. Type of sample evoked currents (pA) response rate (%) Cheongyang Pepper 224.3 43.5 Red pepper 138.3 100 Chilli pepper 125.8 100 Capsaicin 94.0 43.5

As shown in the current records of Table 4 and Figure 3, all water extracts, including capsaicin, generated an inward current that could excite the vagus nerve, which generated cholestokinin, an indicator of satiety. A value similar to or greater than the current generated by 99 ± 29.8 pA was shown.

Experimental Example  2-3: Identify the ingredients of spices that are highly responsive to the vagus nerve

* As described in Experiment 2-2, a component other than capsaicin is expected to affect the stimulation of the vagus nerve, and the presence of ruthenium red, which is an antagonist of TRPV1 and TRPA1 receptors Reactivity to vagus nerves with a voltage clamp at −50 mM using a pepper was tested according to the method of Examples 2 and 3.

As shown in Figure 4, it could be confirmed that the excitement effect on the rice wine component of the pepper was also due to the components other than capsaicin (capsainin), which is the main component of the pepper, which is not completely blocked by Ruthenium red Unreacted reactions show that active ingredients other than capsaicin contribute to the high response rate of pepper.

Experimental Example 2-4: Spices acting on the TRPA1 receptor and other capsaicin Reactions in the vagus nerve of spices that are not active ingredients

Water extracts of garlic, mustard leaf and other spices, such as green onion and leek, which contain the main component that can act as an anti-inflammatory substance of the TRPA1 receptor, were obtained by the method of Example 1, and the selective ingredient of the TRPA1 receptor as the main component of mustard oil was obtained. Using the allyl isothiocyanate (AITC) as a working group as a comparison group, the responsiveness to the voltage clamp vagus nerve with a voltage of -50 mM was tested in the same manner as in Example 2 and 3.

Caused currents and response rate. Spice currents (-pA) % Of reaction AITC 29.384 ± 6.415 27.6 Mustard leaf 103.931 ± 50.374 58.8 lampshade 130.34 ± 58.996 75 garlic 107.27 ± 26.731 25 ginger 132.779 ± 37.656 71.4 Silpa 42.004 ± 11.141 88.9 onion 21.592 ± 7.156 40 Green onion 24.057 ± 7.312 77.8 Sancho 43.688 ± 9.255 75 Sesame 113.078 ± 30.636 100 Buttercup 100.424 ± 38.719 83.3 chives 89.43 ± 25.605 80 Garland chrysanthemum 95.608 ± 29.482 83.3 parsley 110.614 ± 29.245 100

As shown in Table 5 and FIG. 5, spices representing the vagus nerve (pA) approximating or exceeding the current of 99 ± 29.8 pA generated by cholecystokinin include mustard leaves (103.931 ± 50.374), freshly (130.34 ± 58.996), garlic (107.27 ± 26.731), ginger (132.779 ± 37.656), sesame leaf (113.078 ± 30.636), buttercup (100.424 ± 38.719), leek (89.43 ± 25.605), mugwort (95.608 ± 29.482), parsley (parsley) 110.614 ± 29.245).

Experimental Example  3: long-term preservation effects of spices on the vagus nerve

 In order to confirm the preservation of AITC and peppery pepper in response to the vagus nerve, the samples of the peppery pepper (GP) were refrigerated for 6 months at 10 ° C or lower, and the experiment was repeated according to the method of Example 2 and Example 3 for a long time. The change of activity by preservation of was examined.

Current caused by the vagus nerve before and after storing the sample at low temperature sample 6 months ago (-pA) 6 months later (-pA) AITC 29.384 ± 6.415 34.248 ± 12.044 Green pepper (G.P.) 125.82 ± 41.32 153.307 ± 47.32

As shown in FIG. 6 and Table 6, the reactivity and reactivity of pure AITC was similar to the previous, but the water extract of Goji pepper was not reduced in activity even though it is a long-term preservation, rather than higher than 99 ± 29.8 pA, the current generated by cholecystokinin The figures are shown.

Experimental Example 4  : Increasing Effect of Black Pepper Reaction by Mixing Ginseng Water Extract

The extract was prepared according to the method described in Example 1-1, and the extract of ginseng water extract and ginseng water extract of 3: 1, 1: 1, 1: 3 (w / w) The responsiveness to the vagus nerves with the voltage clamped at -50 mM by mixing at a ratio was tested in the same manner as in Examples 2 and 3.

As shown in FIG. 7, it was confirmed that the reaction when mixing the water extract of Goji pepper extract and ginseng water extract 3: 1 shows an overwhelmingly elevated value of 2.3 times or more than that of Goji pepper.

< Formulation example >

Hereinafter, the preparation examples of the pharmaceutical composition and health food composition comprising the extract of the present invention in detail, but the present invention is not limited or limited thereto.

Formulation example  One. Sanje  Produce

20 mg of the extract powder

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

Formulation example  2. Preparation of tablets

10 mg of the extract powder

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation example  3. Preparation of capsules

10 mg of the extract powder

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation example  4. Preparation of injections

10 mg of the extract powder

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na2HPO4,12H2O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation example  5. Liquid  Produce

20 mg of the extract powder

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

Formulation example  6. Manufacture of health food

The extract ..... 1000 mg

Vitamin Mix ............

Vitamin A Acetate ......... 70 μg

Vitamin E ................................. 1.0 mg

Vitamin B1 .................. 0.13 mg

Vitamin B2 ........................ 0.15 mg

Vitamin B6 ............... 0.5 mg

Vitamin B12 ........................ 0.2 μg

Vitamin C ................................. 10 mg

Biotin ......................................... 10 μg

Nicotinic Acid Amide ... 1.7 mg

Folic Acid ... 50 μg

Calcium Pantothenate ......................................... 0.5 mg

Mineral mixture ........................

Ferrous Sulfate ............... 1.75 mg

Zinc Oxide ............... 0.82 mg

Magnesium Carbonate ........................... 25.3 mg

Potassium monophosphate ......................................... 15 mg

Dicalcium Phosphate Dibasic ............... 55 mg

Potassium Citrate ... 90 mg

Calcium Carbonate ... 100 mg

Magnesium Chloride ........................... 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified. The granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation example  7. Manufacture of health drinks

100 mg of the extract powder

15 g of vitamin C

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3g

Water quantification

After mixing the above components in accordance with the conventional healthy beverage manufacturing method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used to prepare the healthy beverage composition of the invention.

 Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (3)

Appetite suppression pharmaceutical composition comprising a ginger water extract as an active ingredient. delete (a) contacting a test substance with vagus nerve cells; And
(b) measuring the membrane current and response rate of the neuron of step (a);
(C) the screening method of the appetite suppressing composition comprising the step of selecting a test substance having a membrane current of 69 to 129 pA in step (b).

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