TW201021814A - Composition for prevention and treatment of irritable bowel syndrome - Google Patents

Abstract

Disclosed is a composition for the prevention and treatment of irritable bowel syndrome, comprising a Myristicae Semen extract as an active ingredient. Being superior in suppressing visceral hypersensitivity and improving stress- or hypersensitivity-induced bowel abnormalities, the Myristicae Semen extract can be used in pharmaceutical compositions and health foods to be effective in the prevention and treatment of irritable bowel syndrome.

Description

201021814 VI. Description of the Invention: [Technical Field] The present invention relates to a composition for preventing and treating intestinal tract, comprising a nutmeg extract as an active ingredient. C Previous Examination; 3 [Background Art] Enterointestinal syndrome (1B s) is a chronic abdominal pain, discomfort, bulging, and intestinal habit changes such as abdominal and constipation, which are characterized by no detectable organic cause. Functional bowel disease. The symptoms can be exacerbated by the stress caused by the mental or social dilemma. According to the study, 27.8% of patients with digestive disease • Outpatients who are ill are diagnosed with intestinal sputum, and female patients in Korea are about 2-4 times more likely than male patients. Among the outpatients, the abdominal hernia system accounted for (four)%, and the constipation system was 24.6%. The alternation of the two was 44.6% of the symptoms. Therefore, appropriate drugs need to be administered in accordance with the type of intestinal sputum (i.e., the type of abdominal thirst, mainly constipation, • & mainly pain). However, the therapeutic chemicals used to treat intestinal cramps have not produced satisfactory results and there has been no significant treatment progression compared to placebo. Chemicals given to patients with intestinal ailments are usually classified as drugs for improving general symptoms or specific single symptoms. The drug is mainly composed of smooth muscle relaxant, anti-stress agent and opioid agonist. It is a secretory agent for intestinal sputum, fiber supplement, carbinol and 5-ΗΤ4 agonist. The composition of the intestinal tract is mainly composed of anti-abdominal and 5-deletion antagonists to alleviate the symptoms [Ue, (10) γ_& Korean Journal of Gastroenterology 47, lli-U95l 2〇〇6; 201021814

Rhee, Poong Lyul, Korean Journal of Gastroenterology, 47, 94-100, 2006; Choi, Myung Gyu, Korean Journal of Gastroenterology, 47, 125-130; Park, Hyo Jin, Korean Journal of Gastroenterology, 47,101- 110 pages, 2006; TT. Ashburn et al., Nat. Rev. Drug Discov., 5(2), 99-100, 2006; MJG Farthing, BMJ, 330, 429-430, 2005; MJG. Farthing, Best Pract. Res. Clin. Gastroenterol., 18(4), 773-786, 2004]. Nutmeg (which belongs to the nutmeg of the nutmeg family) is described as having a warm stomach and spleen. It improves the digestion and transport of the body, promotes digestion and increases the financial properties, and increases the efficacy of vitality [Shin et al., Graphical Herb Great Dictionary 519 - 520 pages, 1989]. Nutmeg contains essential oils in an amount of from 2 to 9% by weight, and the content of myristic acid is as high as 70 - 80% of total fatty acids. Phenylpropionic acid, such as astragaloside, eugenol, methyl eugenol, eucalyptus, and nutmeg oil known as a neurotoxin, monoterpenes, have also been found in oils from Xuan. For example, β-pinene, γ-terpinene and lemon olein, lignins, such as nutmeg lignin, guaiac, glandularin, astrobilignan - 7, and osmanthus [LW. Wulf et al, J. Chromatography, 161, 271-278, 1978; X. Guo et al, Yaowu Fenxi Zazhi, 5, 5, 258-262, 1985; J. Totte et al. Man, Planta Med., 50, 3, pp. 222-226, 1984; J. Forrest et al, J. Chromatography, 89, 113-117, 1974; JS. Liu et al., Y〇uji Huaxue, 8, 227 -228 pages, 1988; T. Murphy et al. 'Aust. J. Chem., 28, pp. 81-90, 1975; KH_ Shin et al., 201021814 Κογ· J. Pharmacogn·, 17, 1, 91-99, 1986; M. Hattori et al., Chem. Pharm. Bull·, 34, 9, 3885-3893, 1986; DJ. Harvey, J. Chromatogr” 110, pp. 91-102, 1975; S. Hada et al., Phytochemistry , 27, 2, 563-568 pages, 19 88; M. Hattori et al, Chem. Pharm. Bull·, 35, 8, 3315-3322, page 1987; S. Hada et al, Phytochemistry, 27, 2, pp. 563-568, 1988]. Neurokinin ( NK) receptors are divided into NK1, NK2 and NIG subtypes, tachykinin family, such as substance P (SP), neurokinin A and neurokinin B (called neuropeptide) (acting on the central nervous system and The peripheral nervous system) is associated with it. [S. Harrison et al., Int_J. Biochem. Cell Biol" 33: 555-576, 2001]. These NK receptors are distributed throughout the central nervous system, such as the tonsils, hippocampus, hypothalamus, striatum, bone marrow, etc., or peripheral nervous systems such as skin, inflammatory cells, and the entire digestive system, respiratory system. The cardiovascular system, etc., is a neuroregulatory medium or a neurotransmitter that is closely related to physiological functions, especially intestinal peristalsis and visceral hypersensitivity [JH La et al., World J. Gastroenterol·, 11 ( 2), pp. 237-241, 2005; MS Kramer, Science, 281 (5383) 1624-1625 pp. 1998; GJ Sanger, Br. J. Pharmacol., 141, pp. 1303-1312, 2004]. Based on the physiological functions of NK receptors, NK receptor antagonists have been actively studied as a new therapeutic target for intestinal tract [R·A. Duffy, Expert Opin. Emerg. Drugs, 9(1), 2004 M. Camilleri, Br. J. Pharmacol., 141, pl237-1248, 2004; GJ Sanger., Br. J. Pharmacol., 141, pl303-1312, 2004; A. Lecci, Br. J. Pharmacol., 141, 1249-1263, 2004]. 201021814 The medicinal compound of the peas is known for its effects on asthma, rhinitis, arthritis, inflammatory diseases of the digestive system, etc. [Hwang et al. Korean Patent No. 10-0579752, 2006]. The therapeutic efficacy of intestinal tract is not mentioned in this patent. Further, the herb composition containing nutmeg is known to have an effect of preventing and treating gastrointestinal motility such as intestinal fistula (Pangen〇miCS, Korean Patent No. 10-0532703, 2005). The drug composition contains, in addition to meat ugly, an extract from one herb (the same weight of the herb extract), which focuses on promoting gastrointestinal (activation 5 deletion and 5-ΗΤ4 receptor). This is therefore different from the point of the present invention, since the extract from the bean stalk has an inhibitory effect against the sputum receptor and plays an important role in the pain pathway and gastrointestinal motility via the ENS (enteric nervous system), thereby slowing the visceral excess Sensitivity and improvement were attributed to intestinal abnormalities that restricted stress (Test Examples 1, 2 and 3). Intensive and sufficient research leading to the improvement of intestinal tract caused by the present inventors of the present invention has led to the discovery that the nutmeg extract is active in inhibiting visceral pain and improving intestinal or visceral hypersensitivity-induced intestinal abnormalities. Therefore, it can be used as an active ingredient for the prevention and treatment of intestinal tract.

[Explanation: J [Explanation] [Technical Problem] Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing and treating intestinal diarrhea, which comprises a nutritic extract as an active ingredient. 201021814 Another object of the present invention is to provide a health food for preventing and treating intestinal cramps comprising a nutmeg extract as an active ingredient. [Technical Solution] The pharmaceutical composition for preventing and treating intestinal fistula according to the present invention is characterized in that it contains a nutmeg extract as an active ingredient. The health food for preventing and treating intestinal ailments according to the present invention is characterized in that it contains a nutmeg extract as an active ingredient. As defined in the present invention, the extract refers to an extract obtained from myristyl mash by using a solvent selected from the group consisting of water, a lower alcohol of c i _ C4, a nonpolar solvent, and the like. Intestinal fistula includes at least one disease selected from the group consisting of diarrhea-based intestinal fistula, constipation-based intestinal fistula, and pain-based intestinal bowel disease. [Advantageous effect] The nutrient extract of the present invention is excellent for inhibiting visceral hypersensitivity and improving stress or excessive sensitivity. The nutmeg extract of the present invention can be used for pharmaceutical compositions and health foods to effectively prevent and treat intestinal cramps. [Description of the Scheme] The first graph is a chromatogram of HPLC (High Performance Liquid Chromatography) of nutmeg extract (MYFT). Figure lb is a mass spectrum of the nutmeg extract (MYFT) obtained using gas chromatography/mass spectrometry (GC/MS). Figure 2 is a mass spectrum of the nutmeg extract (MYFH) obtained using a gas chromatography/mass spectrometer (GC/ms). Figure 3 shows the effect of nutmeg extract (MYFT) on the CRD model 201021814. Figure 4 is a graph showing the efficacy of nutmeg extract (MYFT) on limiting the pressure-induced fecal pellet output pattern. [Embodiment; j [Best Mode] The herb extract of the present invention can be prepared as follows. The nutmeg is dried, ground, and preferably from about 1 to 2 parts by weight, preferably from about 3 to 10 parts by weight, selected from water, a lower alcohol of Cl-Cl (such as ethyl or sterol), containing 5-95 : Solvent extraction of 95-5 or 30-70: 70 - 30 (v/v) water and a mixture of lower alcohols, a non-polar solvent, and mixtures thereof. The extraction itself may be carried out in this solvent at a temperature of '80 ° C for about 1 to 6 hours, such as agitation extraction, hot water extraction, cryoprecipitation extraction, condenser extraction, ultrasonic extraction, or supercritical extraction, and is preferably a system. From 2 to 4 hours, the ~ herb extract (MYFT) of the present invention is produced. According to one aspect thereof, the present invention provides a pharmaceutical composition for preventing and treating intestinal fistula comprising an extract derived from nutmeg prepared as an active ingredient by the method. Preferably, the herb extract is present in an amount from 0.1 to 50% by weight based on the total weight of the pharmaceutical composition of the present invention. However, the amount of the active ingredient is not limited thereto, and may be adjusted depending on the condition of the patient, the type and severity of the disease. The composition based on the extract of the peas according to the present invention may be further contemplated to include the carrier, excipient and/or diluent which are typically employed in the art. 8 201021814 The composition comprising the extract according to the invention may be formulated into an oral dosage form, such as a powder, granules, lozenges, capsules, suspensions, emulsions, syrups, aerosols, etc., or parenteral dosage forms 'For example, for external use, suppositories, and sterile injectables. Carriers, shaped elixirs and diluents for use in the compositions of the present invention comprise lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, Alginate, gelatin, calcium phosphate, calcium citrate, cellulose, methyl cellulose, amorphous cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzene Formate, talc, magnesium stearate, and mineral oil. For practical use, the extract of the present invention can usually be formulated by mixing with a diluent or an excipient such as a filler, a thickener, a binder, a wetting agent, a disintegrating agent, a surfactant, and the like. The solid preparation to be used for oral administration of the extract of the present invention may be in the form of a tablet, a pill, a powder, a granule, a kick, or the like. With respect to such solid pharmaceutical agents, the extract of the present invention is formulated by mixing with at least one excipient such as 'starch, calcium carbonate, sucrose, lactose, or gelatin. Further, a lubricant such as magnesium stearate or talc may be added. Liquid preparations to be used for oral administration include suspensions, solutions for internal use, emulsions, syrups and the like. In addition to a simple diluent such as water or liquid paraffin, various excipients such as wetting agents, sweeteners, aromatic compounds, preservatives, and the like can be included in the liquid preparation. Furthermore, the extract of the present invention can be administered via a parenteral route. For this, a sterile aqueous solution, a nonaqueous solvent, a suspension, an emulsion, a lyophilizate, a suppository or the like can be used. Injectable propylene glycol, polyethylene glycol, vegetable oils (such as eucalyptus oil), and esters (such as ethyl oleate) may be suitable for non-aqueous solvents and suspensions. The basic materials of the suppository 201021814 include Witepsol, macrogol, Tween 61, cocoa butter, lauryl ester, glycerin, and glycerin gelatin. The effective dose of the extract according to the present invention depends on various factors including the condition of the patient, the body weight, the severity of the disease, and the time and route of administration of the drug. The extract according to the present invention may be administered as a single agent, or may be divided into two to six times a day. The daily dose range is from 1 mg/kg to 10 g/kg, and preferably from 1 mg/kg to 1 g / kg. Dosage should not limit the scope of the invention. The composition of the present invention can be administered to milk animals including rats, small rats, babies, humans, and the like via various routes. All modes of administration are contemplated and may be performed by, for example, oral, rectal, intravenous, intramuscular, subcutaneous, intracerebroventricular, or intracranial injection. According to another aspect thereof, the present invention provides a health food for preventing and improving intestinal cramps, comprising a nutmeg extract effective for preventing and treating intestinal cramps in combination with a nutritionally acceptable additive. In this context, the compositions of the present invention are widely used in medicines, foods and beverages to prevent and ameliorate intestinal cramps. For example, the present invention may be added with a beverage, ": hair, a compound, a health supplement, and may be in the form of a powder, granule, a key, a capsule, or a beverage. - Because there is almost no toxicity and side effects. The nutmeg extract of the present invention can be safely used for prophylactic purposes for a long time. The extract of the present invention can also be added to foods or beverages for the purpose of giving food or beverages the function of preventing or treating intestinal cramps. The extract of the invention 10 201021814 can be used in an amount of from 0. 01 to 15% by weight, based on the total weight of the health food, or in an amount from 至3 to 1 gram, preferably from 〇3 to 1 gram. The liquid component of the healthy beverage composition is not particularly limited as long as the extract of the present invention is used in the amount as described above. Like the conventional beverage, the health beverage composition of the present invention can be used. Further included are various flavor modifying agents. Examples of natural carbohydrates for use in the present invention include monosaccharides (such as 'glucose), disaccharides (such as maltose, sucrose, etc.), and more. (such as dextrin, cyclodextrin, etc.), and sugar alcohols (such as xylitol, sorbitol, erythritol, etc.). As for the taste modifier, it is a beneficial natural taste modifier (sweet Protein, stevia extract (ie, stevioside), glycyrrhizic acid, and synthetic sweetener (saccharin, aspartame, etc.). Natural carbohydrates can range from 1 to 100 ml of the inventive health beverage composition. The amount is preferably from 5 to 12 grams. Further, the composition of the present invention may be supplemented with various chemical agents, including nutrients, vitamins, minerals, flavors (synthetic and/or natural), colorants, thickening. Agent (mystery, chocolate), pectic acid or its salt, alginic acid or its salt, organic acid, protective colloid thickener, pH modifier, stabilizer, preservative, glycerin, alcohol, carbonated carbonated beverage For the preparation of fruit juice or vegetable juice, the composition of the present invention may further comprise fresh fruit and/or vegetable soup. These components may be used in a smoke or a mixture. Usually, the amount of the chemical agent is in the range of The composition of the touch weight is from 0 to 2G Parts by weight. [Mode for Invention] Lane. " A better understanding of the present invention can be obtained by the following examples, which are exemplified by 11 201021814, and are not to be construed as limiting the invention. Example 1: Preparation of Nutmeg Extract (MYFT) 100 g of nutmeg (the seed of nutmeg HOUTT from Kyoung Dong Market, Korea) was dried and ground, and then stirred in a water bath at 0.7 liters. % ethanol extraction for 4 hours. After filtration, the filtrate was concentrated and dried to provide 18 g of the nutmeg extract (MYFT). Figure 1 a is an HPLC chromatogram of pattern analysis of nutmeg extract (MYFT) [System: Agilent 1200 system, column: C18 column (250X4.6mm ID, S-5pm, 12nm)], and lb Gas Chromatography/Mass Spectrometry (GC/MS) [System: GC/MS System Perkin Elmer Clarus 600 Series, Column: Elite-5MS (30m, 0.25mm ID, 0.25pmdf), Carrier Gas: Helium The mass spectrum of this extract obtained. Based on the results of the analysis, non-polar ingredients (such as phenylpropionic acid and lignan) and essential oils were found to be the main components of the nutmeg extract (MYFT). Example 2: Preparation of nutmeg extract with hexane (MYFH) Since non-polar components were found to be the main component of nutmeg extract (MYFT) by HPLC and GC/MS analysis, hexane was used to make Non-polar ingredients are extracted from nutmeg (MYFH). 100 grams of nutmeg (purchased from Kyoung Dong Market, Korea) was dried and minced. Then it was burned for 30 hours with 0.3 liters. After filtration, the filtrate was concentrated and dried to provide 8.2 g of the nutmeg extract (MYFH). Figure 2 uses gas chromatography/mass spectrometry (GC/MS) [System: GC/MS system Perkin Elmer Clarus 600 series, column: Elite-5MS (30m, 0.25mm ID, 0.25Mmdf), carrier gas : Helium] Mass spectrum obtained from hexane 12 201021814 extract (MYFH). As seen in this mass spectrum, a pattern similar to that of ^^¥17 is obtained. Test Example 1. Inhibition of visceral pain by extract of MYFT in CRD (colorectal dilation) mode The nutmeg extract (MYFT) prepared in Example 1 was tested by colorectal expansion (CRD) as follows [JH. La et al. Human, World J. Gastroenterol., Dec., 9(12): 2791-2795, 2003; YD Choi et al., Dig. Dis. Sci., Mar 21' Epub ahead of print, 2008] Detection of visceral pain The inhibition effect. After placing two in each cage, weighed 250 - 33 grams

Sprague-Dawley rats (Charles River) were housed at 25 ° C and 50% relative humidity on conditions of 12:12-h light-dark cycle and free access to food and water. After 5 days of adaptation under these conditions, colitis was induced thereafter. The rats were fasted 24 hours before the introduction of colitis. After the rats were anesthetized with isoflurane, a rubber catheter (PE 50) was inserted into the colon 8 cm in length from the anal patch. One milliliter of 3.5% acetic acid (in 0.9% saline) was injected via catheter into the lumen of the intestine, after which the anus was closed for 30 seconds to avoid leakage of the solution. Then, 1 ml of 0.9% saline was injected through the same catheter to wash the acetic acid solution from the lumen of the colon. Each colitis-inducing rat was inserted through the anus with a flexible latex balloon of 2 cm length, and the colorectal expansion was performed by making the balloon 1 ml to 1.0 ml of warm water (37. At the same time, the response of the animal to the induced visceral pain is monitored. In this context, the response of the rat to visceral pain is based on the characteristic behavior of the staged manner according to the intensity of human visceral pain. Retracting the reflex score and indirectly quantifying. While recording the AWR score [Table 1, see ED Al-Chaer et al., Gastroenterology, Nov., 119(5) 1276-1285. 2000], the pulse rate is measured using a pulse meter. The tail artery is measured, and thus, it is used as an auxiliary index of pain response. Table 1 AWR score __ Characteristic posture 0 No special behavioral response to CRD 1 Intermittent transient head movement during CRD, and then does not move during stimulation 2 Abdominal abdominal muscle contraction without raising the abdomen 3 Raising the abdomen 4 The body forms an arch and raises the pelvic structure. On the 7th day after the introduction of colitis, the rat receives CRD to detect the presence of visceral hypersensitivity. The animal model was selected [jh. La 荨人, World J. Gastroenterol" Dec" 9(12): 2791-2795, 2003]. The nutmeg extract prepared in Example 1 in 0.5% CMC (MYFT) ) Oral to a selected animal model at a dose of 300 mg/kg, and alcesetron HC1 (available from Jiangyin Yongda Chemical Co., Ltd.) as a positive control group was orally administered at a dose of 20 mg/kg. After 50-60 minutes of oral administration, the rats received CRD and the AWR score and pulse rate were monitored for visceral pain response. To quantify the response of the vehicle, positive control and MYFT groups, AWR score and pulse rate The change is converted to AUC (area under the curve). The data is used in the Student's T-test of p<〇.〇5 to analyze statistical significance. In Figure 3, “normal” means no colon. In the normal group of inflammation, the "carrier" represents the drug-inducing colitis 14 201021814 induced group, "Alo" represents the positive control group induced by oral colitis of 20 mg / kg, and "MYFT" "represents a dose of 3 〇〇 mg / kg The colitis-induced group of nutmeg extract (MYFT). As shown in the data in Figure 3, 'MYFT (300 mg/kg) reduced the AWR score and pulse rate at CRD to the same level as the positive control group alosetron. Test Example 2 · Limiting the pressure-induced fecal particle output mode of the extract μ γρτ The effect of detecting the stool is based on limiting the pressure-induced fecal particle output pattern [s

Kobayashi et al., jpn. j. pharmcaol., 2001] Example 1 Preparation of the nutmeg extract (MYFT) for the efficacy of defecation. After raising two in each cage, weigh 250-330 grams

Sprague-Dawley rats (Charles River) were housed at 25 ° C and 50% relative humidity under controlled conditions of a 12:12-h light-dark cycle with free access to food and water. On the day of the experiment, the restriction cage was used to induce pressure in the rat to measure the pressure-induced fecal pellet output. In this connection, the nutmeg extract (M YFT) prepared in Example 1 of 5% CMCr was orally administered at a dose of 3 mg/kg, and then the rats were placed in a restraint cage. Special care is required to avoid stress in rats. Once in the restraining cage, the rats were subjected to pressure and began to excrete. The feces were conveniently measured at regular intervals of 60 minutes for 4 hours. During this experiment, only the cage was limited to a slight displacement without moving the cage to avoid confusion in the stool metering. After a long period of time, the stool will not be easily detected because it dries. Therefore, it is necessary to constantly detect the quantity and condition of the output of the fecal pellets. The data system used 15 201021814 for p<0.05 student t-test analysis statistical significance. Compared to the carrier, the MYFT 300 significantly reduces the pressure-induced fecal output. When treated with myft 3 mg/kg, the amount of fecal pellet output decreased to 2.5, while it was 7.5 for the vehicle group. Compared to the vehicle, MYFT 100 mg/kg was observed to reduce the pressure-induced fecal pellet output, but not significant. Therefore, MYFT was found to reduce the pressure-induced fecal pellet output in a dose-dependent manner [Fig. 4]. Test Example 3: Inhibitory activity against neurokinin receptor (NK-1, 2, 3)

The nutmeg extract (MYFT) prepared in Example 1 was tested for its inhibitory activity against the neurokinin receptor. For this, a binding assay was performed with human recombinant C Ο Ο cells (Arch Int Pharmacodyn. 329:161-184, Proc Natl Acad Sci USA, 94:310-315, Proc Natl Acad Sci USA. 94:310-315) . Cell membranes are isolated from human recombinant CHO cells, which are transfected to express individual receptor subtypes. In the presence of MYFT, 0.25 nM [Η3] SR-140333 reacted with the cell membrane of ΝΚ1, 0.5 nM [H3] SR-48968 reacted with the cell membrane of NK2, and 0.06 nM [125I] MePhe-Neurokinin B reacted with the cell membrane of NK3, so that The inhibitory activity of MYFT against the neurokinin receptor was measured. The binding reaction was carried out in HEPES buffer (20 mM HEPES, ρΗ7·4, 1 mM MnC12, 0.01% BSA) at 25 ° C for 90 minutes (NK 1 & 2) and 120 minutes (NK3). After the reaction was completed, the reaction mixture was loaded into a Whatman GF/B filter, and then washed with ice-cold HEPES buffer. The radioactivity combined with the filter was measured using a liquid scintillation counter. The MYFT in 1% DMSO was used at concentrations of 1 pg/mL, 10 gg/mL, and 100 pg/mL. 201021814 From the data in Table 2, the nutmeg extract (MYFT) was found to have excellent inhibitory activity against NK 1, 2 and 3. In particular, when used at a concentration of pg/mL, MYFT inhibited NK2 and 3 at a ratio of 88 and 85% (Ic% 17.5 pg/mL and 76 gg/ml), respectively, and inhibited NK1 at a ratio of 44%. Even if the IC50 is not measured. Table 2 Receptor concentration inhibition % ic5 〇 NK1 100 pg/mL 44 10 pg/mL 2 1 pg/mL -10 NK2 100 pg/mL 88 17.5 ug/ml 10 pg/mL 34 1 pg/mL 6 NK3 100 pg /mL 85 76 ug/ml 10 pg/mL -6 1 pg/mL 1 The preparation examples of the extract of the present invention are shown below to illustrate but not limit the present invention. Preparation Example 1: Powder preparation The extract of Example 1: 20 mg Lactose: 1 g The above ingredients were mixed and filled in an airtight capsule to produce a powder. Formulation Example 2: Tablet Preparation 10 mg 100 mg Extract of Example 1: Corn Starch: 17 201021814 Lactose: 100 mg Magnesium Stearate: 2 mg These ingredients are mixed and prepared using a typical ingot method. Lozenges. Preparation Example 3: Capsule preparation Extract of Example 1 : 10 mg Crystalline cellulose: 3 mg Lactose: 14.8 mg Magnesium stearate: 0.2 mg

These ingredients are mixed and filled into gelatin capsules according to a typical production capsule method. Preparation Example 4: Injection preparation The extract of Example 1 : Mannitol: Sterile steaming water for injection: Na2HP04.12H20: 10 mg 180 mg 2974 mg 26 mg

According to a typical method, the active ingredient is dissolved with the excipient and the solution is filled into a type I ampoule (2 ml). Preparation Example 5: Liquid Preparation Extract of Example 1 : 20 mg of isomerized sugar: 10 g of mannitol: 5 g of purified water in an appropriate amount. According to a typical method, the ingredients are dissolved in purified water and screwed The aroma is added to this solution as appropriate. After complete mixing, the solution was added to a volume of 100 ml of purified 18 201021814 water, loaded into a brown glass vial, and sterilized to produce a liquid preparation. Preparation Example 6: Healthy Food Preparation Extract of Example 1: 1,000 mg of vitamin mixture: Vitamin A acetate 70 pg Vitamin E 1.0 mg Vitamin B1 0.13 mg ❹ Vitamin B2 0.15 mg Vitamin B6 0.5 mg Vitamin B12 0.2 pg Vitamin C 10 Mg biotin ίο μβ in test amine 1.7 mg folic acid 50 pg calcium pantothenate mineral mixture 0.5 mg ferrous sulfate 1.75 mg zinc oxide 0.82 mg carbonate lock 25.3 mg acid filling 15 mg acid potassium dihydrate 55 mg potassium citrate 90 mg carbonic acid Calcium Magnesium Chloride 100 mg 24.8 mg 19 201021814 According to a typical method, these ingredients are mixed and formulated into granules which can be used to prepare a health food. This composition of vitamins and minerals is provided as a preferred embodiment for use in healthy foods, but the contents may vary depending on conditions. Preparation Example 7: Healthy Beverage Preparation The extract of Example 1 was: 1, 〇〇〇 milligram of citric acid: 1,000 mg of oligosaccharide: 100 g of lysine plum liquid extract: 2 g of bovine acid: 1 g of Purified water: q_s. 900 ml These ingredients were uniformly formulated according to a typical method and the formulation was at 85. Heat for about 1 hour and stir-fry, filter and sterilize, fill into a 2 liter bottle, densely, and store in the refrigerator until use. This composition is provided in a preferred embodiment suitable for beverages, but the contents may vary depending on regional and national factors (e.g., 'consumer category, country, etc.'). [tftl day and month 3 The first picture is a chromatogram of HPLC (High Performance Liquid Chromatography) of nutmeg extract (M YFT). Figure lb is a mass spectrum of the nutmeg extract (MYFT) obtained using gas chromatography/mass spectrometry (GC/MS). Figure 2 is a mass spectrum of the nutmeg extract (MYFH) obtained by gas chromatography/mass spectrometry (GC/MS). Figure 3 shows the work of nutmeg extract (MYFT) on CRD mode 201021814

The map of effectiveness. Figure 4 is a graph showing the efficacy of nutmeg extract (MYFT) on limiting the pressure-induced fecal pellet output pattern. [Main component symbol description] (none) 21

Claims (1)

201021814 VII. Scope of Application: 1. A pharmaceutical composition for orchid and for treating intestinal cramps, comprising a nutmeg extract as an active ingredient. 2. The pharmaceutical composition of claim 4, wherein the extract is a solvent of a group consisting of a mixture selected from the group consisting of water, a C1 to C4 lower alcohol, a non-polar solvent, and the like. Prepared. 3. The pharmaceutical composition according to claim 2, wherein the mixture: 匕 contains water in an amount of 5 95 · 95-5 (v/v) and an aqueous alcohol solution of a lower alcohol. 4. The pharmaceutical composition according to claim 2, wherein the non-polar refrigerant is selected from the group consisting of di-methane, gas, diethyl ether, ethyl acetate, hexahydrate, and supercritical liquid. . 5. The pharmaceutical composition according to any one of claims 4 to 4, wherein the extract is obtained by a method of extracting extraction in a solvent, a water bath method, a cold precipitation method, a condensation method Prepared by an ultrasonic method or a supercritical extraction method, which is used in an amount of from 丨 to 叨 times the dry weight of the nutmeg. The pharmaceutical composition according to any one of claims 1 to 4, which is formulated into an oral or parenteral dosage form. The pharmaceutical composition according to any one of the preceding claims, wherein the intestinal fistula is selected from the group consisting of diarrhea-based intestinal fistula, constipation-based intestinal fistula, and pain. At least one disease of the main bowel disease. The pharmaceutical composition of claim 1 of the patent scope 'the extract inhibits a 22 201021814 NK receptor. A health food for preventing and improving intestinal cramps, comprising a nutmeg extract as an active ingredient. 10. A health food as claimed in claim 8 which is prepared in the form of a powder, granule, capsule or beverage. twenty three