WO2010062046A1 - Composition for prevention and treatment of irritable bowel syndrome - Google Patents

Composition for prevention and treatment of irritable bowel syndrome Download PDF

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Publication number
WO2010062046A1
WO2010062046A1 PCT/KR2009/006381 KR2009006381W WO2010062046A1 WO 2010062046 A1 WO2010062046 A1 WO 2010062046A1 KR 2009006381 W KR2009006381 W KR 2009006381W WO 2010062046 A1 WO2010062046 A1 WO 2010062046A1
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extract
bowel syndrome
irritable bowel
pharmaceutical composition
composition according
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PCT/KR2009/006381
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French (fr)
Inventor
Won Suck Sun
Hyo Jin Jeon
Taek Su Kim
Keun Ho Ryu
Dong Sun Min
Yang Hae Park
Hyun Joo Son
Sang Hwan Kang
Sung Soo Pyo
Key An Um
Bong Yong Lee
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Sk Chemicals Co., Ltd.
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Publication of WO2010062046A1 publication Critical patent/WO2010062046A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH

Definitions

  • the present invention relates to a composition for the prevention and treatment of irritable bowel syndrome, comprising Myristicae Semen extract as an active ingredient.
  • oils from the kernel are also found phenylpropanoids, such as safrole, eugenol, methyl eugenol, elemicin, and myristicin known as a neurotoxin, monoterpenes such as ⁇ - pinene, ⁇ -terpinene and limonene, lignins such as macelignan, guaiacin, acuminatin, austrobilignan-7, and fragransin [LW. Wulf et al., J. Chromatography, 161, p 271-278, 1978; X. Guo et al., Yaowu Fenxi Zazhi, 5, 5, p 258-262, 1985; J.
  • phenylpropanoids such as safrole, eugenol, methyl eugenol, elemicin, and myristicin known as a neurotoxin
  • monoterpenes such as ⁇ - pinene,
  • NK receptors are divided into the subtypes of NK1, NK2 and NK3 to which a family of tachykinins, such as substance P (SP), neurokinin A and neurokinin B, which are known as neuropeptides acting on the central nervous system and the peripheral nervous system, bind [S. Harrison et al., Int. J. Biochem. Cell Biol., 33: p 555-576, 2001].
  • SP substance P
  • neurokinin A and neurokinin B which are known as neuropeptides acting on the central nervous system and the peripheral nervous system.
  • NK receptor antagonists As new therapeutic targets of irritable bowel syndrome [R. A.
  • a Myristicae Semen extract is active in suppressing visceral pain and improving stress- or visceral hypersensitivity-induced bowel abnormality and thus can be used as an active ingredient of a composition for the prevention and treatment of irritable bowel syndrome.
  • the pharmaceutical composition for the prevention and treatment of irritable bowel syndrome in accordance with the present invention is characterized in that it comprises a Myristicae Semen extract as an active ingredient.
  • the healthy food for preventing and improving irritable bowel syndrome in accordance with the present invention is characterized in that it comprises a Myristicae Semen extract as an active ingredient.
  • the irritable bowel syndrome includes at least one disorder selected from among diarrhea-predominant irritable bowel syndrome, constipation-predominant irritable bowel syndrome, and pain-predominant irritable bowel syndrome.
  • the Myristicae Semen extract of the present invention can be used in pharmaceutical compositions and health foods to be effective in the prevention and treatment of irritable bowel syndrome.
  • FIG. 1 is an HPLC (high performance liquid chromatography) chromatogram of the Myristicae Semen extract (MYFT).
  • FIG. 2 is a mass spectrum of the Myristicae Semen extract (MYFT), obtained using a gas chromatography/mass spectrometer (GC/MS).
  • MYFT Myristicae Semen extract
  • FIG. 3 is a mass spectrum of the Myristicae Semen extract (MYFH), obtained using a gas chromatography/mass spectrometer (GC/MS).
  • MYFH Myristicae Semen extract
  • FIG. 4 is of graphs showing effects of the Myristicae Semen extract (MYFT) on CRD models.
  • FIG. 5 is of graphs showing effects of the Myristicae Semen extract (MYFT) on restraint stress-induced fecal pellet output models.
  • MYFT Myristicae Semen extract
  • the herbaceous extract of the present invention may be prepared as follows.
  • the present invention provides a pharmaceutical composition for the prevention and treatment of irritable bowel syndrome, comprising as an active ingredient the extract from Myristicae Semen, prepared using the method.
  • the amount of the active ingredient is not limited thereto, but may be adjusted depending on the conditions of a patient, the type and severity of the disorder.
  • composition based on the Myristicae Semen extract in accordance with the present invention may further comprise proper carriers, excipients and/or diluents typically used in the art.
  • composition comprising the extract in accordance with the present invention may be formulated into oral dosage forms, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., or parenteral dosage forms such as agents for external use, suppositories, and sterile injections.
  • oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc.
  • parenteral dosage forms such as agents for external use, suppositories, and sterile injections.
  • Examples of the carriers, excipients and diluents useful in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, non-crystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • the extract of the present invention may be usually formulated in combination with a diluent or excipient, such as a filler, a thickening agent, a binder, a wetting agent, a disintegrant, a surfactant, etc.
  • a diluent or excipient such as a filler, a thickening agent, a binder, a wetting agent, a disintegrant, a surfactant, etc.
  • Solid preparations intended for oral administration of the extract of the present invention may take the form of tablets, pills, powders, granules, capsules, and the like.
  • the extract of the present invention is formulated in combination with at least one excipient such as starch, calcium carbonate, sucrose, lactose, or gelatin.
  • a lubricant such as magnesium stearate, talc, or the like may also be added.
  • Liquid preparations intended for oral administration include suspensions, internal use solutions, emulsions, syrups, and the like.
  • various excipients such as wetting agents, sweetening agents, aromatics, preservatives, and the like may be contained in the liquid preparations.
  • the extract of the present invention may be administered via a parenteral route. For this, sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilizates, suppositories, and the like may be used.
  • Injectable propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and esters such as ethyl oleate may be suitable for non-aqueous solvents and suspensions.
  • the basic materials of suppositories include Witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerol, and glycerogelatin.
  • composition of the present invention may be administered into mammals including rats, mice, poultry, humans, etc., via various routes. All manners of administration are expected and may be performed by, for example, oral, rectal, intravenous, intramuscular, subcutaneous, intrathecal, or intracerebroventricular injection.
  • the present invention provides a health food for the prophylaxis and improvement of irritable bowel syndrome, comprising the Myristicae Semen extract effective in the prophylaxis and treatment of irritable bowel syndrome in combination with sitologically acceptable additives.
  • composition of the present invention may be widely utilized in drugs, foods and drinks for preventing and improving irritable bowel syndrome.
  • the Myristicae Semen extract of the present invention may be added to foods, such as drinks, gum, tea, vitamin complexes, health-aid foods, and may be in the form of powder, granules, tablets, capsules, or drinks.
  • the Myristicae Semen extract of the present invention may be safely taken for a long period of time for preventive purposes.
  • the extract of the present invention may be also added to foods or drinks with the aim of imparting the function of preventing or treating irritable bowel syndrome to the foods or drinks.
  • the extract of the present invention may 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 of from 0.02 to 10 g, preferably in an amount of from 0.3 to 1 g based on 100 mL of the health drink.
  • the health drink composition of the present invention may further comprise various flavor modifiers or natural carbohydrates.
  • natural carbohydrates useful in the present invention include monosaccharides such as glucose, disaccharides such as maltose, sucrose, etc., polysaccharides such as dextrin, cyclodextrin, etc., and sugar alcohols such as xylitol, sorbitol, erythritol, etc.
  • the flavor modifiers are advantageously natural flavor modifiers (taumatin, stebia extracts, i.e., Rebaudioside A, glycyrrhizin), and synthetic sweeteners (saccharin, aspartame, etc.).
  • the natural carbohydrates may be used in an amount of from 1 to 20 g and preferably in an amount of from 5 to 12 g per 100 ml of the health drink composition of the present invention.
  • composition of the present invention may be supplemented with a variety of agents including nutrients, vitamins, minerals, flavoring agents, synthetic and/or natural, colorants, thickeners (cheese, chocolate), pectic acid or salts thereof, alginic acid or salts thereof, organic acids, protective colloidal thickening agents, pH modifiers, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, etc.
  • the composition of the present invention may further comprise fruit fresh and/or vegetable soup. These components may be used separately or in combination. As a rule, the amount of the agents ranges from zero to 20 parts by weight per 100 weight parts of the composition.
  • Myristicae Semen 100 Grams of Myristicae Semen, the kernel of Myristica fragrans HOUTT., purchased from Kyoung Dong Market, Korea, was dried in the shade and minced before it was extracted with 0.7 L of 50 % ethanol for 4 hrs in a water bath with stirring. After filtration, the filtrate was concentrated and dried to afford 18 g of a Myristicae Semen extract (MYFT).
  • MYFT Myristicae Semen extract
  • FIG. 1 is an HPLC chromatogram for pattern analysis of the Myristicae Semen extract (MYFT) [system: Agilent 1200 Series, column: C18 column (250X4.6mm ID, S-5 ⁇ m, 12nm)] and FIG. 2 is a mass spectrum for the extract, obtained with a gas chromatography/mass spectrometer (GC/MS) [system: GC/MS system Perkin Elmer Clarus600 series, column: Elite-5MS (30m, 0.25mm ID, 0.25 ⁇ m df), carrier gas: helium].
  • GC/MS gas chromatography/mass spectrometer
  • non-polar ingredients such as phenylpropanoids and lignans as well as essential oils were found to be the main ingredients of the Myristicae Semen extract (MYFT).
  • MYFT Myristicae Semen extract
  • Myristicae Semen 100 Grams of Myristicae Semen, purchased from Kyoung Dong Market, Korea, was dried in the shade and minced, followed by cold precipitation for 48 hrs with 0.3 L of hexane. After filtration, the filtrate was concentrated and dried to afford 8.2 g of a Myristicae Semen extract (MYFH).
  • MYFH Myristicae Semen extract
  • FIG. 3 is a mass spectrum of the hexane extract (MYFH), obtained using a gas chromatography/mass spectrometer (GC/MS) [system: GC/MS system Perkin Elmer Clarus600 series, column: Elite-5MS (30m, 0.25mm ID, 0.25 ⁇ m df), carrier gas: helium]. As seen in the spectrum, a pattern similar to that of MYFT was obtained.
  • GC/MS gas chromatography/mass spectrometer
  • MYFT Myristicae Semen extract prepared in Example 1 was examined for suppressive effect on visceral pain through a colorectal distension (CRD) test [JH. La et al., World J. Gastroenterol., Dec., 9(12): p 2791-2795, 2003; Y.D. Choi et al., Dig. Dis. Sci., Mar 21, Epub ahead of print, 2008] as follows.
  • CCD colorectal distension
  • mice Male Sprague-Dawley rats (Charles River) weighing 250 - 330 g were bred at 25°C and a relative humidity of 50% under the controlled condition of 12:12-h light-dark cycles, with free access to food and water. They were acclimated for 5 days under the conditions, after which colitis was induced. For 24 hours before the introduction of colitis, the rats were fasted. After the rats were anaesthetized with isoflurane, a rubber catheter (PE 50) was inserted with a length of 8 cm into the colon from the anus.
  • PE 50 rubber catheter
  • Each of the colitis-induced rats was inserted intra-anally with a 2 cm-long flexible latex balloon, and colorectal distensions were made by inflating the balloon with from 0.1 mL to 1.0 mL of warm water (37°C) while the response of the animal to the induced visceral pain was monitored.
  • responses of the rats to visceral pain were indirectly quantified with the scores of abdominal withdrawal reflex responsible for characteristic behaviors in a stepwise manner according to the intensity of visceral pain.
  • pulse rates were measured from the caudal artery using a pulsimeter, so that they were used as auxiliary indices for the pain response.
  • the rats After being tranqualized for 50 - 60 min following the oral administration, the rats were subjected to CRD with AWR scores and pulse rates monitored for responses to visceral pain.
  • AWR score and pulse rate For quantitative analysis of responses in a vehicle group, a positive control group and a MYFT group, changes in AWR score and pulse rate were converted into AUC (area under the curve). Data were analyzed for statistical significance using Student's t-test at p ⁇ 0.05.
  • Normal stands for a normal group with no colitis
  • Vehicle for a colitis-induced group administered with vehicle alone
  • Alo for a colitis-induced positive control group orally administered with alosetron at a dose of 20mg/kg
  • MYFT for a colitis-induced group orally administered with the Myristicae Semen extract (MYFT) at a dose of 300 mg/kg.
  • MYFT 300 mg/kg reduced both the AWR score and the pulse rate upon CRD to the same level as with the positive control alosetron.
  • MYFT Myristicae Semen extract
  • MYFT Myristicae Semen extract
  • MYFT 100 mg/kg was observed to reduce the restraint stress-induced fecal pellet output compared to the vehicle, but with no significance. Hence, MYFT was found to reduce restraint stress-induced fecal pellet output in a dose-dependent manner [FIG. 5].
  • SR-140333 In the presence of MYFT, 0.25 nM [H 3 ] SR-140333 was reacted with the cell membranes for NK1, 0.5 nM [H 3 ] SR-48968 with the cell membrane for NK2, and 0.06 nM [ 125 I] MePhe-Neurokinin B with the cell membrane for NK3, so as to measure the inhibitory activity of MYFT against the neurokinin receptors. Binding reaction was performed at 25°C for 90 min (NK 1&2) and 120 min (NK3) in HEPES buffer (20 mM HEPES, pH7.4, 1mM MnCl2, 0.01% BSA).
  • reaction mixture was loaded on a Whatman GF/B filter which was then washed with ice-cold HEPES buffer. Radioactivity bound to the filter was measured using a liquid scintillation counter. MYFT in 1% DMSO was used at concentrations of 1 ⁇ g/mL, 10 ⁇ g/mL and 100 ⁇ g/mL.
  • Lactose 1 g
  • the active ingredient along with the excipient, was dissolved and the solution was loaded into type I ampoules (2 ml).
  • the ingredients were dissolved in purified water and a lemon aromatic was added in a adequate amount to the solution. After completely mixing, the solution was increased in volume to 100 ml with purified water, loaded into brown vials and sterilized to give a liquid preparation.
  • Vitamin A acetate 70 ⁇ g
  • Vitamin B6 0.5 mg
  • Citric acid 1,000 mg
  • Oligosaccharides 100 g
  • ingredients were homogeneously formulated according to a typical method and the formulation was heated at 85°C for about 1 hour with stirring, sterilized by filtration, loaded into a 2 L bottle, sealed, and stored in a refrigerator until use.
  • composition is provided as a preferred example suitable for use in drinks, but the contents may be changed depending on regional and national factors, such as consumer classes, countries, etc.

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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

COMPOSITION FOR PREVENTION AND TREATMENT OF IRRITABLE BOWEL SYNDROME
The present invention relates to a composition for the prevention and treatment of irritable bowel syndrome, comprising Myristicae Semen extract as an active ingredient.
Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits such as diarrhea and constipation in the absence of any detectable organic cause. Its symptoms may be aggravated by psychiatric or social environments causing stress. According to a survey 27.8% of outpatients who suffered from digestive disorders were diagnosed with irritable bowel syndrome, with about 2 - 4 times more female patients than male patients in Korea. Of the outpatients, diarrhea was predominant accounting for 30.8%, constipation in 24.6%, and an alternation of these two in 44.6% of cases. Thus, proper medication should be prescribed depending on the type of irritable bowel syndrome, that is, diarrhea-predominant, constipation-predominant and pain-predominant types. Therapy using chemicals to treat irritable bowel syndrome, however, has not yet produced satisfactory results, with no significant treatment gains compared to placebos. Chemicals prescribed for patients with irritable bowel syndrome are usually divided into drugs for improving general symptoms or specific single symptoms. Medications may consist of smooth muscle relaxants, anti-depressants and opioid agonists in pain-dominant irritable bowel syndrome, fiber supplements, laxatives and 5-HT4 agonists in constipation-dominant irritable bowel syndrome, and anti-diarrheals and 5-HT3 antagonists in diarrhea-predominant irritable bowel syndrome for mild symptoms [Lee, Oh Young, Korean Journal of Gastroenterology 47, pp 111-119, 2006; Rhee, Poong Lyul, Korean Journal of Gastroenterology, 47, pp 94-100, 2006; Choi, Myung Gyu, Korean Journal of Gastroenterology, 47, p 125-130; Park, Hyo Jin, Korean Journal of Gastroenterology, 47, pp 101-110, 2006; TT. Ashburn et al., Nat. Rev. Drug Discov., 5(2), pp 99-100, 2006; MJG Farthing, BMJ., 330, p 429-430, 2005; MJG. Farthing, Best Pract. Res. Clin. Gastroenterol., 18(4), pp 773-786, 2004].
Myristicae Semen, which is the kernel of Myristica fragrans HOUTT. belonging to the Myristicaceae family, is described to have the medicinal effect of warming the stomach and the spleen, improving digestive transport in the body, promoting digestion and increasing stamina, and increasing vitality [Shin et al., Graphical Herb Great Dictionary pp. 519 - 520, 1989]. Myristicae Semen comprises an essential oil in an amount of from 2 to 9 weight %, with the content of myristic acid accounting for as much as 70 - 80 % of the total fatty acid. In the oils from the kernel are also found phenylpropanoids, such as safrole, eugenol, methyl eugenol, elemicin, and myristicin known as a neurotoxin, monoterpenes such as β- pinene, γ-terpinene and limonene, lignins such as macelignan, guaiacin, acuminatin, austrobilignan-7, and fragransin [LW. Wulf et al., J. Chromatography, 161, p 271-278, 1978; X. Guo et al., Yaowu Fenxi Zazhi, 5, 5, p 258-262, 1985; J. Totte et al., Planta Med., 50, 3, p 222-226, 1984; J. Forrest et al., J. Chromatography, 89, p 113-117, 1974; JS. Liu et al, Youji Huaxue, 8, p 227-228, 1988; T. Murphy et al., Aust. J. Chem., 28, p 81-90, 1975; KH. Shin et al., Kor. J. Pharmacogn., 17, 1, p 91-99, 1986; M. Hattori et al., Chem. Pharm. Bull., 34, 9, p 3885-3893, 1986; DJ. Harvey, J. Chromatogr., 110, p 91-102, 1975; S. Hada et al., Phytochemistry, 27, 2, p 563-568, 1988; M. Hattori et al., Chem. Pharm. Bull., 35, 8, p 3315-3322, 1987; S. Hada et al., Phytochemistry, 27, 2, p 563-568, 1988].
Neurokinin (NK) receptors are divided into the subtypes of NK1, NK2 and NK3 to which a family of tachykinins, such as substance P (SP), neurokinin A and neurokinin B, which are known as neuropeptides acting on the central nervous system and the peripheral nervous system, bind [S. Harrison et al., Int. J. Biochem. Cell Biol., 33: p 555-576, 2001]. These NK receptors are distributed throughout the central nervous system, such as amygdala, hypocampus, hypothalamus, striatum, marrow, etc. or the peripheral nervous system, such as the skin, inflammatory cells, along with throughout the digestive system, the respiratory system, the cardiovascular system, etc., where they act as neuromodulators or neurotransmitters in close relation with physiological functions, particularly with intestinal motility, visceral hypersensitivity, etc. [JH. La et al., World J. Gastroenterol., 11(2), p 237-241, 2005 ; MS Kramer, Science, 281(5383) p 1624-1625. 1998; G. J. Sanger., Br. J. Pharmacol., 141, p1303-1312, 2004]. On the basis of the physiological functions of NK receptors, active studies have therefore been done on NK receptor antagonists as new therapeutic targets of irritable bowel syndrome [R. A. Duffy, Expert Opin. Emerg. Drugs, 9(1), 2004; M. Camilleri, Br. J. Pharmacol., 141, p1237-1248, 2004; G. J. Sanger., Br. J. Pharmacol., 141, p1303-1312, 2004 ; A. Lecci et al., Br. J. Pharmacol., 141, p1249-1263, 2004].
The lignan compounds of Myristicae Semen are well-known for the effect thereof on asthma, rhinitis, arthritis, inflammatory disorders in the digestive system, etc. [Hwang et al., Korean Patent No. 10-0579752, 2006]. Nowhere are therapeutic effects on irritable bowel syndrome mentioned in the patent. In addition, an herbaceous medicinal composition comprising Myristicae Semen is known to have the effect of preventing and treating gastrointestinal dysmotility, such as irritable bowel syndrome (Pangenomics, Korean Patent No. 10-0532703, 2005). The medicinal composition comprises extracts from 10 herbs in addition to Myristicae Semen (herbal extracts in the same weight), laying emphasis on the promotion of gastrointestinal motility (activation of both 5-HT3 and 5-HT4 receptors).
This is therefore different from the gist of the present invention in that an extract from Myristicae Semen has an inhibitory activity against NK receptors and plays an important role in the nociceptive pathway and gastrointestinal motility through the ENS (enteric nervous system), thus relieving visceral hypersensitivity and improving the bowel abnormality attributed to restraint stress (Test Examples 1, 2 and 3).
Leading to the present invention, intensive and thorough research on the improvement of irritable bowel syndrome, conducted by the present inventors, resulted in the finding that a Myristicae Semen extract is active in suppressing visceral pain and improving stress- or visceral hypersensitivity-induced bowel abnormality and thus can be used as an active ingredient of a composition for the prevention and treatment of irritable bowel syndrome.
It is therefore an object of the present invention to provide a pharmaceutical composition for the prevention and treatment of irritable bowel syndrome, comprising Myristicae Semen extract as an active ingredient.
It is another object of the present invention to provide a healthy food for the prevention and treatment of irritable bowel syndrome, comprising Myristicae Semen extract as an active ingredient.
The pharmaceutical composition for the prevention and treatment of irritable bowel syndrome in accordance with the present invention is characterized in that it comprises a Myristicae Semen extract as an active ingredient.
The healthy food for preventing and improving irritable bowel syndrome in accordance with the present invention is characterized in that it comprises a Myristicae Semen extract as an active ingredient.
As defined in the present invention, the extract refers to an extract from Myristicae Semen with the use of a solvent selected from among water, lower alcohols of C1 - C4, non-polar solvents, and combinations thereof.
The irritable bowel syndrome includes at least one disorder selected from among diarrhea-predominant irritable bowel syndrome, constipation-predominant irritable bowel syndrome, and pain-predominant irritable bowel syndrome.
Being superior in suppressing visceral hypersensitivity and improving stress- or hypersensitivity-induced bowel abnormalities, the Myristicae Semen extract of the present invention can be used in pharmaceutical compositions and health foods to be effective in the prevention and treatment of irritable bowel syndrome.
FIG. 1 is an HPLC (high performance liquid chromatography) chromatogram of the Myristicae Semen extract (MYFT).
FIG. 2 is a mass spectrum of the Myristicae Semen extract (MYFT), obtained using a gas chromatography/mass spectrometer (GC/MS).
FIG. 3 is a mass spectrum of the Myristicae Semen extract (MYFH), obtained using a gas chromatography/mass spectrometer (GC/MS).
FIG. 4 is of graphs showing effects of the Myristicae Semen extract (MYFT) on CRD models.
FIG. 5 is of graphs showing effects of the Myristicae Semen extract (MYFT) on restraint stress-induced fecal pellet output models.
The herbaceous extract of the present invention may be prepared as follows.
Myristicae Semen is dried in the shade, ground and extracted with about 1 to 20 weights, preferably about 3 to 10 weights of a solvent selected from among water, a lower alcohol of C1 - C4, such as ethanol or methanol, a mixture comprising water and lower alcohol in the amount of 5-95 : 95-5 or 30 -70 : 70 - 30 (v/v), a nonpolar solvent, and combinations thereof. The extraction itself may be performed at 80℃ for about 1 to 6 hrs and preferably for 2 to 4 hrs in the solvent using a method such as stirring extraction, hot-water extraction, cold precipitation extraction, condenser extraction, ultrasonication extraction, or supercritical extraction to give a herb extract of the present invention (MYFT).
In accordance with an aspect thereof, the present invention provides a pharmaceutical composition for the prevention and treatment of irritable bowel syndrome, comprising as an active ingredient the extract from Myristicae Semen, prepared using the method.
Preferably, the herbal extract is present in an amount of 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, but may be adjusted depending on the conditions of a patient, the type and severity of the disorder.
The composition based on the Myristicae Semen extract in accordance with the present invention may further comprise proper carriers, excipients and/or diluents typically used in the art.
The composition comprising the extract in accordance with the present invention may be formulated into oral dosage forms, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., or parenteral dosage forms such as agents for external use, suppositories, and sterile injections. Examples of the carriers, excipients and diluents useful in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, non-crystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. For practical use, the extract of the present invention may be usually formulated in combination with a diluent or excipient, such as a filler, a thickening agent, a binder, a wetting agent, a disintegrant, a surfactant, etc. Solid preparations intended for oral administration of the extract of the present invention may take the form of tablets, pills, powders, granules, capsules, and the like. In regards to these solid agents, the extract of the present invention is formulated in combination with at least one excipient such as starch, calcium carbonate, sucrose, lactose, or gelatin. In addition, a lubricant such as magnesium stearate, talc, or the like may also be added. Liquid preparations intended for oral administration include suspensions, internal use solutions, emulsions, syrups, and the like. In addition to simple diluents such as water or liquid paraffin, various excipients, such as wetting agents, sweetening agents, aromatics, preservatives, and the like may be contained in the liquid preparations. Also, the extract of the present invention may be administered via a parenteral route. For this, sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilizates, suppositories, and the like may be used. Injectable propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and esters such as ethyl oleate may be suitable for non-aqueous solvents and suspensions. The basic materials of suppositories include Witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerol, and glycerogelatin.
The effective dosage of the extract in accordance with the present invention depends on various factors, including the patient's condition, weight, and severity of disease, and time and route of administration of the drug, etc. The extract according to the present invention may be administered in a single dosage or may be divided into two to six dosages per day at a daily dosage ranging from 0.01 mg/kg to 10 g/kg, and preferably from 1 mg/kg to 1 g/kg. The dose shall not limit the scope of the present invention.
The composition of the present invention may be administered into mammals including rats, mice, poultry, humans, etc., via various routes. All manners of administration are expected and may be performed by, for example, oral, rectal, intravenous, intramuscular, subcutaneous, intrathecal, or intracerebroventricular injection.
In accordance with another aspect thereof, the present invention provides a health food for the prophylaxis and improvement of irritable bowel syndrome, comprising the Myristicae Semen extract effective in the prophylaxis and treatment of irritable bowel syndrome in combination with sitologically acceptable additives.
In this context, the composition of the present invention may be widely utilized in drugs, foods and drinks for preventing and improving irritable bowel syndrome. For example, the Myristicae Semen extract of the present invention may be added to foods, such as drinks, gum, tea, vitamin complexes, health-aid foods, and may be in the form of powder, granules, tablets, capsules, or drinks.
Being almost free of toxicity and side effects, the Myristicae Semen extract of the present invention may be safely taken for a long period of time for preventive purposes.
The extract of the present invention may be also added to foods or drinks with the aim of imparting the function of preventing or treating irritable bowel syndrome to the foods or drinks. On the whole, the extract of the present invention may 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 of from 0.02 to 10 g, preferably in an amount of from 0.3 to 1 g based on 100 mL of the health drink.
No particular limitations are imparted to the liquid component of the health drink composition so long as the extract of the present invention is used in an amount such as the one described above. Like conventional drinks, the health drink composition of the present invention may further comprise various flavor modifiers or natural carbohydrates. Examples of the natural carbohydrates useful in the present invention include monosaccharides such as glucose, disaccharides such as maltose, sucrose, etc., polysaccharides such as dextrin, cyclodextrin, etc., and sugar alcohols such as xylitol, sorbitol, erythritol, etc. As for the flavor modifiers, they are advantageously natural flavor modifiers (taumatin, stebia extracts, i.e., Rebaudioside A, glycyrrhizin), and synthetic sweeteners (saccharin, aspartame, etc.). The natural carbohydrates may be used in an amount of from 1 to 20 g and preferably in an amount of from 5 to 12 g per 100 ml of the health drink composition of the present invention.
In addition, the composition of the present invention may be supplemented with a variety of agents including nutrients, vitamins, minerals, flavoring agents, synthetic and/or natural, colorants, thickeners (cheese, chocolate), pectic acid or salts thereof, alginic acid or salts thereof, organic acids, protective colloidal thickening agents, pH modifiers, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, etc. For use in the preparation of fruit or vegetable juices, the composition of the present invention may further comprise fruit fresh and/or vegetable soup. These components may be used separately or in combination. As a rule, the amount of the agents ranges from zero to 20 parts by weight per 100 weight parts of the composition.
A better understanding of the present invention may be obtained through the following examples which are set forth to illustrate, but are not to be construed as limiting the present invention.
EXAMPLE 1: Preparation of Myristicae Semen Extract (MYFT)
100 Grams of Myristicae Semen, the kernel of Myristica fragrans HOUTT., purchased from Kyoung Dong Market, Korea, was dried in the shade and minced before it was extracted with 0.7 L of 50 % ethanol for 4 hrs in a water bath with stirring. After filtration, the filtrate was concentrated and dried to afford 18 g of a Myristicae Semen extract (MYFT).
FIG. 1 is an HPLC chromatogram for pattern analysis of the Myristicae Semen extract (MYFT) [system: Agilent 1200 Series, column: C18 column (250X4.6mm ID, S-5㎛, 12nm)] and FIG. 2 is a mass spectrum for the extract, obtained with a gas chromatography/mass spectrometer (GC/MS) [system: GC/MS system Perkin Elmer Clarus600 series, column: Elite-5MS (30m, 0.25mm ID, 0.25㎛ df), carrier gas: helium]. On the basis of the analytic results, non-polar ingredients such as phenylpropanoids and lignans as well as essential oils were found to be the main ingredients of the Myristicae Semen extract (MYFT).
EXAMPLE 2: Preparation of Myristicae Semen Extract with Hexane (MYFH)
Because non-polar ingredients were found to arise as main ingredients of the Myristicae Semen extract (MYFT) as analyzed by HPLC and GC/MS, hexane was used to extract the non-polar ingredients from Myristicae Semen (MYFH).
100 Grams of Myristicae Semen, purchased from Kyoung Dong Market, Korea, was dried in the shade and minced, followed by cold precipitation for 48 hrs with 0.3 L of hexane. After filtration, the filtrate was concentrated and dried to afford 8.2 g of a Myristicae Semen extract (MYFH).
FIG. 3 is a mass spectrum of the hexane extract (MYFH), obtained using a gas chromatography/mass spectrometer (GC/MS) [system: GC/MS system Perkin Elmer Clarus600 series, column: Elite-5MS (30m, 0.25mm ID, 0.25㎛ df), carrier gas: helium]. As seen in the spectrum, a pattern similar to that of MYFT was obtained.
TEST EXAMPLE 1: Suppressive Effect of the Extract MYFT on Visceral Pain in CRD (Colorectal Distension) Model
The Myristicae Semen extract (MYFT) prepared in Example 1 was examined for suppressive effect on visceral pain through a colorectal distension (CRD) test [JH. La et al., World J. Gastroenterol., Dec., 9(12): p 2791-2795, 2003; Y.D. Choi et al., Dig. Dis. Sci., Mar 21, Epub ahead of print, 2008] as follows.
After placing two per cage, male Sprague-Dawley rats (Charles River) weighing 250 - 330 g were bred at 25℃ and a relative humidity of 50% under the controlled condition of 12:12-h light-dark cycles, with free access to food and water. They were acclimated for 5 days under the conditions, after which colitis was induced. For 24 hours before the introduction of colitis, the rats were fasted. After the rats were anaesthetized with isoflurane, a rubber catheter (PE 50) was inserted with a length of 8 cm into the colon from the anus.
1 ml of 3.5% acetic acid (in 0.9% saline) was injected into the lumen of the colon through the catheter after which the anus was closed for 30 sec to prevent leakage of the solution. Then, 1 mL of 0.9% saline was injected through the same catheter to wash off the acetic acid solution from the lumen of the colon.
Each of the colitis-induced rats was inserted intra-anally with a 2 cm-long flexible latex balloon, and colorectal distensions were made by inflating the balloon with from 0.1 mL to 1.0 mL of warm water (37℃) while the response of the animal to the induced visceral pain was monitored. In this context, responses of the rats to visceral pain were indirectly quantified with the scores of abdominal withdrawal reflex responsible for characteristic behaviors in a stepwise manner according to the intensity of visceral pain. At the same time with the recoding of AWR scores [Table 1, see E. D. Al-Chaer et al., Gastroenterology, Nov., 119(5), p1276-1285. 2000], pulse rates were measured from the caudal artery using a pulsimeter, so that they were used as auxiliary indices for the pain response.
Figure PCTKR2009006381-appb-I000001
On Day 7 after the introduction of colitis, the rats were subjected to CRD to examine the presence of visceral hypersensitivity, so that animal models with IBS-like symptom were selected [JH. La et al., World J. Gastroenterol., Dec., 9(12): pp 2791-2795, 2003]. The Myristicae Semen extract (MYFT), prepared in Example 1, in 0.5% CMC was orally administered at a dose of 300 mg/kg to the selected animal models whereas alosetron HCl (purchased from Jiangyin Yongda Chemical Co., Ltd.) as a positive control was orally administered at a dose 20 mg/kg. After being tranqualized for 50 - 60 min following the oral administration, the rats were subjected to CRD with AWR scores and pulse rates monitored for responses to visceral pain. For quantitative analysis of responses in a vehicle group, a positive control group and a MYFT group, changes in AWR score and pulse rate were converted into AUC (area under the curve). Data were analyzed for statistical significance using Student's t-test at p<0.05. In FIG. 4, "Normal" stands for a normal group with no colitis, "Vehicle" for a colitis-induced group administered with vehicle alone, "Alo" for a colitis-induced positive control group orally administered with alosetron at a dose of 20mg/kg, and "MYFT" for a colitis-induced group orally administered with the Myristicae Semen extract (MYFT) at a dose of 300 mg/kg. As is apparent from the data of FIG. 4, MYFT (300 mg/kg) reduced both the AWR score and the pulse rate upon CRD to the same level as with the positive control alosetron.
TEST EXAMPLE 2: Effect of the Extract MYFT on Bowel Movement in Restraint Stress-Induced Fecal Pellet Output Model
An examination was made of the effect of the Myristicae Semen extract (MYFT) prepared in Example 1 on bowel movement in a restraint stress-induced fecal pellet output model [S. Kobayashi et al., Jpn. J. Pharmcaol., 2001].
After being housed two per cage, male Sprague-Dawley rats (Charles River) weighing 250 - 330 g were bred at 25℃ and a relative humidity of 50% under the controlled condition of 12:12-h light-dark cycles, with free access to food and water.
On the Day of experiment, restraint cages were used to induce stress in the rats to measure restraint stress-induced fecal pellet output. In this regard, the Myristicae Semen extract (MYFT), prepared in Example 1, in 0.5% CMC was orally administered at a dose of 300 mg/kg to the rats which were then put into restraint cages. An intensive care should be taken to avoid stress for the rats. Once immobilized in the restraint cages, the rats were stressed and started to excrete.
Excrements were counted at regular intervals of 60 min for 4 hours. During the experiment, only the restraint cages were slightly shifted without movement of the housing cage in order to prevent the excrement counting from becoming confused. Excrements which had passed a long time before could not easily be examined for conditions because they had dried. Accordingly, frequent investigation into the number and condition of the fecal pellet outputs was needed. The data were analyzed for statistical significance using Student's t-test at p<0.05. MYFT 300 significantly reduced the restraint stress-induced fecal pellet output compared to the vehicle. The number of fecal pellet output was reduced to 2.5 upon treatment with MYFT 300 mg/kg while it was 7.5 for the vehicle group. MYFT 100 mg/kg was observed to reduce the restraint stress-induced fecal pellet output compared to the vehicle, but with no significance. Hence, MYFT was found to reduce restraint stress-induced fecal pellet output in a dose-dependent manner [FIG. 5].
TEST EXAMPLE 3: Inhibitory Activity against Neurokinin Receptors ( NK-1, 2 ,3 )
The Myristicae Semen extract (MYFT) prepared in Example 1 was examined for inhibitory activity against neurokinin receptors. For this, a binding assay was performed with human recombinant CHO 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 were separated from human recombinant CHO cells which were transfected to express respective receptor subtypes. In the presence of MYFT, 0.25 nM [H3] SR-140333 was reacted with the cell membranes for NK1, 0.5 nM [H3] SR-48968 with the cell membrane for NK2, and 0.06 nM [125I] MePhe-Neurokinin B with the cell membrane for NK3, so as to measure the inhibitory activity of MYFT against the neurokinin receptors. Binding reaction was performed at 25℃ for 90 min (NK 1&2) and 120 min (NK3) in HEPES buffer (20 mM HEPES, pH7.4, 1mM MnCl2, 0.01% BSA). After completion of the reaction, the reaction mixture was loaded on a Whatman GF/B filter which was then washed with ice-cold HEPES buffer. Radioactivity bound to the filter was measured using a liquid scintillation counter. MYFT in 1% DMSO was used at concentrations of 1 ㎍/mL, 10 ㎍/mL and 100 ㎍/mL.
As is apparent from the data of Table 2, the Myristicae Semen extract (MYFT) was found to have excellent inhibitory activity against NK 1, 2 and 3. Particularly, when used at a concentration of 100 ㎍/mL, MYFT inhibited NK 2 and 3 at a rate of 88 and 85% (IC50 17.5 ㎍/mL and 76 ㎍/ml), respectively, and NK1 at a rate of 44% although not measured for IC50.
Figure PCTKR2009006381-appb-I000002
Formulation examples for the extract of the present invention are given herein, below, to illustrate, but not to limit the present invention.
FORMULATION EXAMPLE 1: Powder Preparation
Extract of Example 1: 20 mg
Lactose: 1 g
The above ingredients were mixed and loaded into an airtight sac to produce a powder agent.
FORMULATION EXAMPLE 2: Tablet Preparation
Extract of Example 1: 10 mg
Corn Starch: 100 mg
Lactose: 100 mg
Mg Stearate: 2 mg
These ingredients were mixed and prepared into tablets using a typical tabletting method.
FORMULATION EXAMPLE 3: Capsule Preparation
Extract of Example 1: 10 mg
Crystalline Cellulose: 3 mg
Lactose: 14.8 mg
Mg Stearate: 0.2 mg
These ingredients were mixed and loaded into gelatin capsules according to a typical method of producing capsules.
FORMULATION EXAMPLE 4: Injection Preparation
Extract of Example 1: 10 mg
Mannitol: 180 mg
Sterile Distilled Water for Injection: 2974 mg
Na2HPO4. 12H2O: 26 mg
According to a typical method, the active ingredient, along with the excipient, was dissolved and the solution was loaded into type I ampoules (2 ml).
FORMULATION EXAMPLE 5: Liquid Preparation
Extract of Example 1: 20 mg
Isomerized Sugar: 10 g
Mannitol: 5 g
Purified Water adequate amount
According to a typical method, the ingredients were dissolved in purified water and a lemon aromatic was added in a adequate amount to the solution. After completely mixing, the solution was increased in volume to 100 ml with purified water, loaded into brown vials and sterilized to give a liquid preparation.
FORMULATION EXAMPLE 6: Healthy Food Preparation
Extract of Example 1: 1,000 mg
Vitamin Mixture:
Vitamin A acetate 70 ㎍
Vitamin E 1.0 mg
Vitamin B1 0.13 mg
Vitamin B2 0.15 mg
Vitamin B6 0.5 mg
Vitamin B12 0.2 ㎍
Vitamin C 10 mg
Biotin 10 ㎍
Nicotinamide 1.7 mg
Folic acid 50 ㎍
Calcium Pantothenate 0.5 mg
Mineral Mixture:
Ferrous sulfate 1.75 mg
Zinc oxide 0.82 mg
Magnesium carbonate 25.3 mg
Potassium phosphate monobasic 15 mg
Potassium phosphate dibasic 55 mg
Potassium citrate 90 mg
Calcium carbonate 100 mg
Magnesium chloride 24.8 mg
According to a typical method, these ingredients were mixed and formulated into granules which could be applied to the preparation of healthy foods. This composition of the vitamins and minerals was provided as a preferred example suitable for use in healthy food, but the contents may be changed depending on conditions.
FORMULATION EXAMPLE 7: Healthy Drink Preparation
Extract of Example 1: 1,000 mg
Citric acid: 1,000 mg
Oligosaccharides: 100 g
Japanese Apricot Liquid Extract: 2 g
Taurine: 1 g
Purified water: q.s.900 mL
These ingredients were homogeneously formulated according to a typical method and the formulation was heated at 85℃ for about 1 hour with stirring, sterilized by filtration, loaded into a 2 L bottle, sealed, and stored in a refrigerator until use.
This composition is provided as a preferred example suitable for use in drinks, but the contents may be changed depending on regional and national factors, such as consumer classes, countries, etc.

Claims (10)

  1. A pharmaceutical composition for the prevention and treatment of irritable bowel syndrome comprising a Myristicae Semen extract as an active ingredient.
  2. The pharmaceutical composition according to claim 1, wherein the extract is prepared by using a solvent selected from the group consisting of water, a lower alcohol of C1 to C4, a non-polar solvent, and a mixture of thereof.
  3. The pharmaceutical composition according to claim 2, wherein the mixture is an aqueous alcohol solution comprising water and lower alcohol in the amount of 5-95 : 95-5 (v/v).
  4. The pharmaceutical composition according to claim 2, wherein the non-polar solvent is selected from the group consisting of dichloromethane, chloroform, diethyl ether, ethyl acetate, hexane and supercritical liquid.
  5. The pharmaceutical composition according to one of claims 1 to 4, wherein the extract is prepared by using a stirring extraction method, a water bath method, a cold precipitation method, a condensation method, an ultrasonication method or a supercritical extraction method in a solvent, said solvent being used in an amount one to 20 times as much as a dry weight of Myristicae Semen.
  6. The pharmaceutical composition according to one of claims 1 to 4, formulated into an oral or parenteral dosage form.
  7. The pharmaceutical composition according to one of claims 1 to 4, wherein the irritable bowel syndrome is at least one disorder selected from diarrhea-predominant irritable bowel syndrome, constipation-predominant irritable bowel syndrome and pain-predominant irritable bowel syndrome.
  8. The pharmaceutical composition according to claim 1, wherein the extract inhibits an NK receptor.
  9. A health food for preventing and improving irritable bowel syndrome, comprising a Myristicae Semen extract as an active ingredient.
  10. The health food according to claim 8 prepared in the form of powders, granules, capsules or drinks.
PCT/KR2009/006381 2008-11-03 2009-11-02 Composition for prevention and treatment of irritable bowel syndrome WO2010062046A1 (en)

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CN102697924A (en) * 2012-06-25 2012-10-03 陈慧婷 Semen myristicae Chinese medicinal preparation for treating diarrhea and preparation method thereof
CN113412817A (en) * 2021-05-31 2021-09-21 成都中医药大学附属医院 IBS-D experimental animal model method for improving molding rate and reducing death rate

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WO2001085162A1 (en) * 2000-05-12 2001-11-15 Meracol Corporation Limited Treating irritable bowel syndrome or disease
WO2006073285A1 (en) * 2005-01-07 2006-07-13 Newtree Industry Co., Ltd Use of lignan compounds for treating or preventing inflammatory disease
KR20090093302A (en) * 2008-02-29 2009-09-02 황재관 Pharmaceutical composition for treating or preventing an inflammatory disease comprising licarin E

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102697924A (en) * 2012-06-25 2012-10-03 陈慧婷 Semen myristicae Chinese medicinal preparation for treating diarrhea and preparation method thereof
CN113412817A (en) * 2021-05-31 2021-09-21 成都中医药大学附属医院 IBS-D experimental animal model method for improving molding rate and reducing death rate

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