WO2014010658A1 - Preparation containing indian long pepper - Google Patents

Preparation containing indian long pepper Download PDF

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Publication number
WO2014010658A1
WO2014010658A1 PCT/JP2013/068934 JP2013068934W WO2014010658A1 WO 2014010658 A1 WO2014010658 A1 WO 2014010658A1 JP 2013068934 W JP2013068934 W JP 2013068934W WO 2014010658 A1 WO2014010658 A1 WO 2014010658A1
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Prior art keywords
nausea
ethanol
turmeric
gastrointestinal
powder
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PCT/JP2013/068934
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French (fr)
Japanese (ja)
Inventor
祐太 藤枝
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興和株式会社
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Priority to JP2014524859A priority Critical patent/JPWO2014010658A1/en
Publication of WO2014010658A1 publication Critical patent/WO2014010658A1/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)
    • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
    • 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
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger

Definitions

  • the present invention relates to a drug having an excellent gastrointestinal mucosa protective action and antiemetic action. More specifically, excellent gastrointestinal mucosal protective action against gastrointestinal mucosal damage due to ethanol overdose, stress, overdose, smoking, and nonsteroidal anti-inflammatory drugs, and nausea, nausea or The present invention relates to a drug having an excellent antiemetic action against vomiting.
  • Non-patent Document 1 a gram-negative bacilli
  • Non-patent Document 2 Shay's balance theory
  • antibiotics having anti-Helicobacter pylori activity for example, penicillin, ampicillin, erythromycin, clarithromycin, streptomycin, tetracycline, etc.
  • bismuth preparations are used for the treatment of peptic ulcer caused by Helicobacter pylori. .
  • the mechanism of peptic ulcer caused by an imbalance of attack and defense factors such as hyperacidity is different from that caused by Helicobacter pylori as described above.
  • This includes gastrointestinal mucosa such as overdose of ethanol, stress, dysphagia, smoking, and nonsteroidal anti-inflammatory drugs (aspirin, acetaminophen, ibuprofen, indomethacin, etenzamide, tranexamic acid, loxoprofen, etc.)
  • gastric acid which is an attack factor, becomes relatively excessive due to a reduction in the protective power of the stomach and duodenal mucosa, etc., and damages the gastrointestinal mucosa.
  • gastric acid secretion inhibitors and anti-pepsin agents which are attack factor inhibitors, or mucosal protective agents and tissue repair promoters, which are defense factor enhancers, are used for this treatment.
  • the cause of ulcers in the upper body of the stomach and relapsed refractory ulcers seen in elderly people is often a decrease in protective factors, and it is desired to provide an excellent protective factor enhancer.
  • Patent Document 1 a blend of processed potato, carrot and antacid
  • Patent Document 2 a blend of oxon, turmeric and shochu
  • Hihatsu has the scientific name Piper longum L. Or it is called Pipe retrofractum Vahl and is a plant belonging to the genus Pepperaceae.
  • the dried product of immature fruit spikes has been widely used as a spice with an appetite since ancient times.
  • Hihatsu is also known as a herbal medicine with analgesic / healthy stomach action, blood flow increasing action, antibacterial action, etc., and is used as an antibacterial agent against Helicobacter pylori (Patent Document 3) and as a functional gastroenteropathy treatment agent. It is reported that it is effective for use as a cold improver (Patent Document 5), as a swelling improver (Patent Document 6).
  • baboon is an irritating herbal medicine and enhances gastrointestinal function and promotes gastric acid secretion, so it is not used for the treatment of inflammatory or ulcerative diseases.
  • baboons affect nausea, nausea or vomiting due to ethanol overdose.
  • the present inventors have conducted extensive research, and as a result, found that hihatsu has an excellent gastrointestinal mucosal protective action, and that when combined with turmeric, a synergistic effect can be obtained.
  • the present invention has been completed.
  • the inventor has also found that baboon has an excellent antiemetic action against nausea, nausea or vomiting caused by excessive intake of ethanol, and has completed the present invention. That is, the present invention provides a gastrointestinal mucosal protective agent (hereinafter referred to as the gastrointestinal mucosal protective agent of the present invention) containing hihatsu.
  • the present invention provides an antiemetic containing hihatsu (hereinafter referred to as an antiemetic of the present invention).
  • medical agent which has the outstanding digestive tract mucosa protective effect can be provided.
  • a drug having an excellent gastrointestinal mucosal protective action against gastrointestinal mucosal damage caused by ethanol can be provided. It can be effectively applied to the improvement of various unpleasant symptoms such as stomach pain, nausea and stomach weight after ingestion of ethanol.
  • gastrointestinal mucosal damage caused by stress, heavy drinking and eating, smoking, and nonsteroidal anti-inflammatory drugs can be significantly suppressed.
  • the antiemetic which has the improvement effect excellent with respect to nausea, nausea, or vomiting can be provided. More specifically, it is possible to provide an antiemetic having an excellent improving effect on nausea, nausea or vomiting caused by ethanol intake.
  • the present invention has an excellent ameliorating action particularly on gastrointestinal mucosal damage and vomiting caused by ingestion of ethanol, and therefore can be effectively used as an agent for improving discomfort caused by ingestion of ethanol.
  • the gastrointestinal mucosa protective agent or antiemetic of the present invention contains hihatsu.
  • baboon refers to baboon (Piper longum L. (aka: Indiana pepper) or Piper retrofractum Vahl (aka: Javanaga pepper).
  • Hibatsu is also called Naga Pepper (long pepper), and there is a literature that uses Java Naga Pepper as Hihatu modo in order to distinguish it from Hibatsu in a narrow sense, but in the present invention, Treat both as hihatsu.
  • Hibatsu those made from mature or immature fruit spikes, leaves, petioles, branches, roots, etc. are used.
  • the hihatsu used in the present invention is its fruit head or immature fruit head.
  • These can be used in the form of dried extract powder, which has been appropriately dried, or an extract extracted with water, lower alcohol or a mixed solvent thereof.
  • Specific examples include hihatsu, hihatsu powder, hihatsu extract, hihatsu-style extract, hihatsu dried extract, hihatsu soft extract, and the like.
  • Examples of commercially available products include Hihatsu powder (manufactured by Mikuni Co., Ltd.), Hihatsu extract MF (manufactured by Maruzen Pharmaceutical Co., Ltd.), and the like.
  • Hibatsu used in the present invention is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight in terms of the active ingredient based on the preparation. If this blending amount is less than 0.001% by weight, the effect may be low, and if it exceeds 10% by weight, irritation such as pungency becomes strong, which may be undesirable from the viewpoint of taking feeling.
  • the daily use amount of Hihatsu per adult can be used within the range of 5 g / day, preferably 3 g / day, in terms of the active ingredient, but the single dose is usually 0.001 to The amount is preferably 2 g, preferably in the range of 0.01 to 1 g.
  • turmeric can be used in combination.
  • the turmeric in this case is Ginger family turmeric (Curcuma longa (also known as autumn turmeric) or Curcuma aromatica (also known as spring turmeric)).
  • autumn turmeric and spring turmeric can be used, but it is preferable to use autumn turmeric.
  • Turmeric used in the present invention is preferably rhizome as it is or boiled except for pericarp, and further extracted with powdered turmeric powder, water, lower alcohol or a mixed solvent thereof. What was made into the extracted extract is still more preferable.
  • Specific examples include turmeric, turmeric powder, turmeric extract, turmeric extract, turmeric dry extract, turmeric soft extract, and fermented turmeric, and turmeric powder or turmeric extract is preferred.
  • examples of commercially available products include turmeric powder (manufactured by Nippon Powder Chemical Co., Ltd.), turmeric extract (manufactured by Nippon Powder Chemical Co., Ltd., Maruzen Pharmaceutical Co., Ltd.), and the like.
  • turmeric When turmeric is used together in the present invention, it is preferably 0.1 to 60% by weight, more preferably 0.5 to 30% by weight in terms of the active ingredient based on the preparation. If the blending amount is less than 0.1% by weight, the effect may be low. If the blending amount exceeds 60% by weight, the astringency becomes strong, which is not preferable in terms of taking feeling.
  • the amount of turmeric used per day for an adult can be used in the range of 10 g / day, preferably 6 g / day, in terms of the active ingredient, but the single dose is usually 0.01 to 1 in terms of the active ingredient. The amount is preferably 6 g, preferably in the range of 0.1 to 2 g.
  • the weight ratio of baboon to turmeric is preferably 1: 0.01 to 1: 120, and 1: 0.1 to 1:60 in terms of the active ingredient. Is more preferable, and 1: 1 to 1:10 is particularly preferable.
  • the gastrointestinal mucosal protective agent or antiemetic containing the rabbit of the present invention can be used as a remedy for discomfort caused by ingestion of ethanol, either after ingestion of ethanol (especially the next day), before ingestion of ethanol or even during ingestion of ethanol.
  • the gastrointestinal mucosa protective agent or antiemetic of the present invention is preferably taken orally.
  • the gastrointestinal mucosa protective agent of the present invention can be used for the treatment or prevention of gastrointestinal mucosal disorder or peptic ulcer, and in particular, digestive tract mucosal damage after ethanol intake, digestion caused by excessive intake of ethanol.
  • Excellent therapeutic or preventive effects are observed for gastrointestinal ulcers or gastrointestinal mucosal disorders and peptic ulcers caused by stress, heavy drinking and eating, smoking, and nonsteroidal anti-inflammatory drugs.
  • it can be effectively applied to improve unpleasant symptoms such as gastric pain, nausea, and stomach weight after ingestion of ethanol or after stress, heavy drinking and eating, smoking, and taking non-steroidal anti-inflammatory drugs. .
  • the gastrointestinal mucosa includes gastric mucosa or duodenal mucosa.
  • the antiemetic of the present invention is used for suppressing or preventing nausea, nausea or vomiting, and can be applied as an antiemetic for nausea, nausea or vomiting associated with the following causes or diseases.
  • the causes or diseases of nausea, nausea or vomiting include ethanol overdose, stress, motion sickness, food poisoning, cold body, pregnancy (morning), accidental ingestion of foreign bodies, side effects due to drugs, acute gastritis, stomach Duodenal ulcer, appendicitis, bowel obstruction, acute peritonitis, pancreatitis, migraine, Meniere disease, cerebral hemorrhage, brain tumor, subarachnoid hemorrhage, acute cholecystitis, acute hepatitis, alcoholic hepatitis, cholelithiasis, gastric polyp, fatty liver, pneumonia, glaucoma, Or chronic subdural hematoma etc. are mentioned.
  • the gastrointestinal mucosa protective agent or antiemetic of the present invention can be preferably used as a discomfort symptom improving agent by ingesting ethanol.
  • the unpleasant symptom caused by ingestion of ethanol means stomach pain, nausea, stomach weight, nausea, nausea or vomiting caused by ingestion of ethanol.
  • alcohol is synonymous with ethanol.
  • the gastrointestinal mucosa protective agent or antiemetic of the present invention may be used in combination with other gastrointestinal mucosa protective agent or antiemetic.
  • the gastrointestinal mucosa protective agent or antiemetic of the present invention may further contain the following active ingredients and additives as necessary. Active ingredients include other gastrointestinal mucosal protective agents, other antiemetics, blood alcohol level lowering accelerators, antacids, stomachic agents, liver function improving agents, digestive agents, intestinal regulating agents, antipruritics, analgesic antispasmodics, gastric mucosa Examples include restoration agents, vitamins, and antifoaming agents.
  • Examples of the blood alcohol concentration lowering promoter include turmeric, amino acids (alanine, glutamine), rainbow trout, cordyceps, citrus molasses (derived from Wenzhou oranges), ⁇ -lactalbumin, lactulose, maltitol, lactitol, glycerol, oleanolic acid, Presenegenin, Hederagenin, Protoesigenin, Caffeine, Chixetsunin, Kyokyo, Carnitine chloride, Glycylglycine, Pepino, Kuzune, Mung bean, Red bean, Santo, Malt, Kawamata, Kashiwa, Akiko, Sandhi, Light load, Fructose, Ginseng , Komi-sou hot water or Kazuwa-to fermented lactic acid bacteria, guava, dry activated yeast, fructose, ascorbic acid, aroma substance, citric acid, kinin and the like.
  • amino acids alanine, glut
  • antacids include synthetic hydrotalcite, magnesium oxide, magnesium silicate, magnesium aluminate silicate, aluminum silicate, magnesium aluminate metasilicate, magnesium hydroxide, aluminum hydroxide, magnesium alumina hydroxide, dihydroxy Aluminum aminoacetate, sodium hydrogencarbonate, calcium carbonate, magnesium carbonate, calcium hydrogenphosphate, aminoacetic acid, funnel extract and the like can be mentioned.
  • stomachic agent for example, anise, aloe, fennel, yak, turmeric, life-grass, ogon, oak, auren, processed garlic, garlic, cuckoo, columnar root, psoriasis, rice husk, pheasant, keihi, gentian, Koujin, Kokuboku, Goshuyu, Pepper, Colombo, Conzurango, Sanshishi, Salamander, Yamana, Shisoshi, Shukusha, Shokyo, Shozu, Green peel, Ishizone, Centaurium grass, Assembly, Sowjutsu, Soyo, Daisuke, Daio, Takusha, Chiku Setu carrot, clove, chorei, chimpi, capsicum, spruce, animal gall (including yutan), oyster mushroom, nutmeg, carrot, mint (including Atlantic mint), peanut, broomfish, hops, honey extract, rape leaves (Saisai), Mokk
  • liver function improving agent examples include, for example, liver hydrolyzate, Maria thistle, Tabana carrot, turmeric, indigo, dandelion, western dandelion, burdock, garlic, chrysanthemum, yarrow, gardenia, sesame, asparagus, onion, chicory, Medicinal salvia, Korean thistle (artichoke), wolfberry, legumes / iridaceae / rose family plants (eg, soybeans and kudzu, asparagus linearias belonging to legumes), Japanese quail, elba de pasarinho, cetesangria, red buds, Black tea, Saiko, Peach seed, Peony skin, Safflower, Sanjyo, Gadju, ⁇ -lipoic acid, Flavonols, Flavones, Flavans, Flavanols, Catechins, Isoflavones, Lignanoic acid, Curcuminoids, Gluterin, Prolamin, Glutathione
  • Examples of the digestive agent include starch digestive enzyme, protein digestive enzyme, fat digestive enzyme, fibrin digestive enzyme, ursodesoxycholic acid, oxycoranoates, cholic acid, bile powder, bile extract (powder), dehydrocol Acid, animal gall (including yutan) and the like.
  • intestinal adjusting agent examples include live intestinal fungi components, natto kinase, akame koji, asenyaku, aloe, ubai, ketsumeishi, genokosho, plantago obata and the like.
  • Antidiarrheal agents include, for example, acrinol, berberine chloride, guaiacol, creosote, phenyl salicylate, guaiacol carbonate, berberine tannate, bismuth hyposalicylate, bismuth nitrate, bismuth carbonate, bismuth gallate, tannic acid, albumin tannate , Methylene thymol tannin, kaolin, pectin, medicinal charcoal, calcium lactate, Acacia yam, buckwheat, duckweed, auren, kudin, ganodermone, pentaploid, hawthorn, yellowtail, ivy.
  • analgesic and antispasmodic agents include oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, methyl atropine bromide, methyl anisotropine bromide, methyl scopolamine bromide, butyl scopolamine bromide, methyl bromide- l-hyostiamine, methylbenactidium bromide, belladonna extract, belladonna total alkaloid, iodopropamide, diphenylpiperidinomethyldioxolane iodide, funnel extract, funnel root total alkaloid citrate, papaverine hydrochloride, engosac, licorice, Examples include kokuboku and peonies.
  • gastric mucosa repairing agent examples include sodium azulenesulfonate, aldioxa, glycyrrhizic acid and salts thereof, and licorice extract, L-glutamine, copper chlorophyllin potassium, copper chlorophyllin sodium, histidine hydrochloride, porcine gastric wall pepsin degradation product, porcine gastric wall acid Hydrolysates, methylmethionine sulfonium chloride, red buds, engosac, licorice, sucralfate, rebamipide, marzulene, polaprezinc, sodium alginate, gefarnate, teprenone, troxipide, benexate betadex, prunotol, irsogladine maleate, sofalcone, etc. It is done.
  • vitamins include nicotinic acid amide, calcium pantothenate, biotin, vitamin B 1 or a derivative or salt thereof, vitamin B 2 or a derivative or salt thereof, vitamin B 6 or a derivative or salt thereof, vitamin C or Examples thereof include vitamin E or a derivative thereof or a salt thereof.
  • antifoaming agent examples include dimethylpolysiloxane.
  • antiemetics include, for example, granisetron, domperidone, sulpiride, ondansetron, azasetron, dimenhydrinate, metoclopramide, chlorpromazine, diphenidol hydrochloride, diphenhydramine, diphenhydramine hydrochloride, meclizine, promethazine, chlorpheniramine, chlorpheniline maleate Lamin, amphetamine, atropine, bromvalerylurea, allylisopropylacetylurea, caffeine, theophylline, mint oil, menthol, vitamin B6 and the like can be mentioned.
  • Additives include physiologically excipients, binders, disintegrants, lubricants, stabilizers, thickeners, solubilizers, preservatives, pH adjusters, colorants, sweeteners, etc. There are various acceptable types.
  • excipient examples include lactose, starches, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid and the like.
  • binder examples include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan and the like.
  • disintegrant examples include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, and low-substituted hydroxypropylcellulose.
  • Examples of the lubricant include magnesium stearate and talc.
  • the stabilizer examples include ascorbic acid, edetic acid, and salts thereof.
  • thickener examples include carmellose sodium, agar, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and the like.
  • solubilizer examples include nonionic surfactants such as hydrogenated oil, glyceryl monostearate, polyoxyethylene hydrogenated castor oil, and sucrose fatty acid ester, and lecithin.
  • preservative examples include benzoic acid, sodium benzoate, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, isobutyl paraoxybenzoate and the like.
  • pH adjuster examples include citric acid, malic acid, lactic acid, tartaric acid, acetic acid, hydrochloric acid, phosphoric acid, and salts thereof, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, and the like.
  • Examples of the colorant include titanium oxide, tar pigment, yellow No. 4, yellow No. 5, ferric oxide, yellow ferric oxide, red No. 3 and the like.
  • sweetening agent examples include sucrose, liquid sugar, fructose, fructose glucose liquid sugar, reduced maltose water candy, honey, caramel, sorbitol, maltitol, xylitol, erythritol, sucralose, stevia, glycyrrhizic acid or a salt thereof, aspartame, acesulfame Potassium etc. are mentioned.
  • the gastrointestinal mucosa protective agent or antiemetic of the present invention can be taken alone, or it can be contained in a pharmaceutical composition together with other active ingredients and additives, or in the form of a food additive or food supplement. It can also be used as a health food and drink by containing it in various foods and drinks. Moreover, according to the objective of this invention, it can manufacture in dosage forms, such as a liquid agent, a powder, a granule, a tablet, a chewable tablet, a film-coated tablet, a sugar-coated tablet, a soft capsule, a hard capsule, and a jelly agent by a well-known and usual technique.
  • the gastrointestinal mucosal protective agent of the present invention pharmaceuticals or foods and drinks containing the same are used to improve gastrointestinal mucosal damage caused by alcohol consumption, stress, overdrinking, smoking, and taking non-steroidal anti-inflammatory drugs, etc.
  • An indication that it is used for prevention may be attached. For example, indications such as “to prevent or alleviate stomach pain, nausea, stomach weight, etc.”, “drink before drinking alcohol to prevent nausea”, “energetic next day after drinking”, etc.
  • such a display can be attached to the container packaging means by a known method, whereby the gastrointestinal mucosa protective agent of the present invention, the pharmaceutical or food or drink containing the same, alcohol intake, stress, overdrinking, Since it is clearly stated that it is used for the improvement and / or prevention of gastrointestinal mucosal damage caused by smoking and taking non-steroidal anti-inflammatory drugs, etc. Becomes clear.
  • the antiemetic of the present invention medicines or foods and drinks containing the same may be labeled for use in the improvement and / or prevention of nausea, nausea or vomiting caused by alcohol consumption.
  • indications such as “to prevent or relieve nausea, nausea and vomiting”, “prevent nausea by drinking before drinking”, “energetic next day after drinking”, etc.
  • a display can be attached to the container and packaging means by a publicly known method, whereby the antiemetic of the present invention, a medicine containing the same, or a food or drink can improve various symptoms caused by alcohol intake and / or Or, since it is clearly indicated that it is used for prevention, the distinction from normal agents, pharmaceuticals or foods and drinks becomes clear.
  • Test Example 1 Effect on gastric mucosal damage model A Wistar male rat (8 weeks old) fasted overnight with a suspension of the test substance in physiological saline (but only physiological saline as a control) Oral administration (5 mL / kg) was performed, and 30 minutes later, 99.5 vol% ethanol was orally administered at 1 mL / animal. One hour after ethanol administration, the stomach was removed, fixed with 1% by volume formalin, the stomach was cut open, and the length of damage (damage factor) occurring in the gastric mucosa was measured.
  • test substances were control (saline), turmeric powder (autumn turmeric) 600 mg / kg, chickweed powder (Jawa Naga pepper) 150 mg / kg, and turmeric powder (autumn turmeric) 600 mg / kg + hihatsu powder (Jawa Naga pepper) )
  • test substances were control (saline), turmeric powder (autumn turmeric) 600 mg / kg, chickweed powder (Jawa Naga pepper) 150 mg / kg, and turmeric powder (autumn turmeric) 600 mg / kg + hihatsu powder (Jawa Naga pepper) )
  • Four groups of 150 mg / kg combined. The result of the gastric mucosa damage inhibitory effect when each test substance is administered is shown in FIG.
  • turmeric powder 600 mg / kg suppressed the occurrence of ulcers
  • hihatsu powder 150 mg / kg exhibited an antiulcer action superior to that of the control.
  • a further superior anti-ulcer action was confirmed as compared with chickpea powder 150 mg / kg alone.
  • the average ulcer index of each group was 0.50 in the turmeric powder group and 0.26 in the chickweed powder group when the control was 1, and the product (0.13) was 0.
  • turmeric The anti-ulcer action of baboon was greatly promoted by combined use with turmeric (Burgi method: Keijiro Takagi et al .: Pharmacology, 1987, Nanzan-do). From the above, it was shown that both turmeric and baboon have excellent gastric mucosal protective action against gastric mucosal damage caused by ethanol intake. It was also shown that when turmeric and hihatsu were administered in combination, both components acted synergistically to provide an excellent gastric mucosa protective effect. In this example, in order to create a gastric mucosal damage model, ethanol was used to induce ulcers, but not limited to ethanol, such as stress, heavy drinking and eating, smoking, and after taking nonsteroidal anti-inflammatory drugs, etc. It has the same effect on ulcers caused by factors.
  • Example 1 Preparation of a Japanese pine plant formulation To 10 mL of purified water, 50 mg of pine powder, 45 mg of oxoamidin powder, 135 mg of carrot dry extract, 200 mg of turmeric powder, 0.3 mL of lauren extract, 100 mg of dried gentian powder, 82 mg of licorice extract powder were added. (Formulation liquid 1). Separately, 1.5 g of purified white sugar and 0.09 g of polyvinylpyrrolidone were added to 10 mL of purified water, and this was heated and dissolved. This liquid was mixed with the preparation liquid 1 prepared above, and sodium citrate was added to adjust the pH to 5. An appropriate amount of purified water was added thereto to make a total volume of 50 mL to obtain an internal solution.
  • Formulation liquid 1 Separately, 1.5 g of purified white sugar and 0.09 g of polyvinylpyrrolidone were added to 10 mL of purified water, and this was heated and dissolved. This liquid was mixed with the preparation liquid 1
  • Comparative Example 1 Preparation of a non-hihatsu formulation Water was used as a control.
  • Comparative Example 2 Preparation of non-hihatsu formulation Solmac Plus (Takuma Pharmaceutical Co., Ltd.) was used.
  • Solmac Plus includes turmeric extract 0.3 mL, licorice extract 135 mg, carrot extract 0.5 mL, aurin tincture 0.826 mL, clove tincture 0.126 mL, gentian tincture 0.376 mL, and sojutsu extract 1.2 mL, cinnamon tincture 0.25 mL, and carnitine chloride 120 mg are blended.
  • Test Example 2 Evaluation of antiemetic effect Obtained in Example 1, Comparative Example 1 or Comparative Example 2 using an 11-month-old male Suncus (Suncus murinus) that was given food (CIEA-312) and water freely.
  • n 6 for each group.
  • 40% ethanol was further orally administered to 5 mg / kg, and the vomiting reaction to the test sunx was observed for 60 minutes after ethanol administration. In this experiment, when there was vomiting of the stomach contents, it was considered that there was a vomiting reaction.
  • Example 1 containing hihatsu had fewer vomiting times than Comparative Examples 1 and 2.
  • the time to show vomiting reaction was also reduced. Based on these results, it was shown that the inclusion of baboon has the effect of suppressing the vomiting reaction itself, not the delay of the vomiting reaction, and can contribute to quick recovery from unpleasant conditions such as nausea, nausea or vomiting. .
  • the following production examples 1 to 4 show production examples of the gastrointestinal mucosa protective agent or antiemetic of the present invention.
  • 450 parts by weight of dry aluminum hydroxide gel, 325 parts by weight of magnesium hydroxide, 450 parts by weight of synthetic hydrotalcite, 75 parts by weight of licorice extract powder, 200 parts by weight of fennel powder, 200 parts by weight of turmeric powder (autumn turmeric), carrot A kneaded product was prepared by adding 800 parts by mass of 70% ethanol to a mixed powder comprising 20 parts by mass of a dry extract, 70 parts by mass of polyvinyl alcohol, 30 parts by mass of carmellose calcium, 40 parts by mass of crystalline cellulose, and 1545 parts by mass of xylitol.
  • the kneaded product was extruded and granulated ( ⁇ 0.8 mm), dried, sized and classified to obtain granules (hereinafter referred to as B granules). Further, 6 parts by mass of L-menthol was adsorbed on 24 parts by mass of magnesium aluminate metasilicate to obtain a fragrance powder (hereinafter referred to as C fragrance powder). 165 parts by mass of A granule, 3405 parts by mass of B granule, and 30 parts by mass of C fragrance powder were mixed by a mixer, and further packed by a packaging machine to obtain a granule having a single dose of 1.2 g.
  • 450 parts by weight of dry aluminum hydroxide gel, 325 parts by weight of magnesium hydroxide, 450 parts by weight of synthetic hydrotalcite, 75 parts by weight of licorice extract powder, 200 parts by weight of fennel powder, 200 parts by weight of turmeric powder (autumn turmeric), show Add 700 parts by mass of 90% ethanol to a mixed powder consisting of 100 parts by mass of carp powder, 20 parts by mass of dried carrot extract, 90 parts by mass of hydroxypropyl cellulose, 30 parts by mass of carmellose calcium, 30 parts by mass of crystalline cellulose, and 1445 parts by mass of erythritol. A kneaded product was made.
  • the kneaded product was dried and sized to obtain granules (hereinafter referred to as B granules). Further, 4 parts by mass of L-menthol was adsorbed on 16 parts by mass of magnesium aluminate metasilicate to obtain a fragrance powder (hereinafter referred to as C fragrance powder). 165 parts by mass of A granules, 3415 parts by mass of B granules, and 20 parts by mass of C fragrance powder were mixed with a mixer, and further packaged with a packaging machine to obtain a granule having a single dose of 1.2 g.
  • the gastrointestinal protective agent of the present invention contains baboon, gastrointestinal mucosal damage or peptic ulcer caused by excessive intake of ethanol, stress, violent eating and eating, smoking, and taking non-steroidal anti-inflammatory drugs, etc. Has an excellent preventive and / or therapeutic effect. Furthermore, a synergistic effect is acquired by using turmeric together. Moreover, the antiemetic of this invention has the antiemetic effect excellent with respect to nausea, nausea, or vomiting by containing a hihatsu. In particular, it has an excellent antiemetic action against nausea, nausea or vomiting caused by excessive intake of alcohol, and these symptoms can be quickly improved.

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Abstract

Provided is a medicinal agent which has an excellent effect of preventing/treating gastrointestinal mucosal damage or peptic ulcer induced by the excessive ingestion of ethanol, stress, excessive eating/drinking, smoking, the take of a non-steroidal anti-inflammatory agent and the like, and also has an excellent anti-emetic effect on a feeling of sickness, nausea or vomiting induced by the excessive ingestion of an alcohol. A gastrointestinal mucosa-protecting agent or an anti-emetic agent is prepared by adding Indian long pepper to a preparation. When turmeric is added to the gastrointestinal mucosa-protecting agent, a synergistic effect can be achieved.

Description

ヒハツ配合製剤Hihitsu formulation
　本発明は、優れた消化管粘膜保護作用及び鎮吐作用を有する薬剤に関する。より詳細にはエタノールの過剰摂取、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用等による消化管粘膜障害に対する優れた消化管粘膜保護作用及びエタノールの過剰摂取による吐き気、悪心又は嘔吐に対して優れた鎮吐作用を有する薬剤に関する。 The present invention relates to a drug having an excellent gastrointestinal mucosa protective action and antiemetic action. More specifically, excellent gastrointestinal mucosal protective action against gastrointestinal mucosal damage due to ethanol overdose, stress, overdose, smoking, and nonsteroidal anti-inflammatory drugs, and nausea, nausea or The present invention relates to a drug having an excellent antiemetic action against vomiting.
　消化性潰瘍は、胃液にさらされている範囲内の消化管粘膜の局所組織の欠損である。その発生要因については、グラム陰性棹菌であるヘリコバクター・ピロリとの関連性（非特許文献１）や、攻撃因子と防御因子のバランスの崩れによるというＳｈａｙのバランス説（非特許文献２）が知られている。 Peptic ulcer is a defect in the local tissue of the gastrointestinal mucosa within the area exposed to gastric juice. As for the cause of this, the relationship with Helicobacter pylori, a gram-negative bacilli (Non-patent Document 1), and Shay's balance theory (Non-patent Document 2), which is caused by an imbalance between the attack and defense factors, are known. It has been.
　上記の要因のうち、ヘリコバクター・ピロリによる消化性潰瘍の発生メカニズムについては、ヘリコバクター・ピロリが有する強いウレアーゼ活性により胃内で生じたアンモニアが、胃酸を中和することによって、酸による殺菌を免れたピロリが胃粘膜に定着し、そこで増殖したピロリが胃粘膜に対して障害を与えるためと考えられていた。その後も種々の検討が加えられ、ヘリコバクター・ピロリはモノクロラミンの発生やインターロイキン８の産生にも関与していることが報告され、それらによっても胃粘膜障害が起こるとされている（非特許文献３、非特許文献４）。 Among the above factors, regarding the mechanism of peptic ulcers caused by Helicobacter pylori, ammonia generated in the stomach due to the strong urease activity of Helicobacter pylori was able to avoid sterilization by acid by neutralizing gastric acid. It was thought that H. pylori settled in the gastric mucosa, and the H. pylori grown there would damage the gastric mucosa. Various studies have been made since then, and it has been reported that Helicobacter pylori is also involved in the generation of monochloramine and the production of interleukin 8, which also causes gastric mucosal damage (non-patent literature). 3, Non-Patent Document 4).
　そのため、ヘリコバクター・ピロリによる消化性潰瘍の治療には、抗ヘリコバクター・ピロリ活性を有する抗生物質（例えばペニシリン、アンピシリン、エリスロマイシン、クラリスロマイシン、ストレプトマイシン、テトラサイクリン等）や、ビスマス製剤等が用いられている。 Therefore, antibiotics having anti-Helicobacter pylori activity (for example, penicillin, ampicillin, erythromycin, clarithromycin, streptomycin, tetracycline, etc.) and bismuth preparations are used for the treatment of peptic ulcer caused by Helicobacter pylori. .
　他方、胃酸過多等の攻撃因子と防御因子のバランスの崩れによって引き起こされる消化性潰瘍は、上述したヘリコバクター・ピロリによるものとはメカニズムが異なる。これは、エタノールの過剰摂取、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬（アスピリン、アセトアミノフェン、イブプロフェン、インドメタシン、エテンザミド、トラネキサム酸、ロキソプロフェン等）の服用等による消化管粘膜（胃・十二指腸粘膜等）の保護力低下等により、攻撃因子となる胃酸が相対的に過剰になり、消化管粘膜を損傷させるために起こるのである。 On the other hand, the mechanism of peptic ulcer caused by an imbalance of attack and defense factors such as hyperacidity is different from that caused by Helicobacter pylori as described above. This includes gastrointestinal mucosa (such as overdose of ethanol, stress, dysphagia, smoking, and nonsteroidal anti-inflammatory drugs (aspirin, acetaminophen, ibuprofen, indomethacin, etenzamide, tranexamic acid, loxoprofen, etc.) This occurs because gastric acid, which is an attack factor, becomes relatively excessive due to a reduction in the protective power of the stomach and duodenal mucosa, etc., and damages the gastrointestinal mucosa.
　そのため、この治療には攻撃因子抑制剤である胃酸分泌抑制剤や抗ペプシン剤、又は防御因子増強剤である粘膜保護剤や組織修復促進剤等が用いられている。 For this reason, gastric acid secretion inhibitors and anti-pepsin agents, which are attack factor inhibitors, or mucosal protective agents and tissue repair promoters, which are defense factor enhancers, are used for this treatment.
　一般的に、高齢者にみられる胃体上部の潰瘍や再発難治性の潰瘍の原因は防御因子の低下であることが多く、優れた防御因子増強剤の提供が望まれている。 Generally, the cause of ulcers in the upper body of the stomach and relapsed refractory ulcers seen in elderly people is often a decrease in protective factors, and it is desired to provide an excellent protective factor enhancer.
　また、エタノールの過剰摂取は、もたれ、吐き気、二日酔い等の不快な諸症状を引き起こす事が知られている。そのため、これら不快な諸症状を改善するために、生薬や制酸剤等を組み合わせた胃腸薬が多数市販されている。しかし、未だ十分な効果が得られないといった問題から、新たな薬剤の研究が種々行われている。そのような研究としては、例えば、加工大蒜、ニンジン及び制酸剤を配合したもの（特許文献１）、オウゴン、ウコン及びショウキョウを配合したもの（特許文献２）等が知られている。しかし、これらの研究では、十分な効果が得られているとは言い難い。また、十分な効果を得るためには服用量を多くする必要があり、それに伴うコンプライアンスの低下や他の薬効成分の配合の制限等の問題を生じ、必ずしも満足のいくものではない。
　特に、吐き気、悪心又は嘔吐を伴うほど過剰にエタノールを摂取してしまった場合、身体的な苦痛が大きく、回復までにより長い時間が必要になる。そのため、エタノールの過剰摂取による吐き気、悪心又は嘔吐に対して優れた鎮吐作用を有する薬剤の提供が望まれている。 Moreover, it is known that excessive intake of ethanol causes unpleasant symptoms such as leaning, nausea and hangover. Therefore, in order to improve these unpleasant symptoms, many gastrointestinal drugs combined with herbal medicines, antacids and the like are on the market. However, various researches on new drugs have been conducted due to the problem that sufficient effects are not yet obtained. As such researches, for example, a blend of processed potato, carrot and antacid (Patent Document 1), a blend of oxon, turmeric and shochu (Patent Document 2) are known. However, it cannot be said that sufficient effects have been obtained in these studies. In addition, in order to obtain a sufficient effect, it is necessary to increase the dose, which causes problems such as a decrease in compliance and restrictions on the combination of other medicinal ingredients, which are not always satisfactory.
In particular, if you consume too much ethanol with nausea, nausea, or vomiting, your physical distress will be greater and will require more time to recover. Therefore, it is desired to provide a drug having an excellent antiemetic action against nausea, nausea or vomiting due to excessive intake of ethanol.
　ところで、ヒハツとは学名をＰｉｐｅｒ　ｌｏｎｇｕｍ　Ｌ．又はＰｉｐｅｒ　ｒｅｔｒｏｆｒａｃｔｕｍ　Ｖａｈｌと称し、コショウ科コショウ属の植物である。その未成熟果穂の乾燥物は、辛味性で古来より食欲亢進の香辛料として広く用いられている。また、ヒハツは鎮痛・健胃作用、血流増加作用、抗菌作用などを有する生薬としても知られており、ヘリコバクター・ピロリに対する抗菌剤としての使用（特許文献３）や機能性胃腸症治療剤としての使用（特許文献４）、冷え性改善剤としての使用（特許文献５）、むくみの改善剤としての使用（特許文献６）、に有効であることが報告されている。 By the way, Hihatsu has the scientific name Piper longum L. Or it is called Pipe retrofractum Vahl and is a plant belonging to the genus Pepperaceae. The dried product of immature fruit spikes has been widely used as a spice with an appetite since ancient times. Hihatsu is also known as a herbal medicine with analgesic / healthy stomach action, blood flow increasing action, antibacterial action, etc., and is used as an antibacterial agent against Helicobacter pylori (Patent Document 3) and as a functional gastroenteropathy treatment agent. It is reported that it is effective for use as a cold improver (Patent Document 5), as a swelling improver (Patent Document 6).
　しかし、ヒハツは刺激性のある生薬であり、かつ胃腸の働きを亢進させ胃酸分泌を促進させるため、炎症性又は潰瘍性の疾患の治療には使用されていない。
　また、ヒハツがエタノールの過剰摂取等による吐き気、悪心又は嘔吐に対してどのような影響を与えるかについては知られていない。 However, baboon is an irritating herbal medicine and enhances gastrointestinal function and promotes gastric acid secretion, so it is not used for the treatment of inflammatory or ulcerative diseases.
In addition, it is not known how baboons affect nausea, nausea or vomiting due to ethanol overdose.
特開平８－９９８９０号公報JP-A-8-99890 特開２００３－２２６６５０号公報JP 2003-226650 A 特開２０００－１５４１４６号公報JP 2000-154146 A 特開２００６－３２７９９９号公報JP 2006-327999 A 特開２００３－０４０７８８号公報JP 2003-040788 A 特開２００６－１０４１０９号公報JP 2006-104109 A
　本発明の目的は、優れた消化管粘膜保護作用を有する薬剤を提供することを目的とする。より詳細には、エタノールの過剰摂取、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用等による消化管粘膜障害による消化管粘膜障害に対する優れた消化管粘膜保護作用を有する薬剤を提供することを目的とする。
　また、本発明は、エタノールの過剰摂取等による吐き気、悪心又は嘔吐に対して優れた鎮吐作用を有する薬剤を提供することを目的とする。 An object of the present invention is to provide a drug having an excellent gastrointestinal mucosa protective action. More specifically, a drug having an excellent gastrointestinal mucosal protective action against gastrointestinal mucosal damage due to gastrointestinal mucosal damage caused by excessive intake of ethanol, stress, overdrinking, smoking, and taking nonsteroidal anti-inflammatory drugs, etc. The purpose is to provide.
Another object of the present invention is to provide a drug having an excellent antiemetic action against nausea, nausea or vomiting due to excessive intake of ethanol or the like.
　斯かる実情に鑑み、本発明者は鋭意研究を行った結果、意外にもヒハツが優れた消化管粘膜保護作用を有すること、及び、さらにウコンを併用すると相乗的な効果が得られることを見出し、本発明を完成した。また本発明者は、ヒハツにエタノールの過剰摂取によってもたらされる吐き気、悪心又は嘔吐に対して優れた鎮吐作用があることをも見出し、本発明を完成した。
　すなわち、本発明は、ヒハツを含有する消化管粘膜保護剤（以下、本発明の消化管粘膜保護剤と呼ぶ）を提供するものである。また、本発明は、ヒハツを含有する鎮吐剤（以下、本発明の鎮吐剤と呼ぶ）を提供するものである。 In view of such circumstances, the present inventors have conducted extensive research, and as a result, found that hihatsu has an excellent gastrointestinal mucosal protective action, and that when combined with turmeric, a synergistic effect can be obtained. The present invention has been completed. The inventor has also found that baboon has an excellent antiemetic action against nausea, nausea or vomiting caused by excessive intake of ethanol, and has completed the present invention.
That is, the present invention provides a gastrointestinal mucosal protective agent (hereinafter referred to as the gastrointestinal mucosal protective agent of the present invention) containing hihatsu. In addition, the present invention provides an antiemetic containing hihatsu (hereinafter referred to as an antiemetic of the present invention).
　本発明によれば、優れた消化管粘膜保護作用を有する薬剤を提供できる。特に、エタノール摂取後の消化管粘膜障害を有意に抑制することができるため、エタノールによる消化管粘膜障害に対して優れた消化管粘膜保護作用を有する薬剤を提供できる。そして、エタノール摂取後の胃痛、むかつき、胃重等の不快な諸症状の改善に有効に適用することができる。また、エタノール摂取に起因するものに限らず、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用等による消化管粘膜障害も有意に抑制することができる。
　また、本発明によれば、吐き気、悪心又は嘔吐に対して優れた改善作用を有する鎮吐剤を提供することができる。より詳細には、エタノール摂取によってもたらされる吐き気、悪心又は嘔吐に対して優れた改善作用を有する鎮吐剤を提供することができる。
　本発明は、特にエタノール摂取によりもたらされる消化管粘膜障害及び嘔吐に対して優れた改善作用を有するため、これらのエタノール摂取による不快症状の改善剤として有効に利用できる。 ADVANTAGE OF THE INVENTION According to this invention, the chemical | medical agent which has the outstanding digestive tract mucosa protective effect can be provided. In particular, since gastrointestinal mucosal damage after ingestion of ethanol can be significantly suppressed, a drug having an excellent gastrointestinal mucosal protective action against gastrointestinal mucosal damage caused by ethanol can be provided. It can be effectively applied to the improvement of various unpleasant symptoms such as stomach pain, nausea and stomach weight after ingestion of ethanol. In addition, not only those caused by ethanol intake, but also gastrointestinal mucosal damage caused by stress, heavy drinking and eating, smoking, and nonsteroidal anti-inflammatory drugs can be significantly suppressed.
Moreover, according to this invention, the antiemetic which has the improvement effect excellent with respect to nausea, nausea, or vomiting can be provided. More specifically, it is possible to provide an antiemetic having an excellent improving effect on nausea, nausea or vomiting caused by ethanol intake.
The present invention has an excellent ameliorating action particularly on gastrointestinal mucosal damage and vomiting caused by ingestion of ethanol, and therefore can be effectively used as an agent for improving discomfort caused by ingestion of ethanol.
エタノール誘発胃粘膜損傷マウスに各試験物質を投与した場合の潰瘍指数を表すグラフである。It is a graph showing the ulcer index | exponent at the time of administering each test substance to the ethanol induced gastric mucosa damage mouse | mouth.
　本発明の消化管粘膜保護剤又は鎮吐剤は、ヒハツを含有する。
　本発明においてヒハツとは、コショウ科に属するヒハツ（Ｐｉｐｅｒ　ｌｏｎｇｕｍ　Ｌ．（別名：インドナガコショウ）又はＰｉｐｅｒ　ｒｅｔｒｏｆｒａｃｔｕｍ　Ｖａｈｌ（別名：ジャワナガコショウ、ヒハツモドキ））を意味する。
　なお、ヒハツはナガコショウ（ロングペッパー）とも呼ばれ、植物分類学的に、狭義にはインドナガコショウをヒハツとし、それと区別するためにジャワナガコショウをヒハツモドキとする文献もあるが、本発明では両方をヒハツとして扱う。
　上記のヒハツは、成熟した、または未成熟の果穂、葉、葉柄、枝、根等を原料としたものが用いられる。
　本発明で使用するヒハツは、その果穂又は未成熟果穂であることが好ましい。これらは、適宜、乾燥させて粉末にしたヒハツ末や、水、低級アルコール又はそれらの混合溶媒で抽出した抽出エキスとしたものを使用できる。具体的には、ヒハツ、ヒハツ末、ヒハツエキス、ヒハツ流エキス、ヒハツ乾燥エキス、ヒハツ軟稠エキス等が挙げられ、ヒハツ末であることが好ましい。市販品としては、例えば、ヒハツ末（三國株式会社製）、ヒハツエキスＭＦ（丸善製薬株式会社製）等が挙げられる。
　本発明で使用するヒハツは、製剤に対して原生薬換算量で０．００１～１０重量％であるのが好ましく、０．０１～５重量％であるのがさらに好ましい。この配合量が０．００１重量％未満では、効果が低くなる場合があり、１０重量％を超えると辛み等の刺激が強くなり、服用感の面で好ましくない場合がある。
　なお、成人１日当りのヒハツの使用量は原生薬換算量で通常５ｇ／日、好ましくは３ｇ／日までの範囲で使用できるが、１回服用量は、原生薬換算量で通常０．００１～２ｇ、好ましくは０．０１～１ｇの範囲にすることが好ましい。 The gastrointestinal mucosa protective agent or antiemetic of the present invention contains hihatsu.
In the present invention, baboon refers to baboon (Piper longum L. (aka: Indiana pepper) or Piper retrofractum Vahl (aka: Javanaga pepper).
In addition, Hibatsu is also called Naga Pepper (long pepper), and there is a literature that uses Java Naga Pepper as Hihatu modo in order to distinguish it from Hibatsu in a narrow sense, but in the present invention, Treat both as hihatsu.
As the above-mentioned Hibatsu, those made from mature or immature fruit spikes, leaves, petioles, branches, roots, etc. are used.
It is preferable that the hihatsu used in the present invention is its fruit head or immature fruit head. These can be used in the form of dried extract powder, which has been appropriately dried, or an extract extracted with water, lower alcohol or a mixed solvent thereof. Specific examples include hihatsu, hihatsu powder, hihatsu extract, hihatsu-style extract, hihatsu dried extract, hihatsu soft extract, and the like. Examples of commercially available products include Hihatsu powder (manufactured by Mikuni Co., Ltd.), Hihatsu extract MF (manufactured by Maruzen Pharmaceutical Co., Ltd.), and the like.
Hibatsu used in the present invention is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight in terms of the active ingredient based on the preparation. If this blending amount is less than 0.001% by weight, the effect may be low, and if it exceeds 10% by weight, irritation such as pungency becomes strong, which may be undesirable from the viewpoint of taking feeling.
In addition, the daily use amount of Hihatsu per adult can be used within the range of 5 g / day, preferably 3 g / day, in terms of the active ingredient, but the single dose is usually 0.001 to The amount is preferably 2 g, preferably in the range of 0.01 to 1 g.
　また、本発明の消化管粘膜保護剤においては、ウコンを併用することができる。この場合におけるウコンとは、ショウガ科ウコン（Ｃｕｒｃｕｍａ　ｌｏｎｇａ（別名：秋ウコン）、又はＣｕｒｃｕｍａ　ａｒｏｍａｔｉｃａ（別名：春ウコン））のことである。本発明では秋ウコン及び春ウコンいずれも使用することができるが、秋ウコンを使用することが好ましい。
　本発明で使用するウコンは、根茎をそのまま、又は周皮を除き湯通ししたものであることが好ましく、さらにそれを乾燥させて粉末にしたウコン末や、水、低級アルコール又はそれらの混合溶媒で抽出した抽出エキスにしたものがさらに好ましい。具体的には、ウコン、ウコン末、ウコンエキス、ウコン流エキス、ウコン乾燥エキス、ウコン軟稠エキス、発酵ウコン等が挙げられ、ウコン末又はウコン流エキスであることが好ましい。市販品としては、例えば、ウコン末（日本粉末薬品株式会社製）、ウコン流エキス（日本粉末薬品株式会社製、丸善製薬株式会社製）等が挙げられる。 In the gastrointestinal mucosa protective agent of the present invention, turmeric can be used in combination. The turmeric in this case is Ginger family turmeric (Curcuma longa (also known as autumn turmeric) or Curcuma aromatica (also known as spring turmeric)). In the present invention, both autumn turmeric and spring turmeric can be used, but it is preferable to use autumn turmeric.
Turmeric used in the present invention is preferably rhizome as it is or boiled except for pericarp, and further extracted with powdered turmeric powder, water, lower alcohol or a mixed solvent thereof. What was made into the extracted extract is still more preferable. Specific examples include turmeric, turmeric powder, turmeric extract, turmeric extract, turmeric dry extract, turmeric soft extract, and fermented turmeric, and turmeric powder or turmeric extract is preferred. Examples of commercially available products include turmeric powder (manufactured by Nippon Powder Chemical Co., Ltd.), turmeric extract (manufactured by Nippon Powder Chemical Co., Ltd., Maruzen Pharmaceutical Co., Ltd.), and the like.
　本発明でウコンを併用する場合には、製剤に対して、原生薬換算量で０．１～６０重量％であるのが好ましく、０．５～３０重量％であるのがさらに好ましい。この配合量が０．１重量％未満では効果が低くなる場合があり、また６０重量％を超えると、渋味が強くなり服用感の面で好ましくない。
　なお、成人１日当りのウコンの使用量は原生薬換算量で通常１０ｇ／日、好ましくは６ｇ／日までの範囲で使用できるが、１回服用量は、原生薬換算量で通常０．０１～６ｇ、好ましくは０．１～２ｇの範囲にすることが好ましい。 When turmeric is used together in the present invention, it is preferably 0.1 to 60% by weight, more preferably 0.5 to 30% by weight in terms of the active ingredient based on the preparation. If the blending amount is less than 0.1% by weight, the effect may be low. If the blending amount exceeds 60% by weight, the astringency becomes strong, which is not preferable in terms of taking feeling.
In addition, the amount of turmeric used per day for an adult can be used in the range of 10 g / day, preferably 6 g / day, in terms of the active ingredient, but the single dose is usually 0.01 to 1 in terms of the active ingredient. The amount is preferably 6 g, preferably in the range of 0.1 to 2 g.
　本発明において、ウコンを併用する場合、ヒハツとウコンの重量比としては、原生薬換算量で１：０．０１～１：１２０であるのが好ましく、１：０．１～１：６０であるのがさらに好ましく、１：１～１：１０であるのが特に好ましい。 In the present invention, when turmeric is used in combination, the weight ratio of baboon to turmeric is preferably 1: 0.01 to 1: 120, and 1: 0.1 to 1:60 in terms of the active ingredient. Is more preferable, and 1: 1 to 1:10 is particularly preferable.
　本発明のヒハツを含有する消化管粘膜保護剤又は鎮吐剤は、エタノール摂取による不快症状改善剤として使用することができ、エタノール摂取後（特に翌日）でも、エタノール摂取前でも、或はエタノール摂取中でも服用でき、不快感、或はその予防の期待程度に応じて１日当り１～３回に分けて服用することができる。また、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用等による胃痛、むかつき、胃重、吐き気、悪心又は嘔吐等の不快な諸症状にみまわれた場合には、その都度服用してもよく、予防としてあらかじめ服用しておいてもよい。 The gastrointestinal mucosal protective agent or antiemetic containing the rabbit of the present invention can be used as a remedy for discomfort caused by ingestion of ethanol, either after ingestion of ethanol (especially the next day), before ingestion of ethanol or even during ingestion of ethanol. Can be taken in 1 to 3 doses per day depending on the degree of discomfort or prevention expected. Also, take it whenever you experience uncomfortable symptoms such as stomach pain, nausea, stomach weight, nausea, nausea or vomiting due to stress, heavy drinking and eating, smoking, and taking non-steroidal anti-inflammatory drugs. You may take it beforehand as prevention.
　本発明の消化管粘膜保護剤又は鎮吐剤は、経口で摂取することが好ましい。 The gastrointestinal mucosa protective agent or antiemetic of the present invention is preferably taken orally.
　本発明の消化管粘膜保護剤は、消化管粘膜障害又は消化性潰瘍の治療又は予防のために使用することができ、特に、エタノール摂取後の消化管粘膜障害、エタノールの過剰摂取により引き起こされる消化性潰瘍、又は、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用等による消化管粘膜障害並びに消化性潰瘍に対して優れた治療又は予防効果が認められる。そして、エタノール摂取後、又は、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用後等の胃痛、むかつき、胃重等の不快な諸症状の改善に有効に適用することができる。 The gastrointestinal mucosa protective agent of the present invention can be used for the treatment or prevention of gastrointestinal mucosal disorder or peptic ulcer, and in particular, digestive tract mucosal damage after ethanol intake, digestion caused by excessive intake of ethanol. Excellent therapeutic or preventive effects are observed for gastrointestinal ulcers or gastrointestinal mucosal disorders and peptic ulcers caused by stress, heavy drinking and eating, smoking, and nonsteroidal anti-inflammatory drugs. And it can be effectively applied to improve unpleasant symptoms such as gastric pain, nausea, and stomach weight after ingestion of ethanol or after stress, heavy drinking and eating, smoking, and taking non-steroidal anti-inflammatory drugs. .
　本発明において、消化管粘膜としては、胃粘膜、又は十二指腸粘膜が挙げられる。 In the present invention, the gastrointestinal mucosa includes gastric mucosa or duodenal mucosa.
　また、本発明の鎮吐剤は、吐き気、悪心又は嘔吐の抑制又は予防のために使用するものであり、下記の原因又は疾患に伴う吐き気、悪心又は嘔吐に対する鎮吐剤として適用することができる。
　ここで、吐き気、悪心又は嘔吐の原因又は疾患としては、エタノールの過剰摂取、ストレス、乗り物酔い、食中毒、体の冷え、妊娠（つわり）、異物の誤飲、薬による副作用、急性胃炎、胃・十二指腸潰瘍、虫垂炎、腸閉塞、急性腹膜炎、膵炎、片頭痛、メニエール病、脳出血、脳腫瘍、くも膜下出血、急性胆のう炎、急性肝炎、アルコール性肝炎、胆石症、胃ポリープ、脂肪肝、肺炎、緑内障、又は慢性硬膜下血腫等が挙げられる。
　本発明の鎮吐剤においては、特にエタノールの過剰摂取により、血中エタノールの分解が間に合わずにエタノール代謝物が嘔吐中枢を刺激することにより引き起こされる吐き気、悪心又は嘔吐に対して優れた抑制又は予防効果が認められる。 The antiemetic of the present invention is used for suppressing or preventing nausea, nausea or vomiting, and can be applied as an antiemetic for nausea, nausea or vomiting associated with the following causes or diseases.
The causes or diseases of nausea, nausea or vomiting include ethanol overdose, stress, motion sickness, food poisoning, cold body, pregnancy (morning), accidental ingestion of foreign bodies, side effects due to drugs, acute gastritis, stomach Duodenal ulcer, appendicitis, bowel obstruction, acute peritonitis, pancreatitis, migraine, Meniere disease, cerebral hemorrhage, brain tumor, subarachnoid hemorrhage, acute cholecystitis, acute hepatitis, alcoholic hepatitis, cholelithiasis, gastric polyp, fatty liver, pneumonia, glaucoma, Or chronic subdural hematoma etc. are mentioned.
In the antiemetic of the present invention, particularly due to excessive intake of ethanol, excellent suppression or prevention against nausea, nausea or vomiting caused by ethanol metabolites stimulating the vomiting center due to inadequate decomposition of blood ethanol. The effect is recognized.
　本発明の消化管粘膜保護剤又は鎮吐剤は、好ましくはエタノール摂取による不快症状改善剤として使用することができる。ここで、エタノール摂取による不快症状とは、エタノール摂取によりもたらされる胃痛、むかつき、胃重、吐き気、悪心又は嘔吐を意味する。
　なお、本明細書においてアルコールはエタノールと同義とする。 The gastrointestinal mucosa protective agent or antiemetic of the present invention can be preferably used as a discomfort symptom improving agent by ingesting ethanol. Here, the unpleasant symptom caused by ingestion of ethanol means stomach pain, nausea, stomach weight, nausea, nausea or vomiting caused by ingestion of ethanol.
In this specification, alcohol is synonymous with ethanol.
　本発明の消化管粘膜保護剤又は鎮吐剤は、他の消化管粘膜保護剤又は鎮吐剤と併用してもよい。本発明の消化管粘膜保護剤又は鎮吐剤には、さらに必要に応じて、以下の活性成分や添加物を配合することができる。活性成分としては、他の消化管粘膜保護剤、他の鎮吐剤、血中アルコール濃度低下促進剤、制酸剤、健胃剤、肝機能改善剤、消化剤、整腸剤、止瀉剤、鎮痛鎮痙剤、胃粘膜修復剤、ビタミン類、消泡剤等が挙げられる。 The gastrointestinal mucosa protective agent or antiemetic of the present invention may be used in combination with other gastrointestinal mucosa protective agent or antiemetic. The gastrointestinal mucosa protective agent or antiemetic of the present invention may further contain the following active ingredients and additives as necessary. Active ingredients include other gastrointestinal mucosal protective agents, other antiemetics, blood alcohol level lowering accelerators, antacids, stomachic agents, liver function improving agents, digestive agents, intestinal regulating agents, antipruritics, analgesic antispasmodics, gastric mucosa Examples include restoration agents, vitamins, and antifoaming agents.
　血中アルコール濃度低下促進剤としては、例えば、ウコン、アミノ酸（アラニン、グルタミン）、シジミ、冬虫夏草、柑橘糖蜜（温州みかん由来）、α-ラクトアルブミン、ラクチュロース、マルチトール、ラクチトール、グリセロール、オレアノール酸、プレセネゲニン、ヘデラゲニン、プロトエシゲニン、カフェイン、チクセツニンジン、キキョウ、塩化カルニチン、グリシルグリシン、ペピノ、葛根、緑豆、赤小豆、山査、麦芽、川穹、蒼朮、決明子、砂仁、薄荷、果糖、オタネニンジン、キグシを含む加味雙和湯又は雙和湯乳酸菌発酵物、グアバ、乾燥活性酵母、フルクトース、アスコルビン酸、香気物質、クエン酸、キニン等が挙げられる。 Examples of the blood alcohol concentration lowering promoter include turmeric, amino acids (alanine, glutamine), rainbow trout, cordyceps, citrus molasses (derived from Wenzhou oranges), α-lactalbumin, lactulose, maltitol, lactitol, glycerol, oleanolic acid, Presenegenin, Hederagenin, Protoesigenin, Caffeine, Chixetsunin, Kyokyo, Carnitine chloride, Glycylglycine, Pepino, Kuzune, Mung bean, Red bean, Santo, Malt, Kawamata, Kashiwa, Akiko, Sandhi, Light load, Fructose, Ginseng , Komi-sou hot water or Kazuwa-to fermented lactic acid bacteria, guava, dry activated yeast, fructose, ascorbic acid, aroma substance, citric acid, kinin and the like.
　制酸剤としては、例えば、合成ヒドロタルサイト、酸化マグネシウム、ケイ酸マグネシウム、ケイ酸アルミン酸マグネシウム、ケイ酸アルミニウム、メタケイ酸アルミン酸マグネシウム、水酸化マグネシウム、水酸化アルミニウム、水酸化アルミナマグネシウム、ジヒドロキシアルミニウムアミノアセテート、炭酸水素ナトリウム、炭酸カルシウム、炭酸マグネシウム、リン酸水素カルシウム、アミノ酢酸、ロートエキス等が挙げられる。 Examples of antacids include synthetic hydrotalcite, magnesium oxide, magnesium silicate, magnesium aluminate silicate, aluminum silicate, magnesium aluminate metasilicate, magnesium hydroxide, aluminum hydroxide, magnesium alumina hydroxide, dihydroxy Aluminum aminoacetate, sodium hydrogencarbonate, calcium carbonate, magnesium carbonate, calcium hydrogenphosphate, aminoacetic acid, funnel extract and the like can be mentioned.
　健胃剤としては、例えば、アニス実、アロエ、ウイキョウ、ウヤク、ウコン、延命草、オウゴン、オウバク、オウレン、加工大蒜（ニンニク）、ガジュツ、カッコウ、カラムス根、乾薑、枳殻、キジツ、ケイヒ、ゲンチアナ、コウジン、コウボク、ゴシュユ、胡椒、コロンボ、コンズランゴ、サンシシ、サンショウ、山奈、シソシ、シュクシャ、ショウキョウ、ショウズク、青皮、石菖根、センタウリウム草、センブリ、ソウジュツ、ソヨウ、大茴香、ダイオウ、タクシャ、チクセツニンジン、チョウジ、チョレイ、チンピ、トウガラシ、トウヒ、動物胆（ユウタンを含む）、ニガキ、ニクズク、ニンジン、ハッカ（セイヨウハッカを含む）、ビャクジュツ、ブクリョウ、ホップ、ホミカエキス、睡菜葉（スイサイヨウ）、モッコウ、ヤクチ、リュウタン、リョウキョウ、ウイキョウ油、ケイヒ油、ショウキョウ油、ショウズク油、チョウジ油、トウヒ油、ハッカ油、レモン油、ｌ－メントール、ｄｌ－メントール、塩酸ベタイン、グルタミン酸塩酸塩、塩化カルニチン、塩化ベタネコール、乾燥酵母等が挙げられる。 As a stomachic agent, for example, anise, aloe, fennel, yak, turmeric, life-grass, ogon, oak, auren, processed garlic, garlic, cuckoo, columnar root, psoriasis, rice husk, pheasant, keihi, gentian, Koujin, Kokuboku, Goshuyu, Pepper, Colombo, Conzurango, Sanshishi, Salamander, Yamana, Shisoshi, Shukusha, Shokyo, Shozu, Green peel, Ishizone, Centaurium grass, Assembly, Sowjutsu, Soyo, Daisuke, Daio, Takusha, Chiku Setu carrot, clove, chorei, chimpi, capsicum, spruce, animal gall (including yutan), oyster mushroom, nutmeg, carrot, mint (including Atlantic mint), peanut, broomfish, hops, honey extract, rape leaves (Saisai), Mokko, yak , Ryutan, Ryokyo, Fennel oil, Keihi oil, Pepper oil, Pepper oil, Clove oil, Spruce oil, Pepper oil, Lemon oil, l-menthol, dl-menthol, Betaine hydrochloride, Glutamate hydrochloride, Carnitine chloride, Chloride Examples include betanecol and dry yeast.
　肝機能改善剤としては、例えば、肝臓加水分解物、マリアアザミ、田七ニンジン、ウコン、藍、タンポポ、西洋タンポポ、ゴボウ、ニンニク、キク、西洋ノコギリソウ、クチナシ、ゴマ、アスパラガス、タマネギ、チコリ、薬用サルビア、朝鮮アザミ（アーティチョーク）、クコ、マメ科・アヤメ科・バラ科の植物（例えば大豆やクズ、マメ科に属するアスパラサス・リネアリス）、ミヤマウズラ、エルバ・デ・パサリーニョ、セテサングリア、赤芽柏、紅茶、柴胡、桃仁、牡丹皮、紅花、三稜、ガジュツ、α－リポ酸、フラボノール類、フラボン類、フラバン類、フラバノール類、カテキン類、イソフラボン類、リグナン酸、クルクミノイド類、グルテリン、プロラミン、グルタチオン、レシチン、バリン、ロイシン、イソロイシン、プロリン、アルギニン、アルギン酸、ヒスチジン、トリプトファン、キチンオリゴ糖、キトサンオリゴ糖、エタノールアミン、ホスホエタノールアミン、ホスホグリセロエタノールアミン、アラキドン酸、リノール酸、γ－リノレン酸、エイコサペンタエン酸、ドコサヘキサエン酸等が挙げられる。 Examples of the liver function improving agent include, for example, liver hydrolyzate, Maria thistle, Tabana carrot, turmeric, indigo, dandelion, western dandelion, burdock, garlic, chrysanthemum, yarrow, gardenia, sesame, asparagus, onion, chicory, Medicinal salvia, Korean thistle (artichoke), wolfberry, legumes / iridaceae / rose family plants (eg, soybeans and kudzu, asparagus linearias belonging to legumes), Japanese quail, elba de pasarinho, cetesangria, red buds, Black tea, Saiko, Peach seed, Peony skin, Safflower, Sanjyo, Gadju, α-lipoic acid, Flavonols, Flavones, Flavans, Flavanols, Catechins, Isoflavones, Lignanoic acid, Curcuminoids, Gluterin, Prolamin, Glutathione, lecithin, valine, leucine, isoleucine, Examples include phosphorus, arginine, alginic acid, histidine, tryptophan, chitin oligosaccharide, chitosan oligosaccharide, ethanolamine, phosphoethanolamine, phosphoglyceroethanolamine, arachidonic acid, linoleic acid, γ-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, etc. It is done.
　消化剤としては、例えば、でんぷん消化酵素、たん白消化酵素、脂肪消化酵素、繊維素消化酵素、ウルソデスオキシコール酸、オキシコーラン酸塩類、コール酸、胆汁末、胆汁エキス（末）、デヒドロコール酸、動物胆（ユウタンを含む）等が挙げられる。 Examples of the digestive agent include starch digestive enzyme, protein digestive enzyme, fat digestive enzyme, fibrin digestive enzyme, ursodesoxycholic acid, oxycoranoates, cholic acid, bile powder, bile extract (powder), dehydrocol Acid, animal gall (including yutan) and the like.
　整腸剤としては、例えば、整腸生菌成分、納豆キナーゼ、赤芽柏、アセンヤク、アロエ、ウバイ、ケツメイシ、ゲンノショウコ、プランタゴ・オバタ等が挙げられる。 Examples of the intestinal adjusting agent include live intestinal fungi components, natto kinase, akame koji, asenyaku, aloe, ubai, ketsumeishi, genokosho, plantago obata and the like.
　止瀉剤としては、例えば、アクリノール、塩化ベルベリン、グアヤコール、クレオソート、サリチル酸フェニル、炭酸グアヤコール、タンニン酸ベルベリン、次サリチル酸ビスマス、次硝酸ビスマス、次炭酸ビスマス、次没食子酸ビスマス、タンニン酸、タンニン酸アルブミン、メチレンチモールタンニン、カオリン、ペクチン、薬用炭、乳酸カルシウム、アセンヤク、ウバイ、オウバク、オウレン、クジン、ゲンノショウコ、五倍子、サンザシ、センブリ、ヨウバイヒ等が挙げられる。 Antidiarrheal agents include, for example, acrinol, berberine chloride, guaiacol, creosote, phenyl salicylate, guaiacol carbonate, berberine tannate, bismuth hyposalicylate, bismuth nitrate, bismuth carbonate, bismuth gallate, tannic acid, albumin tannate , Methylene thymol tannin, kaolin, pectin, medicinal charcoal, calcium lactate, Acacia yam, buckwheat, duckweed, auren, kudin, ganodermone, pentaploid, hawthorn, yellowtail, ivy.
　鎮痛鎮痙剤としては、例えば、塩酸オキシフェンサイクリミン、塩酸ジサイクロミン、塩酸メチキセン、臭化水素酸スコポラミン、臭化メチルアトロピン、臭化メチルアニソトロピン、臭化メチルスコポラミン、臭化ブチルスコポラミン、臭化メチル－ｌ－ヒヨスチアミン、臭化メチルベナクチジウム、ベラドンナエキス、ベラドンナ総アルカロイド、ヨウ化イソプロパミド、ヨウ化ジフェニルピペリジノメチルジオキソラン、ロートエキス、ロート根総アルカロイドクエン酸塩、塩酸パパベリン、エンゴサク、カンゾウ、コウボク、シャクヤク等が挙げられる。 Examples of analgesic and antispasmodic agents include oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, methyl atropine bromide, methyl anisotropine bromide, methyl scopolamine bromide, butyl scopolamine bromide, methyl bromide- l-hyostiamine, methylbenactidium bromide, belladonna extract, belladonna total alkaloid, iodopropamide, diphenylpiperidinomethyldioxolane iodide, funnel extract, funnel root total alkaloid citrate, papaverine hydrochloride, engosac, licorice, Examples include kokuboku and peonies.
　胃粘膜修復剤としては、例えば、アズレンスルホン酸ナトリウム、アルジオキサ、グリチルリチン酸及びその塩類並びに甘草抽出物、Ｌ－グルタミン、銅クロロフィリンカリウム、銅クロロフィリンナトリウム、塩酸ヒスチジン、ブタ胃壁ペプシン分解物、ブタ胃壁酸加水分解物、メチルメチオニンスルホニウムクロライド、赤芽柏、エンゴサク、カンゾウ、スクラルファート、レバミピド、マーズレン、ポラプレジンク、アルギン酸ナトリウム、ゲファルナート、テプレノン、トロキシピド、塩酸ベネキサートベータデクス、プラウノトール、マレイン酸イルソグラジン、ソファルコン等が挙げられる。 Examples of the gastric mucosa repairing agent include sodium azulenesulfonate, aldioxa, glycyrrhizic acid and salts thereof, and licorice extract, L-glutamine, copper chlorophyllin potassium, copper chlorophyllin sodium, histidine hydrochloride, porcine gastric wall pepsin degradation product, porcine gastric wall acid Hydrolysates, methylmethionine sulfonium chloride, red buds, engosac, licorice, sucralfate, rebamipide, marzulene, polaprezinc, sodium alginate, gefarnate, teprenone, troxipide, benexate betadex, prunotol, irsogladine maleate, sofalcone, etc. It is done.
　ビタミン類としては、例えば、ニコチン酸アミド、パントテン酸カルシウム、ビオチン、ビタミンＢ1又はその誘導体もしくはその塩類、ビタミンＢ2又はその誘導体もしくはその塩類、ビタミンＢ6又はその誘導体もしくはその塩類、ビタミンＣ又はその誘導体もしくはその塩類等、ビタミンＥ又はその誘導体もしくはその塩類が挙げられる。 Examples of vitamins include nicotinic acid amide, calcium pantothenate, biotin, vitamin B 1 or a derivative or salt thereof, vitamin B 2 or a derivative or salt thereof, vitamin B 6 or a derivative or salt thereof, vitamin C or Examples thereof include vitamin E or a derivative thereof or a salt thereof.
　消泡剤としては、例えば、ジメチルポリシロキサン等が挙げられる。 Examples of the antifoaming agent include dimethylpolysiloxane.
　他の鎮吐剤としては、例えば、グラニセトロン、ドンペリドン、スルピリド、オンダンセトロン、アザセトロン、ジメンヒドリナート、メトクロプラミド、クロルプロマジン、塩酸ジフェニドール、ジフェンヒドラミン、塩酸ジフェンヒドラミン、メクリジン、プロメタジン、クロルフェニラミン、マレイン酸クロルフェニラミン、アンフェタミン、アトロピン、ブロムワレリル尿素、アリルイソプロピルアセチル尿素、カフェイン、テオフィリン、ハッカ油、メントール、ビタミンＢ６等が挙げられる。 Other antiemetics include, for example, granisetron, domperidone, sulpiride, ondansetron, azasetron, dimenhydrinate, metoclopramide, chlorpromazine, diphenidol hydrochloride, diphenhydramine, diphenhydramine hydrochloride, meclizine, promethazine, chlorpheniramine, chlorpheniline maleate Lamin, amphetamine, atropine, bromvalerylurea, allylisopropylacetylurea, caffeine, theophylline, mint oil, menthol, vitamin B6 and the like can be mentioned.
　また、添加物としては、賦形剤、結合剤、崩壊剤、滑沢剤、安定化剤、増粘剤、可溶化剤、保存剤、ｐＨ調節剤、着色剤、甘味剤等、生理学的に許容される種々のものが挙げられる。 Additives include physiologically excipients, binders, disintegrants, lubricants, stabilizers, thickeners, solubilizers, preservatives, pH adjusters, colorants, sweeteners, etc. There are various acceptable types.
　賦形剤としては、例えば、乳糖、デンプン類、結晶セルロース、蔗糖、マンニトール、軽質無水ケイ酸等が挙げられる。 Examples of the excipient include lactose, starches, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid and the like.
　結合剤としては、例えば、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルセルロース、ゼラチン、アルファー化デンプン、ポリビニルピロリドン、ポリビニルアルコール、プルラン等が挙げられる。 Examples of the binder include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan and the like.
　崩壊剤としては、例えば、カルメロース、カルメロースカルシウム、クロスカルメロースナトリウム、クロスポピドン、トウモロコシ澱粉、低置換度ヒドロキシプロピルセルロース等が挙げられる。 Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, and low-substituted hydroxypropylcellulose.
　滑沢剤としては、例えば、ステアリン酸マグネシウム、タルク等が挙げられる。 Examples of the lubricant include magnesium stearate and talc.
　安定化剤としては、例えば、アスコルビン酸、エデト酸、又はそれらの塩等が挙げられる。 Examples of the stabilizer include ascorbic acid, edetic acid, and salts thereof.
　増粘剤としては、例えば、カルメロースナトリウム、寒天、ゼラチン、ポリビニルアルコール、ポリビニルピロリドン等が挙げられる。 Examples of the thickener include carmellose sodium, agar, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and the like.
　可溶化剤としては、例えば、硬化油、モノステアリン酸グリセリン、ポリオキシエチレン硬化ヒマシ油、ショ糖脂肪酸エステル等の非イオン性界面活性剤、レシチン等が挙げられる。 Examples of the solubilizer include nonionic surfactants such as hydrogenated oil, glyceryl monostearate, polyoxyethylene hydrogenated castor oil, and sucrose fatty acid ester, and lecithin.
　保存剤としては、例えば、安息香酸、安息香酸ナトリウム、パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル、パラオキシ安息香酸イソプロピル、パラオキシ安息香酸ブチル、パラオキシ安息香酸イソブチル等が挙げられる。 Examples of the preservative include benzoic acid, sodium benzoate, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, isobutyl paraoxybenzoate and the like.
　ｐＨ調節剤としては、例えば、クエン酸、リンゴ酸、乳酸、酒石酸、酢酸、塩酸、リン酸、及びそれらの塩、水酸化ナトリウム、水酸化カリウム、水酸化マグネシウム、水酸化カルシウム等が挙げられる。 Examples of the pH adjuster include citric acid, malic acid, lactic acid, tartaric acid, acetic acid, hydrochloric acid, phosphoric acid, and salts thereof, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, and the like.
　着色剤としては、例えば、酸化チタン、タール色素、黄色４号、黄色５号、三二酸化鉄、黄色三二酸化鉄、赤色３号等が挙げられる。 Examples of the colorant include titanium oxide, tar pigment, yellow No. 4, yellow No. 5, ferric oxide, yellow ferric oxide, red No. 3 and the like.
　甘味剤としては、例えば、白糖、液糖、果糖、果糖ブドウ糖液糖、還元麦芽糖水アメ、ハチミツ、カラメル、ソルビトール、マルチトール、キシリトール、エリスリトール、スクラロース、ステビア、グリチルリチン酸またはその塩、アスパルテーム、アセスルファムカリウム等が挙げられる。 Examples of the sweetening agent include sucrose, liquid sugar, fructose, fructose glucose liquid sugar, reduced maltose water candy, honey, caramel, sorbitol, maltitol, xylitol, erythritol, sucralose, stevia, glycyrrhizic acid or a salt thereof, aspartame, acesulfame Potassium etc. are mentioned.
　本発明の消化管粘膜保護剤又は鎮吐剤は、単独で服用することもできるし、又は他の活性成分や添加物と共に医薬品組成物に含有させることや、食品添加剤もしくは食品補助剤の態様で用いて、種々の飲食品に含有させて健康飲食品として提供することもできる。また、本発明の目的に応じて公知慣用技術により液剤、散剤、顆粒剤、錠剤、チュアブル錠、フィルムコーティング錠、糖衣錠、軟カプセル剤、硬カプセル剤、ゼリー剤等の剤型に製造できる。 The gastrointestinal mucosa protective agent or antiemetic of the present invention can be taken alone, or it can be contained in a pharmaceutical composition together with other active ingredients and additives, or in the form of a food additive or food supplement. It can also be used as a health food and drink by containing it in various foods and drinks. Moreover, according to the objective of this invention, it can manufacture in dosage forms, such as a liquid agent, a powder, a granule, a tablet, a chewable tablet, a film-coated tablet, a sugar-coated tablet, a soft capsule, a hard capsule, and a jelly agent by a well-known and usual technique.
　本発明の消化管粘膜保護剤、これを含有する医薬品又は飲食品は、アルコール摂取、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用等に起因する消化管粘膜障害の改善及び／又は予防のために用いられるものである旨の表示を付してもよい。例えば「胃痛、むかつき、胃重等の予防や緩和に」「お酒を飲む前に飲んで、むかつきを防止」「飲み会の次の日も元気に」等の表示が挙げられる。
　なお、このような表示は、公知の方法で容器包装手段に付すことができ、これによって本発明の消化管粘膜保護剤、これを含有する医薬品又は飲食品は、アルコール摂取、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用等に起因する消化管粘膜障害の改善及び／又は予防のために用いられるものであることが明示されるので、通常の剤又は飲食物との区別が明確となる。 The gastrointestinal mucosal protective agent of the present invention, pharmaceuticals or foods and drinks containing the same are used to improve gastrointestinal mucosal damage caused by alcohol consumption, stress, overdrinking, smoking, and taking non-steroidal anti-inflammatory drugs, etc. An indication that it is used for prevention may be attached. For example, indications such as “to prevent or alleviate stomach pain, nausea, stomach weight, etc.”, “drink before drinking alcohol to prevent nausea”, “energetic next day after drinking”, etc.
In addition, such a display can be attached to the container packaging means by a known method, whereby the gastrointestinal mucosa protective agent of the present invention, the pharmaceutical or food or drink containing the same, alcohol intake, stress, overdrinking, Since it is clearly stated that it is used for the improvement and / or prevention of gastrointestinal mucosal damage caused by smoking and taking non-steroidal anti-inflammatory drugs, etc. Becomes clear.
　また、本発明の鎮吐剤、これを含有する医薬品又は飲食品は、アルコール摂取に起因する吐き気、悪心又は嘔吐の改善及び／又は予防のために用いられるものである旨の表示を付してもよい。例えば「吐き気や悪心、嘔吐の予防や緩和に」「お酒を飲む前に飲んで、吐き気を防止」「飲み会の次の日も元気に」等の表示が挙げられる。
　なお、このような表示は、公知の方法で容器包装手段に付すことができ、これによって本発明の鎮吐剤、これを含有する医薬品又は飲食品は、アルコール摂取に起因する諸症状の改善及び／又は予防のために用いられるものであることが明示されるので、通常の剤、医薬品又は飲食物との区別が明確となる。 In addition, the antiemetic of the present invention, medicines or foods and drinks containing the same may be labeled for use in the improvement and / or prevention of nausea, nausea or vomiting caused by alcohol consumption. Good. For example, indications such as “to prevent or relieve nausea, nausea and vomiting”, “prevent nausea by drinking before drinking”, “energetic next day after drinking”, etc.
In addition, such a display can be attached to the container and packaging means by a publicly known method, whereby the antiemetic of the present invention, a medicine containing the same, or a food or drink can improve various symptoms caused by alcohol intake and / or Or, since it is clearly indicated that it is used for prevention, the distinction from normal agents, pharmaceuticals or foods and drinks becomes clear.
　以下に、実施例を用いて本発明を具体的に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited thereto.
試験例１：胃粘膜損傷モデルに対する効果
　被験物質を生理食塩水で懸濁したもの（但し、コントロールでは生理食塩水のみ）を、一晩絶食したウィスター(Wistar)系雄性ラット（８週齢） に経口投与（５ｍＬ／ｋｇ）し、その３０分後に９９．５体積％エタノールを１ｍＬ／匹ずつ経口投与した。エタノール投与から１時間後に胃を摘出し、１体積％ホルマリンで固定した後、胃を切り開き、胃粘膜に発生した損傷の長さ（損傷係数）を測定した。なお、被験物質は、コントロール（生理食塩水）、ウコン末（秋ウコン）６００ｍｇ／ｋｇ、ヒハツ末（ジャワナガコショウ）１５０ｍｇ／ｋｇ、およびウコン末（秋ウコン）６００ｍｇ／ｋｇ＋ヒハツ末（ジャワナガコショウ）１５０ｍｇ／ｋｇ併用の４群である。各被験物質を投与した際の胃粘膜損傷抑制効果の結果を図１に示す。 Test Example 1: Effect on gastric mucosal damage model A Wistar male rat (8 weeks old) fasted overnight with a suspension of the test substance in physiological saline (but only physiological saline as a control) Oral administration (5 mL / kg) was performed, and 30 minutes later, 99.5 vol% ethanol was orally administered at 1 mL / animal. One hour after ethanol administration, the stomach was removed, fixed with 1% by volume formalin, the stomach was cut open, and the length of damage (damage factor) occurring in the gastric mucosa was measured. The test substances were control (saline), turmeric powder (autumn turmeric) 600 mg / kg, chickweed powder (Jawa Naga pepper) 150 mg / kg, and turmeric powder (autumn turmeric) 600 mg / kg + hihatsu powder (Jawa Naga pepper) ) Four groups of 150 mg / kg combined. The result of the gastric mucosa damage inhibitory effect when each test substance is administered is shown in FIG.
　図１の結果より、コントロールに対し、ウコン末６００ｍｇ／ｋｇは潰瘍の発生を抑制させたが、ヒハツ末１５０ｍｇ／ｋｇはそれよりも優れた抗潰瘍作用を示すことが確認された。また、ウコン末６００ｍｇ／ｋｇとヒハツ末１５０ｍｇ／ｋｇとの併用では、ヒハツ末１５０ｍｇ／ｋｇ単独に比べて更に優れた抗潰瘍作用が確認された。各群平均の潰瘍指数は、コントロールを１とした時ウコン末群で０．５０、ヒハツ末群で０．２６であり、その積（０．１３）はウコン末とヒハツ末併用群の０．１２にくらべて大であり、ヒハツの抗潰瘍作用はウコンとの併用により大きく促進された（Burgi法：高木敬次郎他：薬物学、1987、南山堂）。以上より、ウコン及びヒハツのいずれもエタノール摂取により引き起こされる胃粘膜障害に対して優れた胃粘膜保護作用を奏することが示された。また、ウコン及びヒハツを併用して投与すると両成分が相乗的に作用し、さらに優れた胃粘膜保護作用を奏することが示された。
　本実施例では、胃粘膜損傷モデルを作製するために、エタノールを用いて潰瘍を誘発したが、エタノールに限らず、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用後等の要因による潰瘍にも同様の効果を奏する。 From the results shown in FIG. 1, it was confirmed that turmeric powder 600 mg / kg suppressed the occurrence of ulcers, whereas hihatsu powder 150 mg / kg exhibited an antiulcer action superior to that of the control. Further, in the combined use of turmeric powder 600 mg / kg and chickpea powder 150 mg / kg, a further superior anti-ulcer action was confirmed as compared with chickpea powder 150 mg / kg alone. The average ulcer index of each group was 0.50 in the turmeric powder group and 0.26 in the chickweed powder group when the control was 1, and the product (0.13) was 0. The anti-ulcer action of baboon was greatly promoted by combined use with turmeric (Burgi method: Keijiro Takagi et al .: Pharmacology, 1987, Nanzan-do). From the above, it was shown that both turmeric and baboon have excellent gastric mucosal protective action against gastric mucosal damage caused by ethanol intake. It was also shown that when turmeric and hihatsu were administered in combination, both components acted synergistically to provide an excellent gastric mucosa protective effect.
In this example, in order to create a gastric mucosal damage model, ethanol was used to induce ulcers, but not limited to ethanol, such as stress, heavy drinking and eating, smoking, and after taking nonsteroidal anti-inflammatory drugs, etc. It has the same effect on ulcers caused by factors.
実施例１：ヒハツ配合製剤の調製
　精製水１０ｍＬに、ヒマツ末５０ｍｇ、オキソアミヂン末４５ｍｇ、ニンジン乾燥エキス１３５ｍｇ、ウコン末２００ｍｇ、オウレン流エキス０．３ｍL、ゲンノショウコ乾燥エキス１００ｍｇ、カンゾウエキス末８２ｍｇを加えた（調合液１）。これとは別に精製水１０ｍＬに、精製白糖１．５ｇ、ポリビニルピロリドン０．０９ｇを加え、これを加温して溶解させた。この液を、前記で調合した調合液１と混合し、クエン酸ナトリウムを加え、ｐＨを５に調整した。これに精製水適量を加えて全量５０ｍＬとして内服液剤を得た。 Example 1: Preparation of a Japanese pine plant formulation To 10 mL of purified water, 50 mg of pine powder, 45 mg of oxoamidin powder, 135 mg of carrot dry extract, 200 mg of turmeric powder, 0.3 mL of lauren extract, 100 mg of dried gentian powder, 82 mg of licorice extract powder were added. (Formulation liquid 1). Separately, 1.5 g of purified white sugar and 0.09 g of polyvinylpyrrolidone were added to 10 mL of purified water, and this was heated and dissolved. This liquid was mixed with the preparation liquid 1 prepared above, and sodium citrate was added to adjust the pH to 5. An appropriate amount of purified water was added thereto to make a total volume of 50 mL to obtain an internal solution.
比較例１：ヒハツ非配合製剤の調製
　コントロールとして水を使用した。 Comparative Example 1: Preparation of a non-hihatsu formulation Water was used as a control.
比較例２：ヒハツ非配合製剤の調製
　ソルマックプラス（大鵬薬品工業（株））を使用した。なお、ソルマックプラスには、５０ｍL中にウコン流エキス０．３ｍL、カンゾウ抽出物１３５ｍｇ、ニンジン流エキス０．５ｍL、オウレンチンキ０．８２６ｍL、チョウジチンキ０．１２６ｍL、ゲンチアナチンキ０．３７６ｍL、ソウジュツ流エキス１．２ｍL、ケイヒチンキ０．２５ｍL、カルニチン塩化物１２０ｍｇが配合されている。 Comparative Example 2: Preparation of non-hihatsu formulation Solmac Plus (Takuma Pharmaceutical Co., Ltd.) was used. In addition, Solmac Plus includes turmeric extract 0.3 mL, licorice extract 135 mg, carrot extract 0.5 mL, aurin tincture 0.826 mL, clove tincture 0.126 mL, gentian tincture 0.376 mL, and sojutsu extract 1.2 mL, cinnamon tincture 0.25 mL, and carnitine chloride 120 mg are blended.
試験例２：鎮吐作用の評価
　自由に餌（ＣＩＥＡ－３１２）及び水を与えられていた１１カ月齢の雄性スンクス（Ｓｕｎｃｕｓ　ｍｕｒｉｎｕｓ）を用い、実施例１、比較例１又は比較例２で得られた薬剤試料をそれぞれ２０ｍＬ／ｋｇ、２０ｍＬ／ｋｇ、１０ｍＬ／ｋｇとなるように経口投与した（各群ｎ＝６）。その１０分後、さらに４０％エタノールを５ｍｇ／ｋｇとなるように経口投与し、エタノール投与から６０分間の被験スンクスに対する嘔吐反応を観察した。なお、本実験では胃の内容物の嘔吐があった場合に、嘔吐反応があったとみなした。エタノール投与から６０分後までの嘔吐回数、嘔吐開始時間、及び嘔吐反応持続時間を計測し、その結果を表１にまとめた。
　本実験において、実験動物（スンクス）の飼育・管理に関する一般的な取り扱いは、Ｔｈe  Ｇｕｉｄｅ　ｆｏｒ　ｔｈｅ　Ｃａｒｅ　ａｎｄ　Ｕｓｅ　ｏｆ　Ｌａｂｏｒａｔｏｒｙ　Ａｎｉｍａｌｓ（Ｎａｔｉｏｎａｌ　Ａｃａｄｅｍｙ　Ｐｒｅｓｓ，　Ｗａｓｈｉｎｇｔｏｎ，Ｄ．Ｃ．，２０１０）に従った。 Test Example 2: Evaluation of antiemetic effect Obtained in Example 1, Comparative Example 1 or Comparative Example 2 using an 11-month-old male Suncus (Suncus murinus) that was given food (CIEA-312) and water freely. The drug samples were orally administered at 20 mL / kg, 20 mL / kg, and 10 mL / kg, respectively (n = 6 for each group). Ten minutes later, 40% ethanol was further orally administered to 5 mg / kg, and the vomiting reaction to the test sunx was observed for 60 minutes after ethanol administration. In this experiment, when there was vomiting of the stomach contents, it was considered that there was a vomiting reaction. The number of vomiting, the vomiting start time, and the duration of vomiting reaction until 60 minutes after ethanol administration were measured, and the results are summarized in Table 1.
In this experiment, general handling for breeding and management of experimental animals (Sunks) was in accordance with The Guide for the Care and Use of Laboratory Animals (National Academy Press, Washington, D.C., 2010).
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　表１に示す通り、ヒハツを含む実施例１の製剤は比較例１、２に対して嘔吐回数が少なかった。また、嘔吐回数が少なかったことから、嘔吐反応を示す時間も低減された。これらのことから、ヒハツを含有すれば嘔吐反応の遅延ではなく、嘔吐反応そのものの抑制効果が認められ、吐き気、悪心又は嘔吐等の不快な状態からの素早い回復に貢献できる可能性が示された。 As shown in Table 1, the formulation of Example 1 containing hihatsu had fewer vomiting times than Comparative Examples 1 and 2. In addition, since the number of times of vomiting was small, the time to show vomiting reaction was also reduced. Based on these results, it was shown that the inclusion of baboon has the effect of suppressing the vomiting reaction itself, not the delay of the vomiting reaction, and can contribute to quick recovery from unpleasant conditions such as nausea, nausea or vomiting. .
　以下の製造例１～４に、本発明の消化管粘膜保護剤又は鎮吐剤の製造例を示す。 The following production examples 1 to 4 show production examples of the gastrointestinal mucosa protective agent or antiemetic of the present invention.
製造例１
　精製水（８０～９０℃）５００Ｌに安息香酸ナトリウム５００ｇ及びパラオキシ安息香酸エチル４０ｇ、精製白糖７０ｋｇ、カルメロースナトリウム３ｋｇを加え、攪拌しながら溶解させた。この液を冷却後、硝酸チアミン３７７ｇ及びリン酸水素ナトリウム１００ｇを加え、攪拌しながら溶解させる。別に精製水（８０～９０℃）２００Ｌに人参乾燥エキス１．４ｋｇ（人参として２０ｋｇ）及びヒハツ末（ジャワナガコショウ）０．５ｋｇ、ショウキョウエキス９７０ｇ（ショウキョウとして１０ｋｇ）、ウコン流エキス１１Ｌ(秋ウコンとして１１ｋｇ)、クエン酸１．５ｋｇ、酒石酸１．５ｋｇを加え、攪拌溶解した液を冷却後、ろ過した。これら２液を混合した後、ハッカ油１６７ｇ及びウイキョウ油３３ｇ、チョウジ油３３ｇを加え、攪拌しながら混合した。この混合液に精製水を適量加え、全量を１０００Ｌとすることにより、内服液を製した。 Production Example 1
To 500 L of purified water (80 to 90 ° C.), 500 g of sodium benzoate and 40 g of ethyl paraoxybenzoate, 70 kg of purified white sugar and 3 kg of carmellose sodium were added and dissolved while stirring. After cooling this solution, 377 g of thiamine nitrate and 100 g of sodium hydrogen phosphate are added and dissolved while stirring. Separately, 200 L of purified water (80-90 ° C), 1.4 kg of ginseng extract (20 kg as ginseng), 0.5 kg of Hihatu powder (Jawaga pepper), 970 g of pepper extract (10 kg as pepper), 11 L of turmeric extract ( 11 kg of autumn turmeric), 1.5 kg of citric acid and 1.5 kg of tartaric acid were added, and the stirred and dissolved solution was cooled and filtered. After mixing these two solutions, 167 g of peppermint oil, 33 g of fennel oil, and 33 g of clove oil were added and mixed while stirring. An appropriate amount of purified water was added to this mixed solution to make the total amount 1000 L, thereby preparing an internal solution.
製造例２
　精製水（８０～９０℃）５００Ｌに安息香酸ナトリウム０．７ｋｇ及びパラオキシ安息香酸ブチル０．１４ｋｇ、精製白糖７０ｋｇ、カルメロースナトリウム６ｋｇを加え、攪拌しながら溶解させた。この液を冷却後、人参乾燥エキス１．８ｋｇ（人参として２５ｋｇ）及びヒハツ末（ジャワナガコショウ）３ｋｇ、ショウキョウ流エキス６Ｌ（ショウキョウとして６ｋｇ）、ウコン流エキス６Ｌ(秋ウコンとして６ｋｇ)、ウイキョウ流エキス６Ｌ（ウイキョウとして６ｋｇ）、チョウジ流エキス６Ｌ（チョウジとして６ｋｇ）、香料０．５Ｌを加え、攪拌溶解した。別に精製水（８０～９０℃）３００Ｌに合成ヒドロタルサイト６ｋｇを加え、攪拌混合した後、高圧ホモゲナイザーで循環分散した。分散液を冷却後、先の混合液と合わせたものに精製水を適量加え、全量を１０００Ｌとすることにより、内服液を調製した。 Production Example 2
To 500 L of purified water (80 to 90 ° C.), 0.7 kg of sodium benzoate and 0.14 kg of butyl paraoxybenzoate, 70 kg of purified white sugar and 6 kg of carmellose sodium were added and dissolved while stirring. After cooling this liquid, dried carrot extract 1.8 kg (25 kg as ginseng) and powdered lark (Java pepper) 3 kg, pepper extract 6 L (6 kg as pepper), turmeric extract 6 L (6 kg as autumn turmeric), 6 L of fennel flow extract (6 kg as fennel), 6 L of clove extract (6 kg as clove), and 0.5 L of fragrance were added and dissolved by stirring. Separately, 6 kg of synthetic hydrotalcite was added to 300 L of purified water (80 to 90 ° C.), mixed with stirring, and then circulated and dispersed with a high-pressure homogenizer. After cooling the dispersion, an appropriate amount of purified water was added to the mixture with the previous mixture to make the total volume 1000 L, whereby an internal liquid was prepared.
製造例３
　ヒハツ末（ジャワナガコショウ）４０質量部、ビタミンＢ１ ２５質量部、硬化油５０質量部、モノステアリン酸グリセリン２０質量部、トウモロコシデンプン１５質量部、カルメロースカルシウム１５質量部からなる混合末にエタノール１２質量部を加え練合物を製した。練合物を押出し造粒し（φ０．８mm）、乾燥、整粒、分級し顆粒を得た（以下Ａ顆粒と称する）。
　また、乾燥水酸化アルミニウムゲル４５０質量部、水酸化マグネシウム３２５質量部、合成ヒドロタルサイト４５０質量部、カンゾウエキス末７５質量部、ウイキョウ末２００質量部、ウコン末（秋ウコン）２００質量部、ニンジン乾燥エキス２０質量部、ポリビニルアルコール７０質量部、カルメロースカルシウム３０質量部、結晶セルロース４０質量部、キシリトール１５４５質量部からなる混合末に７０％エタノール８００質量部を加え練合物を製した。練合物を押出し造粒し（φ０．８mm）、乾燥、整粒、分級し、顆粒を得た（以下Ｂ顆粒と称する）。
　さらにメタケイ酸アルミン酸マグネシウム２４質量部にL－メントール６質量部を吸着させ、香料末を得た（以下Ｃ香料末と称する）。
　Ａ顆粒１６５質量部、Ｂ顆粒３４０５質量部、Ｃ香料末３０質量部を混合機にて混合し、さらに分包機にて分包し１回服用量１．２gの顆粒剤を得た。 Production Example 3
Ethanol 12 in a mixed powder consisting of 40 parts by weight of Hihatsu powder, 25 parts by weight of vitamin B1, 50 parts by weight of hardened oil, 20 parts by weight of glyceryl monostearate, 15 parts by weight of corn starch and 15 parts by weight of carmellose calcium A mass part was added and the kneaded material was manufactured. The kneaded product was extruded and granulated (φ0.8 mm), dried, sized and classified to obtain granules (hereinafter referred to as A granules).
Also, 450 parts by weight of dry aluminum hydroxide gel, 325 parts by weight of magnesium hydroxide, 450 parts by weight of synthetic hydrotalcite, 75 parts by weight of licorice extract powder, 200 parts by weight of fennel powder, 200 parts by weight of turmeric powder (autumn turmeric), carrot A kneaded product was prepared by adding 800 parts by mass of 70% ethanol to a mixed powder comprising 20 parts by mass of a dry extract, 70 parts by mass of polyvinyl alcohol, 30 parts by mass of carmellose calcium, 40 parts by mass of crystalline cellulose, and 1545 parts by mass of xylitol. The kneaded product was extruded and granulated (φ0.8 mm), dried, sized and classified to obtain granules (hereinafter referred to as B granules).
Further, 6 parts by mass of L-menthol was adsorbed on 24 parts by mass of magnesium aluminate metasilicate to obtain a fragrance powder (hereinafter referred to as C fragrance powder).
165 parts by mass of A granule, 3405 parts by mass of B granule, and 30 parts by mass of C fragrance powder were mixed by a mixer, and further packed by a packaging machine to obtain a granule having a single dose of 1.2 g.
製造例４
　ヒハツ末（ジャワナガコショウ）３０質量部、ビタミンＢ１ ２５質量部、硬化油５５質量部、モノステアリン酸グリセリン２５質量部、トウモロコシデンプン１５質量部、カルメロースカルシウム１５質量部からなる混合末にエタノール１２質量部を加え練合物を製した。練合物を押出し造粒し（φ０．５ｍｍ）、乾燥、整粒し顆粒を得た（以下Ａ顆粒と称する）。
　また、乾燥水酸化アルミニウムゲル４５０質量部、水酸化マグネシウム３２５質量部、合成ヒドロタルサイト４５０質量部、カンゾウエキス末７５質量部、ウイキョウ末２００質量部、ウコン末（秋ウコン）２００質量部、ショウキョウ末１００質量部、ニンジン乾燥エキス２０質量部、ヒドロキシプロピルセルロース９０質量部、カルメロースカルシウム３０質量部、結晶セルロース３０質量部、エリスリトール１４４５質量部からなる混合末に９０％エタノール７００質量部を加え練合物を製した。練合物を乾燥、整粒し顆粒を得た（以下Ｂ顆粒と称する）。
　さらにメタケイ酸アルミン酸マグネシウム１６質量部にL－メントール４質量部を吸着させ、香料末を得た（以下Ｃ香料末と称する）。
　Ａ顆粒１６５質量部、Ｂ顆粒３４１５質量部、Ｃ香料末２０質量部を混合機にて混合し、さらに分包機にて分包し１回服用量１．２ｇの顆粒剤を得た。 Production Example 4
Ethanol 12 in a mixed powder consisting of 30 parts by weight of Hihatsu powder, 25 parts by weight of vitamin B1, 55 parts by weight of hardened oil, 25 parts by weight of glyceryl monostearate, 15 parts by weight of corn starch and 15 parts by weight of carmellose calcium A mass part was added and the kneaded material was manufactured. The kneaded product was extruded and granulated (φ0.5 mm), dried and sized to obtain granules (hereinafter referred to as A granules).
Also, 450 parts by weight of dry aluminum hydroxide gel, 325 parts by weight of magnesium hydroxide, 450 parts by weight of synthetic hydrotalcite, 75 parts by weight of licorice extract powder, 200 parts by weight of fennel powder, 200 parts by weight of turmeric powder (autumn turmeric), show Add 700 parts by mass of 90% ethanol to a mixed powder consisting of 100 parts by mass of carp powder, 20 parts by mass of dried carrot extract, 90 parts by mass of hydroxypropyl cellulose, 30 parts by mass of carmellose calcium, 30 parts by mass of crystalline cellulose, and 1445 parts by mass of erythritol. A kneaded product was made. The kneaded product was dried and sized to obtain granules (hereinafter referred to as B granules).
Further, 4 parts by mass of L-menthol was adsorbed on 16 parts by mass of magnesium aluminate metasilicate to obtain a fragrance powder (hereinafter referred to as C fragrance powder).
165 parts by mass of A granules, 3415 parts by mass of B granules, and 20 parts by mass of C fragrance powder were mixed with a mixer, and further packaged with a packaging machine to obtain a granule having a single dose of 1.2 g.
　本発明の消化管保護剤は、ヒハツを含有することにより、エタノールの過剰摂取、ストレス、暴飲暴食、喫煙、及び、非ステロイド性抗炎症薬の服用等によりもたらされる消化管粘膜損傷又は消化性潰瘍に対して優れた予防及び／又は治療効果を有する。さらにウコンを併用することにより、相乗的な効果が得られる。
　また、本発明の鎮吐剤は、ヒハツを含有することにより、吐き気、悪心又は嘔吐に対して優れた鎮吐作用を有する。特に、アルコールの過剰摂取によりもたらされる吐き気、悪心又は嘔吐に対して優れた鎮吐作用を有し、これらの症状を速やかに改善できる。 Since the gastrointestinal protective agent of the present invention contains baboon, gastrointestinal mucosal damage or peptic ulcer caused by excessive intake of ethanol, stress, violent eating and eating, smoking, and taking non-steroidal anti-inflammatory drugs, etc. Has an excellent preventive and / or therapeutic effect. Furthermore, a synergistic effect is acquired by using turmeric together.
Moreover, the antiemetic of this invention has the antiemetic effect excellent with respect to nausea, nausea, or vomiting by containing a hihatsu. In particular, it has an excellent antiemetic action against nausea, nausea or vomiting caused by excessive intake of alcohol, and these symptoms can be quickly improved.

Claims (9)

  1. 　ヒハツを含有する消化管粘膜保護剤。 Gastrointestinal mucosa protective agent containing hihatsu.
  2. 　さらにウコンを含有する、請求項１に記載の消化管粘膜保護剤。 The gastrointestinal mucosa protective agent according to claim 1, further comprising turmeric.
  3. 　エタノールによる消化管粘膜障害を抑制するものである、請求項１又は２に記載の消化管粘膜保護剤。 The gastrointestinal mucosa protective agent according to claim 1 or 2, which suppresses gastrointestinal mucosal damage caused by ethanol.
  4. 　エタノールによる消化管粘膜障害が、エタノール摂取後の胃痛、むかつき又は胃重である、請求項１～３のいずれか１項に記載の消化管粘膜保護剤。 The gastrointestinal mucosa protective agent according to any one of claims 1 to 3, wherein the gastrointestinal mucosal disorder caused by ethanol is gastric pain, nausea or stomach weight after ethanol intake.
  5. 　前記消化管粘膜が、胃粘膜又は十二指腸粘膜である、請求項１～４のいずれか１項に記載の消化管粘膜保護剤。 The gastrointestinal mucosa protective agent according to any one of claims 1 to 4, wherein the gastrointestinal mucosa is gastric mucosa or duodenal mucosa.
  6. 　請求項１～５のいずれか１項に記載の消化管粘膜保護剤を含有する医薬品又は飲食品。 A pharmaceutical or a food or drink containing the gastrointestinal mucosa protective agent according to any one of claims 1 to 5.
  7. 　ヒハツを含有する鎮吐剤。 An antiemetic containing hihatsu.
  8. 　エタノール摂取によりもたらされる吐き気、悪心又は嘔吐に対するものである、請求項７に記載の鎮吐剤。 The antiemetic according to claim 7, which is for nausea, nausea or vomiting caused by ethanol intake.
  9. 　請求項７又は８に記載の鎮吐剤を含有する医薬品又は飲食品。 A pharmaceutical product or food or drink containing the antiemetic according to claim 7 or 8.
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