TW592706B - Gastrointestinal drug against helicobacter pyroli - Google Patents

Abstract

This invention provides a gastrointestinal drug which contains the combination of pulveratum or extraction of Coptidis rhizoma and/or Phellodendri cortex and pulverata or extraction of Aurantii nobilis pericarpium. Such gastrointestinal drug possesses anti-Helicobacter pylori activity and is useful in the prevention, the treatment or the recidivating prevention for gastritis, gastric ulcer, duodenal ulcer or the like.

Description

592706 V. Description of the invention (1) [Technical Field] The present invention relates to Coptis lutea and / or extracts of crude medicinal powders or extracts from Chenpi and / or Chenpi, which have anti-Helicobacter pylori activity. The gastrointestinal ulcer, ulcer of duodenum, etc., and prevention, treatment of gastritis, stomach [Technical Background] * A variety of crude drugs are known to have antibacterial effects on pylorus snails, for example, Japanese Patent Laid-Open No. 8-295632. Examples or extracts of Helicobacter pylori ^ • Ding _ 3 kinds of crude drug powder such as Coptis chinensis on the surface revealed a kind of extract containing the second anti-cimicidal fungus spinapine f extract and Putian histamine H2 receptor antagonist, proton Which tube two = Lunar mucosal defense-type meningitis and peptic ulcer treatment !, at least one of the medicinal composition made, of which the crude drug is Huang Lianzhi and other writing agents May 1996, the 47th Japan Toyo On page 78 of the Proceedings of the General Assembly of the Medical Academic Association, PPI (proton capsule inhibitor) or histamine & blocker was administered to ulcer cases, and then a traditional Chinese medicine prescription agent, Pingwei San, was administered. [Problems to be Solved by the Invention] The current bactericidal treatment method for Helicobacter pylori uses more than one antibiotic such as penicillin, cephalosporin, tetracycline, neopyridone, and macrolide. It is mainstreamed with three doses of bismuth preparation and proton capsule inhibitor (pp 〖). However, although the antibacterial effect of antibiotics is strong, it may cause side effects such as allergies or diarrhea and there may be problems such as resistant bacteria. Therefore, we look forward to the development of prevention and treatment of gastroenteritis, gastric ulcer, duodenal ulcer and other gastrointestinal diseases caused by Helicobacter pylori infection.

C: \ Program Files \ Patent \ 310650.ptd Page 4 592706 V. Description of the invention (2) Effective, and has a strong anti-pyloric screw rod, ^ ^ ^ ^ ^ gastrointestinal drugs containing crude drug ingredients. Mycorrhizal fungi are also very safe for the human body. [Methods to solve the problem] In order to solve the above problems, the inventors have found that a specific combination of crude drugs can play a similar role # 夕 Λ „淑 仃 研 九 ... Fruit hair ^ ^ ^ ^ ^ / Hui Multiplication of Helicobacter pylori proliferation inhibition, in addition, by using a histamine H2 receptor antagonist or proton, a tube inhibitor (eg Lansoplasol, Rabeprazole (1 讣 61 > 1 "〇1), Ormeprazole (^) 11 ^? 183〇1), etc., gastric mucosal defense type gastritis. Peptic ulcer treatment drugs The bismuth preparation is combined with antacids and other clinically used antacids such as gastritis, gastric ulcer, duodenal ulcer, etc. It was unexpectedly found that the effects of preventing, treating gastritis, gastric ulcer and preventing recurrence can be obtained, and the present invention has been completed. That is, the present invention relates to a gastrointestinal drug having anti-Helicobacter pylori activity, which is composed of (1) crude drug powder or extract of Coptis chinensis and / or Scutellaria baicalensis and (2) crude drug powder or extract of Chenpi, · The gastrointestinal drug according to item 1 above, wherein (1) the crude drug powder or extract of Coptis chinensis is converted to 1 part by weight of the native drug (2) the raw drug of the raw drug powder or extract of Chenpi is about 2 to 200 parts by weight, 3. The gastrointestinal drug according to item 1 above, wherein (1) the crude drug powder or extract of Scutellaria baicalensis is converted to the native drug by 1 part by weight to (2) the crude drug powder or extract of the peel The native medicine is about 1 to 100 parts by weight. 4. The gastrointestinal medicine according to item 1 above, wherein the powder or extract of Coptis chinensis and Scutellaria baicalensis is converted into a native medicine by 1 part by weight (2) Crude drug

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V. Description of the invention (3) Approximately 1 to 200 parts by weight of the powder or extract of the native drug, spirulina infection causes histamine H2 receptor antagonist gastritis • digestive ulcer 5. • gastrointestinal drug as described in item 1 above, Prophylactic or therapeutic drugs for gastrointestinal diseases due to pylori, 6. The gastrointestinal drugs according to item 丨 above, which contain at least one anti-agent, proton capsule inhibitor, gastric mucosal defense-type ulcer treatment agent, antacid and For antidiarrheal agents, I. As described above (the gastrointestinal drug of item 丨 contains histamine & receptor antagonist

The gastrointestinal drug of item 7 in which the histamine H2 called antagonist is cimetidine or a pharmacologically acceptable one 9. The gastrointestinal drug of item 1 above, which contains an antacid Those two '1 〇 · # gastrointestinal drugs made of (1) crude drug powder or extract of Coptis chinensis and / or Scutellaria baicalensis and (2) crude drug powder or extract of Chenpi as raw materials, 11. Gastrointestinal drugs are those containing at least one histamine JJ2 receptor antagonist, proton capsule inhibitor, gastric mucosal defense type gastritis and peptic ulcer treatment agent, antacid and antidiarrheal agent It is also a gastrointestinal drug with anti-Helicobacter pylori activity, which is made from the crude drug powder or extract of Chenpi. And 13. A method of using a raw powder or extract of Chenpi to enhance the anti-Helicobacter pylori activity of Coptis chinensis and / or Scutellaria baicalensis.

The gastrointestinal medicament of the present invention is a medicine having the following characteristics: (1) a combination of crude drug powder or extract of Coptis Chinensis and raw powder or extract of Citrus sinensis, (2) crude drug powder or extract of Cotinus coggygria and crude drug powder or extract of Chitin Combination of things,

592706 V. Description of the invention (4)

Or (3) The combination of the crude drug powder or extract of Coptis chinensis and Cotinus coggygria and the crude drug powder or extract of Codonopsis spp. D is especially a combination of the crude drug powder or extract of Coptis chinensis Coptis and the peel or extract of Chenpi. The above-mentioned crude drug powder or extract may be used in combination with various preparations or as a mixture.

Among them, (1) the ratio of the crude drug powder or extract of Coptis chinensis and / or Scutellaria baicalensis to the combination of the crude drug powder or extract of Scutellaria baicalensis can be appropriately selected. Compared with the easy-to-take and inexpensive sage peel, Coptis chinensis and Scutellaria baicalensis Bitter and very expensive. In the gastrointestinal medicament of the present invention, a synergistic effect can be obtained based on a special combination of crude drug ingredients (refer to the test examples below), and the dosage of Coptis chinensis and Cotinus coggygria can be relatively reduced. From this point of view, when considering the combination ratio of the above crude drugs, when the crude drug powder or extract of Coptis chinensis is converted to 1 part by weight of the original drug, the peel (converted to the original drug) is about 2 to 200 parts by weight, preferably in terms of the raw drug. About 5 to 100 parts by weight, more preferably a combination of about 10 to 50 parts by weight based on the native drug. In addition, when the crude drug powder or extract of Scutellaria baicalensis is converted into a native drug in an amount of 1 part by weight, the peel (converted into a native drug) is about 1 to 100 parts by weight, preferably about 2 to 50 parts by weight, more preferably A combination of about 3 to 30 parts by weight based on the native medicine is suitable. When the crude drug powder or extract of Coptis chinensis and Scutellaria baicalensis can be converted into a native drug in an amount of 1 part by weight, the peel (converted into a native drug) is about 1 to 200 parts by weight, preferably about 5 to 1 in terms of a native drug. It is more preferably a combination of about 10 to 50 parts by weight. Moreover, in this case, the combination ratio of Coptis chinensis and Cotinus coggygria is crude drug powder or extract of Coptis chinensis, which is converted into native medicine by 1 part by weight, and scutellaria (converted into native medicine) is 0.02 to 30 parts by weight. The amount is about 0.5 to 10 parts by weight, and more preferably about i to 3 parts by weight. ^

C: \ ProgramFiles \ Patent \ 310650.ptd Page 7 592706 V. Description of the invention (5) The gastrointestinal drug of the present invention is preferably another at least one histamine h2 receptor antagonist, a proton inhibitor, and gastric mucosal defense Type of gastritis • Peptic ulcer treatment, antacid and antidiarrheal combination. Histamine H2 receptor antagonists include, for example, acetonitrile, Ranitidine, Famotidine, Roxatidine, Nizatidine, and the like Among them, pharmacologically acceptable hydrazones or derivatives may be selected from one or more of them. Examples of pharmaceutically acceptable derivatives or derivatives include ranitidine and ranitidine, and derivatives of rosidine, and rosatidine, and derivatives of rosidine, and rosatidine acetate, and the like. Proton capsule inhibitors can be exemplified by numtropazole, omiprazole, pantepril (? 〇] 11: 1) 133〇1), rabepox, leminoplasol, and the like Pharmaceutically acceptable tinctures can be selected from among them and used. In order to use num Thorpe 0 sit, Ome Pu. It is better to sit or sniff. Proton capsule inhibitors are preferably used in combination with the antacids shown below, or they can be controlled by enteric preparations or stabilizing preparations (for example, basic inorganic dysprosium of magnesium or calcium) to control the effect on gastric acid. Lunar membrane defensive gastritis • Peptic ulcer treatments can be exemplified by Aldioxa, Pf, Metamagnesium Alumino Silicate, Sucralfate, Promid (Proglumide), Teprenone, Cetraxate HC1, piaunoto, Sofalcone, Beneky satopetadesk , Irsogladine maleate, Rabamite, Sodium Ecalate, Prapridine

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Moiypreding), etc., from which to choose-more than one use. Desucletide, Sicherash, teprodone or sofacant are: β The use of antacids can be exemplified by anhydrous chlorine oxide knee, magnesium oxalate, synthetic aluminum silicate, synthetic water Talc, Nuxi preparation, long mouth and feet, κ, pore-forming rank wind emulsified chain magnesium, lice emulsified aluminum glue, lice alumina, sodium bicarbonate co-precipitate, magnesium hydroxide mixed anhydrous glue, aluminum hydroxide, magnesium carbonate, and carbonic acid Calcium co-precipitates, magnesium hydroxide, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, meta-silica ^ Magnesium aluminate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate and other non-mechanical acid drugs; amino acid agents such as aminoacetic acid ; Dihydroxyaluminum aminoacetate; Japanese ^ belladonna extract, etc., select one or more of them for use. Antidiarrheal agents can be exemplified by bismuth agents (for example, bismuth salicylate, bismuth hyponitrate, bismuth hypocarbonate, bismuth hypogallate, etc.), tannins (for example, tannin, tannin albumin , Thorium thymol tannin, etc.), one or more of which can be selected for use by τ. Among them, a bismuth agent that is particularly effective against Helicobacter pylori is preferred. The gastrointestinal drug of the present invention must contain at least one selected from Areca, Punica granatum, Licorice root, and Cimicifuga rhizome , Artemisiae capillaris herba, Corydalis tuber, Senna, perilla herb, Actium lappa, Salviae miltiorrhizae, Forsythiae f ructus, peony Moutan cortex, Crataegus, Aconitum carmichaeli, Honeysuckle (Loicwra japonica), Cyperus rh i zome, Carnation (C ar t ham i)

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V. Description of the invention (7) flos), Lindera strychnifolia, Lotus family (Lotus seed), Rhubarb, Ginger, Sophora root, Aloe Peony root, peony root, Clove, Scutellaria root, Immature orange, Magnolia bark, etc., or at least one kind of ginger, Herbal powder or extract of yellow answer, stalk, clove, licorice, Magnolia officinalis or Yanhusuo. The crude drug powder and extract used in the present invention can be used as a single-drug or traditional Chinese medicine prescription since ancient times, and the crude drug powder or extract prepared according to a conventional method can be directly used. The form of the crude drug powder or extract may be a commercially available product or a processed product thereof. For the crude drug powder, for example, a dried filamentous processed product can be further pulverized into a finer powder or a finely powdered dried product (drug powder). In addition, the form of Shengle's extract is not particularly limited. For example, it can be used in any form such as dry extraction powder, extraction powder, paste extract, liquid extract, alcohol or tincture containing alcohol and water. It is preferable to use an extract having a high degree of freedom in formulation, such as a dry extraction powder. The extract can be obtained by a conventional method, for example, using a solvent to extract an active ingredient having an anti-Helicobacter pylori effect from the pharmaceutical described in the present invention. As the extraction solvent, for example, water, a hydrophilic solvent, or a mixture of these is mostly used. Examples of the hydrophilic solvent include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, second butanol, and third butanol (preferably methanol, ethanol, propanol, Isopropyl alcohol and other water-soluble alcohols with about 1 to 3 carbon atoms, more preferably ethanol); Methylcellosolvin and ethylcellosolvin, etc .; ketones, such as acetone; dioxane, tetrahydrofuran, etc. Ethers; pyridine, morpholine, acetonitrile, N, N-dimethyl

592706 V. Description of the invention (8) Nitrogen solvents such as formamidine, dimethylacetamide, and N-f-pyrrolidine. The ★ and other hydrophilic solvents can be used alone or in combination of two or more. In order to efficiently extract components having anti-Helicobacter pylori activity, it is preferable to use, for example, the above-mentioned alcohols, or a mixed solvent of the above-mentioned alcohols and water as an extraction solvent. When a mixed solvent of water and a hydrophilic solvent is used as the above-mentioned extraction solvent, water is "hydrophilic"; the ratio of cereals is, for example, water / hydrophilic solvent = about 95/5 to about 5/9 5 (weight ratio) , Preferably water / hydrophilic solvent = about 90/100 to about 50/50 (weight ratio), particularly preferably about 85/15 to about 60/40 (weight ratio). The extraction operation is performed at Appropriate temperature, for example, the reflux temperature of the solvent to the solvent, preferably in the range of about 15 to 70 ° C. Also, it can be cold-soaked at room temperature for extraction. The extraction solution obtained by extraction with the extraction solvent can be directly It is used as an extractor or diluted with water. The extracted extract can also be concentrated and used as a concentrated extract. Generally, most of the concentrated extracts obtained by concentrating the extraction solution or adding necessary additives to the extract ， Dry extract powder obtained by powder drying by spray drying method, freeze drying method, etc. The amount of crude drug powder or extract of Coptis chinensis, Cotinus coggygria and Chenpi used in the gastrointestinal medicine of the present invention is antibacterial to Helicobacter pylori An effective amount is sufficient, and there is no particular limitation. When administered to humans, it varies depending on the dosage form, route of administration, target of treatment, degree or type of symptoms, for example, it is administered to adults (60 kg in weight) about once a day, and Coptis chinensis in the amount of about 0.1 to 0.1 10 g, preferably about 0.03 to 6 g; Scutellaria baicalensis, about 0.000 to 20 g, preferably about 003 to 10 g; tangerine peel, about 0.01 to 50 g, preferably about 0.03 Up to 10§. There are no special restrictions on the number of administrations, which can be administered once a day or in fractions. Histamine H2 receptor antagonists, usually acetonitrile and ranitide C: \ ProgramFiles \ Patent \ 310650.ptd Page 592706 Description of the invention (9) Any one of hydrazone, morphotidine, rosatidine, nizatidine, etc. In these groups, the amount of amine I receptor antagonists can be appropriately selected by those skilled in the art, Let's set it up. It is good to use the dosage range for medical treatment (for example, the adult (kg) mother day is about 1 to 800 mg). For example, the adult (60 kg) daily dosage It is preferably about 10 to 8001112, ranitidine is preferably ranitidine gallate, 15 to 300 mg, morphinidine is preferably about 1 to 40 mg, and rosartidine is Vinegar acetic acid roxatidine given, preferably from about 5 to 150mg, preferably from about 3〇 nizatidine given to 300mg. In addition, the administration times can be appropriately set and the usage.

The dosage of the proton inhibitor of s proton is preferably used in the same range as that used for general treatment (for example, an adult (60 kg) per day is about 0.001 to ⑽ ⑽ ^). The artist can select and set it appropriately. For example, the adult (6Qkg) is preferably about 0.01 to SO mg per day of ampthopramine, and preferably about 0.001 to 20 mg of omeprazole.

It can also be administered once or daily in two to three times. The period of administration should not exceed the 8-week period compared with the treatment standard for gastric ulcer, and the 6-week period compared with the treatment standard for duodenal ulcer. These proton capsule inhibitors are used in combination with (1) crude drug powder or extract of Coptis chinensis and / or Scutellaria baicalensis and (2) crude drugs or extracts of chrysanthemum to obtain gastrointestinal diseases caused by Helicobacter pylori. Stronger and faster treatment or prevention of recurrence, the results vary depending on the dosage form, route of administration, treatment target, degree or type of symptoms, etc. Generally speaking, gastric ulcer is treated for 8 weeks and duodenal treatment is available for 6 weeks during the administration period Full effect. Lupus anti-type gastritis and peptic ulcer treatment drugs are generally used (for example, adults (60kg) about 0.01 to 360 Omg daily), this technology

C: \ ProgramFiles \ Patent \ 310650.ptd Page 12 592706 V. Description of Invention (ίο) The artist can choose and set it appropriately. The number of injections can be set according to the medically set conditions, and it is better to consider together with other ingredients, and it is advisable to administer it once or divided into 2 to 4 times.

The antacids are generally used in the dosage range, and these antacids can also be used in combination of more than one kind. For example, the maximum daily use amount of an inorganic antacid is about 1 to 30 g, and the minimum daily use amount is 1/1 000, that is, about 0.001 to 0.3 g. The amino acid of the amino acid agent is about 0.01 to 2 g per day for adults (60 kg); the dihydroxyaluminum aminoacetate is about 0.1 to 10 g per day for adults (60 kg). ; Buttercup extract, adult (60kg) daily dosage of about 0.1 to 100mg. The skilled person can appropriately select and set the dosage. Antidiarrheal drugs are generally used in the range of dosage, such as syrup, adult (60kg) daily dosage of about 0.01 to 10 tannins, adult (60kg) daily dosage of about 0.01 to 10g. The skilled person can appropriately select and set the dosage. These histamine H2 receptor antagonists, proton capsule inhibitors, gastric mucosal defense-type gastritis, peptic ulcer treatments, antacids, antidiarrheals can also be combined or combined with other gastrointestinal ingredients such as digestion Active ingredients such as medicine, intestinal remedy, analgesic and spasm medicine, mucosal repair medicine, antifoaming agent dimethyl polysiloxane.

The gastrointestinal drugs of the present invention are generally administered orally. The type of oral preparation of the gastrointestinal drug is not particularly limited, and may be a solid preparation such as a doubt, a granule, a fine granule, a pill, a capsule, a chewable tablet, or a liquid preparation such as a syrup, a suspension, or an emulsion. . When manufacturing a preparation, a conventional carrier may be used depending on the kind of the preparation. For example, in the manufacture of solid formulations, conventional ingredients that can be used are, for example, starch,

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> 1-, recorded sugars such as λ μ mannitol, corn starch; crystalline fiber 肀 · L, excipients, light anhydrous silicic acid and other excipients; polyvinyl alcohol, ^ tannin, sundial ^ Ketones, -Polyvinyl ether, ethyl cellulose, gum arabic, sira /, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, lemon, dextrin, pectin and other binders; magnesium stearate , Calcium stearate, slippery: Formazan: Lubricants such as colloidal silica; disintegrating agents such as starch, ^ methyl cellulose, m cross-linked lean methyl cellulose, disintegration aids, and humectants Or surfactants.

In addition, for the purpose of covering taste, imparting entericity or persistence, it can be made into an oral preparation by the coating method. The coating agent can be, for example, hydroxypropyl methacrylate, vitamins, ethyl cellulose, hydroxymethyl cellulose, hydroxypropyl fibers, polyethylene oxide, Tween 8 (), and polyether (pluronic). F68, Cellulose Acetate from Sodium Acetate, Hydroxypropyl Methyl Cellulose Phthalate, Hydroxymethyl Methyl Cellulose, Quaternary Acetate Stearate, Eudrakit (Rhom, Germany) =) Co., Ltd., methacrylic acid / acrylic acid copolymer), and pigments such as titanium oxide and red pigment. Preferably, for example, an oral preparation can be prepared according to the method described in Japanese Patent Publication No. 3-38247 or by referring to this method.

Liquid preparation can use conventional ingredients, such as water (including water for injection), ethanol, ethylene glycol and other solvents; ethanol, polyethylene glycol, propylene glycol, mannitol, cholesterol, triethanolamine, sodium carbonate, sodium citrate and other auxiliary Solvents; Surfactants such as stearyl triethanolamine, sodium lauryl sulfate, lecithin, glyceryl monostearate; polyethylene glycol, polyvinylpyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, hydroxyl Suspensions of hydrophilic polymers such as methyl oryzin, hydroxyethyl cellulose, and propyl cellulose; rhenium phosphate, beta

592706

Buffers such as osmium carbonate, osmium carbonate, osmium citrate, etc. In the solid preparation or liquid preparation, if necessary, amino acids and the like. Chemical agents, emulsifiers, dispersants, tackifiers, preservatives, solubles, colorants, wall flavors, sweeteners, fragrances, etc. Wanli tincture and antioxidant The gastrointestinal drug of the present invention can be manufactured by conventional methods such as β training, granulation, tabletting, coating, sterilization, emulsification and the like depending on the type of preparation. ", The general provisions of the Japanese Ledian preparations have been safely used as medicinal raw medicines to include humans. The gastrointestinal drugs of the present invention are based on ancient ingredients and have no toxic side effects. Therefore, they are mammals. The intestinal medicine of the present invention is effective in treating various gastrointestinal diseases caused by Helicobacter pylori, including gastritis, gastric ulcer, duodenal intestinal ulcer, etc., and the treatment and prevention of recurrence of gastric cancer. ^ The gastrointestinal medicine of the present invention is not only (1) The mixture of the crude medicinal powder or extract of Coptis chinensis and / or Scutellaria baicalensis and (2) the crude medicinal powder or extract of Citrus sinensis can also be used to make various formulations with various active ingredients, and the same object can be administered at the same time or at different times. The above-mentioned crude drug powder or extract is not only capable of antagonizing at least one histamine H2 receptor; a proton capsule inhibitor; a gastric mucosa defense against pear's gastritis • a peptic ulcer treatment; an antacid; an antidiarrheal agent; the above-mentioned Mixtures of crude drug powders or extracts other than Coptis chinensis, Scutellaria baicalensis, and Chenpi can also be used together with other active ingredients to make various formulations, at the same time or staggered. The same object administration.

592706 V. Description of the invention (13) [Implementation style of the invention] In the following, examples are given to explain the present invention. The invention is not limited to these embodiments. [Example] Reference Example: Dry extract powder production 50 g of Coptis chinensis filaments was added to about 7 bodies, ^ ^ Λ. 30% by volume of an aqueous solution of alcohol at 50 C, 30r dm 撙Pull π — ^, · p · m · Stir extraction for 1.5 hours. Filter by standard f (size 7 5 to m) to residues q q lin, soil 1 a /, Mao / check with 30 volumes 150% alcohol solution in water was washed. The recovered filtrate and washing solution were combined and attracted and splashed. The solution was concentrated under reduced pressure to 50 ° C at 50 ° C. The thief / nongshizhu aum1 was obtained to obtain a soft extract. The soft extract was obtained from the dried extraction powder by freeze-drying for 2 to 4 hours. The dried powder of bark and bark was obtained by the same method. Test example Helicobacter pylori proliferation inhibition test, using the obtained from the reference example The dried powders of Coptis chinensis, Huang Le and Chenpi were tested for their anti-Helicobacter pylori activity by a pidgin plate dilution comparison method. The dry extraction powder was dissolved in sterilized distilled water and made into a 2-fold dilution series with sterilized water. And composed of various dilution series of extract 2 ml of the test sample and 18 ml of Prussian arugula (] Brucel la agar) medium supplemented with 7% horse serum were mixed to make a plate for testing. The test strain used (a) clinical isolates CPY43 3, TN2, TN58, (b ) Metronidazole resistant strain NCTC11916. CPY433 and NCTC11916 are described in the European Journal of Clinical Microbiology and Infectious Diseases, Section η

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592706 V. Description of the Invention (14), pages 391 to 399, 1995 (European Journal of Clinical Microbiology and Infections Disease, 14,391-399, (1995). Also, it is equivalent to 92-244 of TN 2 and TN The 91-196 of 58 can be cultured from those obtained from Oita Medical University. The above-mentioned test bacteria can use Bruceiia broth medium supplemented with 2.5% bovine embryo serum, and are inserted with Campy PakTM (BBL BBL Beckton Dickinson Microbiology system (BBL Beckton Dickinson Microbiology system) in a gas-filled tank, shaking culture at 37 ° C for 20 hours. Using the same medium, adjust the above bacterial solution to a concentration of about 106CFU (colony forming unit) / 5 ml of each, inoculated on each agar plate for measurement, and cultured in a gas-filled tank inserted with absorbent cotton containing Campy PakTM and water, and cultured at 37 ° C for 4 days. After cultivation, observe the bacteria with the naked eye Grow with the lowest concentration at which growth cannot be confirmed as the MIC (Minimum Growth Inhibition Concentration) of the extract to be tested. Confirm the strongest interaction >> Degree, and find the graded inhibitory concentration of each of the two stroke extracts. FIC (fractional inhibitory concentration), the two kinds of the FIC extracts were calculated from the sum of FIC index .FIC indicators described in Krogstad DJ, Mollering RC; Antimicrobial combinations In.

Lorian Vced): Anti-biotics in laboratory medicine · Williams & wilkins, Baltimore, 1 986, p537-595. Based on this, it is determined that when the FIC index is less than 0.5, it is a multiplicative effect, > 0.5 to 丨 · 〇 is an additive effect, > 1.0 to 2.0 is no interaction (no effect), and greater than 2.0 is an antagonistic effect. The results are shown in Table 1. Table 1 shows the F 1C value obtained from the value of each individual MIC and the combined (combined) MIC and the FIC index obtained from the sum.

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V. Description of the invention Table 1 (15) Antibiotic active strain FIC of H. pylori linked with a crude drug extract (a combination of MIC / 氺 箪 一 MIC) _ FIC index Coptis chinensis CPY433 0 · 5 0 (62 · 5/1 25 ) 0. 5 0 (1 25/250) 1.00 TN2 0. 5 0 (62. 5/1 25) 0.5 0 (1 25/250) 1.00 TN58 0 · 5 0 (62 · 5/1 25) 0.5 0 ( 1 25/250) 1.00 NCTC1 1 91 6 0. 5 0 (62. 5/1 25) 0.5 0 (1 25/250) 1.00 Coptis Chinensis CPY433 0.13 (15. 6/125) ^ 0. 2 5 (5 00 / ^ 200 0) $ 0 · 38 TN2 0 · 13 (15.6 / 125) ^ 0. 2 5 (5 00 / ^ 200 0) is 38 TN58 0 · 13 (15 · 6/125) $ 0.2 5 (5 0 0 / ^ 200 0) $ 0.38 NCTC 11916 0. 13 (15. 6/125) 2 5 (5 00/2 2000) < 0.38 Huangpi Chenpi CPY433 0. 2 5 (6 2. 5/250) $ 0 2 5 (5 00 / $ 2000) $ 0 · 50 TN2 0. 2 5 (6 2. 5/250) $ 0 · 2 5 (5 00/2 2000) $ 0 · 50 TN58 0 2 5 (62 · 5 / 250) Dragon 13 (250 / ^ 2000) $ 0.38 NCTC 11916 0.2. 5 (6 2.5 / 250) $ 0 · 2 5 (5 00/2 2000) $ 0 · 50 * The unit of MIC and separate MIC is [# g / ml] FIC index of Coptis chinensis and Cotinus coggygria is 1 for addition , One hand, when the F 1C indicator when the berberine or HuangBo with orange peel and used as $ 0.38 to $ 0 1.5 0 indicates synergistic action, especially when the Rhizoma Coptidis with orange peel and may determine that have significant synergistic action when used.

C: \ ProgramFiles \ Patent \ 310650.ptd Page 18 592706 V. Description of the invention (16) Specifically, compared with the agronomic activity of Coptis chinensis and Cotinus coggygria showing anti-Helicobacter pylori activity, respectively, the addition of tannins can enhance the 8 Times, Scutellaria baicalensis can increase the activity by about 4 times. In addition, compared with the undulation of anti-Helicobacter pylori activity of Chenpi alone, the addition of Coptis chinensis or Scutellaria baicalensis increased the activity by 4 times or more, respectively. It can be seen that when Coptis chinensis or Cotinus coggygria is combined with Chenpi, it can be judged that it has a significant multiplication effect. Eighth, when reviewing the effect of Coptis chinensis, Cotinus coggygria, and Chenpi in the same way as the above test, it was found that when copier was used together, the MIC value was reduced to less than 1/4 of that of Coptis chinensis and Cotinus coggygria. From the fact that the M 1C value of Coptis chinensis and Cotinus coggygria to Helicobacter pylori was significantly reduced when the three doses were used in combination, it was found that the use of Chenpi in Coptis chinensis and Cotinus coggygria significantly increased the activity against H. pylori. Hereinafter, the formulation examples of the present invention will be specifically described, but the present invention is not limited thereto. In addition, in the following examples, unless specifically stated, the amount of each component represents the amount of adult (60 kg) per day, which is obtained by conventional preparation. Example 1 (Prescription) Coptis chinensis dry extract powder, dried peel, dried peel powder, nitrile imidamine, Sucret, crystalline cellulose starch, hydroxypropyl cellulose, lactose, 1 dose per adult (in 3 packs) (mg) 10 250 300 1,500 1,200 450 180 520

C: \ ProgramFiles \ Patent \ 310650.ptd P.19 592706 V. Description of the invention (17) > 4,410 According to the above formula, a mixed powder is made. According to the general principles of the Japanese Pharmacopoeia, granules are subject to manufacture. . Example 2 (Prescription) Scutellaria baicalensis dry extract powder, dried peel peel powder, scutellaria baicalensis dry extract powder, synthetic hydrotalcite, bismuth gallate, crystalline cellulose starch, hydroxypropyl cellulose, lactose, total adult dosage (3 packs) ) [Mg] 50 500 450 700 800 1,000 900 600 180 _ 690 5, 870 According to the above prescription, granules are manufactured according to the general principles of the pharmacopoeia preparations and granules. Example 3 [Nude spin]

(Prescription) 1-day dose for adults (in 9 tablets) [mg] Coptis chinensis extract powder 10 Cotinus chinensis extract powder 20 Citrus bark extract 300 C: \ ProgramFiles \ Patent \ 310650.ptd Page 20 592706 V. Description of the invention ( 18) Ginger dry extraction powder 500 Methonitrile 300 Crystalline cellulose 444 Starch 295 Hydroxypropyl cellulose 103 Magnesium stearate 20 Lactose 700 Total 2, 692 [Sugar bond] Naked bond 2, 692 Talc 1, 141.1 Gum arabic 75. 3 Titanium oxide 46 · 3 White sugar 1,104 · 3 Total 5,059. 0 According to the above prescription, the general principles of the Japanese Pharmacopoeia preparations, the tablets are naked tablets and sugar-coated tablets. Example 4 (Prescription) Adult dosage (60ml dried Coptis chinensis extract powder 10 mg dried scutellaria baicalensis extract powder 30 mg dried peel peel powder soil 600 mg hydroxide 1,000 mg aluminum hydroxide colloid 60 0 mg

C: \ Program Files \ Patent \ 310650.ptd Page 21 592706 V. Description of the invention (19) Nitrile imidamine refined white sugar 0 · 6mg Appropriate amount of butyl p-hydroxybenzoate flavoring agent 钠 sodium oxide refined water (add to full amount ) 60 melon 1 According to the above prescription, the liquid formulation is based on the general provisions of the pharmacopoeia preparation and the liquid formulation. After filtering, sterilize and fill the glass bottle. [Effects of the invention] The gastrointestinal drug of the present invention exhibits stronger antibacterial activity, especially its activity against Helicobacter pylori. In addition, there is no need to worry about side effects such as appearance, symptoms, or diarrhea, and bacterial resistance. Furthermore, allergies to several substances are used for the prevention and treatment of bowel disease and prevention of recurrence by Helicobacter pylori, especially as a gastrointestinal drug. In addition, various kinds of gastritis and gastric ulcers, such as gastritis and gastric ulcers, are expensive and have a bitter taste, which is difficult to import. Coptis or medicinal powder or extracts are particularly small, so it can provide easy to take and the amount of scutellaria can be reduced and more. The preparation is also economically advantageous. C: \ ProgramFiles \ Patent \ 310650.ptd page 22

Claims (1)

592706 Case No. 88109752 Rev. G Date ] () 650 (Revised version) .ptc Page 24 592706 Amendment No. 88109752 Sixth, the scope of patent application The anti-oxidant is cyanamide (c i m e t i d i n e) or one which is pharmacologically acceptable. 8. The gastrointestinal drug according to item 5 of the patent application is a combination of antacids. 9. The gastrointestinal drug according to any one of claims 1 to 3 is in the form of a mixture. 10. If the gastrointestinal drug according to any one of the claims 1 to 3 of the scope of patent application, the active ingredients are formulated into a form, and can be administered at the same time or at different times. 3] 0650 (revised) .pic p. 25