JP2000063280A - Anti-helicobacter pylori active gastrointestinal drug - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a gastrointestinal drug which contains the combination of Coptidis rhizoma and/or Pbellodendri cortex puverata and Aurantii nobilis pericarpium pulveratum, possesses anti-Helicobacter pylori activity and is useful in the prevention, the treatment or the recidivation prevention for gastritis, gastric ulcer, duodental ulcer or the like. SOLUTION: This gastrointestinal drug is obtained by including the combination of (A) Coptidis rhizoma and/or Phellodendri cortex pulverata or extracts and (B) Aurantii nobilis pericarpium pulveratum or extract. On this gastrointestinal drug, it is favorable to use 2-200 pts.wt. of the raw crude drug of the component B based on 1 pt.wt. of the raw crude drug of the component A. Further, it is favorable that this gastrointestinal drug includes at least one kind of histamine H2 receptor antagonist (e.g. cimetidine or the like), proton pump inhibitor (e.g. lansoprazole or the like), gastric mucosa protection type gastritis-peptic ulcer therapeutic drug (e.g. aldioxa or the like), antacid and stegnotic. On the amounts of the components A and B used, Coptidis rhizoma and Phellodendri cortex or Aurantii nobilis pericarpium are preferably used at daily doses of 0.03-6 g and 0.03-10 g, respectively, per an adult based on the raw crude drugs.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a gastrointestinal drug in which a crude drug powder or extract component of Coptis chinensis and / or Oataku is combined with a crude drug powder or extract component of Chimpi.
This gastrointestinal drug has anti-Helicobacter pylori activity and gastritis,
It is useful for prevention, treatment and recurrence prevention of gastric ulcer, duodenal ulcer, etc.

[0002]

2. Description of the Related Art It is already known that certain herbal medicines have an antibacterial action against Helicobacter pylori. For example, Japanese Unexamined Patent Publication No. 8-295632 discloses a Helicobacter pylori antibacterial agent containing at least one crude drug powder such as Coptis or extracted components, and Japanese Unexamined Patent Publication No. 10-109942 discloses (a) a crude drug having anti-Helicobacter pylori activity. Pharmaceutical composition containing powder or its extract and (b) at least one of histamine H ₂ receptor antagonist, proton pump inhibitor, gastric mucosa-protective gastritis / peptic ulcer therapeutic agent, antacid and antidiarrheal The thing is described, and ouren etc. are described as this crude drug. 47th Annual Meeting of the Japanese Society of Oriental Medicine
Proceedings, May 1996, page 78, PPI for ulcer cases in right column
Alternatively, it is described that a H ₂ blocker was administered, followed by administration of one of the Kampo medicines, Heishigan.

[0003]

As a therapy for eradicating Helicobacter pylori, one or more penicillin-based therapies,
The mainstream is a combination of three antibiotics such as cephalosporins, tetracyclines, new quinolones, macrolides and bismuth preparations, proton pump inhibitors (PPI), but antibiotics have a strong eradication effect. There are side effects such as hypersensitivity and diarrhea, and the emergence of resistant bacteria. Therefore, it contains a herbal medicine component that has a stronger anti-Helicobacter pylori activity, which is effective in the prevention or treatment of gastrointestinal diseases such as gastritis, gastric ulcer, and duodenal ulcer caused by Helicobacter pylori infection, and is extremely safe for the human body. The development of a gastrointestinal drug that can be used is desired.

[0004]

[Means for Solving the Problems] As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the combination of specific crude drugs exerts a Helicobacter pylori growth inhibitory activity synergistically. Conventional Helicobacter
Histori H ₂ receptor antagonists or proton pump inhibitors (eg, lansoprazole, rabeprazole, omeprazole, etc.), which are said to have no or very weak antibacterial activity against Helicobacter pylori, gastric mucosa-protective gastritis / peptic ulcer By combining therapeutic agents, bismuth agents, and antacids that are commonly used clinically in gastritis, etc., surprisingly significant preventive, therapeutic, and recurrence-preventive effects on gastritis, gastric ulcer, duodenal ulcer, etc. can be obtained. It was found that the present invention has been completed. That is, the present invention relates to (1) a gastrointestinal drug having an anti-Helicobacter pylori activity, which comprises a combination of a crude drug powder or extract component of Oren or Oataku and a crude drug powder or extract component of Chinpi,
(2) The gastrointestinal drug according to the above (1), wherein about 2 to 200 parts by weight of the crude drug powder of chimpi or the extracted component in terms of the crude drug is used per 1 part by weight of the crude drug powder of Oren or the extracted component in terms of the crude drug. 3) The gastrointestinal drug according to (1) above, wherein about 1 to 100 parts by weight of the crude drug powder of Chingpi or the extracted component is converted to 1 part by weight of the crude drug powder of Oataku or the extracted component. ) A gastrointestinal drug according to the above (1), wherein about 1 to 200 parts by weight of crude drug powder of chimpi or the extracted component is converted to 1 part by weight of the crude drug powder or extracted component of oren and Oataku. 5) The gastrointestinal drug according to (1) above, which is a preventive or therapeutic drug for gastrointestinal diseases caused by Helicobacter pylori infection, (6) histamine H ₂ receptor antagonist, proton pump inhibitor, gastric mucosal protection type Gastritis Peptic ulcer therapeutic agents, gastrointestinal agents according to the above (1) comprising at least one antacid and antidiarrheal, (7) gastrointestinal agents according to the above (1) comprising a histamine H ₂ receptor antagonists, (8) Histamine
The gastrointestinal drug according to the above (7), wherein the H ₂ receptor antagonist is cimetidine or a pharmaceutically acceptable salt thereof, (9) the gastrointestinal drug according to the above (1), including an antacid drug, (10) As a crude drug component, (1) a gastrointestinal drug comprising a crude drug powder or an extract component of oren and / or an ox and (2) a crude drug powder or an extract component of chimpi, (11) a histamine H ₂ receptor antagonist, a proton pump inhibitor, a stomach The gastrointestinal drug according to (10) above, which comprises at least one of a mucosa-protective drug for treating gastritis / peptic ulcer, an antacid, and an antidiarrheal;
A gastrointestinal drug having an anti-Helicobacter pylori activity, which comprises the crude drug powder or extract component of Oataku and Chimp, and (13) a crude drug powder or extract component of Chimpi for enhancing the anti-Helicobacter pylori activity of Oren and / or Opac Regarding usage.

The gastrointestinal drug of the present invention comprises (1) a combination of a crude drug powder or an extract component of Coptis chinensis and a crude drug powder or an extract component of Chimpi, and (2) a crude drug powder or an extract component of Oataku and a crude drug powder or an extract component of Chinpi. A combination of
Alternatively, (3) a medicine characterized by a combination of a crude drug powder or extract component of Oren and Oataku and a crude drug powder or extract component of Chimpi. In particular, a combination of a crude drug powder or extract component of Coptis and a crude drug powder or extract component of Chimpi is preferable. These crude drug powders or extracted components may be used in combination as separate preparations or may be used as a mixture. The ratio of these (1) Coptis vulgaris or / and the crude drug powder or extract component of Oat and (2) The crude drug powder or extract component of Chingpi can be appropriately selected, but it is easy to take and compared to cheap Chimpi. Coptis and Oat are extremely bitter and very expensive. In the gastrointestinal drug of the present invention, the doses of Oren and Oataku can be relatively reduced based on the synergistic effect of the specific combination of crude drug components (see Test Example below). Considering the ratio of these crude drug combinations from this point of view, 1 part by weight of crude drug powder of Oren or the extracted component of the crude drug is equivalent to about 2 parts of the crude drug equivalent.
˜200 parts by weight, preferably about 5 to 100 parts by weight in terms of drug substance, and more preferably about 10 to 50 parts by weight in terms of drug substance. About 1 part by weight of crude drug powder or extract component of Oataku equivalent to crude drug, chimp is about 1 to 100 parts by weight, preferably about 2 to 50 parts by weight, and more preferably about 3 parts by weight of crude drug.
They can be combined in a proportion of ˜30 parts by weight. 1 part by weight of crude drug powder of both Oren and Oataku or the extracted component is converted into crude drug by about 1 to 2
The amount can be combined in an amount of 00 parts by weight, preferably about 5 to 100 parts by weight in terms of the drug substance, and more preferably about 10 to 50 parts by weight in terms of the drug substance. Further, the ratio of the combination of Coptis chinensis and Oataku at this time is 0.2 to 30 parts by weight of the crude drug of Ouren equivalent to 1 part by weight of the crude drug or the extracted component of the original drug, preferably about 0 of the original drug. 0.5 to 10 parts by weight, more preferably about 1 to 3 parts by weight.

It is preferable that the gastrointestinal drug of the present invention further comprises at least one of a histamine H ₂ receptor antagonist, a proton pump inhibitor, a gastric mucosa-protective drug for treating gastritis / peptic ulcer, an antacid and an antidiarrheal. . Examples of histamine H ₂ receptor antagonists include cimetidine, ranitidine, famotidine, roxatidine, nizatidine, and the like, and pharmaceutically acceptable salts or derivatives thereof.
One or more selected from these can be used. Examples of the pharmaceutically acceptable salt or derivative include, for example,
Ranitidine salts include ranitidine hydrochloride, and roxatidine derivatives include roxatidine acetate hydrochloride. Examples of the proton pump inhibitor include lansoprazole, omeprazole, pantoprazole, rabeprazole, reminoprazole and the like, and pharmaceutically acceptable salts thereof, and one or more selected from these can be used. Lansoprazole, omeprazole or rabeprazole are preferably used. Proton pump inhibitors should be used in combination with the antacids listed below, or by suppressing the effects of gastric acid by methods such as using enteric-coated preparations or stabilized preparations (eg, basic inorganic salts of magnesium or calcium). Is preferred.

[0007] Examples of gastric mucosa-protective agents for the treatment of gastritis / peptic ulcer include aldiquiosa, aldioxa / magnesium aluminometasilicate aluminate, sucralfate, proglumide, teprenone, cetraxate hydrochloride, plaunotol, sofalcone, benexate beta desk hydrochloride,
Ilsogladine maleate, rebapimide, sodium ecabet, polaprezinc and the like can be mentioned, and one or more selected from these can be used. Of these, sucralfate, cetraxate hydrochloride, teprenone or sofalcone are preferably used. Examples of the antacid include dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate,
Synthetic hydrotalcite, magnesium oxide, alumina magnesium hydroxide, aluminum hydroxide gel, aluminum hydroxide, sodium hydrogen carbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate Inorganic antacids such as precipitation products, magnesium hydroxide, sodium hydrogen carbonate, magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate; amino acid agents such as aminoacetic acid; Dihydroxyaluminum aminoacetate; funnel extract and the like, and selected from these 1
More than one seed is used. Examples of the antidiarrheal include bismuth agents (eg, bismuth subsalicylate, bismuth subnitrate, bismuth subcarbonate, bismuth subgallate, etc.), tannin agents (eg, tannic acid, albumin tannate, methylenethymol tannin, etc.) and the like. One or more selected from these can be used. Of these, a bismuth agent that acts effectively on Helicobacter pylori is particularly preferable.

The gastrointestinal medicine of the present invention may be used, if necessary, for example, areca (Areca) and eucalyptus (Punica granatu).
m), licorice (Licorice root), zebra (Cimicifu)
ga rhizome), Inchinko (Artemisiae capillaris)
herba), Engosaku (Corydalis tuber), Senna (Se
nna), perilla herb, burdock (Actium
lappa), Tanjin (Salviae miltiorrhizae), Forsythia (Forsythiae fructus), Buttonpi (Moutan corte)
x), hawthorn (Crataegus), hobushi (Aconitum car)
michaeli), Goldfish (Lonicera japonica), Louicwra japon
ica), kobushi (Cyperus rhizome), kouka (Cartha)
mi flos), oyster (Lindera strychnifolia), rennik (range, Lotus seed), rhubarb (Rhubarb),
Ginger, Gin, Sophora root, Aloe, Peony root, Peony root, Clove, Scutellaria root, Pheasant (Imma)
tureorange), Magnolia bark, etc., and at least one crude drug powder or its extract component, preferably at least the extract or extract component of Ginger, Gourd, Pheasant, Clove, Citrus, Koboku or Engosaku One kind may be further added.

The crude drug powder and the extract component used in the present invention have been used for medicinal purposes as plain or Kampo medicines since ancient times, and the crude drug powder or extract component obtained by a conventional method is used as it is. be able to. Regarding the form of the crude drug powder or the extracted component, an ordinary commercially available product or a processed product thereof can be used. As the crude drug powder, for example, a dry chopped product may be further finely pulverized to be used as a powdery or fine powdery dry product (crude drug dry powder). The form of the extracted component from the crude drug is not particularly limited, and for example, any form such as dry extract powder, extract powder, soft extract, flow extract, ethanol or tincture containing ethanol and water can be used. Preferably, an extract component having a high degree of freedom in formulation, such as a dry extract powder, is used.

The extract component can be obtained by a conventional method, for example, by extracting the active component having an anti-Helicobacter pylori action from the crude drug of the present invention with an extraction solvent. As the extraction solvent, for example, water, a hydrophilic solvent, or a mixture thereof is often used. As the hydrophilic solvent, for example, methanol, ethanol, propanol, isopropanol, butanol, isobutanol,
Alcohols such as s-butanol and t-butanol (preferably water-soluble alcohols having about 1 to 3 carbon atoms such as methanol, ethanol, propanol and isopropanol, more preferably ethanol); methyl cellosolve,
Cellosolves such as ethyl cellosolve; Ketones such as acetone; Ethers such as dioxane and tetrahydrofuran; Pyridine, morpholine, acetonitrile, N, N-
Examples thereof include nitrogen-containing solvents such as dimethylformamide, dimethylacetamide, N-methylpyrrodoline, and the like. You may use these hydrophilic solvents individually or as a mixed solvent of 2 or more types. In order to efficiently extract a component having anti-Helicobacter pylori activity, it is preferable to use, for example, the alcohol or a mixed solution of the alcohol and water as an extraction solvent. When a mixed solvent of water and a hydrophilic solvent is used as the extraction solvent, the mixing ratio of water and the hydrophilic solvent is, for example, water / hydrophilic solvent = about
95/5 to about 5/95 (weight ratio), preferably water / hydrophilic solvent = about 90/10 to about 50/50 (weight ratio), particularly preferably about 85
/ 15 to about 60/40 (weight ratio). The extraction operation is carried out at a suitable temperature, for example, about 10 ° C to the reflux temperature of the solvent, preferably about
It is performed at about 15-70 ℃. It is also possible to perform cold immersion extraction at room temperature. The extract extracted with the extraction solvent may be used as it is as an extraction component, may be diluted with water, or may be used as a concentrated extract obtained by concentrating the extracted extract. Usually, in many cases, an additive is added to a concentrated extract or extract obtained by concentrating the extract, and the powder is used as a dry extract powder powdered by a method such as spray drying or freeze drying.

The amount of the herbal medicine powder or extract component of Coptis chinensis, Oataku and Chinpi used in the gastrointestinal drug of the present invention is not particularly limited as long as it is an effective amount for exhibiting an antibacterial activity against Helicobacter pylori, and when administered to humans. , Oral dosage form, administration route, treatment target, degree and type of symptoms, etc., for example, for adult (body weight 60 kg) per day equivalent to crude drug, about 0.01 to 10 g, preferably about 0.03 to 6 g for lauren; About 0.01 to 20 g, preferably about
0.03 to 10g; about 0.01 to 50g for chimp, preferably about 0.03
~ 10g. The frequency of administration is not particularly limited, and the administration can be performed once a day or divided into several times. As the histamine H ₂ receptor antagonist, usually any one kind of cimetidine, ranitidine, famotidine, roxatidine, nizatidine and the like is used. The dose of these histamine H ₂ receptor antagonists can be appropriately selected and set by those skilled in the art. Usually, it is preferable that the dose range used for treatment is medically (for example, about 1 to 800 mg per day for an adult (60 kg)). For example, the daily dose for an adult (60 kg) is preferably about 10 to 800 mg cimetidine, ranitidine is preferably about 5 to 300 mg ranitidine hydrochloride, and famotidine is preferably about 1 to 4 mg.
0 mg, roxatidine is roxatidine hydrochloride hydrochloride preferably about 5-150 mg, nizatidine preferably about 30-30
It is 0 mg. Further, the administration frequency and usage can be set appropriately.

[0012] The dose of the proton pump inhibitor is in the dose range used in usual treatment (eg, adult (60 kg)).
It is preferably used at about 0.01 to 100 mg per day). The dose can be appropriately selected and set by those skilled in the art. For example, the daily dose for an adult (60 kg) is preferably about 0.01 to 30 mg of lansoprazole and about 0.01 to 20 mg of omeprazole. The number of administrations may be once or divided into 2 to 3 times a day, but not more than 8 weeks according to the gastric ulcer treatment standard and 6 weeks according to the duodenal ulcer treatment standard. The administration period is preferred. These proton pump inhibitors are
(1) A combination of a crude drug powder or extract component of Coptis chinensis and / or an oyster plant and (2) a crude drug component obtained by combining a crude drug powder or extract component of Chingpi makes the gastrointestinal diseases caused by Helicobacter pylori stronger and faster. As a result of treatment and prevention of recurrence, it varies depending on the dosage form, administration route, treatment target, degree and type of symptoms, etc., but generally 8 weeks for gastric ulcer treatment and 6 for duodenal ulcer treatment.
A sufficient effect can be obtained with a weekly administration period.

[0013] Gastric mucosa-protective gastritis / peptic ulcer therapeutic agents are generally used in doses (eg, adult (60 kg))
A person skilled in the art can appropriately select from about 0.01 to 3600 mg per day,
Can be set. The frequency of administration may be set according to the medical setting conditions, but it is preferably administered once or divided into 2 to 4 times as appropriate in consideration of the balance with other ingredients to be mixed.

The antacid is used in a generally used dose range, and one or more kinds of these antacid may be combined and blended. For example, the maximum daily usage of inorganic antacids is about 1 to 30 g.
And the minimum daily usage is 1/100 that is, about 0.01
~ 0.3g. Adults with amino acid acetic acid (60
kg) daily dose is about 0.01-2g, adult (60kg) daily dose of dihydroxyaluminum aminoacetate is about 0.1-10g
Is. Adult (60 kg) daily dose of Rohto extract is about 0.1 ~
It is 100 mg. The dose can be appropriately selected and set by those skilled in the art. Antidiarrheals are generally used in a dose range, for example, about 0.01 to 10 g for bismuth is the adult (60 kg) daily dose, and tannin is about 0.01 to 10 g for adults (60 k
g) Make the daily dose. The dose can be appropriately selected and set by those skilled in the art. These histamine H ₂ receptor antagonists,
In addition to proton pump inhibitors, gastric mucosa-protective gastritis / peptic ulcer remedies, antacids, antidiarrheal agents, other ingredients that are normally added as gastrointestinal agents, such as digestive agents, intestinal agents,
An active ingredient such as an analgesic / spasmodic agent, a mucous membrane repair agent, and an antifoaming agent dimethylpolysiloxane may be used together or blended.

The gastrointestinal drug of the present invention is usually administered orally. The type of the oral preparation of the gastrointestinal drug is not particularly limited and includes, for example, solid preparations such as tablets, granules, fine granules, pills, capsules, chewable preparations, or syrups, suspensions, It may be a liquid agent such as an emulsion. In the production of the preparation, a conventional carrier component can be used depending on the kind of the preparation. For example, in the production of solid preparations, conventional ingredients, for example, sugars such as starch, lactose, sucrose, mannitol and corn starch; excipients such as crystalline cellulose, carboxymethyl cellulose and light anhydrous silicic acid; polyvinyl alcohol, polyvinyl pyrrolidone, Polyvinyl ether, ethyl cellulose, gum arabic, tragacanth,
Binders such as gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, calcium citrate, dextrin, pectin; lubricants such as magnesium stearate, calcium stearate, talc, polyethylene glycol, colloidal silica; starch;
A disintegrating agent such as carboxymethyl cellulose, carboxymethyl cellulose calcium, and croscarmellose sodium, a disintegrating aid, a moisturizing agent or a surfactant can be used. Further, for the purpose of taste masking, enteric coating or sustainability, coating can be carried out by a method known per se to give an oral administration preparation. Examples of the coating agent include hydroxypropylmethyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, polyoxyethylene glycol, Tween 80, Pluronic
F68, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, hydroxymethyl methyl cellulose acetate succinate, Eudragit (manufactured by Rohm, Germany, methacrylic acid / acrylic acid copolymer), and pigments such as titanium oxide and red iron oxide are used. Preferably, for example, Japanese Patent Publication No. 3-38247
An oral administration preparation can be prepared by the method described or a method similar thereto.

For the preparation of liquid preparations, conventional ingredients such as water (including water for injection), solvents such as ethyl alcohol and ethylene glycol; ethanol, polyethylene glycol, propylene glycol, D-mannitol, cholesterol, triethanolamine, carbonic acid. Solubility aids such as sodium and sodium citrate; stearyl triethanolamine, sodium lauryl sulfate, lecithin,
Surfactants such as glyceryl monostearate; polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose,
Suspending agents such as hydrophilic polymers such as hydroxypropyl cellulose; buffering agents such as phosphates, acetates, carbonates, citrates; glucose, amino acids and the like can be used. The solid preparations and liquids, if necessary, preservatives, solubilizers, emulsifiers, dispersants, thickeners, plasticizers, adsorbents, flavors, colorants, flavoring agents, sweeteners, preservatives, Antioxidants and the like can be used.

The gastrointestinal drug of the present invention can be produced by a conventional method such as mixing, kneading, granulation, tableting, coating, sterilization, emulsification and the like depending on the kind of the preparation. Regarding the production of the preparation, it can be produced according to each item of the general rules for preparations of the Japanese Pharmacopoeia. Since the gastrointestinal drug of the present invention uses, as a main component, a crude drug component that has been used for medicinal purposes since ancient times, it can be safely administered to mammals including humans without toxicity and side effects. The gastrointestinal drug of the present invention is effective for treating various gastrointestinal diseases caused by Helicobacter pylori, particularly gastritis, gastric ulcer, duodenal ulcer, etc., and in some cases, for treating and preventing gastric cancer. The gastrointestinal drug of the present invention is not only a combination of (1) Coptis chinensis and / or Oat's crude drug powder or extract and (2) Chinpi's crude drug powder or extract, and a combination thereof,
That is, each active ingredient prepared separately may be administered to the same subject at the same time or with a time lag.
Furthermore, a histamine H ₂ receptor antagonist that can be combined with these crude drug powders or extract components; a proton pump inhibitor; a gastric mucosa-protective drug for treating gastritis / peptic ulcer; an antacid; an antidiarrheal; , At least one of herbal medicine powders or extract components other than Oataku and Chinpi are used not only as a combination drug, but also in combination, that is, each active ingredient is separately formulated and administered to the same subject at the same time or with a time lag. You may.

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.

[Examples] Reference example Production of dried extract powder To 50 g of chopped laurel powder, about 7 times amount (that is, 350 ml) of 30% by volume aqueous ethanol solution was added, and the mixture was extracted at 50 ° C for 1.5 hours while stirring at 30 rpm. It is filtered using a standard sieve (nominal size 75 μm), and the residue is 150 ml of 30% by volume ethanol aqueous solution.
Washed with. The collected filtrate and washing solution were combined and suction filtered. The recovered filtrate was concentrated under reduced pressure at a temperature of 50 ° C. or lower until the volume became about 50 ml to obtain a soft extract. This soft extract was freeze-dried for 24 hours to obtain a dry extract powder. In the same manner, dried extract powder was obtained from Oataku and Chimpi.

Test Example Growth Inhibition Test of Helicobacter pylori The dried Hexobacter pylori extract powder obtained in Reference Example was used to measure the anti-Helicobacter pylori activity in combination by the agar plate dilution checkerboard method. The dried extract powder was dissolved in sterile distilled water, and a 2-fold dilution series was prepared with sterile distilled water. 2 ml of a test sample obtained by combining each dilution series of the extracts to be used in combination was mixed with 18 ml of Brucella agar medium containing 7% horse serum to prepare a measurement plate. As test bacteria, (a) clinically isolated strains CPY433, TN2, TN58, and (b) metronidazole-resistant strain NCTC 11916 were used. In addition, CPY433 and
NCTC 11916 is the European Journal of Clinical Microbiology and Infectious
Dizzy Geese, Vol. 14, pp. 391-399, 1995 (Europe
an Journal of Clinical Microbiology and Infectious
Diseases, 14, 391-399, (1995)).
Also, TN2 was obtained by culturing 92-244 and TN58 was obtained as 91-196 by Oita Medical University. These test bacteria were used in CampyPak ^™ (BBL Beckton Dickinson Microbiology) using Brucella broth medium supplemented with 2.5% fetal bovine serum.
System)) in a gas pack jar at 37 ° C for 2
Culture was performed with shaking for 0 hours. Inoculate each agar plate for measurement with 5 μl of each bacterial solution adjusted to a concentration of about 10 ⁶ CFU (colony forming units) / ml in the same medium, and place it in a gas pack jar containing CampyPak ^™ and absorbent cotton containing water. The cells were cultured at 37 ° C for 4 days.
After culturing, visually observe the growth of the bacteria, and the lowest concentration at which no growth is observed is the MIC (minimum inhibitory concentration) of the test extract.
And The FICs (fractional inhibitory conceins) of both extracts at the combination concentration in which the strongest interaction was observed
ntration) and the FIC index, which is the sum of the FICs of both extracts
Was calculated. The FIC index is edited by Lorinbuy (Edie), Antibiotics in Laboratories Medicine, William and Wilkins, Baltimore, 1986, 537-595, Anti-Micro Vial Combinations (Clogstad Dj, Moerle Ring, AR See) section. (Kr
ogstad DJ, Mollering RC: Antimicrobial combination
s. In: Lorian V (ed): Antibiotics in laboratory medic
ine. Williams & Wilkins, Baltimore, 1986, P.537-59
5), based on this, FIC index of 0.5 or less is synergistic,> 0.5 to 1.0 is additive,> 1.0 to 2.0 is no interaction (no effect), and greater than 2.0 is judged to be antagonistic. did.

The results are shown in Table 1. Table 1 shows each individual MI
FI calculated from the MIC value in combination with C (combination)
The FIC index consisting of the C value and its sum is shown.

[Table 1] The FIC index is 1.00 when Oren and Oat are used together.
It shows that there is an additive effect, on the other hand, FIC index in the case of combined use of chili and Oren or oat is ≦ 0.38 ~ ≦
It was found to be 0.50, which shows a synergistic effect, and in particular, a remarkable synergistic effect is exhibited in the combination of Coptis japonica and chimpi. Specifically, by adding chimpi to concentrations higher than those at which the anti-Helicobacter pylori activity was exhibited in Coptis aureus and C. aureus alone, the activity was enhanced about 8 times for Coptis aureus and about 4 times for C. aureus. In addition, in chimpanzee, the activity was enhanced four-fold or more by adding Oren or Oataku than the concentration showing anti-Helicobacter pylori activity alone. from these things,
It was found that there is a clear synergistic effect in the combination of Coptis with Coptis or Astratum. Also,
When the effect of the combined use of Oataku and Chinpi was examined in the same manner as in the above-mentioned test, the combined use of Chinpi reduced the MIC value in the case of only Oren and Oataku to 1/4 or less. The fact that the combination of the three drugs significantly reduced the MIC values for Helicobacter pylori in Coptis and Abacus, suggesting that the combination of Chimpi with Coptis and C.
It was found that the H. pylori activity was significantly enhanced.

The formulation examples of the present invention are specifically described below, but the present invention is not limited thereto. In the following examples, unless otherwise specified, the amount of each component is the adult (60 kg) daily dose, and the formulation is carried out according to the usual method. Example 1 (prescription) Adult daily dose (in 3 capsules) [mg] Ouren dry extract powder 10 Chinpi dry extract powder 320 Cimetidine 300 Sucralfate 1,500 Crystalline cellulose 1,200 Starch 450 Hydroxypropyl cellulose 180 Lactose 520 Total 4,
480 According to the above prescription, a mixed powder is produced, and the Japanese Pharmacopoeia general rules,
Granules were produced according to the section of Granules.

Example 2 (prescription) Adult daily dose (in 3 packets) [mg] Oat dry extract powder 50 Chinpi dry extract powder 400 Ougon dry extract powder 450 Synthetic hydrotalcite 700 Magnesium oxide 800 Secondary bismuth gallate 1,000 Crystalline cellulose 900 Starch 600 Hydroxypropyl cellulose 180 Lactose 690 Total 5,770 According to the above formulation, granules were produced according to the general rules of the Japanese Pharmacopoeia, Granules.

Example 3 [Uncoated Tablets] (Prescription) Adult Daily Dosage (of 9 Tablets) [mg] Dried Extract of Oren 10 Dried Extract of Oat Oak 20 Dried Extract of Chinpi 300 Dried Extract of Ginger 500 Cimetidine 300 Crystal Cellulose 444 Starch 295 Hydroxypropyl cellulose 103 Magnesium stearate 20 Lactose 700 Subtotal 2,692 [sugar-coated tablets] Uncoated tablets 2,692 Talc 1,141.1 Gum arabic 75.3 Titanium oxide 46.3 Sucrose 1,104.3 Total 5,059.0 According to the above general rules of the Japanese Pharmacopoeia, tablets Plain and sugar-coated tablets were produced.

Example 4 (prescription) Daily dose for adults (in 60 ml) Dried laurel extract powder 10 mg Oat dried extract powder 30 mg Chinpi dried extract powder 600 mg Magnesium hydroxide 1,000 mg Aluminum hydroxide gel 600 mg Cimetidine 240 mg Purified sucrose 3,000 mg Butyl paraoxybenzoate 7.5 mg Flavor 0.06 ml Sodium hydroxide suitable amount Purified water (plus total amount) 60 ml According to the above prescription, a liquid preparation was prepared according to the Japanese Pharmacopoeia General Rules, Liquid Preparation. After filtration, it was sterilized and filled in a glass bottle.

[0025]

INDUSTRIAL APPLICABILITY The gastrointestinal drug of the present invention exhibits stronger antibacterial activity, especially anti-Helicobacter pylori activity. In addition, there is no concern about side effects such as hypersensitivity and diarrhea seen in antibiotics, and appearance of resistant bacteria. Further, it is useful as a medicine, especially as a gastrointestinal drug, for preventing or treating gastrointestinal diseases such as gastritis, gastric ulcer or duodenal ulcer caused by Helicobacter pylori, or preventing recurrence / relapse. Furthermore, since it is possible to reduce the amount of the individual herbal medicine powder or extract component, in particular, oren and / or Oataku that is expensive and has a strong bitterness and is difficult to take, it is possible to provide a formulation that is easier to take, and at the same time, it is economical. Is also advantageous.

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Claims (13)

[Claims] 1. A gastrointestinal drug having anti-Helicobacter pylori activity, which is obtained by combining (1) a crude drug powder or extract component of Coptis chinensis and / or Oataku and (2) a crude drug powder or extract component of Chimpi. 2. The use of (2) about 2 to 200 parts by weight of the crude drug powder of Chorpi or the extracted component in terms of the crude drug, based on 1 part by weight of the crude drug powder of orren or the extracted component in terms of the crude drug. The described gastrointestinal drug. 3. The use of about 1 to 100 parts by weight of (2) crude drug powder of Chimpi or the amount of the crude drug of the extracted component with respect to 1 part by weight of the crude drug powder of Oat or the extracted component (1). The described gastrointestinal drug. 4. (1) 1 part by weight of crude drug powder or extract component of Oren and Oataku in terms of the original drug, (2) Crude drug powder of Chimpi or crude drug equivalent in the extract amount of about 1 to 20
The gastrointestinal drug according to claim 1, wherein 0 part by weight is used. 5. The gastrointestinal drug according to claim 1, which is a preventive or therapeutic drug for gastrointestinal diseases caused by Helicobacter pylori infection. 6. The gastrointestinal drug according to claim 1, which contains at least one of a histamine H ₂ receptor antagonist, a proton pump inhibitor, a gastric mucosa-protective gastritis / peptic ulcer therapeutic agent, an antacid and an antidiarrheal. . 7. The method according to claim 1, which comprises a histamine H ₂ receptor antagonist.
The described gastrointestinal drug. 8. The gastrointestinal drug according to claim 7, wherein the histamine H ₂ receptor antagonist is cimetidine or a pharmaceutically acceptable salt thereof. 9. The gastrointestinal drug according to claim 1, which contains an antacid. 10. A crude drug component (1) Oren or /
And a gastrointestinal drug comprising a crude drug powder or extract component of Oataku and (2) crude drug powder or extract component of Chinpi. 11. A histamine H ₂ receptor antagonist, a proton pump inhibitor, a gastric mucosa-protective remedy for gastritis / peptic ulcer,
11. At least one of an antacid and an antidiarrheal is included.
The described gastrointestinal drug. 12. A gastrointestinal drug having an anti-Helicobacter pylori activity, which comprises a crude drug powder or an extract component of Coptis chinensis, Oataku and Chimpi. 13. A method of using a crude drug powder or extract of chimpanzee for enhancing the anti-Helicobacter pylori activity of Oren and / or Oat.