CN1238694A - Compositions for treatment of gastro intestinal disorders containing bismuth and NSAID - Google Patents

Compositions for treatment of gastro intestinal disorders containing bismuth and NSAID Download PDF

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Publication number
CN1238694A
CN1238694A CN97199982A CN97199982A CN1238694A CN 1238694 A CN1238694 A CN 1238694A CN 97199982 A CN97199982 A CN 97199982A CN 97199982 A CN97199982 A CN 97199982A CN 1238694 A CN1238694 A CN 1238694A
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bismuth
compositions
nsaid
composition
days
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J·D·考尼茨
O·R·卡赖
田中信
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Procter and Gamble Co
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Procter and Gamble Co
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/245—Bismuth; Compounds 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

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  • Pharmacology & Pharmacy (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
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  • Inorganic Chemistry (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present invention relates to methods and compositions for treating a gastrointestinal disorder caused or mediated by Helicobacter pylori comprising bismuth, and a gastropathic amount of a non-steroidal anti-inflammatory drug. The inventions may further comprise therapeutically effective amounts of one or more anti-secretory drugs.

Description

Bismuth-containing that the treatment gastroenteropathy is used and the compositions of NSAID
Background of invention
For most of people, epigastrium pain and other gastroenteropathy are common chronic problems.In the individuality that checked by the doctor and diagnose, many people have the disease such as peptic ulcer or other ulcer.Until the mid-80, these diseases are considered to be caused by anxiety, diet or other environmental factors.Now, studies show that, helicobacter pylori (Helicobacter pylori) (back claims " H.pylori "), a kind of antibacterial of only finding in people's gastric mucus plays a major role in the pathology of these diseases and other gastroenteropathy.
Existing the whole bag of tricks and reagent are used to treat and/or eliminate the gastroenteropathy that helicobacter pylori causes.They comprise and give antacid, H 2Antagonist and antimicrobial such as antibiotic.In addition, the supposition of handling helicobacter pylori according to other method also is can realize in this area.An example like this is at Tanaka, S., etc., " Gastroprotective Effect of Ranitidine Bismuth Citrate Is Associated With IncreasedMucus Bismuth Concentration In Rats ", Gut, 39:164-171 (1996).Yet, because the universality and the sickness rate of helicobacter pylori infection, the patient who treats this type of gastroenteropathy of suffering from the helicobacter pylori mediation or causing has difficulties, and the drug resistance that contains antibiotic therapeutic scheme, therefore, still need Therapeutic Method, especially effective method in a large amount of helicobacter pylori carriers as treatment in enormous quantities to the safe and effective amount of helicobacter pylori.
The present invention has had been found that and has been used for the treatment of that helicobacter pylori causes or the compositions and the method for the gastroenteropathy that mediates that this method comprises that giving bismuth salt (removes H 2The salt that receptor antagonist and bismuth and carboxylate ligand compound form is outer) and NSAID (non-steroidal anti-inflammatory drug).The present invention also comprises and randomly gives one or more antisecretory drugs.The bi concns of gastric mucus of having thought strengthening of bismuth and NSAID (non-steroidal anti-inflammatory drug).Therefore, an object of the present invention is to provide the compositions of safe and effective amount and treatment is caused by helicobacter pylori or the method for the gastroenteropathy that mediates.
Summary of the invention
The present invention relates to a kind ofly treat that helicobacter pylori causes or the compositions of the gastroenteropathy that mediates, said composition comprises the bismuth of about 50-5000 milligram every day; The NSAID (non-steroidal anti-inflammatory drug) of gastropathy amount; With pharmaceutically acceptable carrier.
The invention still further relates to treatment and suffer from that helicobacter pylori causes or the people of the gastroenteropathy that mediates or the method for lower animal subject, this method comprises the bismuth that gives the about 50-5000 milligram of object every day, about 1-42 days, and the NSAID (non-steroidal anti-inflammatory drug) of gastropathy amount.
Detailed Description Of The Invention
The method and composition that the present invention relates to comprises bismuth and NSAID (non-steroidal anti-inflammatory drug), to be used for treating the gastroenteropathy that helicobacter pylori causes or mediates.The present invention also randomly comprises one or more secretion inhibitor agent for the treatment of effective dose.Said composition also comprises pharmaceutically acceptable carrier.Hereinafter will describe the present invention and essential and optional components in detail.
Helicobacter pylori
Helicobacter pylori is a kind of spirillum under one's belt.When its when identified first the eighties in early days, helicobacter pylori is called as campylobacter pylori (Campylobater pyloridis).In recent years, these antibacterials are considered to the essential factor of gastritis, non-ucler dyspepsia and various intestines and stomach ulcer.These biologies have in following publication in more detail to be described, it is for referencial use that these publications are all included this paper in: Korman, M.G., Tygat, G.N., " Helicobacter pylori and Peptic Ulcer ", Scandinavian Journal ofGastroenterology, Suppl., 210:92-96 (1995); Marshall, B.J., " Helicobacter pylori ", American Journal of Gastroenterology, 89 (8 increase version): S116-128 (in August, 1994); Calam, J., " Helicobacter pylori ", European Clinical Investigation, 24 (8): 501-510 (in August, 1994); NIH Consensus Conference, " Helicobacter pylori in Peptic Ulcer Disease.NIHConsensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease ", JAMA, 272 (1): 65-69 (on July 6th, 1994); And Marchall, B.J., Warren, J.R., " Unidentified Curved Bacilli in the Stomach of Patients with Gastritis and PepticUlceration ", The Lancet, 1311-1315 (1984).
Gastroenteropathy
Term used herein " gastroenteropathy " comprises any infection, disease or intravital other disease, the disease that is caused or mediated by helicobacter pylori in the intestines and stomach above and/or under normally.There is the individuality of this gastroenteropathy symptom can be arranged or do not have symptom.This type of disease for example comprises that not by the helicobacter pylori disease that existence confirmed of ulcer in the gastric mucosa, it comprises chronic active gastritis or atrophic gastritis, non-ucler dyspepsia, esophageal reflux disease and gastric motility disorder; And peptic ulcer disease, i.e. preceding pylorus, edge (marginal), stomach, duodenum and/or the jejunal ulcer of helicobacter pylori mediation.
In the present invention, helicobacter pylori causes or the existence of the gastroenteropathy that mediates is preferably measured by any medical circle approval and the diagnostic method that uses.Details about these methods has more detailed description in following publication, it is for referencial use that all these publications are all included this paper in: Megraud, F., " Diagosis ofHelicobacter pylori Infection ", Scandinavian Journal of Gastroenterology, increase version, 214:44-46,57-60 (1996); Cutler, A.F., " Testing for Helicobacter pylori In ClinicalPractice ", American Journal of Medicine, 100 (5A): 35S-39S, 39S-41S (on May 20th, 1996); Megraud, F., " Diagnosis of Helicobacter pylori ", Baillieres ClinicalGastroenterology, 9 (3): 507-518 (nineteen ninety-five JIUYUE); And Feldman, R.A., etc., " Accuracy ofDiagnostic Methods Used for Epidemiological Studies of Helicobacter pylori ", Alimentary Pharmacology and Therapeutics, 9 increase version, 2:21-31 (1995).
Bismuth
The present invention relates to the administration of bismuth.As used herein, the consumption of bismuth is represented with the weight of bismuth element.
In the present invention, bismuth can be the pharmaceutically acceptable salt form, maybe can be to contain the organic coordination compound form of bismuth as active component.These organic coordination compounds comprise 2,2 '-spiral shell two [1,3,2-benzene and Evil are than Si Maer (benzodoxabismole)].H 2The salt that forms between the coordination compound of receptor antagonist and bismuth and carboxylic acid is not comprised being used for the present invention.Preferable, the bismuth that gives in the inventive method is a pharmaceutically acceptable salt.These bismuth salt comprise bismuth aluminate, bismuth subcarbonate, alkali formula bismuth citrate, bismuth citrate, TDB, basic bismuth gallate, basic bismuth nitrate, Bismuth tartrate., basic bismuth salicylate and composition thereof.Bismuth citrate, alkali formula bismuth citrate, TDB, Bismuth tartrate., basic bismuth salicylate are to be used for preferable bismuth salt of the present invention.
Bismuth used herein can be individually dosed, or be combined in the bismuth-containing compositions with other pharmaceutically acceptable component.Various these based compositions that contain bismuth salt are commercially available.These compositionss comprise DeNol, contain TDB (Brocades); Bislumina contains bismuth aluminate (Mazuelos); Roter contains basic bismuth nitrate (Roterpharma); Devram , contain basic bismuth gallate (Parthenon Co., Inc.); With Pepto-Bismol , contain basic bismuth salicylate (Procter﹠amp; Gamble company).
Usually, the dosage of bismuth is about 50-5000 milligram every day, and preferable is 50-2500 milligram every day, and about 1-42 days, preferable the highest about 28 days, best the highest about 14 days.
NSAID (non-steroidal anti-inflammatory drug)
The present invention comprises makes bismuth and NSAID (non-steroidal anti-inflammatory drug) (" NSAID ") administration together.Term used herein " NSAID " refers to have antiinflammatory, any reagent of analgesic and pain relieving performance.The example of NSAID is described in 459 (the authorizing Sunshine etc. on January 15th, 1991) to some extent at United States Patent (USP) 4,985, and it is for referencial use that this patent is all included this paper in.Detailed content about the chemical constitution of non-steroidal anti-inflammatory agent, synthetic, side effect etc. can comprise Anti-Inflammatory and Anti-Rheumatic Drugs referring to national textbook, K.D.Rainsford, I-III volume, CRC publishing house, Boca Raton (1985) and Anti-Inflammatory agents, Chemistryand Pharmacology, l R.A.Scherrer, etc., Academic Press, New York (1974), it is for referencial use that both all include this paper in.
Being used for concrete NSAID of the present invention includes but is not limited to: former times health class medicine, as piroxicam, isoxicam, tenoxicam, sudoxicam and CP-14,304; Salicylic acid is as aspirin, Di Shaxi (disalcid), benorylate, Te Lailisi (trilisate), the general woods of sofa (safapryn), Suo Pulin (solprin), diflunisal and fendosal; Acetogenin is as voltaren see diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, Isoxepac, furofenac, tiopinac, zidometacin, acemetacin, fentiazac, zomepirac, clidanac, Oxepinac and felbinac; Fragrant that esters is as mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid and tolfenamic acid; Propanoic derivatives is as ibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indoprofen, pirprofen, carprofen, Evil promazine, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen and tiaprofenic acid; And pyrazoles, as Phenylbutazone, oxyphenbutazone, feprazone, azapropazone and front three ancestor.Also can adopt the mixture of these NSAID, and the pharmaceutically acceptable salt of these reagent and ester.
Another kind of NSAID is disclosed in U.S. Patent No. 4,708, in 966 (the authorizing Loomans etc. on November 24th, 1987).This patent disclosure the class I non-steroid anti-inflammatory compound, it specifically comprises the phenyl compound of replacement, especially replace 2,6-two-tert-butyl benzene amphyl.For example, adoptable chemical compound is selected among the present invention: 4-(4 '-penta-3 '-ketone)-2, the 6-DI-tert-butylphenol compounds; 4-(5 '-the hexanone base)-2, the 6-DI-tert-butylphenol compounds; 4-((S)-(-)-3 '-methyl-5 '-the hexanone base)-2, the 6-DI-tert-butylphenol compounds; 4-((R)-(+)-3 '-methyl-5 '-the hexanone base) 2, the 6-DI-tert-butylphenol compounds; And 4-(3 ', 3 '-the dimethoxy propionyl)-2,6-two-tert-butyl phenol.
Being used for preferable NSAID example of the present invention includes but is not limited to: aspirin, ibuprofen, fragrant ibuprofen, fenoprofen, flurbiprofen, indomethacin, ketoprofen, naproxen, their pharmaceutically acceptable salt, its enantiomer and composition thereof.Be used for of the present invention good especially be ibuprofen, indomethacin, aspirin and naproxen.
NSAID gives with the gastropathy amount.Term used herein " gastropathy amount " refers to that the administration level of NSAID and frequency are enough in one week of normal subjects interior therapeutic back generation gastropathy (as detecting fixed mucosa injury through fibre optic endoscopes).According to other medical factor that the build of the specific NSAID that gives, the object of receiving treatment and/or situation and/or other administration doctor determine, this consumption can be different.The gastropathy amount of concrete NSAID is known in this field.For example, giving about 2.4 to the 3.9 acetic acid salicylic acid that restrain every day continues a week will produce mucosa injury all the time and not lead to complications.The gastropathy that the gastropathy that level produced of the gastropathy amount of other NSAID and aspirin disclosed herein produce is suitable.
Following publication provides in more detail about the situation of gastropathy and NSAID and all to include this paper in for referencial use: Heigh, R.I., " Use of NSAIDs.An Assault on the Upper Gastrointestinal Tract ", Postgraduate Medicine, 96 (6): 63-68 (on November 1st, 1996); Levi, S. etc., " Non-steroidalAnti-Inflammatory Drugs:How Do They Damage the Gut? ", British Journal ofRheumatology, 33 (7): 605-612 (in July, 1994); And Bower, P.R., " Non-Steroidal Anti-Inflammatory Drugs ", and British Journal of Rheumatology, 32 increase version, 4:35-38 (in June, 1993).
In the present invention, the administration time of NSAID can be up to about 14 days, and is preferable in about 1 to 10 day.Should be shorter than during the administration and produce the relevant time of complication.Therefore, Zui Jia NSAID administration time is about 1 to 7 day.The publication of in the last period, mentioning, NSAID uses the complication of following at Fenn, G.C., " Review Article:Controversies in NSAID-induced Gastroduodenal Damage--Do They Matter? " Alimentary Pharmacology and Therapeutics, 8 (1): describe to some extent among the 15-27 (in February, 1994), and it is for referencial use all to include this paper in.
The secretion inhibitor agent
The present invention can randomly comprise one or more secretion inhibitor agent.The reagent that term used herein " secretion inhibitor agent " refers to is selected from H 2Receptor antagonist, proton pump inhibitor and composition thereof.These reagent give with the treatment effective dose.Known to term used herein " treatment effective dose " refers in this area usually, medical circle approval and the level that adopts.This consumption will depend on the bodily form of the particular agent that gives, the individuality of receiving treatment and/or situation or by other medical factor of administration doctor decision.
H 2Receptor antagonist is disclosed in U.S. Patent No. 5,294,433 (authorizing Singer etc. on March 15th, 1994), and it is for referencial use that this article is all included this paper in.Preferable H 2Receptor antagonist comprises cimetidine, etintidine, ranitidine, ICIA-5165, tiotidine, ORF-17578, lupitidine, many naphthalenes are for fourth, famotidine, roxatidine, the piperazine method is for fourth, lamtidine, BL-6548, BMY-25271, zaltidine, nizatidine, mifentidine, BMY-52368, SKF-94482, BL-6341A, ICI-162846, ramixotidine, Wy-45727, SR-58042, BMY-25405, loxtidine, DA-4634, bisfentidine, sufotidine, ebrotidine, HE-30-256, D-16637, FRG-8813, FRG-8701, impromidine, L-643728, HB-4-08 and composition thereof.
Be used for preferably cimetidine of the present invention, ranitidine, famotidine, roxatidine, nizatidine, mifentidine and composition thereof.Best is cimetidine and ranitidine.
Proton pump inhibitor has in following publication in more detail to be described, it is for referencial use that they all include this paper in: U.S. Patent No. 4,786,505 (authorizing Lovgren on November 22nd, 1988), U.S. Patent No. 4,255,43l (authorizing Junggren on March 10th, 1981) and U.S. Patent No. 4,853,230 (authorizing Lovgren on August 1st, 1989).Be used for preferably omeprazole, lansoprazole (lansoprazole), pantoprazole (pantoprazole) of the present invention and composition thereof.Best is omeprazole.
The administration of secretion inhibitor agent can be at about 1 to 42 day, and preferable is up to 28 days, and the highest of the best is about 14 days.
Pharmaceutically acceptable carrier
Compositions of the present invention can contain the optional components of influential present composition physics and therapeutic properties.Particularly, according to particular dosage form to be adopted, can comprise various pharmaceutically acceptable carriers and excipient.Various peroral dosage forms be can adopt, solid form such as tablet, capsule, granule and bulk powder comprised.But tablet can tabletting, abrasive disc, enteric coating, sugar-coat coating, film coating or tabletting repeatedly, contains suitable bonding, lubricant, diluent, disintegrating agent, coloring agent, flavoring agent, flow-induction agent and fusion agent.Liquid peroral dosage form comprises aqueous solution, Emulsion, suspension, solution and/or suspension that reassembles into from non-effervescent granule and the effervescent formulation that reassembles into from effervescent granule, and it contains suitable solvent, antiseptic, emulsifying agent, suspending agent, diluent, sweetener, fusion agent, coloring agent and flavoring agent.
Can be used to prepare the pharmaceutically acceptable carrier of peroral dosage form of the present invention and excipient object lesson at United States Patent (USP) 3,903, describe to some extent in 297 (JIUYUE was authorized Robert on the 2nd in 1975), it is for referencial use that this patent is included this paper in.The method and the component that prepare useful dosage form are herein described in following document to some extent, and it is for referencial use that they all include this paper in: 7Modern Pharmaceutics, the 9th and 10 chapters (editor is Banker and Rhodes, 1979); Pharmaceutical Dosage Forms:Tablets (1981) such as Lieberman; And Ansel, Introduction to Pharmaceutical Dosage Forms (the 2nd edition, 1976).
But compositions the method according to this invention of the present invention is come administration, gives compositions every day 1 to 4 time, preferable is every day 1 to 2 time; Administration in 1 to 28 day, preferable in about 1 to 21 day, best administration in about 1 to 14 day.Specific administration frequency depends on these factors, mix the feature and the order of severity of the content in the said composition, the state of an illness to be treated and the feature of any while Therapeutic Method (if any) as used concrete NSAID, bismuth compound or compositions and antimicrobial, component.
Using method
Method of the present invention comprises and causing or the people of the gastroenteropathy that mediate or the method that lower animal subject is treated suffering from by helicobacter pylori, and this method comprises to object and gives bismuth and NSAID (non-steroidal anti-inflammatory drug) (back title NSAID).This method also can comprise and gives one or more secretion inhibitor agent.
Term used herein " administration " refers in correct medicine practice to send compound used therefor of the present invention or the compositions any method with effective treatment gastroenteropathy to object to be treated.Preferable, bismuth, NSAID and secretion inhibitor agent (if present) are suitable oral.
Present invention includes simultaneously, (beginning on the same day and finishing), parallel (overlapping but different during the administration) or continuous (carry out successively, but the treatment phase being continuous basically) give bismuth, NSAID and randomly secretion inhibitor agent.Preferable, bismuth and the NSAID administration that can walk abreast, the administration of bismuth and NSAID can begin on the same day.In addition, if also there are one or more secretion inhibitor agent, then preferably bismuth and secretion inhibitor agent administration simultaneously.
Following non-limiting examples has been described compositions of the present invention and using method.
The embodiment I
By a large amount of The selection result, identify an asymptomatic young volunteer and suffer from helicobacter pylori infection, with the inventive method it is treated.Object oral about 2500 milligrams basic bismuth salicylate (Procter﹠amp every day; Gamble Company sells in trade name " Pepto-Bismol  ") bismuth of form, be divided into isodose four parts, continue 28 days; Take the indomethacin of about 100-200 milligram every day, be divided into isodose four parts, continue about 14 days.One or after two months, the volunteer is carried out diagnostic test, find not have helicobacter pylori.
In the above-described embodiments, replace basic bismuth salicylate with TDB, Bismuth tartrate., bismuth citrate and basic bismuth nitrate respectively, the result is basic identical.
The embodiment II
People's object suffers from chronic active gastritis.Diagnostic test shows has helicobacter pylori to exist.Individuality is treated, and oral about 500 milligrams bismuth every day (Brocades sells for the form of alkali formula bismuth citrate, " DeNol ") is divided into isodose two parts, continues about 28 days; Every day, oral about 3.9 gram aspirin were divided into isodose three parts, continued about 14 days; And every day oral about 20 milligrams omeprazole, continue 28 days.All three kinds of reagent are beginning administration on the same day.After 1 to 2 months, repeat diagnostic test.The result shows does not have helicobacter pylori.
The embodiment III
People's object suffers from non-ucler dyspepsia.From the stomach of object, take out gastric mucus and carry out biopsy.To the analysis showed that of biopsy samples, in the stomach of object, there are urase and helicobacter pylori.Give about 1200 milligram bismuth (with compositions Pepto-Bismol  (Procter﹠amp to object every day; Gamble Company) form administration of basic bismuth salicylate in), is divided into isodose four parts, continues about 21 days; Every day about 1200-3200 milligram ibuprofen, be divided into isodose three parts or four parts, continue about 7 days; And every day 150 milligrams ranitidine, be divided into isodose two parts, continue about 21 days.The administration of three kinds of reagent is beginning on the same day.Take out biopsy samples after 1 to 2 months, the analysis showed that does not have helicobacter pylori.

Claims (9)

1. a treatment is caused by helicobacter pylori or the compositions of the gastroenteropathy that mediates that said composition comprises:
A) every day the 50-5000 milligram bismuth;
B) NSAID (non-steroidal anti-inflammatory drug) of gastropathy amount; With
C) pharmaceutically acceptable carrier.
2. compositions according to claim 1, it also comprises one or more secretion inhibitor agent for the treatment of effective dose, and this secretion inhibitor agent is selected from H 2Receptor antagonist, proton pump inhibitor and composition thereof.
3. compositions according to claim 1 and 2, wherein the secretion inhibitor agent is selected from cimetidine, ranitidine, famotidine, roxatidine, nizatidine, mifentidine, omeprazole, lansoprazole, pantoprazole and composition thereof.
4. according to the arbitrary described compositions of claim 1-3, wherein bismuth is selected from bismuth aluminate, bismuth subcarbonate, alkali formula bismuth citrate, bismuth citrate, TDB, basic bismuth gallate, basic bismuth salicylate, Bismuth tartrate. and composition thereof, its administration level is 50-2500 milligram every day, continues 7 to 28 days.
5. according to the arbitrary described compositions of claim 1-4, wherein NSAID (non-steroidal anti-inflammatory drug) is selected from ibuprofen, indomethacin, aspirin and naproxen, wherein NSAID (non-steroidal anti-inflammatory drug) administration in the highest 14 days, one or more secretion inhibitor agent administration in 7 to 28 days.
6. the arbitrary described compositions of claim 1-5 is used for treating application in the compositions of people or lower animal subject in preparation, this object suffers from the gastroenteropathy that is caused or mediated by helicobacter pylori, it comprises and gives the bismuth of 50-5000 milligram every day to object, continue 1-42 days, and the NSAID (non-steroidal anti-inflammatory drug) that gives the gastropathy amount continues maximum 14 days.
7. the application of the arbitrary described compositions of claim 1-6 in a kind of compositions of preparation, said composition comprises one or more secretion inhibitor agent for the treatment of effective dose, and this secretion inhibitor agent is selected from bisfentidine, proton pump inhibitor and composition thereof.
8. the application of the arbitrary described compositions of claim 1-7 in a kind of compositions of preparation, wherein bismuth is selected from bismuth aluminate, bismuth subcarbonate, alkali formula bismuth citrate, bismuth citrate, TDB, basic bismuth gallate, basic bismuth salicylate, Bismuth tartrate. and composition thereof, its administration level is 50-2500 milligram every day, continues 7 to 28 days.
9. the application of the arbitrary described compositions of claim 1-8 in a kind of compositions of preparation, wherein NSAID (non-steroidal anti-inflammatory drug) is selected from ibuprofen, indomethacin, aspirin and naproxen, and the secretion inhibitor agent is selected from cimetidine, ranitidine, famotidine, roxatidine, nizatidine, mifentidine, omeprazole, lansoprazole, pantoprazole and composition thereof.
CN97199982A 1996-11-22 1997-11-21 Compositions for treatment of gastro intestinal disorders containing bismuth and NSAID Pending CN1238694A (en)

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