EP0707492A1 - Combinaisons d'agents anti-h 2? et d'agents de motilite gastro-intestinale - Google Patents

Combinaisons d'agents anti-h 2? et d'agents de motilite gastro-intestinale

Info

Publication number
EP0707492A1
EP0707492A1 EP94923918A EP94923918A EP0707492A1 EP 0707492 A1 EP0707492 A1 EP 0707492A1 EP 94923918 A EP94923918 A EP 94923918A EP 94923918 A EP94923918 A EP 94923918A EP 0707492 A1 EP0707492 A1 EP 0707492A1
Authority
EP
European Patent Office
Prior art keywords
cisapride
gastrointestinal
mgs
relief
pharmaceutically acceptable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP94923918A
Other languages
German (de)
English (en)
Inventor
Robert T. Sims
William Slivka
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Johnson and Johnson Consumer Inc
Original Assignee
Merck and Co Inc
McNeil PPC Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck and Co Inc, McNeil PPC Inc filed Critical Merck and Co Inc
Publication of EP0707492A1 publication Critical patent/EP0707492A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/80—Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases

Definitions

  • the present invention relates to a combination of H2 antagonists selected from famotidine and pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs thereof, with a gastro ⁇ intestinal motility agent, and optionally an antiflatulent.
  • the invention further relates to pharmaceutically effective compositions which are used to treat gastrointestinal disorders and to methods of treating and preventing these disorders.
  • H2 antagonists are commonly prescribed to treat and prevent ulcers in the walls of the stomach, duodenum or esophagus. H2 antagonists are also used to treat non-ulcerative conditions. Damage to the mucus lining surrounding these tissues enables destructive action of stomach acids which erodes the underlying tissue. Commonly known H2 antagonists for the treatment of ulcers include cimetidine, ranitidine, nizatidine, roxatidine and famotidine.
  • Cisapride has the molecular formula:
  • This compound is used as a peristaltic stimulant. See A. Reyntjens et al., Drug Div. Res., 8, 251 (1986) and Curr. Ther. Res., 36, 1029-1070 (1984).
  • the compound is marketed internationally under trade names such as ACENALIN®, PREPSULID®, RISAMOL®, PULSAR®, and PROPULSIN®. See EP application 76,530.
  • Cisapride stimulates gastrointestinal motility and beneficial responses have been reported in treating chronic constipation, chronic dyspepsia, post ⁇ operative gastroparesis and reflux-oesphagitis in children. See Martindale's The Extra Pharmacopoeia, p. 1086 (1989) and references cited therein.
  • a combination wherein an advantage is that the overall symptoms of gastrointestinal distress can be effectively treated with a combination of the most powerful H2 antagonist available (famotidine) with a gastrointestinal motility agent such as cisapride, and optionally including an anti-flatulent.
  • famotidine most powerful H2 antagonist available
  • the instant combination provides a dual action approach to the treatment of gastrointestinal disorders in that a gastrointestinal motility agent such as cisapride offers enhanced motility while famotidine offers a systemic effect of reduced acid production.
  • the instant combination simultaneously treats, relieves and/or prevents symptoms associated with excess gastric acid secretion or evolution in the stomach and esophagus respectively, while also promoting esophagal acid emptying with an effective motility agent such as cisapride.
  • Promotility agents generally promote clearance of refluxed acid from the esophagus by increasing the pressure of the lower esophageal sphincter.
  • Conditions or symptoms relieved by the promotion of gastric emptying include but are not limited to gastric stasis, flatulence, dyspepsia, peptic ulcer and reflux esophagitis.
  • the present invention therefore provides an effective dual treatment of gastrointestinal disorders using the combination of famotidine with a gastrointestinal motility agent such as cisapride, and optionally with simethicone or ADG.
  • a gastrointestinal motility agent such as cisapride
  • simethicone or ADG optionally with simethicone or ADG.
  • the claimed combination is particularly useful for treating gastrointestinal distress.
  • Other H2 antagonists that can be used with this invention include ranitidine, cimetidine, nizatidine and roxatidine.
  • compositions for use in the prevention, treatment and relief of mild to moderate gastro ⁇ intestinal distress and disorders including heartburn, indigestion, sour stomach, overindulgence, gastroesophogeal reflux (GER), constipation, dyspepsia and optionally flatulence.
  • the composition comprises:
  • This invention is also directed to a method of preventing, treating and relieving heartburn, indigestion, sour stomach, over ⁇ indulgence, gastroesophogeal reflux, constipation, dyspepsia and other gastrointestinal disorders, and optionally flatulence, in mammals, including humans, in need of treatment thereof, comprising administering to such organism:
  • treatment encompasses the complete range of therapeutically positive effects associated with pharmaceutical medication including reduction of, alleviation of and relief from the symptoms or illness which affect the organism.
  • Famotidine may be purchased in bulk quantities as it is currently available on the market, and formulated via typical formulation processes with motility agents selected from cisapride or a stereoisomer, salt or hydrate thereof which is suitable for tablet, capsule, effervescent, chewable tablet, or liquid formulations of the claimed combination. Famotidine as a prescription drug product is sold in the United States under the trademark PEPCID®. Janssen is a listed manufacturer of cisapride. See also European Patent Application 0,076,530 published on April 13, 1983. Simethicone or alpha-D- galactosidase (ADG) antiflatulents may be added to the above combination to provide maximum and broad relief of gastrointestinal disorders. Simethicone is a well-known and commercially available antiflatulent. ADG is a commercially available enzyme preparation used to hydrolyze indigestible sugars found in beans or bean products. The active ingredients in the claimed combination are therefore readily available.
  • ADG alpha-D- galactosidase
  • the absence of the inactive stereoisomer of the gastrointestinal motility agent in the present composition avoids undesirable side effects that may accompany ingestion and metabolism of the non-biologically active stereoisomer. These include any toxic interactions and in addition metabolic energy is saved when only one stereoisomer of the gastro ⁇ intestinal motility agent is used in the claimed combination.
  • the use of the potent H2 antagonist such as famotidine combined with a gastro ⁇ intestinal motility agent or an active stereoisomer of a gastrointestinal motility agent provides significant dosage form advantages since less of the H2 antagonist and the gastrointestinal motility agent is needed to formulate a suitable dosage form and provides for a more practical size tablet or capsule.
  • compositions of the present invention are useful in the prevention, treatment and relief of various mild to moderate gastrointestinal disorders including indigestion, sour stomach, overindulgence, heartburn, gastroesophageal reflux, constipation, dyspepsia, other gastrointestinal disorders and optionally flatulence.
  • a gastrointestinal motility agent selected from cisapride or a therapeutically active stereoisomer or a pharmaceutically acceptable salt, hydrate, or polymorph thereof, combined with an H2 antagonist selected from famotidine, a compound of the formula:
  • the utilization of the currently known biologically active stereoisomers and/or salts, hydrates or polymorphs of famotidine in combination with cisapride or its pharmacologically active stereoisomers, salts, hydrates, or polymorphs is advantageously used to prevent, relieve and treat mild to moderate gastrointestinal disorders.
  • the claimed combination is used to prevent, relieve and treat the symptoms associated with gastric acid secretion while simultaneously treating the symptoms of gastrointestinal distress, and optionally flatulence. Therefore, the animal, patient, or organism in need of treatment thereof benefits from the claimed pharmaceutical composition.
  • H2 antagonists are well known in the treatment of ulcers and other gastrointestinal disorders and may be used according to the present invention in combination with a gastrointestinal motility agent such as cisapride and optionally simethicone or ADG.
  • H2 antagonists used for ulcer therapy fall into four major structural classes: imidazole derivatives; substituted furans; aminoalkylphenoxy derivatives and guanidinothiazole compounds.
  • Famotidine (N'-(aminosulfonyl)-3-[[[2- [(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide), a member of the last named class above, is a competitive inhibitor of histamine H2-receptors and its primary pharmacological activity is the inhibition of gastric acid secretion. Famotidine suppresses both the acid concentration and the volume of gastric acid secretion. Famotidine is well tolerated and has minimal side effects and thus advantageously may be used in the present invention in combination with cisapride and optionally simethicone or ADG. Famotidine is also the most potent and selective H2 antagonist.
  • Cisapride (cis-4-amino-5-chloro-N-(l -[3-(4-fluoro- phenoxy)propyl] -3-methoxy-4-piperidinyl)-2-methoxybenzamide) is known to stimulate gastrointestinal motility and apparently is also devoid of antidopaminergic activity. Cisapride is also known to provide beneficial effects in a number of gastrointestinal disorders including chronic constipation, chronic dyspepsia, improvement in stool characteristics in patients that have cystic fibrosis, pseudoobstruction in neonatal short gut, severe postoperative gastroparisis, possible prevention of the aeration syndrome and reflux esophagitis in children.
  • Symptoms associated with the dysfunction of the control mechanism for motility of the gastrointestinal tract or with abnormality of the smooth muscle include nausea, vomiting, anorexia, dysphagia, abdominal distension, constipation and diarrhea.
  • Drugs known to affect the smooth muscle to relieve the above symptoms include bethanechol, acylatonium (cholinergic drugs); neostigmine (cholinesterase inhibitors); metoclopramide, clebopride, domperidone (dopamine antagonists); trimebutine and acetylcholine releasing drugs including cisapride.
  • the claimed invention is also directed to combinations of famotidine with any of the known motility drugs listed above wherein the combination is useful to broadly relieve, treat and prevent the symptoms listed above.
  • a therapeutically active stereoisomer of a gastrointestinal motility agent such as cisapride, substantially free of its other inactive or less active stereoisomers may be employed in the instant invention.
  • the phrase "a therapeutically active stereoisomer substantially free of its other inactive or less active stereoisomers” means that the ratio of active stereoisomer to inactive or less active stereoisomer(s) is at least 90:10.
  • HPLC high performance liquid chromatography
  • suitable chromatographic or separation means may be used to purify or isolate the active stereoisomer (enantiomer or diastereomer) from its readily available racemic mixture.
  • famotidine or its pharmaceutically effective salts, hydrates, stereoisomers or polymorphs thereof with cisapride provides an effective combination which simultaneously and selectively provides prevention, treatment and relief from discomfort and injury to the stomach, esophagus, or duodenum from excess production of gastric acid.
  • famotidine in combination with cisapride and optionally simethicone or ADG may not interact with alcohol so that it may be administered prior to or during ingestion of meals or beverages which contain alcohol and, therefore, a patient in need of rapid treatment of gastrointestinal distress may take the drug combination at an appropriate time which may be during a meal in which alcohol was consumed.
  • cisapride with famotidine provides relief of gastroesophageal reflux while also providing long acting relief from and treatment of gastrointestinal disorders associated with gastric acid secretion.
  • simethicone or ADG the claimed combination further provides antiflatulent relief.
  • famotidine which is a highly potent H2 antagonist with cisapride, and optionally simethicone or ADG, reduces the size and weight of all pharmaceutical delivery forms or combination formulations and therefore improves patient compliance or tolerance.
  • the tablet or capsule form of this combination is more readily swallowable by patients in need of treatment thereof.
  • Famotidine or a pharmaceutically acceptable salt, hydrate stereoisomer or polymorph thereof, is advantageously used in the present invention in combination with cisapride and optionally with simethicone or ADG.
  • the amount of famotidine used in the present invention in humans may range from 2.5 mgs/dosage to 80 mgs/dosage.
  • 5 to 40 mgs/dosage is administered in combination with 5 to 40 mgs/dosage of cisapride.
  • a tablet containing 5 mgs of famotidine may be administered 4 times daily with an effective amount of cisapride and suitable inert ingredients also contained within the tablet.
  • the amount of simethicone per dosage may vary depending upon the degree of antiflatulent strength desired, and may range from 20 to 80 mgs. Maxium strength antiflatulents administered in tablet form four times per day may contain 125 mgs of simethicone per tablet.
  • Maxium strength antiflatulents administered in tablet form four times per day may contain 125 mgs of simethicone per tablet.
  • antacid/anti- gas formulations contain, for example, 20-40 mgs/chewable tablet or teaspoonful of liquid suspension of simethicone and 200 mgs of aluminum hydroxide and 200 mgs of magnesium hydroxide. Two to four tablets between meals or at bedtime or 2-4 teaspoonfuls between meals and at bedtime containing the above quantities are administered daily.
  • ADG is an enzyme known to assist in the hydrolysis of indigestible sugars which are often found in beans or bean products.
  • the quantity of ADG utilized in the present invention depends upon the concentration of active enzyme and upon the quantity of beans or other source of indigestible sugars ingested. Generally, the amount of ADG that may be employed ranges from about 675 to 31,000 GalU ("alpha- galactosidase units"), and preferably from about 675 to 2250 GalU. See WO90/14101 or PCT/US90/02643.
  • each of the active ingredients may vary depending upon the severity of the condition and the particular biochemistry and need of the patient or other organism in need of such treatment.
  • the quantities of the active ingredients may also vary depending upon whether the active ingredients are administered in tablet or liquid form or via some other suitable delivery method.
  • a physician or clinician or veterinarian of ordinary skill in the art may readily determine suitable dosages of any prescription medication containing the claimed invention.
  • the combination claimed in the instant invention is advantageously administered orally. However, in patients with hypersecretory conditions, intractable ulcers, or in patients who are unable to take oral medication, the claimed combination may be administered intravenously in a suitable dosage within the limits described for oral treatment.
  • the present composition may be administered in the form of tablets, caplets, gelcaps, capsules, elixirs, syrups, chewable tablets, lozenges, fast-dissolving wafers, effervescent formulations or suspensions or other known and effective delivery modes.
  • the active ingredients may be admixed with a pharmaceutically acceptable diluent such as lactose, sucrose, cellulose, dicalcium phosphate, calcium sulfate, mannitol, and, in a liquid composition, ethyl alcohol.
  • Acceptable emulsifying or suspending agents such as PVP, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as acacia, sodium cisapride, guar gum, agar, bentonite, carboxymethylcellulose sodium, polyethylene glycol and waxes, may also be admixed with the active components.
  • lubricants such as magnesium stearic acid talc or magnesium stearate, and disintegrators or superdisintegrators such as starch, sodium starch glycolate or cross-linked PVP may also be included.
  • Electrolytes such as dicalcium phosphate, sodium benzoate, sodium acetate and sodium chloride may also be used.
  • the active components may also be formulated in sustained release or effervescent formulations. These formulations depending upon whether they are sustained release or effervescent may be employed in oral, dermal, rectal or vaginal administrations.
  • the sustained release formulations also include layered formulations which provide for distinct release ratio and thus may be more effective in allowing for short and long term relief.
  • Simethicone or alpha-D-galactosidase may be added to each of the above formulations or examples to provide anti-flatulent relief.
  • the quantity of simethicone administered to a patient in need of treatment thereof may vary according to patient need, but may be, for example, the typical known dosage range to treat flatulence (20-40 mgs per tablet or per 5 ml liquid dosage for ) or may be increased as necessary.
  • the amount of ADG that may be employed in the above formulations ranges from about 675 to about 2250 GalU or may be increased as necessary.
  • the inactive ingredients in the tablet form may further include dextrates, mannitol, magnesium stearate, Yellow 10, collodial silicon dioxide and Blue 1 or Red 27 while the liquid form(s) may further include inactives such as butylparaben, carboxy- methylcellulose sodium, flavors, hydroxypropyl methylcellulose, microcrystalline cellulose, propylparaben, and purified water.
  • inactives such as butylparaben, carboxy- methylcellulose sodium, flavors, hydroxypropyl methylcellulose, microcrystalline cellulose, propylparaben, and purified water.
  • the previous examples are to be construed as non-limiting and additional dosages and dosage forms or routes of administration may be varied depending upon the individual patient being treated for either the primary (excess acid leading to gastrointestinal or esophageal disturbance or damage) or secondary (infections) symptoms of gastrointestinal disorders.
  • known pharmaceutically acceptable excipients or agents may be added as inactive ingredients to the claimed active combination in a variety of forms including

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des préparations pharmaceutiques destinées à la prévention, au traitement et au soulagement des indigestions, de l'hyperacidité gastrique, des brûlures épigastriques, des reflux gastro-oesophagiens, des dyspepsies, des constipations, des excès et autres troubles gastro-intestinaux des mammifères, y compris de l'homme, par administration de composés associant: (i) une quantité d'anti-H2 suffisante pour soulager les désordres gastro-intestinaux ou oesophagiens, l'anti-H2 étant sélectionné dans la famille de composés dont la formulation est (I) ainsi que de leurs dérivés sous forme de sels, d'hydrates, de stéréoisomères ou de polymorphes de qualité pharmaceutiques; (ii) un agent facilitant la motilité gastro-intestinale tel que le cisapride, en quantité suffisante pour soulager les troubles gastro-intestinaux ou oesophagiens et accélérer le transit gastro-duodénal; et le cas échéant (iii) du siméthicone ou de l'alpha-D-galactosidase en quantité suffisante pour soulager les flatulences.
EP94923918A 1993-07-06 1994-07-05 Combinaisons d'agents anti-h 2? et d'agents de motilite gastro-intestinale Withdrawn EP0707492A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US8759093A 1993-07-06 1993-07-06
US87590 1993-07-06
PCT/US1994/007520 WO1995001803A1 (fr) 1993-07-06 1994-07-05 Combinaisons d'agents anti-h2 et d'agents de motilite gastro-intestinale

Publications (1)

Publication Number Publication Date
EP0707492A1 true EP0707492A1 (fr) 1996-04-24

Family

ID=22206098

Family Applications (1)

Application Number Title Priority Date Filing Date
EP94923918A Withdrawn EP0707492A1 (fr) 1993-07-06 1994-07-05 Combinaisons d'agents anti-h 2? et d'agents de motilite gastro-intestinale

Country Status (5)

Country Link
EP (1) EP0707492A1 (fr)
JP (1) JPH08512322A (fr)
AU (1) AU7397194A (fr)
CA (1) CA2166730A1 (fr)
WO (1) WO1995001803A1 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08502031A (ja) * 1992-07-07 1996-03-05 セプラコア インコーポレーテッド 胃食道逆流疾患およびその他の障害を治療するために▲（＋）▼シサプリドを使用する方法
WO1994001112A1 (fr) * 1992-07-07 1994-01-20 Sepracor Inc. Procedes d'utilisation de cisapride (-) pour le traitement du reflux gastro-×sophagien et d'autres troubles
US5712293A (en) * 1995-06-07 1998-01-27 Sepracor, Inc. Methods for treating gastro-esophageal reflux disease and other disorders associated with the digestive tract using optically pure (-) norcisapride
EP0866707A1 (fr) * 1995-12-01 1998-09-30 Janssen Pharmaceutica N.V. Liberation retard de cisapride
SE9600072D0 (sv) * 1996-01-08 1996-01-08 Astra Ab New oral formulation of two active ingredients II
DE69713948D1 (de) * 1996-04-23 2002-08-22 Janssen Pharmaceutica Nv Rasch-freisetzende pH-unabhängige feste Dosisformen enthaltend Cisaprid
EP0803251B1 (fr) * 1996-04-23 2002-07-17 Janssen Pharmaceutica N.V. Formes solides d'administration de cisapride à libération immédiate et indépendente du PH
US5739151A (en) * 1996-07-19 1998-04-14 Sepracor Inc. Method for treating emesis and central nervous system disorders using optically pure (+) norcisapride
US6147093A (en) 1996-07-19 2000-11-14 Sepracor Inc. Methods for treating gastroesophageal reflux disease
CA2292628A1 (fr) * 1997-06-11 1998-12-17 Janssen Pharmaceutica, N.V. Forme galenique solide a liberation immediate independante du ph de (+)- ou (-)-cisapride
IT1298269B1 (it) * 1998-02-18 1999-12-20 Promefarm S R L Uso di un polietilenglicole come mezzo di contrasto in ecografia
HUP0102026A3 (en) 1998-06-15 2002-12-28 Sepracor Inc Marlborough Use of optically pure (-) norcisapride for producing pharmaceutical compositions suitable for treating apnea, bulimis, and other disorders
US6362202B1 (en) 1999-03-02 2002-03-26 Sepracor Inc. Methods and compositions using (−) norcisapride in combination with proton pump inhibitors or H2 receptor antagonists
US6353005B1 (en) 1999-03-02 2002-03-05 Sepracor, Inc. Method and compositions using (+) norcisapride in combination with proton pump inhibitors or H2 receptor antagonist
US6676933B2 (en) 2001-05-23 2004-01-13 Osmotica Corp. Pharmaceutical composition containing mosapride and pancreatin
US6986901B2 (en) * 2002-07-15 2006-01-17 Warner-Lambert Company Llc Gastrointestinal compositions
EP1729743A1 (fr) * 2004-01-06 2006-12-13 Panacea Biotec Limited Compositions pharmaceutiques comprenant un inhibiteur de pompe a protons et un agent pro-cinetique
CO5790164A1 (es) * 2006-08-10 2007-08-31 Procaps S A Composicion farmaceutica solida que incluye en combinacion un agente regulador de la motilidad intestinal y un agente antiflatulento
MX2010012480A (es) * 2010-11-16 2012-05-16 Posi Visionary Solutions Llp Composicion farmaceutica adaptada para administrarse oralmente y proceso para su preparación para su prevencion y tratamiento, del sindrome del intestino irritable, a base de un odificador dela motalidad intestinal y a-d- galactosidasa.
MX2010012479A (es) * 2010-11-16 2012-05-16 Posi Visionary Solutions Llp Composicion farmaceutica de administracion oral para el tratamiento del sindrome de intestino irritable, a base de un modificador de la motilidad intestinal, un agente que previene la retencion de gases y enzimas digestivas y proceso para su preparacion.

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Publication number Priority date Publication date Assignee Title
US5229137A (en) * 1992-05-06 1993-07-20 Brigham And Women's Hospital, Inc. Methods and pharmaceutical compositions for treating episodic heartburn

Non-Patent Citations (1)

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Title
See references of WO9501803A1 *

Also Published As

Publication number Publication date
JPH08512322A (ja) 1996-12-24
WO1995001803A1 (fr) 1995-01-19
AU7397194A (en) 1995-02-06
CA2166730A1 (fr) 1995-01-19

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