WO1994008594A1 - Pharmaceutical composition containing an antimicrobial agent and an antibiotic - Google Patents
Pharmaceutical composition containing an antimicrobial agent and an antibiotic Download PDFInfo
- Publication number
- WO1994008594A1 WO1994008594A1 PCT/GB1993/002122 GB9302122W WO9408594A1 WO 1994008594 A1 WO1994008594 A1 WO 1994008594A1 GB 9302122 W GB9302122 W GB 9302122W WO 9408594 A1 WO9408594 A1 WO 9408594A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibiotic
- composition
- antimicrobial agent
- stomach
- pharmaceutical composition
- Prior art date
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- 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
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Definitions
- the present invention relates to pharmaceutical compositions active against Helicobacter pylori and their use in the treatment of gastrointestinal disorders associated with Helicobacter pylori infection.
- H.pylori (formerly known as Campylobacter pyloridis') is a spiral-shaped Gram-negative organism which appears to live beneath the mucus layer of the stomach. Many recent studies have shown an association between the presence of H.pylori in the gastric mucosa and histologically confirmed gastritis.
- the organism may be a pathogen which causes, or at least exacerbates, gastritis, and may also be important in the aetiology of peptic and duodenal ulceration.
- Reviews on the state of the art include those by C.A.M. McNulty in J. Infection. 1986, 12, 107-113, and by C.S. Goodwin ei al. in J. Clin. Pathol. 1986, 22, 353-365.
- H.pylori is known to be susceptible to a large number of antimicrobial agents in vitro. It has however proven considerably more difficult to achieve in vivo eradication of the organism. Indeed, monotherapy with a wide range of drugs is largely unsuccessful in achieving significant levels of in vivo eradication of H. pylori.
- Triple Therapy now typically relies upon what is known as Triple Therapy consisting of co- administration of three separate drugs.
- Triple Therapy currently consists of a combination of a bismuth salt and two antibiotics. Even Triple Therapy is not entirely successful in achieving long-term eradication of H. pylori.
- follow-up of patients cleared of H. pylori infection has shown that relapse (rather than reinfection) can be a problem.
- Treatment of H. pylori associated gastric disorders with antimicrobial agents given by conventional oral dosing regimens may thus require a prolonged course of therapy to be effective.
- Long-term treatment with current therapies is not however recommended in view of side-effects, the build-up of drug resistance and, in particular, the inherent toxicity risk associated with bismuth compounds. Accordingly, there is a need for a safe and effective treatment which does not depend on administration of bismuth agents.
- GB 2 243 549 A claims the use of the non-antibiotic antimicrobial agent triclosan for the preparation of a medicament for the treatment of gastrointestinal disorders associated with Helicobacter pylori infection.
- GB 2243 549 A discloses the in vitro testing of a number of antimicrobial compounds in addition to triclosan versus Helicobacter pylori, based on methods described by McNulty et al. (Antimicrobial Agents & Chemotherapy, 2S, 837- 838, 1985). These include cetyl pyridinium chloride and hexetidine.
- WO 92/18111 discloses that activity against Helicobacter pylori is conferred by a range of readily available substances which already have utililty as antimicrobial agents, including cationic antimicrobial agents, benzene derivatives, phenols, amines, and certain naturally occuring substances, for example certain plant extracts. Included in this range of antimicrobial agents are the compounds cetyl pyridinium chloride, hexetidine and miconazole.
- compositions are advantageous when compared with current Triple Therapy in that a bismuth agent is not required. The risk associated with the administration of bismuth agents is hence avoided.
- the present invention provides a pharmaceutical composition
- a pharmaceutical composition comprising an antimicrobial agent and an antibiotic, characterised in that the antimicrobial agent is miconazole, cetyl pyridinium chloride, hexetidine or hexetidine citrate.
- Suitable antibiotics for combination with antimicrobial agents according to the present invention include orally administrable antibiotics belonging to the classes of ⁇ -lactam antibiotics, tetracyclines, imidazoles and macrolide antibiotics.
- Preferred antibiotics include amoxycillin, tetracycline, metronidazole and clindomycin.
- a composition having utility for the treatment of gastric disorders associated with H. pylori comprises an antimicrobial agent as hereinbefore defined in combination with one antibiotic agent.
- a therapy comprising an antimicrobial agent and two antibiotics is not however precluded.
- a preferred composition according to the invention comprises a combination of hexetidine and amoxycillin or a combination of cetyl pyridinium chloride and amoxycillin.
- the invention provides a pharmaceutical composition as hereinbefore defined for use in therapy, in particular for use in the treatment of gastric disorders associated with Helicobacter pylori.
- the invention also provides a method of treatment of gastric disorders associated with
- Helicobacter pylori in mammals comprising orally administering an effective amount of a pharmaceutical composition comprising an antimicrobial agent selected from cetyl pyridinium chloride, miconazole, hexetidine or hexetidine citrate and an antibiotic.
- an antimicrobial agent selected from cetyl pyridinium chloride, miconazole, hexetidine or hexetidine citrate and an antibiotic.
- compositions comprising an antimicrobial agent and an antibotic having activity against H. pylori may be formulated as gastric controlled release compositions, more especially as compositions which prolong residence time of the antimicrobial agent within the stomach.
- Bioadhesive materials have received considerable attention as platforms for controlled drug delivery. They can be targetted to specific drug administration sites, prolong the residence time and ensure an optimal contact with the absorbing surface. Many different types of bioadhesive materials, both natural and synthetic, can be used in the design of controlled drug delivery systems.
- Sucralfate a basic aluminium sulphate sucrose complex
- the preparation and use of sucralfate is described in for example US patent No.3432489 and "The Merck Index" 11th edition (1989) pl400 entry No 8853.
- US 4,615 697 discloses a controlled release composition
- a treating agent which may be a medicament
- a bioadhesive material which is a water-swellable and water-insoluble, fibrous, cross-linked carboxy- functional polymer.
- the controlled release compositions are described as adhering to the skin or the mucous membranes in the presence of water.
- the present invention provides a pharmaceutical composition as hereinbefore defined, further comprising one or more substances providing a sustained release and/or prolonged retention of the active components in the stomach, so as to overcome, or at least mitigate, the disadvantages associated with conventionally formulated H. pylori treatment and provide an effective treatment for H.pylori infections of the gastric and duodenal mucosa in humans and domestic animals.
- the present invention extends to these compositions for use in therapy and to the use of these compositions in the manufacture of a medicament for the treatment of gastric disorders associated with Helicobacter pylori.
- a combination of antimicrobial agent and antibiotic may for example be co-formulated, suitably by intimate admixture, with a muco-adherent or bioadhesive substance to form a bioadhesive complex.
- a bioadhesive complex confers the additional benefit of locally targetting the antimicrobial agent to the mucus layer of the stomach wall.
- Bioadhesive materials suitable for use in compositions of the present invention include materials, both natural and synthetic, which are capable of adhering to biological surfaces such as mucus membranes.
- bioadhesive materials include natural gums and plant extracts and synthetic materials such as sucralfate, cellulose derivatives, acrylic acid and methacrylic acid derivatives, for example cross-linked acrylic and methacrylic acid copolymers available under the Trade Names CARBOPOL and POLYCARBOPHTJL.
- compositions effective against H.pylori may alternatively be formulated to produce a floating alginate raft within the stomach.
- Such formulations may include solid and liquid dosage forms, and may be prepared according to processes known to persons skilled in the art, for example as described in GB 2 243 549 A.
- Controlled release dosage forms for example beadlets or granules, optionally encapsulated or compressed to form tablets, also form part of the invention.
- beadlets or granules are coated, layered, or form an intimate, homogeneous matrix with release-delaying materials.
- dosage forms may be prepared using conventional techniques known in the art.
- composition of the invention may be made up in the form of a swallow tablet, a chewable tablet or a water dispersible tablet. Alternatively it may be supplied as a water-dispersible powder, either for dispersion immediately prior to administration or for dispensing in liquid form, as a suspension or as a liquid emulsion. Suitable water- dispersible formulations include soluble effervescent or non-effervescent powders.
- compositions of the present invention may also contain appropriate additives, for example preservatives, buffering agents, suspending agents, flavourings, bulking agents, binders, adhesives, lubricants, disintegrants, colouring agents, sweeteners, adsorbents, thickeners, suspending agents, and diluents including water, appropriate to their form.
- appropriate additives for example preservatives, buffering agents, suspending agents, flavourings, bulking agents, binders, adhesives, lubricants, disintegrants, colouring agents, sweeteners, adsorbents, thickeners, suspending agents, and diluents including water, appropriate to their form.
- the release of the active components of the composition may be altered by changing particle size, or by applying a suitable coating particularly to tablet forms.
- Coatings able to retard the release of pharmaceuticals are well known in the art of pharmaceutical formulation, and include polymers such as acrylic resins (for example the material sold by Rohm Pharma under the trade name 'Eudragit') and cellulose esters (for example ethyl cellulose).
- An encapsulated or delayed release formulation according to the invention may be any such form well known in the art.
- Suitable coating materials include water-based coatings, solvent-based coatings and colloidal dispersions. Lipids may also be used to form liposome-type formulations.
- Antimicrobial and antibiotic agents are present in compositions of the invention in appropriate amounts to provide an effective dose, which will depend on the pharmacological properties of the active compounds and the formulation employed for any given treatment.
- compositions containing cetylpyridinium chloride a suitable daily dose lies in the range 0.01 to 100 mg, more suitably 0.1 to 20mg, and typically 7.5 to 15mg.
- compositions containing hexetidine a suitable daily dose lies in the range 0.01 to 100 mg, more suitably 0.1 to 20mg, and typically 5 to lOmg.
- compositions containing miconazole a suitable daily dose lies in the range 100 to 3000mg, more suitably 1000 to 2000mg, and typically 1400 to 1600mg.
- a suitable daily dose lies in the range 500 to 5000mg, more suitably 1000 to 3000mg and typically 1200 to 1800mg.
- compositions containing metronidazole a suitable daily dose lies in the range 100 to 2000mg, more suitably 400 to 1500mg and typically 600 to lOOOmg.
- compositions containing tetracycline a suitable daily dose lies in the range 100 to 2000mg, more suitably 300 to 1500mg and typically 500 to 1200mg.
- compositions of the present invention may also include additional therapeutic agents useful in the treatment of peptic ulcers and gastritis, and agents which delay gastric emptying, for example methylcellulose, guar gum, fats such as triglyceride esters, and triethanolamine myristate.
- Compositions of the invention may be administered as often as a physician directs, having regard to the severity of the H.pylori infection. Normally, it is recommended to take a dose two or three times daily, advantageously after meals.
- compositions hereinbefore identified against Helicobacter pylori may be enhanced if these agents are administered in combination with various materials which are not recognised as antimicrobial agents per se, for example chelating agents, surfactants and mixtures thereof.
- compositions as hereinbefore described for use in the treatment of Helicobacter pylori further comprising a chelating agent, a surfactant or mixtures thereof also form part of the invention.
- Suitable chelating agents include alkyldiamine tetraacetates, for example ethylenediaminetetraacetic acid (EDTA), CaEDTA, and CaNa2EDTA, EGTA and citrate.
- Suitable surfactants include ionic and non-ionic surfactants. Examples of non-ionic surfactants include glycerides and the materials commercially available under the Trade Names Tweens and Tritons. Ionic surfactants include fatty acids and quaternary compounds, the anionic surfactant sodium dodecyl sulphate, and amphoteric surfactants such as cocamidopropyl betaine and emulsifiers.
- compositions of the invention may be prepared by conventional pharmaceutical techniques.
- the composition may, for example, be prepared by mixing together the required ingredients with stirring or grinding to ensure adequate dispersion. Alternatively, some of the ingredients may be mixed together before other ingredients are added. Granulation and/or coating techniques may be used at a convenient stage in the process if required.
- compositions of the invention are illustrative of pharmaceutical compositions of the invention.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP93922602A EP0664709A1 (en) | 1992-10-15 | 1993-10-14 | Pharmaceutical composition containing an antimicrobial agent and an antibiotic |
JP6509768A JPH08502281A (en) | 1992-10-15 | 1993-10-14 | Pharmaceutical compositions containing antibacterial agents and antibiotics |
AU51543/93A AU5154393A (en) | 1992-10-15 | 1993-10-14 | Pharmaceutical composition containing an antimicrobial agent and an antibiotic |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9221707.4 | 1992-10-15 | ||
GB929221707A GB9221707D0 (en) | 1992-10-15 | 1992-10-15 | Pharmaceutical composition |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994008594A1 true WO1994008594A1 (en) | 1994-04-28 |
Family
ID=10723525
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1993/002122 WO1994008594A1 (en) | 1992-10-15 | 1993-10-14 | Pharmaceutical composition containing an antimicrobial agent and an antibiotic |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0664709A1 (en) |
JP (1) | JPH08502281A (en) |
CN (1) | CN1089839A (en) |
AU (1) | AU5154393A (en) |
GB (1) | GB9221707D0 (en) |
WO (1) | WO1994008594A1 (en) |
ZA (1) | ZA937592B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5549911A (en) * | 1994-01-14 | 1996-08-27 | Laboratoires Des Produits Ethiques Ethypharm | Galenic form of 5-nitromidazole derivatives which is effective for the treatment of parasitoses and infections of the entire gastrointestinal tract |
WO1997023207A1 (en) * | 1995-12-22 | 1997-07-03 | Teikoku Chemical Industries Co., Ltd. | Anti-helicobacter pylori agent |
EP1170013A1 (en) * | 1999-03-17 | 2002-01-09 | MORINAGA & CO. LTD. | Drugs, foods, drinks and feeds containing cocoa component |
WO2007021167A1 (en) * | 2005-08-12 | 2007-02-22 | Espinosa Abdala Leopoldo De Je | Pharmaceutical formulations in the form of solids, semisolids, in suspension, in solution, in emulsion or in syrup, containing clindamycin and one or more members of the azole family |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI489984B (en) * | 2006-08-04 | 2015-07-01 | Wyeth Corp | Formulations for parenteral delivery of compounds and uses thereof |
JP2011178722A (en) * | 2010-03-01 | 2011-09-15 | Synmosa Biopharma Corp | PHARMACEUTICAL COMPOSITION TO ELIMINATE HELICOBACTER PYLORI (H.pylori) AND METHOD FOR PRODUCING THE SAME |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990007325A1 (en) * | 1988-12-30 | 1990-07-12 | Edko Trading And Representation Company Limited | A pessary containing antibacterial drugs |
-
1992
- 1992-10-15 GB GB929221707A patent/GB9221707D0/en active Pending
-
1993
- 1993-10-13 ZA ZA937592A patent/ZA937592B/en unknown
- 1993-10-14 EP EP93922602A patent/EP0664709A1/en not_active Ceased
- 1993-10-14 WO PCT/GB1993/002122 patent/WO1994008594A1/en not_active Application Discontinuation
- 1993-10-14 JP JP6509768A patent/JPH08502281A/en active Pending
- 1993-10-14 CN CN93118473A patent/CN1089839A/en active Pending
- 1993-10-14 AU AU51543/93A patent/AU5154393A/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990007325A1 (en) * | 1988-12-30 | 1990-07-12 | Edko Trading And Representation Company Limited | A pessary containing antibacterial drugs |
Non-Patent Citations (5)
Title |
---|
CHEMICAL ABSTRACTS, vol. 100, no. 9, 27 February 1984, Columbus, Ohio, US; abstract no. 64820, CSUKAS, ZSUZSANNA ET AL.: "Antibacterial effect-spectrum of the combination of miconazole and miconazole-metronidazole" page 315; column 2; * |
CHEMICAL ABSTRACTS, vol. 82, no. 11, 17 March 1975, Columbus, Ohio, US; abstract no. 68422, PEETERS F. ET AL.: "Controlled trial with miconazole in the prevention of yeast infections occurring after treatment of vaginal trichomoniasis" page 45; column 2; * |
EGESZSEGTUDOMANY, vol. 26, no. 3, 1982, HUNG, pages 235 - 240 * |
EUR. J. OBSTET., GYNECOL. REPROD. BIOL., vol. 4, no. 3, 1974, ENG., pages 95 - 99 * |
See also references of EP0664709A1 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5549911A (en) * | 1994-01-14 | 1996-08-27 | Laboratoires Des Produits Ethiques Ethypharm | Galenic form of 5-nitromidazole derivatives which is effective for the treatment of parasitoses and infections of the entire gastrointestinal tract |
WO1997023207A1 (en) * | 1995-12-22 | 1997-07-03 | Teikoku Chemical Industries Co., Ltd. | Anti-helicobacter pylori agent |
EP1170013A1 (en) * | 1999-03-17 | 2002-01-09 | MORINAGA & CO. LTD. | Drugs, foods, drinks and feeds containing cocoa component |
EP1170013A4 (en) * | 1999-03-17 | 2004-11-03 | Morinaga & Co | Drugs, foods, drinks and feeds containing cocoa component |
WO2007021167A1 (en) * | 2005-08-12 | 2007-02-22 | Espinosa Abdala Leopoldo De Je | Pharmaceutical formulations in the form of solids, semisolids, in suspension, in solution, in emulsion or in syrup, containing clindamycin and one or more members of the azole family |
Also Published As
Publication number | Publication date |
---|---|
AU5154393A (en) | 1994-05-09 |
GB9221707D0 (en) | 1992-12-02 |
ZA937592B (en) | 1994-06-01 |
EP0664709A1 (en) | 1995-08-02 |
CN1089839A (en) | 1994-07-27 |
JPH08502281A (en) | 1996-03-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0589893B1 (en) | Use of a bacteriocin antimicrobial agent for the manufacture of a medicament for the treatment of gastric disorders associated with Helicobacter pylori. | |
AU736243B2 (en) | Film coated tablet compositions having enhanced disintegration characteristics | |
CA2041400C (en) | Preparation of a medicament | |
KR100780156B1 (en) | Taste masking coating composition | |
EP0264187B1 (en) | Pharmaceutical composition containing ibuprofen and aluminium hydroxide | |
US6071959A (en) | Pharmaceutical products containing a complex of an amide-type local anesthetic and a polyacrylate | |
JPH05112445A (en) | Transfer system that hastens initiation of action and increases latent characteristics | |
EP1275381A4 (en) | Time-release coated solid compositions for oral administration | |
NZ234019A (en) | Pharmaceutical compositions containing sucralfate and an antacid, antiulcer or gastro unstable medicament | |
WO1992018111A2 (en) | Pharmaceutical composition for the treatment of gastritis | |
US5296241A (en) | Therapeutic composition and method of using same for treatment of hangover | |
WO2006103551A1 (en) | Controlled release formulations of oxycodone | |
EP0643967A2 (en) | Pharmaceutical compositions containing analgesic, e.g. morphine, and a laxative, e.g. bisacodyl | |
JPH1036269A (en) | Drug for reducing dysmenorrhoe and/or syndrome before menstruation | |
EP0063266A2 (en) | Galenic preparation | |
EP0664709A1 (en) | Pharmaceutical composition containing an antimicrobial agent and an antibiotic | |
EP1004297B1 (en) | Pharmaceutical compositions for oral administration containing a gastroresistant coating based on acrylic polymers | |
IL99471A (en) | Pharmaceutical compositions for treating helicobacter bacteria infections containing 5-fluoromethoxy-2-(3,4-dimethoxy-2-pyridyl)methylsulphinyl)-1h-benzimidazole and salts thereof in combination with an antimicrobial agent | |
WO1992003135A1 (en) | Pharmaceutical compositions containing 5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridyl) methylsulfinyl] benzimidazole and an anti-helicobacter agent for the treatment of gastrointestinal disorders | |
DE4139883A1 (en) | Prodn. of bio-adhesive medicament, e.g. oral or vaginal tablet - comprises mixing drug with swellable, bio-adhesive polymer, dispersant and opt. binder | |
KR100320140B1 (en) | Micro granules of 5-nitroimidazole derivatives | |
US6099860A (en) | Controlled release oral preparation with naproxen sodium and pseudoephedrine | |
KR20030076287A (en) | Remedy for hemicrania | |
CA2010584A1 (en) | Chemical compositions | |
NZ250737A (en) | Powdered suspension of acetaminophen with one or more antacid agents |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
ENP | Entry into the national phase |
Ref country code: US Ref document number: 1993 157199 Date of ref document: 19931207 Kind code of ref document: A Format of ref document f/p: F |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AT AU BB BG BR BY CA CH CZ DE DK ES FI GB HU JP KP KR KZ LK LU MG MN MW NL NO NZ PL PT RO RU SD SE SK UA US VN |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1993922602 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1993922602 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
NENP | Non-entry into the national phase |
Ref country code: CA |
|
WWR | Wipo information: refused in national office |
Ref document number: 1993922602 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1993922602 Country of ref document: EP |