WO1995027486A1 - Low dosage ranitidine compositions for the treatment of minor gastrointestinal disorders associated with excess acid secretion - Google Patents

Low dosage ranitidine compositions for the treatment of minor gastrointestinal disorders associated with excess acid secretion Download PDF

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Publication number
WO1995027486A1
WO1995027486A1 PCT/EP1995/001271 EP9501271W WO9527486A1 WO 1995027486 A1 WO1995027486 A1 WO 1995027486A1 EP 9501271 W EP9501271 W EP 9501271W WO 9527486 A1 WO9527486 A1 WO 9527486A1
Authority
WO
WIPO (PCT)
Prior art keywords
ranitidine
pharmaceutical composition
treatment
oral pharmaceutical
disorders associated
Prior art date
Application number
PCT/EP1995/001271
Other languages
French (fr)
Inventor
Alan Bye
Jill Evans
Derrick Paul Huckle
Laurence Francis Lacey
John Peter Rue
Original Assignee
Glaxo Group Limited
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 Glaxo Group Limited filed Critical Glaxo Group Limited
Priority to JP7526068A priority Critical patent/JPH10502331A/en
Priority to AU21380/95A priority patent/AU690664B2/en
Priority to BR9507312A priority patent/BR9507312A/en
Priority to EP95914346A priority patent/EP0755251A1/en
Priority to NZ283354A priority patent/NZ283354A/en
Publication of WO1995027486A1 publication Critical patent/WO1995027486A1/en
Priority to MXPA/A/1996/004553A priority patent/MXPA96004553A/en
Priority to KR1019960705716A priority patent/KR970702034A/en

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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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • 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

Definitions

  • the present invention relates to low dosage formulations containing the histamine H 2 -receptor antagonist ranitidine and their use in the treatment of gastric disorders such as episodic heartburn.
  • Ranitidine N-[2-[[[5-(dimethylamino)methyl-2-furanyl]methylJthio]ethyl]-N'- methyl-2-nitro-1,1-ethenediamine, and its physiologically acceptable salts are described and claimed in British Patent Specification No. 1565966, and a particular crystalline form of ranitidine hydrochloride is described and claimed in British Patent Specification No. 2084580.
  • formulations for oral administration which may take the form of for example tablets, capsules, granules, powders, solutions, syrups, suspensions, or tablets or lozenges for buccal administration.
  • Oral administration constitutes a preferred route for administering ranitidine.
  • US Patent No. 5229137 describes the use of a combination of ranitidine and an antacid for the treatment of episodic heartburn.
  • H 2 -antagonists such as ranitidine
  • an antacid needs to be administered with the Hr-antagonist in order to obtain rapid relief.
  • the doses used in the combination are between 100 and 150mg.
  • EP0193400 Compositions containing reduced doses of H 2 -antagonists are described in EP0193400 and W093/12779.
  • EP0193400 describes a combination of an H 2 _antagonist, such as ranitidine, and sodium polyacrylate for use in the treatment of gastritis or gastro-duodenal ulcers. According to EP0193400, the synergistic effect between the H 2 -antagonist and polyacrylate affords the possibility of the lower doses of H 2 -antagonist being used.
  • W093/12779 describes the use of a combination of an Hr-antagonist, including ranitidine, and an antacid in the treatment of gastric disorders, where the combination is buffered to confer a pH substantially equal to that of the pKa of the H 2 -antagonist and where the dose of the H 2 -antagonist per unit dosage form is less than 25mg.
  • the lower dose is said to be effective since the combination of active agents increases bioavailability of the Hr-antagonist at the local stomach wall receptor site.
  • EP0492247 also describes a composition having a reduced dose of H 2 _antagonist for the treatment of heartburn etc.
  • the composition uses a combination of water-soluble H 2 -antagonist and an effervescent delivery system, such as an alkali metal bicarbonate and citric acid.
  • the use of the effervescent delivery system is said to decrease the time for onset of action of the H 2 _antagonist and increases its potency such that the formulation requires about twenty-five per cent of the H 2 -antagonist dosage currently prescribed for the treatment of active duodenal ulcer.
  • the effervescent delivery system reduces the dosage from 150mg to less than about 37.5mg.
  • Dosage levels between 50 and 600mg, such as 150 and 300mg, of ranitidine when administered alone are conventionally regarded as conferring therapeutic benefit.
  • the present invention provides an oral pharmaceutical composition, such as a tablet, comprising ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient, characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base.
  • a swallow tablet comprising ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient, characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base.
  • the present invention provides a method of treating minor gastrointestinal disorders associated with excess acid secretion which comprises administering to a patient in need of such, an oral pharmaceutical composition which consists essentially of ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base.
  • compositions according to the invention are substantially free from antacids, a polyacrylate or an effervescent delivery system.
  • Ranitidine may be employed in the tablets according to the invention in the form of either its free base or a physiologically acceptable salt.
  • Such salts include salts with inorganic or organic acids such as the hydrochloride, hydrobromide, sulphate, acetate, maleate, succinate, citrate, tartrate, fumarate and ascorbate salts.
  • a particularly preferred salt of ranitidine is the hydrochloride.
  • Ranitidine may be employed in the tablets according to the invention in conventional form or coated or encapsulated forms of ranitidine may be used. Suitable coated and encapsulated forms are described in, for example, EP538034, EP523847, W092/21328, EP473431, EP459695, EP349103, CA2068366 and US5084278. Ranitidine resin adsorbates as described in UK2218333 may also be incorporated into the tablets according to the present invention.
  • ranitidine and its salts are used in conventional form.
  • the amount of ranitidine, preferably in the form of a physiologically acceptable salt, particularly ranitidine hydrochloride, in the composition according to the invention is preferably in the range of 10 to 30mg per dosage unit (for example per tablet), e.g. 25mg, expressed as the weight of free base.
  • the unit dose (for example contained in one tablet according to the invention) may be administered up to, for example, 12 times a day depending upon the nature and severity of the conditions being treated, and the age and weight of the patient.
  • minor gastrointestinal disorders associated with excess acid secretion such as, for example, acid indigestion, over-indulgence of food or drink (e.g. alcoholic beverages), acid stomach, sour stomach, waterbrash/regurgitation, heartburn, such as episodic heartburn, nocturnal heartburn, and meal-induced heartburn, gastritis and dyspepsia
  • a 10-30mg dose of ranitidine e.g. a 25mg dose, expressed as the weight of free base, may be administered up to 12 times a day, for example 6 times a day, as and when required.
  • compositions according to the invention may also contain other excipients conventional to the art such as fillers, binders, disintegrants, lubricants and dessicants. Suitable excipients are well-known to those skilled in the art.
  • Suitable binders include methylcellulose, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, alginic acid, ethylcellulose, acacia, gelatin, pregelatinised starch, sucrose syrup, polyvinylpyrrolidone (povidone) and guar gum.
  • Suitable lubricants include magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate, hydrogenated vegetable oils, glyceryl palmitostearate, glyceryl behenate, sodium benzoate, sodium lauryl sulphate, magnesium lauryl sulphate, mineral oil, talc and mixtures thereof.
  • Magnesium stearate is a preferred lubricant.
  • Suitable dessicants include silica gel.
  • Suitable fillers include microcrysalline cellulose.
  • Suitable disintegrants include croscarmellose sodium.
  • Such chewable tablets comprise ranitidine, or a physiologically acceptable salt thereof, a chewable base selected from sucrose, glucose, lactose, maltose, or a mixture thereof, a flavouring and, optionally an intense sweetener.
  • the chewable tablets may be prepared using the conventional stages of mixing, granulation, drying, blending, compression and packing.
  • Suitable swallow tablet cores may be prepared in a conventional manner, for example in a similar manner to that described in British Patent Specification No.
  • ranitidine or its salt a lubricant, such as magnesium stearate and optionally a pharmaceutically acceptable disintegrant, such as croscarmellose sodium, are mixed and compressed into tablet cores.
  • a lubricant such as magnesium stearate
  • a pharmaceutically acceptable disintegrant such as croscarmellose sodium
  • Swallow tablets are conventionally film-coated according to conventional procedures either by aqueous or organic techniques.
  • a preferred film coat is described in British Patent specification No. 2218336 which is incorporated herein by reference.
  • Opaspray white K-1-7000 is a suspension of titanium dioxide and hydroxypropyl cellulose in industrial methylated spirits.
  • Opadry Yellow Y S-1 -12606 is a mixture of hydroxypropyl methylcellulose 2910, titanium dioxide, triacetin and iron oxide yellow. Both Opaspray and Opadry are the tradenames of Colorcon Inc., West Point, Philadelphia, USA.
  • Reference Example 1

Abstract

The present invention relates to low dosage formulations containing the histamine H2-receptor antagonist ranitidine and their use in the treatment of gastric disorders such as episodic heartburn.

Description

DOSAGE RANITIDINE COMPOSITIONS FOR THE TREATMENT OF MINOR GASTROINTESTINAL DISORDERS ASSOCIATED WITH EXCESS ACID SECRETION
The present invention relates to low dosage formulations containing the histamine H2-receptor antagonist ranitidine and their use in the treatment of gastric disorders such as episodic heartburn.
Ranitidine, N-[2-[[[5-(dimethylamino)methyl-2-furanyl]methylJthio]ethyl]-N'- methyl-2-nitro-1,1-ethenediamine, and its physiologically acceptable salts are described and claimed in British Patent Specification No. 1565966, and a particular crystalline form of ranitidine hydrochloride is described and claimed in British Patent Specification No. 2084580. In both these specifications there is reference to formulations for oral administration, which may take the form of for example tablets, capsules, granules, powders, solutions, syrups, suspensions, or tablets or lozenges for buccal administration. Oral administration constitutes a preferred route for administering ranitidine.
US Patent No. 5229137 describes the use of a combination of ranitidine and an antacid for the treatment of episodic heartburn. According to US 5229137, when H2-antagonists such as ranitidine are administered alone, relief from episodic heartburn is not experienced until some time after the medication is ingested. Specifically, when 150mg of ranitidine were administered to two patients suffering from episodic heartburn, relief was obtained 45 and 60 minutes after ingestion. Therefore, according to US 5229137, an antacid needs to be administered with the Hr-antagonist in order to obtain rapid relief. When the H2-antagonist is ranitidine, the doses used in the combination are between 100 and 150mg.
Compositions containing reduced doses of H2-antagonists are described in EP0193400 and W093/12779. EP0193400 describes a combination of an H2_antagonist, such as ranitidine, and sodium polyacrylate for use in the treatment of gastritis or gastro-duodenal ulcers. According to EP0193400, the synergistic effect between the H2-antagonist and polyacrylate affords the possibility of the lower doses of H2-antagonist being used. W093/12779 describes the use of a combination of an Hr-antagonist, including ranitidine, and an antacid in the treatment of gastric disorders, where the combination is buffered to confer a pH substantially equal to that of the pKa of the H2-antagonist and where the dose of the H2-antagonist per unit dosage form is less than 25mg. The lower dose is said to be effective since the combination of active agents increases bioavailability of the Hr-antagonist at the local stomach wall receptor site.
EP0492247 also describes a composition having a reduced dose of H2_antagonist for the treatment of heartburn etc. Here the composition uses a combination of water-soluble H2-antagonist and an effervescent delivery system, such as an alkali metal bicarbonate and citric acid. The use of the effervescent delivery system is said to decrease the time for onset of action of the H2_antagonist and increases its potency such that the formulation requires about twenty-five per cent of the H2-antagonist dosage currently prescribed for the treatment of active duodenal ulcer. In the case of ranitidine, the effervescent delivery system reduces the dosage from 150mg to less than about 37.5mg.
Dosage levels between 50 and 600mg, such as 150 and 300mg, of ranitidine when administered alone are conventionally regarded as conferring therapeutic benefit.
Surprisingly, it has now been found that very low doses of ranitidine, administered alone, are effective in the treatment of minor gastrointestinal disorders associated with excess acid secretion, such as episodic heartburn for example, and that relief from symptoms occurs within 30-45 minutes after ingestion. Duration of control of acid secretion is also advantageous with the dosage of the invention.
Thus, the present invention provides an oral pharmaceutical composition, such as a tablet, comprising ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient, characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base. According to a further aspect the present invention provides a swallow tablet comprising ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient, characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base.
According to a further aspect the present invention provides a method of treating minor gastrointestinal disorders associated with excess acid secretion which comprises administering to a patient in need of such, an oral pharmaceutical composition which consists essentially of ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base.
It will be understood that the compositions according to the invention are substantially free from antacids, a polyacrylate or an effervescent delivery system.
Ranitidine may be employed in the tablets according to the invention in the form of either its free base or a physiologically acceptable salt. Such salts include salts with inorganic or organic acids such as the hydrochloride, hydrobromide, sulphate, acetate, maleate, succinate, citrate, tartrate, fumarate and ascorbate salts. A particularly preferred salt of ranitidine is the hydrochloride.
Ranitidine may be employed in the tablets according to the invention in conventional form or coated or encapsulated forms of ranitidine may be used. Suitable coated and encapsulated forms are described in, for example, EP538034, EP523847, W092/21328, EP473431, EP459695, EP349103, CA2068366 and US5084278. Ranitidine resin adsorbates as described in UK2218333 may also be incorporated into the tablets according to the present invention.
Preferably ranitidine and its salts are used in conventional form. The amount of ranitidine, preferably in the form of a physiologically acceptable salt, particularly ranitidine hydrochloride, in the composition according to the invention is preferably in the range of 10 to 30mg per dosage unit (for example per tablet), e.g. 25mg, expressed as the weight of free base.
The unit dose (for example contained in one tablet according to the invention) may be administered up to, for example, 12 times a day depending upon the nature and severity of the conditions being treated, and the age and weight of the patient. Thus, for example, in the treatment of minor gastrointestinal disorders associated with excess acid secretion such as, for example, acid indigestion, over-indulgence of food or drink (e.g. alcoholic beverages), acid stomach, sour stomach, waterbrash/regurgitation, heartburn, such as episodic heartburn, nocturnal heartburn, and meal-induced heartburn, gastritis and dyspepsia, a 10-30mg dose of ranitidine, e.g. a 25mg dose, expressed as the weight of free base, may be administered up to 12 times a day, for example 6 times a day, as and when required.
The pharmaceutical compositions according to the invention may also contain other excipients conventional to the art such as fillers, binders, disintegrants, lubricants and dessicants. Suitable excipients are well-known to those skilled in the art.
Suitable binders include methylcellulose, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, alginic acid, ethylcellulose, acacia, gelatin, pregelatinised starch, sucrose syrup, polyvinylpyrrolidone (povidone) and guar gum.
Suitable lubricants include magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate, hydrogenated vegetable oils, glyceryl palmitostearate, glyceryl behenate, sodium benzoate, sodium lauryl sulphate, magnesium lauryl sulphate, mineral oil, talc and mixtures thereof.
Magnesium stearate is a preferred lubricant.
Suitable dessicants include silica gel. Suitable fillers include microcrysalline cellulose. Suitable disintegrants include croscarmellose sodium.
Suitable chewable tablets are described in our co-pending PCT Application No. PCT/EP93/02763. Chewable tablets specifically disclosed in this co-pending application are not included within the scope of the present invention.
Such chewable tablets comprise ranitidine, or a physiologically acceptable salt thereof, a chewable base selected from sucrose, glucose, lactose, maltose, or a mixture thereof, a flavouring and, optionally an intense sweetener.
The chewable tablets may be prepared using the conventional stages of mixing, granulation, drying, blending, compression and packing.
Suitable swallow tablet cores may be prepared in a conventional manner, for example in a similar manner to that described in British Patent Specification No.
2084580 which is incorporated herein by reference. Thus, for example the required quantities of ranitidine or its salt, a lubricant, such as magnesium stearate and optionally a pharmaceutically acceptable disintegrant, such as croscarmellose sodium, are mixed and compressed into tablet cores.
Swallow tablets are conventionally film-coated according to conventional procedures either by aqueous or organic techniques. A preferred film coat is described in British Patent specification No. 2218336 which is incorporated herein by reference.
The following are illustrations of non-limiting examples of the pharmaceutical compositions according to the invention. Opaspray white K-1-7000 is a suspension of titanium dioxide and hydroxypropyl cellulose in industrial methylated spirits. Opadry Yellow Y S-1 -12606 is a mixture of hydroxypropyl methylcellulose 2910, titanium dioxide, triacetin and iron oxide yellow. Both Opaspray and Opadry are the tradenames of Colorcon Inc., West Point, Philadelphia, USA. Reference Example 1
Chewable Tablet
Ingredient mg/tablet
Ranitidine HCI 28.0 Sucrose 2268.0 Aspartame 37.5 Povidone 50.0
Peppermint Flavour 41.5 Silica Gel 50.0
Magnesium Stearate 25.0 Isopropyl Alcohol + qs
+ not present in final product
Example 2 Swallow Tablet
Tablet Core mg/tablet
Ranitidine HCI 28.0 Microcrystalline Cellulose 263.75 Croscarmellose Sodium Type A 6.00 Magnesium Stearate 2.25
Target compression weight 300mg
Film Coat % w w Unit amounts (mg/tablet)*
Methylhydroxypropyl Cellulose 4.0 11.3
Opaspray White K-1-7000 3.3 4.7
Isopropyl Alcohol ** 26.3 qs
Dichloromethane ** 66.4 qs The amount of film coat applied per tablet may be less than that stated, depending on the efficiency of the process.
Not present in the final product.
Example 3 Swallow Tablet
Tablet Core Unit Amounts
(mg/tablet)
Ranitidine HCI 28.000
Microcrystalline Cellulose 120.875
Magnesium Stearate 1.125
Total Compression Weight 150.00
Film Coat
Opadry Yellow YS-1 -12606 6.75
Purified Water** 42.34
** Removed during processing
Clinical Studies
in double-blind placebo controlled studies to evaluate the efficacy of 25mg ranitidine (administered as the hydrochloride) in the treatment of episodic heartburn in the general population, both the chewable tablets of Example 1 and the swallow tablets of Example 2 were effective within 30-45 minutes of administration.

Claims

Claims
1. An oral pharmaceutical composition comprising ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient, characterised in that the dose of ranitidine per unit dosage form is between 10 and 30 mg, expressed as the weight of free base.
2. An oral pharmaceutical composition as claimed in claim 1 where the dose of ranitidine per dosage unit is 25mg expressed as the weight of free base.
3. An oral pharmaceutical composition as claimed in claim 1 or claim 2 where the ranitidine is in the form of its hydrochloride salt.
4. An oral pharmaceutical composition as claimed in any one of claims 1 to 3 in the form of a tablet.
5. An oral pharmaceutical composition as claimed in claim 4 in the form of a swallow tablet.
6. A method of treating minor gastrointestinal disorders associated with excess acid secretion which comprises administering to a patient in need of such, an oral pharmaceutical composition as claimed in any one of claims 1 to 5.
7. Use of an oral pharmaceutical composition as claimed in any one of claims 1 to 5 in the manufacture of a medicament for treating minor gastrointestinal disorders associated with excess acid secretion.
PCT/EP1995/001271 1994-04-12 1995-04-10 Low dosage ranitidine compositions for the treatment of minor gastrointestinal disorders associated with excess acid secretion WO1995027486A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP7526068A JPH10502331A (en) 1994-04-12 1995-04-10 Low-dose ranitidine compositions for treating gastrointestinal disorders due to hyperacid secretion
AU21380/95A AU690664B2 (en) 1994-04-12 1995-04-10 Low dosage ranitidine compositions for the treatment of minor gastrointestinal disorders associated with excess acid secretion
BR9507312A BR9507312A (en) 1994-04-12 1995-04-10 Oral pharmaceutical composition process to treat minor gastrointestinal disorders associated with excess acid secretion and use of the oral pharmaceutical composition
EP95914346A EP0755251A1 (en) 1994-04-12 1995-04-10 Low dosage ranitidine compositions for the treatment of minor gastrointestinal disorders associated with excess acid secretion
NZ283354A NZ283354A (en) 1994-04-12 1995-04-10 Oral pharmaceutical comprising low dosage amount of ranitidine as sole active ingredient for treating minor gastrointestinal disorders associated with excess acid secretion
MXPA/A/1996/004553A MXPA96004553A (en) 1994-04-12 1996-10-03 Compositions of dosing ranitidine b
KR1019960705716A KR970702034A (en) 1994-04-12 1996-10-11 Low Dosage Ranitidine Compositions for the Treatment of Minor Gastrointestinal Disorders Associated with Excess Acid Secretion

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9407235A GB9407235D0 (en) 1994-04-12 1994-04-12 Pharmaceutical compositions
GB9407235.2 1994-04-12

Publications (1)

Publication Number Publication Date
WO1995027486A1 true WO1995027486A1 (en) 1995-10-19

Family

ID=10753423

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1995/001271 WO1995027486A1 (en) 1994-04-12 1995-04-10 Low dosage ranitidine compositions for the treatment of minor gastrointestinal disorders associated with excess acid secretion

Country Status (11)

Country Link
EP (1) EP0755251A1 (en)
JP (1) JPH10502331A (en)
KR (1) KR970702034A (en)
CN (1) CN1146150A (en)
AU (1) AU690664B2 (en)
BR (1) BR9507312A (en)
CA (1) CA2187651A1 (en)
GB (1) GB9407235D0 (en)
NZ (1) NZ283354A (en)
WO (1) WO1995027486A1 (en)
ZA (1) ZA952931B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992009286A1 (en) * 1990-11-27 1992-06-11 Beecham Group Plc Composition containing antihistamine h2 receptor antagonists and bioadhesive material
EP0492247A1 (en) * 1990-12-21 1992-07-01 Miles Inc. Effervescent H2 blocker formulation
WO1993012779A1 (en) * 1991-12-20 1993-07-08 Smithkline Beecham Plc Compositions containing histamine-h2-receptor antagonists at low dosage

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992009286A1 (en) * 1990-11-27 1992-06-11 Beecham Group Plc Composition containing antihistamine h2 receptor antagonists and bioadhesive material
EP0492247A1 (en) * 1990-12-21 1992-07-01 Miles Inc. Effervescent H2 blocker formulation
WO1993012779A1 (en) * 1991-12-20 1993-07-08 Smithkline Beecham Plc Compositions containing histamine-h2-receptor antagonists at low dosage

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
KOSS M A ET AL: "CAN LOW DOSE RANITIDINE EFFECTIVELY INHIBIT MEAL-STIMULATED GASTRIC ACID SECRETION", 91ST ANNUAL MEETING OF THE AMERICAN GASTROENTEROLOGICAL ASSOCIATION AND DIGESTIVE DISEASE WEEK, SAN ANTONIO, TEXAS, USA, MAY 12-18, 1990.;& GASTROENTEROLOGY,, VOL. 98, NO. 5 PART 2, PAGE(S) A71, 1990. *
KOSS MA ET AL: "Anti-secretory effects and pharmacokinetics of low dose ranitidine.", ALIMENT PHARMACOL THER (ENGLAND), AUG 1993, VOL. 7, NO. 4, PAGE(S) 417-22, *
UCHIDA E ET AL: "EFFECT OF LOW-DOSE RANITIDINE ON GASTRIC ACIDITY AFTER TETRAGASTRIN ADMINISTRATION IN HEALTHY YOUNG VOLUNTEERS", 66TH ANNUAL MEETING OF THE JAPANESE PHARMACOLOGICAL SOCIETY, YOKOHAMA, JAPAN, MARCH 24-27, 1993.;& JPN J PHARMACOL,, VOL. 61, SUPPL. 1, PAGE(S) 318P, 1993. *

Also Published As

Publication number Publication date
AU690664B2 (en) 1998-04-30
BR9507312A (en) 1997-10-07
MX9604553A (en) 1997-11-29
ZA952931B (en) 1996-01-05
EP0755251A1 (en) 1997-01-29
GB9407235D0 (en) 1994-06-08
JPH10502331A (en) 1998-03-03
KR970702034A (en) 1997-05-13
NZ283354A (en) 1998-08-26
CA2187651A1 (en) 1995-10-19
AU2138095A (en) 1995-10-30
CN1146150A (en) 1997-03-26

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