CA2166731A1 - H2 antagonist-alginate-antacid combinations - Google Patents
H2 antagonist-alginate-antacid combinationsInfo
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- CA2166731A1 CA2166731A1 CA002166731A CA2166731A CA2166731A1 CA 2166731 A1 CA2166731 A1 CA 2166731A1 CA 002166731 A CA002166731 A CA 002166731A CA 2166731 A CA2166731 A CA 2166731A CA 2166731 A1 CA2166731 A1 CA 2166731A1
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- Prior art keywords
- relief
- gastrointestinal
- antacid
- amount effective
- disorders
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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
-
- 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
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/08—Oxides; Hydroxides
-
- 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
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/10—Carbonates; Bicarbonates
-
- 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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- Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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)
- Medicinal Preparation (AREA)
Abstract
This invention relates to pharmaceutical composition for use in the treatment and relief of indigestion, sour stomach, heartburn and other gastrointestinal disorders in mammals, including humans, by administering compositions comprising: (i) an amount effective in the relief of gastrointestinal or esophagus disorders of an H2 antagonist selected from a compound of formula (I) and its pharmaceutically acceptable salts, hydrates, stereoisomersor polymorphs and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of the alginates and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate.
Description
- wo 95,0l7g5 2 ~ 6 ~- 7 3 ~ PCT/US94/07519 TITLE OF T~F. ~IVENTION
H2 ANTAGONIST-ALGINATE-AN~ACID COMBINATIONS
.
BACKGROUND OF THE ~VENTION
H2 antagonisls are c~mmrnly prescAbed to treat and prevent ulcers in the walls of the stom~rh, duo~3c~ or esophagus. H2 antagonists are alsb used to treat non-ulcerative con~lition~. Damage to the mucus lining ~ul~v~ lin~ these tissues en~bles destructive action of stom~rh acids which erodes the underlying tissue. ~ommonly known H2 antagonists for the tre~tmPnt of ulcers include cim~Ptlin~.? r~niti-lin~, nizatidine, rox~ti~line and famoti~lin~q Combinations of ~l~in~tes with certain H2 antagonists have been disclosed. See U.S. Pat No. 5,007,790 which discloses a solid state drug c~--t~ g (cimetidine)/polymer (sodium ~lgin~t~); GB 2æ2772 which discloses the H2 antagonist r~niti~line and ~lginir acid. GB
H2 ANTAGONIST-ALGINATE-AN~ACID COMBINATIONS
.
BACKGROUND OF THE ~VENTION
H2 antagonisls are c~mmrnly prescAbed to treat and prevent ulcers in the walls of the stom~rh, duo~3c~ or esophagus. H2 antagonists are alsb used to treat non-ulcerative con~lition~. Damage to the mucus lining ~ul~v~ lin~ these tissues en~bles destructive action of stom~rh acids which erodes the underlying tissue. ~ommonly known H2 antagonists for the tre~tmPnt of ulcers include cim~Ptlin~.? r~niti-lin~, nizatidine, rox~ti~line and famoti~lin~q Combinations of ~l~in~tes with certain H2 antagonists have been disclosed. See U.S. Pat No. 5,007,790 which discloses a solid state drug c~--t~ g (cimetidine)/polymer (sodium ~lgin~t~); GB 2æ2772 which discloses the H2 antagonist r~niti~line and ~lginir acid. GB
2,207,865 discloses a wound h~lin~ agent co~lising H-2 antagonist (famotidine) with carrier such as an ~ in~te wherein the composition is used to treat wounds rather than as a gastric acid inhibitor. EP-290,229-B discloses an H2-antagonist (cim~oti~line) plus an antacid and/or ~l~in~te. See also U.S. Pat. No. 4,996,222. It is known that with certain H2 antagonists, an ~lgin~t~ added to treat gastroesophageal reflux can promote oxi~l~tion of the H2 antagonist to a biological inactive form and additional ingre~i~nts have to be added to prevent this re~ction Combin~tion~ of antacids and ~l~in~tes have been used to provide ~y~ omatic relief of gastroesophageal reflu~. See Martindale's Extra Pharmacopoeia at page 1432. Combinations of H2 antagonists and antacids have been disclosed: See FR2648710, GB2219940, EP- 294933-A, EP-286,781-A, SU 1,362,477-A, U.S.
c 4,824,664, EP 233,853 and WO 9209286 Al. There is a need, however, to employ a drug combin~tion with the advantages of an ~lpin~te or ~l inic acid and an antacid to prevent gastroesoph~e~
reflux (GER) in cQmbin~tion with an H2 antagonist selected from famotidine or its salts, hydrates, stereoisomers or polymorphs to treat and prevent the discol~foll associated wi~ indigestion, sour ætQrn~Cll, WO 95/0179~ 2 i 6 6 7 3 I PCT/US94107S19 hcall~ or other gaslr~ al disorders including GER.
Additional ~nto~ nt~ may be added to the cl~ime~l famotidine/
in~te/antacid co.~ ;on to prevent o~ t on of famotidine to a less active metabolite.There is a need to employ a combination v~l~il~ an 5 advantage is that the overall ~y~ toms of ga~lr~ s~ l distress can be effectively treated with a combin~tion of the most powerful H2 antagonist av~ ble with an ~lgin~t~ and an ~nt~ci~ such as a c~l,.~nate salt or m~gn~sjllm or ~1...";..1.... hydroxide wherein the combination simlllt~nP,ously relieves and prevents s~ln~toms associated with excess gastric acid secretion or evolution in the stom~rh and esophagus respectively.
The present illv~ ion th~.~role provides an effective synergistic tre~tm~nt of ga~lr~ estin~l disorders using the combin~tion of famotidine and its salts, hydrates, or ph~rm~cologically active stereoisomers or polymorphs ~,vith an ~ ,in~t~ and an antacid. The c!~ime~l combin~ti~ is particularly useful for treating gastro-esophageal reflux disorder at ni~h*me since famotidine or the biologically active forms of ~mot~ n~ has a long-l~*n~ effect (9 hours) thereby aiding in the prevention of he~ ~ l and other gasL..,i,llestinal distress while the ~l~in~te aids in elimin~tin~ the rafting effect and the ~ntar,i~l provides rapid 1, lrrelillg relief in the stomach.
Other H2 antagonists that may be employed in this illvelltion include cimP-litine, r~niti~line, ni7~tit1inP, and roY~ti~linP.
DETA~ED DESCRIPTION OF THE INVENTION
This invention claims ~ ce~llir~l composidons for use in the tr~tmP-nt of mild stom~h and esophagus disorders including the prevention and l-e~t~ -t of L~lL..Ill.. The composition colrll~lises:
(i) an amPunt erre.,live in the relief of ga~o;.. ~estin~l or '' esophagus disorders of an H2 antagonist selected from a colllp~,ulld of the form~
*rB
WO 95/01795 . 2 1 ~ 6 7 ~ T PCTIUS94/07519 NH2` NSO2NH2 ~C=Ny~N~CH2SCH2CH2C\
NH2 S - b NH2 and its ph~rm~celltic~lly accephble salts, hydrates, stereoi~ m~.rs or polymorphs and (ii) an amount effective in relief of gaslrol~l~esffn~l or o esophagus disorders of at least one of an ~l~in~te and (iii) an amount effective in relief of ga~LIo;.,~s~
distress of an arltacid wherein the ~n~cid provides a ;.~g effect and generates carbon dioxide to aerate the ~l~in~te and optionally (iv) an ~ntifl~tlll~.nt amount of s;~lle~ cone~
This invention is also directed to a method of preventing 20 and treating indigestion, sour stomach, he~~ "l, overindulgence, gastroesoph~e~l reflux and other ga~lr~ estinal disorders in m~mm~ls, inchldinp 1.~ , in need of tre~tmtont thereof, conlplising ini~tering to such or~ni~m:
(i) an amount effective in the relief of ga~,.Jillt~stinal or esoph~ls disorders of an H2 antagonist selected from a compound of the formnl~.
NH2 ~NSO2NH2 ~C=Ny~N~CH2SCH2CH2C\
c 4,824,664, EP 233,853 and WO 9209286 Al. There is a need, however, to employ a drug combin~tion with the advantages of an ~lpin~te or ~l inic acid and an antacid to prevent gastroesoph~e~
reflux (GER) in cQmbin~tion with an H2 antagonist selected from famotidine or its salts, hydrates, stereoisomers or polymorphs to treat and prevent the discol~foll associated wi~ indigestion, sour ætQrn~Cll, WO 95/0179~ 2 i 6 6 7 3 I PCT/US94107S19 hcall~ or other gaslr~ al disorders including GER.
Additional ~nto~ nt~ may be added to the cl~ime~l famotidine/
in~te/antacid co.~ ;on to prevent o~ t on of famotidine to a less active metabolite.There is a need to employ a combination v~l~il~ an 5 advantage is that the overall ~y~ toms of ga~lr~ s~ l distress can be effectively treated with a combin~tion of the most powerful H2 antagonist av~ ble with an ~lgin~t~ and an ~nt~ci~ such as a c~l,.~nate salt or m~gn~sjllm or ~1...";..1.... hydroxide wherein the combination simlllt~nP,ously relieves and prevents s~ln~toms associated with excess gastric acid secretion or evolution in the stom~rh and esophagus respectively.
The present illv~ ion th~.~role provides an effective synergistic tre~tm~nt of ga~lr~ estin~l disorders using the combin~tion of famotidine and its salts, hydrates, or ph~rm~cologically active stereoisomers or polymorphs ~,vith an ~ ,in~t~ and an antacid. The c!~ime~l combin~ti~ is particularly useful for treating gastro-esophageal reflux disorder at ni~h*me since famotidine or the biologically active forms of ~mot~ n~ has a long-l~*n~ effect (9 hours) thereby aiding in the prevention of he~ ~ l and other gasL..,i,llestinal distress while the ~l~in~te aids in elimin~tin~ the rafting effect and the ~ntar,i~l provides rapid 1, lrrelillg relief in the stomach.
Other H2 antagonists that may be employed in this illvelltion include cimP-litine, r~niti~line, ni7~tit1inP, and roY~ti~linP.
DETA~ED DESCRIPTION OF THE INVENTION
This invention claims ~ ce~llir~l composidons for use in the tr~tmP-nt of mild stom~h and esophagus disorders including the prevention and l-e~t~ -t of L~lL..Ill.. The composition colrll~lises:
(i) an amPunt erre.,live in the relief of ga~o;.. ~estin~l or '' esophagus disorders of an H2 antagonist selected from a colllp~,ulld of the form~
*rB
WO 95/01795 . 2 1 ~ 6 7 ~ T PCTIUS94/07519 NH2` NSO2NH2 ~C=Ny~N~CH2SCH2CH2C\
NH2 S - b NH2 and its ph~rm~celltic~lly accephble salts, hydrates, stereoi~ m~.rs or polymorphs and (ii) an amount effective in relief of gaslrol~l~esffn~l or o esophagus disorders of at least one of an ~l~in~te and (iii) an amount effective in relief of ga~LIo;.,~s~
distress of an arltacid wherein the ~n~cid provides a ;.~g effect and generates carbon dioxide to aerate the ~l~in~te and optionally (iv) an ~ntifl~tlll~.nt amount of s;~lle~ cone~
This invention is also directed to a method of preventing 20 and treating indigestion, sour stomach, he~~ "l, overindulgence, gastroesoph~e~l reflux and other ga~lr~ estinal disorders in m~mm~ls, inchldinp 1.~ , in need of tre~tmtont thereof, conlplising ini~tering to such or~ni~m:
(i) an amount effective in the relief of ga~,.Jillt~stinal or esoph~ls disorders of an H2 antagonist selected from a compound of the formnl~.
NH2 ~NSO2NH2 ~C=Ny~N~CH2SCH2CH2C\
3 o NH2 S--Y NH2 and its ph~ celltic~lly acceptable salts, hydrates, stereoisomers or polymorphs and wo 95,0l7g5 2 1 6 6 7 3 t PCT/US94/07519 (ii) an amount effective in relief of gasllo;..l~s(;~-~l or eso~h~ls disorders of at least one of an ~l~in~te (iii) an amount effective in relief of ga~ro;..~.stin~l distress of an antacid ~11~l~ the antacid provides a l~urre~ g effect and generates carbon dio~ide to aerate the ~l~in~t~. and optionally o (iv) an ~ntifl~hll~P.nt amount of simPthicone.
The te~n m~mm~l~ or m~mm~ n or~ni~m includes but is not limited to hllm~n~, dogs, cats, horses and cows.
The term tre~SmPnt çnromr~cses the complete range of therapelltir.~lly positive effects associated with ~.h~ ell~
me-lic~tion including reduction of, alleviation of and relief from the s~m~oms or illness which affect the org~ n~
Famotidine may be purchq~e.~ in buLk or ot~er suitable ~l~ntitiçs as it is cu~lly available on the ma~ket and formlll~tr-3 via typical form~ tiQn processes with ~l~n~tes selecte~3 from ~1 inir, acid which is suitable for tablet forml~l~tion~ or ~o~ m ~l~in~tP. which is suitable for liquid form~ tions of the cl~imP,~ combination and antacids which are also known including calcium c~l,onate and other carbonate salts as well as ~ -l--n and m~ npsillm hydroxides. In ~dition, simethicone, a known ~ntifl~tl~lent~ may be added to the above 25 combination to provide ma~ and broad relief of gasll~stinal diblulb~..res and distress. Famotidine as a prescription drug product is sold in the United States under the tr~-iPm~rk PEPCID~).
The ph~rm~cel)hc.~l co~ ositions of the present invention are useful in the tre~tmP,nt of various mild ga~lr~i..tes~ l disorders including indigestion, sour stomach, overindulgence and heall~ul~. In particular, an ~lgin~te and ~nt~cid coml~inP~ with an H2 antagonist selected from famotidine, a coll~ound of the fo~
WO 95/01795 ;~ l 6 6 7 3 1 PCI/US94/07519 NH2~ ~NSO2NH2 ~C =Ny~NycH2scH2cH2c\
NH2 s_b NH2 or its rh~rm^^~ c~lly acceptable salts, hydrates, stereoisomers or polymorphs is useful for the prevention and tr~ of various ga~lloi~ stinal disorders such as indigestion,- sour stom~rh, or h~ . The llhli7~tion of the ~ lly known biologically active o forms and/or salts or hydrates of famotidine in combination with an ~1 in~te selected from ~1 inic acid or sodinm ~l~in~te or other ph~rm~ceutically acceptable ~ tç salts or hydrates and an antacid is advantageously used to treat mild ga~lruilltestinal disorders.
SimP,thirone or another anti-fl~ lent such as alpha-galactosid~ee (ADG) 15 may be added to this ~l~f~ d co~nbin~tion to provide anti-fl~t~ t relief. In particular, the cl~imed combin~tion is used to treat the ~y~ ullle associated with ~t ic acid secretion while simlllt~neously treating the Sylll~tOlllS of gastroesoph~ge~l reflux and fl~t~llenr~. The - ~nim~l, p~ti~nt, or org~niem in need of tre~ -nt thereof the,e~o~e 20 bençfite from the Gl~ime~l ph~rm - elltic~l compositi~n-H2 antagonists are well known in the tre~nent of ulcers and other ga~llo;nlestin~l disorders and may be used, according to the present inv~ntion, in combination with an ~lgin~te and an antacid and optional anti-fl~ t H2 antagonists used for ulcer ~lel~y fall into 25 four major structural cl~ses imi~l~701e denvalives; s~lbsl ;l~e~l furans, ~mino~lkylrh.ono~y de~ivalives and ~li...;.l;l.othiazole compounds.
Famotidine (N-(~minoslllfonyl)-3-[[[2-[~i~...;.-nln~thylene)~minQ]4-thiazolyl]methyl]thio] yloy~ mi~le)~ a m~mber of the latter class, is a colllye~iliv-e inhibitor of hist~min~ H2-rec~tol;, and its primary 3 0 y~ cQlogical activity is the inhibition of gastric acid secretion.
Famotidine su~l~sses both the acid co--cæ-~ alion and the volume of gastric acid secretion. Famotidine is well tolerated and has ~I;t~it~ side effects and thus advantageously may be used in the present invention in combin~tion with an ~1 in~te and an antacid. Famotidine is also the most potent and selective H2 antagonist.
WO 95tO1795 2 1 6 6 7 3 t PCT/US94/07519 The combination of famotidine or its ph~ celltie~lly effective salts, hydrates, ~lereoi~omPrs or polymorphs with an antacid and an ~l~in~te and optionally simP-thirone provides a combin~tir~n which simnlt~neously and selectively provides relief from and prevention of disco nfoll and injury to the stom~h, esophagus, or dllo~lenllm from excess production of gastric acid. I;,llll.P-I...ore, famotidine in combination with an ~l~in~te and an antacid may not interact with ~lr,ohol so that it may be ~lmini~tered prior to or during ingestion of meals or beverages which Cû~ lcQhol and, thef~fol~, a p~tiPnt in need of rapid tre~tment of ga~ l distress may take the drug combination at an &~pf~ll&te time which may be during a meal in which alcohol was c~ ecl The combin~ti~ n of an alginate and antacid with famotidine provides relief of gastroesoph~ge~l reflux while also providing long acting relief from and tre~tmP-nt of ga~ 'estin~l disorders associ~te~l with gastric acid secretion. The ~nt~rid ~ min;~tered in the cl~imP~ comkinqtion provides both a l~urrt~ g effect and sim~11t~nPously generates c~l,ull dioxide to aerate the ~ n~te raft formed from the ~1 in~te The raft has a lower density after this aeration effect and floats on the stom~r~ co~ s;
A ~l~"~eulically active stereoisomer or polymorph of famotidine may be employed sllbst~nti~lly free of other stereoisomeric forms of polymorphs, sllbst~nti~lly free should be taken to mean at least 90% of one ~ tinct stereoisomer or polymorph.
The combin~tion of famotidine which is a highly potent H2 antagonist with an ~l~in~te and an ~nt~cid re-lllces the size and weight of all pl-~fm~r,eutical delivery forms or combination form~ tions and lllelefole i~ wes p~ti~ t compliance or tolerance. The tablet or capsule form of this co~ tion is more readily swallowable by p~tirnt~ in need of tre~tmpnt thereof.
F~moti-line or its ~rm~r,elltiG~lly acceptable salts, hydrates, stereoisomers or polymorphs is adv~nt~eously used in the present invention in combination with ~l~inir acid or sodium ~1 in~te and calcium c~l~ . Of course, other suitable and known antacids such as the ~1--...;..--.~. hydroxide or m~esillm hydroxide salts or WO 95/0179~ ~ 1 6 6 7 3 1 PCTtUS94/07519 ~ ,s or com~in~tions thereof may be used in the cl~imP(l form~ tion. For example, a one to one ratio of m~gnP,,cium hydroxide to ~11... ~ hydroxide salts may be ntili7~jcl in the p~,se-ll invention.
The ~mount of famotidine used in the ~ t invention in hllm~nc may range from 2.5 mg/day to 80 mg/day. Adv~nt~g-P,ously, 2.5 to 40 mgs/day is ~llrnini~tered in co~l,;- .~l ;c!n with 200-500 mgs/day mg of an ~l~n~te and 250-750 mgs/day of calcium carbonate. The qll~ntitieS of each of the active ingre-lientc may vary depen~1in~ upon the severity of the con~lition and the particular biocl~f ~ and need of the p~tipnt or other or~ni.cm in need of tre~tn~-nt thereof. A physician or clinician or veterinarian of ordinary skill in ~e art may readily detel~ine suitable dosages of any prescription mP~lic~tiQn C~ 'E the cl~ime~l invPntion- The combination cl~imPi-l in the ;..~ invention is advantageously ~rlmini~ctered orally. The antacid employed herein may 15 be selec~ed from any of the co~ -~ially available or known antacids or com~in~tions thereof such as ~l.. ;.. ~ hydro~cide, calcium c~bollate, m~3yl~s~ l hydroxide or so~ m bicarbonate. The simP-thicone optionally employed herein is also available con~lelically and the ~t1mini~tered oral dosage may range in hllm~n~ from 10-1,000 mgs/day. This ~mollnt varies depen~lin~ upon the severity of the con~ition and typical dosages are described in the Physicians Desk Reference at pages 1155-56 (1992). ADG may be employed as an anti-fl~ in doses of 290 to 31,000 ('J~ tosidase ~ ;o~l Units (GaIU) particularly 675 to 2250 GaIU.
The present composition may be ~ministered to a p~l;.ont in need of ~e~ ..t thereof in ~e form of tablets, caplets, gelcaps, capsules, elixirs, lozenges, wafers, effervescent formnl~tioll.c, chewable tablets, syrups, or s~lepeneioI c or via other known and effective delivery methods. For oral ~lminictr~tion~ the acfive ingredients may be 30 ~-lmise~ with a ph~ celltir~lly acceptable dilnPnt such as lactose, sucrose, cellulose, dicalcium phosph~te, c~l~illm slllf~te, ..~,..ilol, and, in a liquid composit-io~ ethyl alcohol. Acceptable e-ml~leifying or sllepen-lin~ agents such as PVP, gelatin, natural sugars, com swe~teners, natural and synthetic gums such as ~ ci~, sodium ~1 in~te, guar gum, wOgS/0l79!i 2 1 ~7 ~ PCT/US94/07519 agar, I~.to~ e, ca,l~ymethylcellulose so~ m) polyethylene glycol r and waxes, may also be qtlmixe~l with the active cG~ Jo~?~ . Where n~ce~ssqry~ lubricants such as m-q~sillm stearic acid talc or mqgn~sillm st~qr-qte, and ~ inte~atol~ or supe~;~intçg~dtol~ such as starch, sodium starch glycolate or cross-linked PVP may also be in~ etl~ Electrolytes such as lic--q-lcillm ~os~ e, so~lillm ~ c~te, sodium qcet~q~te and so~ m chloride may also be used. The inactive ingreflients may also include m~psillm or ~ ;n~ tricilirqt~, sodium or potq..~sillm salts including c~l,o late salts, -q~ .. hydroxide gel, lqr,tose, sorbitol, as~al~lle or sodium sqcrh~ri~
The active comrQn~-nts may also be form~ ted in sust~in release or effervescent forml~lqtio~ . The sust-q-in~ release form~ tions also include layered formnl-qtiQn~ which provide for tinct release ratios and thus may be more er~c~ive in allowing for short and long term relief.
The following eY-qmrles illustrate tbe compositions of the ~.~se.ll invention which may be readily ~pa~d and as such are not to be considered as limiting the lll./e~lion set forth in the claims.
al~in~t~lantacid/famotidine Tablet ~lginic acid 500 mg famotidine 40 mg PVP 15 mg Avicel PHlOl 40 mg .e~ St~ate 4 mg c~lcillm c~l~ale 500 mg m~ lm tri~ c~te 25 mg soflillm bic~l,o~ e 170 mg ~l.. ;... hydroxide gel 100 mg WO 95/~17~5 2 1 ~ 6 7 } ~ ~/US94107519 t~/antacid/f~mc)tidine Tablet ~lpinir acid 500 mg famotidine 20 mg PVP 15 mg Avicel PH101 40 mg .jllm Stearate 4 mg 0 C~lcjnm c~l~l~ate 500 mg EXAMp~ .F. 3 in~te/antacid/f~motidine Tablet ~lpiniG acid 500 mg famotidine 15 mg PVP 15 mg Avicel PH101 40 mg 2 Ma~siul~ Stearate 4 mg calcium c~l,ol.ate 500 mg 25 al~inate/antacid/famotidine Tablet ~l inicacid g famotidine 10 mg PVP 15 mg 3 Avicel PH101 . 40 mg ~gneSjllm Stearate 4 mg c.~lci~m c~o-~ate 500 mg wo 95/0l7g5 2 1 6 ~ 7 3 1 PCT/USg4l075lg EXA~IP! .F. 5 ~in~tt~./antacid/famotidine Tablet ~1 iniC acid 500mg famotidine 5 mg PVP 1~ mg Avicel PH101 40 mg Magnesium Stearate 4 mg calcium c~l~ollat~ 500 mg 15 ~l~in~te/antacid/f~m~ tidine Sustained Release ~1 inir.acid 600mg famotidine 40 mg PVP 30 mg Avicel PH101 80 mg Magnesium Stearate 8 mg Me~hocel ElOMCR 66 mg Meth~cel KlOOMLV 200 mg calcinm c~l~ale 600 mg EXAMP! P 7 ~l~inate/famotidine/antacid Sus~lled Release ~1 inicacid 600mg famotidine 20 mg PVP 30 mg AvicelPH101 80 mg M~esil~mStearate 8 mg WO 95/017g5 2 1 6 6 7 3 1PCT/US94/07S19 MethooelElOMCR 66 mg Methocel KlOOMLV 200 mg calcium c&ll~nale 600 mg EXAl~IPLE 8 in~tP/antacidtfamotidine Solut;on sodium ~ n~te 500 mg o famotidine 10 mg g.s. syrup 5 ml c~ -m c~l,o~le 500mg EXAMP~.F, g al~inate/~nt~id~f~motidine Solution sodium ~l~in~te 500 mg famotidine 20 mg g.s. syrup 5 ml c~lcillm carbonate 500 mg Simethirone may be added to each of the above form~ hions or examples to provide anti-fl~hllent relief. The ~u~lily Of ~imethic ?ne ~lminictered to a p~ti~nt in need of tre~tm~-*t thereof is 25 the typical known dosage range to treat fl~tnlPnre. The dose may be, for example 2~40 mgs of ~imethiconP per 5 mls of a liquid form cl~ime~ c~ mbin~tion or per chewable tablet wherein the other active ingre~ P-nt~ inrl~ P famoti~line (20~0 mgs), m~eSi~lm hydroxide (200 mg), ~ll.. li.. ~. hydroxide (dried gel, 200 mg). The inactive 30 ingreflient~ in the tablet form may fur~her include dextrates, m~nnitol, m~ ea.ate, Yellow 10, collodial silicondioxide andBlue 1 or Red 27 while the liquid form(s) may ru~ r incl~fle inactives such as butylparaben, c&lbo~ymethylcel11-lose sodium, flavors, hyd~ypr~yl methylcellulose, microcryst~lline cellulose, propylparaben, and purified wo gS/01795 2 1 6 6 7 3 ~ PCT~S94/07519 water. Tbe previous examples are to be construed as non-limi*ng and ~di*on~l dosages and ~los~ge forms or routes of ~ nini~tration may be varied lepen~1in upon tbe individual ~ t being treated for ei~er the primary (e~cess acid I~P~r1;n~ to ga~ estinal or esophap~e~l dislu~ lce or tl~m~ge) or secondary (infections) sylllptoms of gasllu~lestinal disorders. ~ ~d~lition, known ~ "~e~?l*r~lly acceptab}e exci~k,~s or agents may be added as inactive ingre~lipnt~ to the cl~ime~ active combination in a variety of forms including tablets, capsules, or time-release me~lic~m~nts
The te~n m~mm~l~ or m~mm~ n or~ni~m includes but is not limited to hllm~n~, dogs, cats, horses and cows.
The term tre~SmPnt çnromr~cses the complete range of therapelltir.~lly positive effects associated with ~.h~ ell~
me-lic~tion including reduction of, alleviation of and relief from the s~m~oms or illness which affect the org~ n~
Famotidine may be purchq~e.~ in buLk or ot~er suitable ~l~ntitiçs as it is cu~lly available on the ma~ket and formlll~tr-3 via typical form~ tiQn processes with ~l~n~tes selecte~3 from ~1 inir, acid which is suitable for tablet forml~l~tion~ or ~o~ m ~l~in~tP. which is suitable for liquid form~ tions of the cl~imP,~ combination and antacids which are also known including calcium c~l,onate and other carbonate salts as well as ~ -l--n and m~ npsillm hydroxides. In ~dition, simethicone, a known ~ntifl~tl~lent~ may be added to the above 25 combination to provide ma~ and broad relief of gasll~stinal diblulb~..res and distress. Famotidine as a prescription drug product is sold in the United States under the tr~-iPm~rk PEPCID~).
The ph~rm~cel)hc.~l co~ ositions of the present invention are useful in the tre~tmP,nt of various mild ga~lr~i..tes~ l disorders including indigestion, sour stomach, overindulgence and heall~ul~. In particular, an ~lgin~te and ~nt~cid coml~inP~ with an H2 antagonist selected from famotidine, a coll~ound of the fo~
WO 95/01795 ;~ l 6 6 7 3 1 PCI/US94/07519 NH2~ ~NSO2NH2 ~C =Ny~NycH2scH2cH2c\
NH2 s_b NH2 or its rh~rm^^~ c~lly acceptable salts, hydrates, stereoisomers or polymorphs is useful for the prevention and tr~ of various ga~lloi~ stinal disorders such as indigestion,- sour stom~rh, or h~ . The llhli7~tion of the ~ lly known biologically active o forms and/or salts or hydrates of famotidine in combination with an ~1 in~te selected from ~1 inic acid or sodinm ~l~in~te or other ph~rm~ceutically acceptable ~ tç salts or hydrates and an antacid is advantageously used to treat mild ga~lruilltestinal disorders.
SimP,thirone or another anti-fl~ lent such as alpha-galactosid~ee (ADG) 15 may be added to this ~l~f~ d co~nbin~tion to provide anti-fl~t~ t relief. In particular, the cl~imed combin~tion is used to treat the ~y~ ullle associated with ~t ic acid secretion while simlllt~neously treating the Sylll~tOlllS of gastroesoph~ge~l reflux and fl~t~llenr~. The - ~nim~l, p~ti~nt, or org~niem in need of tre~ -nt thereof the,e~o~e 20 bençfite from the Gl~ime~l ph~rm - elltic~l compositi~n-H2 antagonists are well known in the tre~nent of ulcers and other ga~llo;nlestin~l disorders and may be used, according to the present inv~ntion, in combination with an ~lgin~te and an antacid and optional anti-fl~ t H2 antagonists used for ulcer ~lel~y fall into 25 four major structural cl~ses imi~l~701e denvalives; s~lbsl ;l~e~l furans, ~mino~lkylrh.ono~y de~ivalives and ~li...;.l;l.othiazole compounds.
Famotidine (N-(~minoslllfonyl)-3-[[[2-[~i~...;.-nln~thylene)~minQ]4-thiazolyl]methyl]thio] yloy~ mi~le)~ a m~mber of the latter class, is a colllye~iliv-e inhibitor of hist~min~ H2-rec~tol;, and its primary 3 0 y~ cQlogical activity is the inhibition of gastric acid secretion.
Famotidine su~l~sses both the acid co--cæ-~ alion and the volume of gastric acid secretion. Famotidine is well tolerated and has ~I;t~it~ side effects and thus advantageously may be used in the present invention in combin~tion with an ~1 in~te and an antacid. Famotidine is also the most potent and selective H2 antagonist.
WO 95tO1795 2 1 6 6 7 3 t PCT/US94/07519 The combination of famotidine or its ph~ celltie~lly effective salts, hydrates, ~lereoi~omPrs or polymorphs with an antacid and an ~l~in~te and optionally simP-thirone provides a combin~tir~n which simnlt~neously and selectively provides relief from and prevention of disco nfoll and injury to the stom~h, esophagus, or dllo~lenllm from excess production of gastric acid. I;,llll.P-I...ore, famotidine in combination with an ~l~in~te and an antacid may not interact with ~lr,ohol so that it may be ~lmini~tered prior to or during ingestion of meals or beverages which Cû~ lcQhol and, thef~fol~, a p~tiPnt in need of rapid tre~tment of ga~ l distress may take the drug combination at an &~pf~ll&te time which may be during a meal in which alcohol was c~ ecl The combin~ti~ n of an alginate and antacid with famotidine provides relief of gastroesoph~ge~l reflux while also providing long acting relief from and tre~tmP-nt of ga~ 'estin~l disorders associ~te~l with gastric acid secretion. The ~nt~rid ~ min;~tered in the cl~imP~ comkinqtion provides both a l~urrt~ g effect and sim~11t~nPously generates c~l,ull dioxide to aerate the ~ n~te raft formed from the ~1 in~te The raft has a lower density after this aeration effect and floats on the stom~r~ co~ s;
A ~l~"~eulically active stereoisomer or polymorph of famotidine may be employed sllbst~nti~lly free of other stereoisomeric forms of polymorphs, sllbst~nti~lly free should be taken to mean at least 90% of one ~ tinct stereoisomer or polymorph.
The combin~tion of famotidine which is a highly potent H2 antagonist with an ~l~in~te and an ~nt~cid re-lllces the size and weight of all pl-~fm~r,eutical delivery forms or combination form~ tions and lllelefole i~ wes p~ti~ t compliance or tolerance. The tablet or capsule form of this co~ tion is more readily swallowable by p~tirnt~ in need of tre~tmpnt thereof.
F~moti-line or its ~rm~r,elltiG~lly acceptable salts, hydrates, stereoisomers or polymorphs is adv~nt~eously used in the present invention in combination with ~l~inir acid or sodium ~1 in~te and calcium c~l~ . Of course, other suitable and known antacids such as the ~1--...;..--.~. hydroxide or m~esillm hydroxide salts or WO 95/0179~ ~ 1 6 6 7 3 1 PCTtUS94/07519 ~ ,s or com~in~tions thereof may be used in the cl~imP(l form~ tion. For example, a one to one ratio of m~gnP,,cium hydroxide to ~11... ~ hydroxide salts may be ntili7~jcl in the p~,se-ll invention.
The ~mount of famotidine used in the ~ t invention in hllm~nc may range from 2.5 mg/day to 80 mg/day. Adv~nt~g-P,ously, 2.5 to 40 mgs/day is ~llrnini~tered in co~l,;- .~l ;c!n with 200-500 mgs/day mg of an ~l~n~te and 250-750 mgs/day of calcium carbonate. The qll~ntitieS of each of the active ingre-lientc may vary depen~1in~ upon the severity of the con~lition and the particular biocl~f ~ and need of the p~tipnt or other or~ni.cm in need of tre~tn~-nt thereof. A physician or clinician or veterinarian of ordinary skill in ~e art may readily detel~ine suitable dosages of any prescription mP~lic~tiQn C~ 'E the cl~ime~l invPntion- The combination cl~imPi-l in the ;..~ invention is advantageously ~rlmini~ctered orally. The antacid employed herein may 15 be selec~ed from any of the co~ -~ially available or known antacids or com~in~tions thereof such as ~l.. ;.. ~ hydro~cide, calcium c~bollate, m~3yl~s~ l hydroxide or so~ m bicarbonate. The simP-thicone optionally employed herein is also available con~lelically and the ~t1mini~tered oral dosage may range in hllm~n~ from 10-1,000 mgs/day. This ~mollnt varies depen~lin~ upon the severity of the con~ition and typical dosages are described in the Physicians Desk Reference at pages 1155-56 (1992). ADG may be employed as an anti-fl~ in doses of 290 to 31,000 ('J~ tosidase ~ ;o~l Units (GaIU) particularly 675 to 2250 GaIU.
The present composition may be ~ministered to a p~l;.ont in need of ~e~ ..t thereof in ~e form of tablets, caplets, gelcaps, capsules, elixirs, lozenges, wafers, effervescent formnl~tioll.c, chewable tablets, syrups, or s~lepeneioI c or via other known and effective delivery methods. For oral ~lminictr~tion~ the acfive ingredients may be 30 ~-lmise~ with a ph~ celltir~lly acceptable dilnPnt such as lactose, sucrose, cellulose, dicalcium phosph~te, c~l~illm slllf~te, ..~,..ilol, and, in a liquid composit-io~ ethyl alcohol. Acceptable e-ml~leifying or sllepen-lin~ agents such as PVP, gelatin, natural sugars, com swe~teners, natural and synthetic gums such as ~ ci~, sodium ~1 in~te, guar gum, wOgS/0l79!i 2 1 ~7 ~ PCT/US94/07519 agar, I~.to~ e, ca,l~ymethylcellulose so~ m) polyethylene glycol r and waxes, may also be qtlmixe~l with the active cG~ Jo~?~ . Where n~ce~ssqry~ lubricants such as m-q~sillm stearic acid talc or mqgn~sillm st~qr-qte, and ~ inte~atol~ or supe~;~intçg~dtol~ such as starch, sodium starch glycolate or cross-linked PVP may also be in~ etl~ Electrolytes such as lic--q-lcillm ~os~ e, so~lillm ~ c~te, sodium qcet~q~te and so~ m chloride may also be used. The inactive ingreflients may also include m~psillm or ~ ;n~ tricilirqt~, sodium or potq..~sillm salts including c~l,o late salts, -q~ .. hydroxide gel, lqr,tose, sorbitol, as~al~lle or sodium sqcrh~ri~
The active comrQn~-nts may also be form~ ted in sust~in release or effervescent forml~lqtio~ . The sust-q-in~ release form~ tions also include layered formnl-qtiQn~ which provide for tinct release ratios and thus may be more er~c~ive in allowing for short and long term relief.
The following eY-qmrles illustrate tbe compositions of the ~.~se.ll invention which may be readily ~pa~d and as such are not to be considered as limiting the lll./e~lion set forth in the claims.
al~in~t~lantacid/famotidine Tablet ~lginic acid 500 mg famotidine 40 mg PVP 15 mg Avicel PHlOl 40 mg .e~ St~ate 4 mg c~lcillm c~l~ale 500 mg m~ lm tri~ c~te 25 mg soflillm bic~l,o~ e 170 mg ~l.. ;... hydroxide gel 100 mg WO 95/~17~5 2 1 ~ 6 7 } ~ ~/US94107519 t~/antacid/f~mc)tidine Tablet ~lpinir acid 500 mg famotidine 20 mg PVP 15 mg Avicel PH101 40 mg .jllm Stearate 4 mg 0 C~lcjnm c~l~l~ate 500 mg EXAMp~ .F. 3 in~te/antacid/f~motidine Tablet ~lpiniG acid 500 mg famotidine 15 mg PVP 15 mg Avicel PH101 40 mg 2 Ma~siul~ Stearate 4 mg calcium c~l,ol.ate 500 mg 25 al~inate/antacid/famotidine Tablet ~l inicacid g famotidine 10 mg PVP 15 mg 3 Avicel PH101 . 40 mg ~gneSjllm Stearate 4 mg c.~lci~m c~o-~ate 500 mg wo 95/0l7g5 2 1 6 ~ 7 3 1 PCT/USg4l075lg EXA~IP! .F. 5 ~in~tt~./antacid/famotidine Tablet ~1 iniC acid 500mg famotidine 5 mg PVP 1~ mg Avicel PH101 40 mg Magnesium Stearate 4 mg calcium c~l~ollat~ 500 mg 15 ~l~in~te/antacid/f~m~ tidine Sustained Release ~1 inir.acid 600mg famotidine 40 mg PVP 30 mg Avicel PH101 80 mg Magnesium Stearate 8 mg Me~hocel ElOMCR 66 mg Meth~cel KlOOMLV 200 mg calcinm c~l~ale 600 mg EXAMP! P 7 ~l~inate/famotidine/antacid Sus~lled Release ~1 inicacid 600mg famotidine 20 mg PVP 30 mg AvicelPH101 80 mg M~esil~mStearate 8 mg WO 95/017g5 2 1 6 6 7 3 1PCT/US94/07S19 MethooelElOMCR 66 mg Methocel KlOOMLV 200 mg calcium c&ll~nale 600 mg EXAl~IPLE 8 in~tP/antacidtfamotidine Solut;on sodium ~ n~te 500 mg o famotidine 10 mg g.s. syrup 5 ml c~ -m c~l,o~le 500mg EXAMP~.F, g al~inate/~nt~id~f~motidine Solution sodium ~l~in~te 500 mg famotidine 20 mg g.s. syrup 5 ml c~lcillm carbonate 500 mg Simethirone may be added to each of the above form~ hions or examples to provide anti-fl~hllent relief. The ~u~lily Of ~imethic ?ne ~lminictered to a p~ti~nt in need of tre~tm~-*t thereof is 25 the typical known dosage range to treat fl~tnlPnre. The dose may be, for example 2~40 mgs of ~imethiconP per 5 mls of a liquid form cl~ime~ c~ mbin~tion or per chewable tablet wherein the other active ingre~ P-nt~ inrl~ P famoti~line (20~0 mgs), m~eSi~lm hydroxide (200 mg), ~ll.. li.. ~. hydroxide (dried gel, 200 mg). The inactive 30 ingreflient~ in the tablet form may fur~her include dextrates, m~nnitol, m~ ea.ate, Yellow 10, collodial silicondioxide andBlue 1 or Red 27 while the liquid form(s) may ru~ r incl~fle inactives such as butylparaben, c&lbo~ymethylcel11-lose sodium, flavors, hyd~ypr~yl methylcellulose, microcryst~lline cellulose, propylparaben, and purified wo gS/01795 2 1 6 6 7 3 ~ PCT~S94/07519 water. Tbe previous examples are to be construed as non-limi*ng and ~di*on~l dosages and ~los~ge forms or routes of ~ nini~tration may be varied lepen~1in upon tbe individual ~ t being treated for ei~er the primary (e~cess acid I~P~r1;n~ to ga~ estinal or esophap~e~l dislu~ lce or tl~m~ge) or secondary (infections) sylllptoms of gasllu~lestinal disorders. ~ ~d~lition, known ~ "~e~?l*r~lly acceptab}e exci~k,~s or agents may be added as inactive ingre~lipnt~ to the cl~ime~ active combination in a variety of forms including tablets, capsules, or time-release me~lic~m~nts
Claims (8)
1. A pharmacetical composition for use in the treatment of gastrointestinal disorders such as indigestion, sour stomach, overindulgence and heartburn in a mammals, including humans comprising:
(i) an amount effective in the relief of gastrointestinal or espohagus disorders of an H2 antagonist selected from a compound of the formula:
and its pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of an alginate; and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate and optionally (iv) an antiflatulent amount of simethicone.
(i) an amount effective in the relief of gastrointestinal or espohagus disorders of an H2 antagonist selected from a compound of the formula:
and its pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of an alginate; and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate and optionally (iv) an antiflatulent amount of simethicone.
2. The composition of Claim 1 comprising between 5 mg to 40 mgs of famotidine.
3. The composition of Claim 2 comprising 200-500 mgs of an alginate selected from alginic acid or sodium alginate and 500-1000 mgs of an antacid wherein the antacid is selected from sodium or calcium carbonate salts or aluminum hydroxide or magnesium hydroxide salts.
4. The composition according to Claim 3 comprising (i) a tablet of 10 mgs of famotidine and (ii) 500 mgs of alginic acid and (iii) 500 mgs of calcium carbonate and optionally (iv) 20-40 mgs of simethicone.
5. A method of treating gastrointestinal disorders such as indigestion, sour stomach, overindulgence, gastroesophageal reflux and heartburn in a mammalian organism in need of such treatment, comprising administering to such organism:
(i) an amount effective in the relief of gastrointestinal or esophagus disorders of an H2 antagonist selected from a compound of the formula:
and its pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of the alginates and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate and optionally (iv) an antiflatulent amount of simethicone.
(i) an amount effective in the relief of gastrointestinal or esophagus disorders of an H2 antagonist selected from a compound of the formula:
and its pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of the alginates and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate and optionally (iv) an antiflatulent amount of simethicone.
6. A method according to Claim 5 wherein the composition administered to a mammalian organism in need thereof comprises:
(i) a tablet of 10 mgs of famotidine and (ii) 500 mgs of alginic acid and (iii) 500 mgs of calcium carbonate and optionally (iv) 20-40 mgs of simethicone.
(i) a tablet of 10 mgs of famotidine and (ii) 500 mgs of alginic acid and (iii) 500 mgs of calcium carbonate and optionally (iv) 20-40 mgs of simethicone.
7. A method of reducing the size and weight of a pharmaceutically effective amount of an alginate/antacid/H2 antagonist combination dosage form which comprises combining (i) an amount effective in the relief of gastrointestinal or esophagus disorders of an H2 antagonist selected from a compound of the formula:
and its pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of the alginates and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate and optionally (iv) an antiflatulent amount of simethicone.
and its pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of the alginates and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate and optionally (iv) an antiflatulent amount of simethicone.
8. A method of treating gastrointestinal disorders, overindulgence and pain before or during ingestion of a meal accompanied by alcoholic beverages, comprising:
administration of a combination of (i) an amount effective in the relief of gastrointestinal or esophagus disorders of an H2 antagonist selected from a compound of the formula:
and its pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs wherein the famotidine does not interact with ethanol from the ingestion of the alcoholic beverage; and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of the alginates wherein the alginate absorbs the ethanol; and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate and optionally (iv) an antiflatulent amount of simethicone.
administration of a combination of (i) an amount effective in the relief of gastrointestinal or esophagus disorders of an H2 antagonist selected from a compound of the formula:
and its pharmaceutically acceptable salts, hydrates, stereoisomers or polymorphs wherein the famotidine does not interact with ethanol from the ingestion of the alcoholic beverage; and (ii) an amount effective in relief of gastrointestinal or esophagus disorders of at least one of the alginates wherein the alginate absorbs the ethanol; and (iii) an amount effective in relief of gastrointestinal distress of an antacid wherein the antacid provides a buffering effect and generates carbon dioxide to aerate the alginate and optionally (iv) an antiflatulent amount of simethicone.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8793793A | 1993-07-06 | 1993-07-06 | |
| US087,937 | 1993-07-06 | ||
| PCT/US1994/007519 WO1995001795A1 (en) | 1993-07-06 | 1994-07-05 | H2 antagonist-alginate-antacid combinations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2166731A1 true CA2166731A1 (en) | 1995-01-19 |
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|---|---|---|---|
| CA002166731A Abandoned CA2166731A1 (en) | 1993-07-06 | 1994-07-05 | H2 antagonist-alginate-antacid combinations |
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| EP (1) | EP0707484A4 (en) |
| JP (1) | JPH08512321A (en) |
| AU (1) | AU7218194A (en) |
| CA (1) | CA2166731A1 (en) |
| WO (1) | WO1995001795A1 (en) |
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| SE9600071D0 (en) | 1996-01-08 | 1996-01-08 | Astra Ab | New oral formulation of two active ingredients I |
| AU3566697A (en) * | 1996-05-02 | 1997-11-19 | Warner-Lambert Company | Method of preventing gastrointestinal upset |
| ES2274550T3 (en) * | 1996-10-04 | 2007-05-16 | MERCK & CO., INC. | PROCEDURES AND COMPOSITIONS TO PREVENT AND TREAT BURNING OF STOMACH. |
| WO1998023272A1 (en) * | 1996-11-27 | 1998-06-04 | The Procter & Gamble Company | Compositions and methods for the treatment of gastrointestinal disorders |
| AU1453600A (en) * | 1998-11-04 | 2000-05-22 | Mcneil-Ppc, Inc. | Solid oral dosage forms containing alginic acid and famotidine |
| US6930119B2 (en) | 2002-07-17 | 2005-08-16 | Reliant Pharmaceuticals, Inc. | Liquid pharmaceutical composition |
| WO2007102726A1 (en) * | 2006-03-09 | 2007-09-13 | World-Trade Import-Export, Wtie, Ag. | Synergic combination of h2-receptor inhibitors, inert silicone and a hydroxymagnesium aluminate complex |
| DE102006037298A1 (en) | 2006-08-08 | 2008-02-14 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Pharmaceutical composition, in particular antacid |
| DE102008019339A1 (en) * | 2008-04-16 | 2009-10-22 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Composition for medical use, in particular antacids |
| US20180140630A1 (en) * | 2016-11-23 | 2018-05-24 | M. Michael Wolfe | Combination of an h2-receptor antagonist, antacid, and alginic acid to treat episodic heartburn |
| IT201800002625A1 (en) * | 2018-02-13 | 2019-08-13 | Drugs Minerals And Generics Italia S R L In Forma Abbreviata D M G Italia S R L | Solid form composition for use in the treatment of extra-oesophageal symptoms of gastric reflux |
| IT201800007771A1 (en) * | 2018-08-02 | 2020-02-02 | Drugs Minerals And Generics Italia Srl In Forma Abbreviata Dmg Italia Srl | Combination for use in the treatment of extra-oesophageal symptoms of gastric reflux |
| IT202100029657A1 (en) * | 2021-11-24 | 2023-05-24 | Mauro Leonardis | STERILE ANTI-REFLUX SYRUP WITHOUT PRESERVATIVES |
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| FR2636532B1 (en) * | 1988-09-20 | 1993-11-19 | Glaxo Group Ltd | PHARMACEUTICAL COMPOSITIONS |
| US5229137A (en) * | 1992-05-06 | 1993-07-20 | Brigham And Women's Hospital, Inc. | Methods and pharmaceutical compositions for treating episodic heartburn |
| GB9224855D0 (en) * | 1992-11-27 | 1993-01-13 | Smithkline Beecham Plc | Pharmaceutical compositions |
| AU7218294A (en) * | 1993-07-06 | 1995-02-06 | Mcneil-Ppc, Inc. | H2 antagonist-alginate combinations |
-
1994
- 1994-07-05 CA CA002166731A patent/CA2166731A1/en not_active Abandoned
- 1994-07-05 JP JP7504108A patent/JPH08512321A/en active Pending
- 1994-07-05 EP EP94921465A patent/EP0707484A4/en not_active Withdrawn
- 1994-07-05 AU AU72181/94A patent/AU7218194A/en not_active Abandoned
- 1994-07-05 WO PCT/US1994/007519 patent/WO1995001795A1/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0707484A1 (en) | 1996-04-24 |
| EP0707484A4 (en) | 1998-07-01 |
| WO1995001795A1 (en) | 1995-01-19 |
| JPH08512321A (en) | 1996-12-24 |
| AU7218194A (en) | 1995-02-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |