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WO1996000569A1 - Compositions pharmaceutiques renfermant du triclosan ou ses derives et de l'edta ou de l'egta - Google Patents

Compositions pharmaceutiques renfermant du triclosan ou ses derives et de l'edta ou de l'egta Download PDF

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Publication number
WO1996000569A1
WO1996000569A1 PCT/GB1995/001544 GB9501544W WO9600569A1 WO 1996000569 A1 WO1996000569 A1 WO 1996000569A1 GB 9501544 W GB9501544 W GB 9501544W WO 9600569 A1 WO9600569 A1 WO 9600569A1
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WO
WIPO (PCT)
Prior art keywords
triclosan
salt
derivative
pharmaceutical composition
edta
Prior art date
Application number
PCT/GB1995/001544
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English (en)
Inventor
Peter William Dettmar
Andrew William Smith
Original Assignee
Reckitt & Colman Products 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
Priority claimed from GB9413072A external-priority patent/GB9413072D0/en
Priority claimed from GBGB9505032.4A external-priority patent/GB9505032D0/en
Application filed by Reckitt & Colman Products Limited filed Critical Reckitt & Colman Products Limited
Priority to JP8502954A priority Critical patent/JPH11503404A/ja
Priority to AU28016/95A priority patent/AU686829B2/en
Priority to EP95923465A priority patent/EP0768874A1/fr
Publication of WO1996000569A1 publication Critical patent/WO1996000569A1/fr

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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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/66—Phosphorus compounds
    • 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
    • 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 and, in particular, to pharmaceutical compositions for the treatment of gastrointestinal disorders associated with Helicobacter pylori infections.
  • Helicobacter pylori (formerly Campylobacter pyloridis or C. pylori) is a spiral-shaped Gram negative microorganism which appears to live beneath the mucus layer of the stomach.
  • An association between the presence of H. pylori in the gastric mucosa and histologically confirmed gastritis, duodenal ulceration and/or gastric cancer has been shown in several studies.
  • EP-A-0206626 and EP-A-0206627 (Marshall) describe the use of bismuth salts whilst EP-A-0206625 (Marshall) and WO-A-86/05981 (Borody) describe the use of a combination of bismuth with a single antibiotic for the treatment of Helicobacter pylori.
  • bismuth alone achieves low (30 to 70%) initial clearance rates for Helicobacter pylori and recurrence of the infection approaches 100% by twelve months post therapy.
  • Bismuth together with a single antibiotic appears to be relatively effective as a short term means of reducing the symptoms but it is now clear that the use of bismuth together with a single antibiotic frequently fails to eradicate the infection and has a high rate of reinfection (Rauw ⁇ , Erik A.D. et al. Gastroenterology, 1988, 94: 33-40) .
  • WO-A-89/03219 (Borody) describes the use of a combination of bismuth, a first antimicrobial agent and a second antimicrobial agent. This treatment regimen is not only complicated and expensive but still has unacceptably high relapse rates.
  • EP-A-0282132 and EP-A-0282131 (Procter and Gamble) describe the use of H 2 antagonists in combination with bismuth or Campylobacter inhibiting antimicrobial agents. This approach has still led to high relapse rates and may lead to many of the undesirable side effects of the individual treatment components.
  • WO-A-92/18143 (S ithKline Beecham) describes the use of a bacteriocin antimicrobial agent, such as nisin, gramicidin or tyrothricin, optionally co-administered with a release delaying substance.
  • GB-A-2243549 (Reckitt & Colman) describes the use of triclosan for the preparation of medicaments for the treatment of gastrointestinal disorders associated with Helicobacter pylori infections.
  • WO-A-92/18111 (SmithKline Beecham) describes the use of various antimicrobial agents for the treatment of Helicobacter pylori, the antimicrobial agent being optionally combined with a chelating agent or a surfactant.
  • Triclosan is included amongst the list of antimicrobial agents which are suggested for use in combination with a chelating agent or a surfactant, but no specific teaching is given or exemplification provided of any such compositions.
  • the present invention provides a pharmaceutical composition in oral unit dosage form for the treatment of gastrointestinal disorders associated with Helicobacter pylori infections wherein each unit comprises from 0.1 to 300mg, more preferably 0.1 to 200mg, still more preferably 0.1 to lOOmg of triclosan or a derivative thereof, or an amount of an ester of triclosan or a derivative thereof, a cationic salt of an ester of triclosan or a derivative thereof, or a cationic salt of triclosan or a derivative thereof, to provide 0.1 to 300 mg of triclosan or the said derivative thereof, and from 1 to 600mg, preferably 1 to 200mg, of EDTA or a salt thereof, or from 1 to 3600mg, preferably 1 to 1200mg of EGTA or a salt thereof, the weight ratio of triclosan to the EDTA or a salt thereof in each unit being in the range of from 1:2 to 1:60, or the weight ratio of triclosan to the EGTA
  • Triclosan (2-hydroxy- , 2' , 4 '-trichlorodiphenyl ether) is described in various formulations in GB-A-1022744, GB-A-1024022 and GB-A-1038185.
  • triclosan or a derivative thereof as used herein is intended to encompass the use of an amount of an ester of triclosan or a derivative thereof, a cationic salt of an ester of triclosan or a derivative thereof, or a cationic salt of triclosan or a derivative thereof which will provide the equivalent amount of triclosan or the said derivative thereof.
  • esters of triclosan or esters of the derivatives thereof for use in the present invention are the phosphate, phosphonate, sulfate, glucuronide, succinate and glutamate esters.
  • Particularly preferred phosphate esters are the phosphate esters of the formula:
  • R, and R 2 are hydrogen or a pharmaceutically acceptable cation; and n is 0 or an integer of from 1 to 3.
  • the phosphate esters may be prepared by the phosphorylation of triclosan or a derivative thereof, using methods well known in the art.
  • esters may be present in the form of the cationic salts thereof, for example the sodium, potassium, calcium or magnesium salts.
  • the cationic salts of triclosan may also be used in the present invention, for example, the sodium or potassium salts.
  • Derivatives of triclosan which may be used in the present invention further include those compounds in which one or both of the phenyl groups is/are substituted by one or more substituent groups in addition to the chloro substituents already present on the phenyl rings.
  • suitable substituents are alkyl groups containing 1 to 4 carbon atoms, haloalkyl groups containing 1 to 4 carbon atoms, alkoxy groups . -
  • substituents containing 1 to 4 carbon atoms, cyano, allyl, amino and acetyl groups.
  • Preferred substituents are methyl, methoxy and trifluoromethyl groups. It will be understood that if triclosan is substituted by more than one substituent, then the substituents may be the same or different.
  • derivatives of triclosan as used herein is intended also to include the analogues of triclosan, for example those as described in GB-1024022 having the general formula:
  • Hal is a halogen atom and when p is greater than 1 the halogen atoms may be the same or different, and the corresponding compounds in which one or both of the benzene groups contain one or more substituent groups selected from alkyl groups containing from 1 to 4 carbon atoms, haloalkyl groups containing from 1 to 4 carbon atoms, alkoxy groups containing 1 to 4 carbon atoms, cyano, alkyl, amino and acetyl groups.
  • substituent groups selected from alkyl groups containing from 1 to 4 carbon atoms, haloalkyl groups containing from 1 to 4 carbon atoms, alkoxy groups containing 1 to 4 carbon atoms, cyano, alkyl, amino and acetyl groups.
  • compositions according to the invention triclosan is the most preferred active ingredient.
  • compositions of the present invention preferably comprise, in each unit, triclosan or a derivative thereof in an amount of from 1 to 60mg, more preferably from 2 to 45mg, still more preferably from 2.5 to 30mg, yet more preferably from 2.5 to 25mg, and most preferably from 5 to 15mg.
  • the pharmaceutical compositions of the present invention preferably comprise, in each unit, EDTA or a salt thereof in an amount of from 1 to 150mg, more preferably 5 to lOOmg, still more preferably 10 to lOO g, yet more preferably 15 to 75mg, and even more preferably from 25 to 50mg, with the weight ratio of triclosan or a derivative thereof to EDTA being within the above-defined limits.
  • compositions of the present invention comprise EGTA or a salt thereof they preferably comprise, in each unit, 40 to 800mg, more preferably 100 to 600mg, and still more preferably 200 to 400mg, with the weight ratio of triclosan or a derivative thereof to EGTA being within the above defined limits.
  • the triclosan or a derivative thereof is preferably formulated in the compositions of the present invention with EDTA in the form of its tetra-sodium, di-sodium, di-calcium, disodium-calcium or dipotassium salt.
  • the salts may be hydrated.
  • compositions of the present invention in which the weight ratio of triclosan or a derivative thereof to EDTA or a salt thereof is within the range of from 1:2 to 1:60, or those compositions in which the weight ratio of triclosan or a derivative thereof to EGTA or a salt thereof is within the range of from 1:10 to 1:500, show a surprising and unexpected synergism which could not have been predicted by a person skilled in the art from any data relating to the effect of triclosan or its derivatives in the treatment of gastrointestinal disorders associated with Helicobacter pylori, or from a knowledge of the use in pharmaceutical compositions of EDTA or EGTA as a chelating agent.
  • the weight ratio of triclosan or a derivative thereof to EDTA or a salt thereof is preferably within the range of from 1:3 to 1:40, more preferably within the range of from 1:5 to 1:10.
  • the weight ratio of triclosan or a derivative thereof to EGTA or a salt thereof is preferably within the range of from 1:25 to 1:300, more preferably 1:40 to 1:80. It will be understood that the effective oral dose of the compositions of the present invention will depend upon the severity of the condition which is to be treated. The frequency of the dosing regime will also depend upon the severity of the condition and its response to the treatment. Typically the oral dosage form will be taken up to three times a day.
  • compositions of the present invention are in a form suitable for oral administration and will generally be in the form of tablets or capsules; or in the form of powders, granules or spheroids packed into sachets; or in the form of solutions or suspensions in which case a unit dose will generally comprise from 5 to 20ml of the liquid formulation.
  • compositions of the present invention when presented in the form of granules may be prepared by standard methods such as wet or dry granulation (slugging) . They may be effervescent or non-effervescent to be mixed with a suitable quantity of water for administration as a drink. They may also be chewable granules.
  • compositions of the present invention when presented in the form of spheroids may be prepared by the following method.
  • the triclosan or a derivative thereof, EDTA or EGTA and a carrier (for example microcrystalline cellulose) plus any other excipients are mixed with a sufficient quantity of water to form a 'plastic' wet mass.
  • the mass is extruded into cylinders of uniform diameter and equal length.
  • the extrudates are rolled into spheres using a spheroniser and then dried, preferably in a fluid bed dryer.
  • compositions of the present invention when presented in the form of powders may be prepared by blending triclosan or a derivative thereof, EDTA or EGTA and one or more pharmaceutically acceptable excipients such as bulking agents/diluents.
  • the pharmaceutical compositions of the present invention when presented in the form of tablets may be prepared by standard methods such as granulation or direct compression. They may be buffered and effervescent, or non-effervescent, and include tableting aids known in the art such as a lubricant, for example magnesium stearate, or a disintegrating agent, such as sodium starch glycolate.
  • compositions of the present invention when presented in the form of capsules may be prepared by standard methods such as filling powders, granules or spheroids into hard gelatine capsules, or adding the triclosan or a derivative thereof and EDTA or EGTA to melted pharmaceutically acceptable excipients before filling into capsules.
  • compositions of the present invention when presented in the form of solutions or suspensions may be prepared by mixing the components with a suitable liquid, such as water.
  • a suitable liquid such as water.
  • the liquid formulations will be formulated to provide the unit dosage in 5 to 20ml. They may include pharmaceutically acceptable conventional excipients such as suspending agents or buffer systems.
  • a preservative therein for example a combination of methyl- and propyl-para-hydroxybenzoate (methyl and propyl parabens) .
  • the pharmaceutical compositions may also include one or more colouring, sweetening or flavouring agents, if desired.
  • the composition of the present invention may also include an antacid. Suitable materials include sodium bicarbonate, calcium carbonate, aluminium hydroxide and mixtures thereof. Use of these materials, in particular sodium bicarbonate, also results in a reduction in the viscosity of the liquid compositions, thereby providing some degree of viscosity control in the design of readily pourable liquid preparations.
  • the pharmaceutical compositions may be formulated as gastric sustained release compositions, having a prolonged residence time within the stomach and continuously releasing the triclosan or a derivative thereof during that time. In this aspect the compositions may be formulated so as to produce floating alginate rafts within the stomach, or as ucoadherent-coated granules or spheroids, by techniques known in the art.
  • Mucoadherent-coated granules or spheroids may be produced by forming triclosan or a derivative thereof and EDTA/EGTA containing granules or spheroids as described above, and coating them with one or more known mucoadherent polymers such as carboxymethylcellulose, sodium carboxymethyl-cellulose, carbomer, polycarbophil, tragacanth, sodium or potassium alginate, methyl- cellulose,hydroxyethylcellulose, hydroxypropylmethyl- cellulose, carageenan or chitosan.
  • the coating may be carried out by any conventional technique, for example spray coating. Once coated and dried the granules or spheroids may be filled into sachets or gelatine capsules or, if sufficiently robust microadherent coatings have been used, compressed to form tablets.
  • compositions of the present invention when presented in tablet form may comprise a mucoadherent polymer in the tablet matrix.
  • the mucoadherent polymer which is preferred for use in the present invention is carbomer which is described in the British Pharmacopeia and the United States National Formulary as being a synthetic high molecular weight cross-linked polymer of acrylic acid containing 56 to 68% of carboxylic acid groups.
  • the British Pharmacopeia specifies cross-linking with allylsucrose.
  • Carbomer is used in the form of neutralised gel as a suspending agent in pharmaceutical preparation for internal and external uses.
  • suitable commercial grades of carbomer are those sold by B.F. Goodrich under the Registered Trade Marks Carbopol 910, 934, 934P, 940, 941, 971P, 974P, 980, 981 and 1342. These carbomer grades have molecular weights between approximately 750,000 and 4,000,000. Others examples are those sold by Nihon Junyaku as Junlon PW110, Junlon PW150 and Junlon PWlll, and Acrisint 400 (Sigma, Italy) . Specific grades of carbomer which are preferred for use in the present invention are Carbopol 934P and Carbopol 974P.
  • compositions formulated so as to produce floating alginate rafts within the stomach may be in solid single dosage form as tablets, powders or granules, or in liquid form.
  • the alginate containing gastric sustained release compositions of the present invention will generally comprise, in addition to the triclosan or a derivative thereof and EDTA/EGTA within the above stated ranges, from 200 to 600mg of alginic acid and/or a salt thereof, preferably a sodium, potassium or magnesium salt; 50 to 250mg of a sodium or potassium carbonate or bicarbonate salt; and optionally up to lOOmg calcium carbonate.
  • the compositions may also contain standard tableting excipients known in the art, such as soluble fillers, binders, lubricants and flavours.
  • the tablets may be produced by standard procedures such as direct compression, or by wet or dry granulation followed by tablet compression.
  • the alginate containing gastric sustained release compositions of the present invention will generally comprise, 0.1 to 2% w/v triclosan or a derivative thereof; 0.2 to 4% w/v EDTA or a salt thereof, or 1 to 35% w/v EGTA or a salt thereof; 1 to 8% w/v sodium or potassium alginate; 1.3 to 6.5% w/v sodium or potassium carbonate or bicarbonate salt; 0.5 to 4% calcium carbonate and optionally 0.3 to 1.7% w/v of a suspending agent, preferably carbomer, with the ratio of triclosan or a derivative thereof to EDTA or EGTA being within the above stated ranges.
  • a suspending agent preferably carbomer
  • liquid compositions may also contain standard excipients known in the art such as preservatives, flavouring and colouring agents.
  • the alginate containing liquids may be produced by dispersing all of the ingredients, except carbomer in water. If carbomer is used it will be added to the dispersion as a neutralised suspension in water.
  • carbomer If carbomer is used it will be added to the dispersion as a neutralised suspension in water.
  • the Minimum Inhibitory Concentrations (MIC) of each composition were determined using an agar dilution technique.
  • the MIC was defined as that concentration mg/1 at which less than 1 in 10 5 organisms produced visible colonies after incubation.
  • Helicobacter pylori strains NCTC 11637, 11916, 12384, 12386, 12455 and 12823 were obtained from the National Collection of Type Cultures, London.
  • Helicobacter pylori strain HP34 was a clinical isolate 1 7 -
  • Helicobacter acinonvx is a Helicobacter species which causes gastritis in cheetahs.
  • Columbia Blood Agar (OXOID, U.K.) containing 5% horse blood was prepared according to the manufacturer's instructions and used to prepare a dilution series of each compound or composition under test.
  • a multipoint innoculator was used to deliver to the plates, an innoculum of 1 to 5 ⁇ l, depending on the contact surface, of a culture of each Helicobacter strain against which the compound or composition was being tested.
  • the innoculum of each Helicobacter strain was prepared by scraping two lO ⁇ l innoculating loops of culture from plates of each strain and resuspending the culture in 600 ⁇ l of Tryptone Soya Broth (TSB-Difco, U.S.A.)
  • Table 1 presents data for the testing of triclosan alone, EDTA-disodium salt dihydrate alone, and compositions comprising 0.05mM, 0.125mM or 0.20mM EDTA-disodium salt dihydrate with varying concentrations of triclosan against the Helicobacter pylori strains and the Helicobacter acinonvx strain as a comparison.
  • Example 2 Following the general procedures of Example 1 using agar dilution techniques, the effect of EDTA-disodium salt dihydrate combination with triclosan, ampicillin and CPC was examined.
  • Helicobacter pylori strain 12385 was obtained from the National Collection of Type Cultures, London.
  • the EDTA-disodium salt dihydrate (E) was used at a concentration of 22mg/l in each combined study. The results are given in Table 2 below.
  • Zone of inhibition studies were carried out to determine the degree of diffusion of triclosan/EDTA- disodium salt dihydrate through a mucin plug. In these experiments, the greater the zone of inhibition, the higher the Helicobacter pylori inhibition.
  • ME Microbicidal effect
  • the aim is to achieve a microbicidal effect of greater than 5 Log reductions within 5 minutes.
  • a preparation in the form of tablets was prepared from the following ingredients:
  • Microcrystalline Cellulose 2705g (Avicel PH101)
  • the sodium carbonate, EDTA-disodium salt dihydrate, and microcrystalline cellulose were mixed and to the mixture was added triclosan in isopropanol.
  • the resulting mixture was blended in a high speed blender, dried in a forced air drier and sieved through an 840 ⁇ mesh sieve.
  • Sodium bicarbonate and water was then added to the mixture and the mixture granulated with a small amount of water in a high speed blender.
  • the granules were dried in a fluid bed dryer and then passed through an 840 ⁇ mesh sieve.
  • the magnesium sterate as a tableting aid was added to the granules and the mixture blended in a tumble blender.
  • the mixture was compressed into tablets each having a final weight of 470mg.
  • Each tablet contained 15mg of triclosan and 76.5mg of EDTA- disodium salt dihydrate.
  • Similar tablets may also be prepared with the addition of other optional ingredients such as a mucoadherent polymer for example carbomer (e.g. lOOOg in the above composition) , or tablet disintegrants, for example sodium starch glycolate (e.g. 300g in the above composition) .
  • a mucoadherent polymer for example carbomer (e.g. lOOOg in the above composition)
  • tablet disintegrants for example sodium starch glycolate (e.g. 300g in the above composition) .
  • a preparation in the form of capsules was prepared from the following ingredients:
  • the ingredients were uniformly mixed together and filled and sealed into size 0 hard gelatin capsules with a capsule fill weight of 750mg. Each capsule contained 15mg triclosan and 76.5mg EDTA-disodium salt dihydrate.
  • Example 6 Following the procedure of Example 6, similar tablets were prepared containing 7.5mg triclosan and 38.25mg of EDTA-disodium salt dihydrate, or 3.75mg triclosan and 19.125mg of EDTA-disodium salt dihydrate.
  • Example 6 was repeated replacing the EDTA by 4800g of EGTA.
  • the mixture was compressed into tablets each having a final weight of 888mg and containing I5mg triclosan and 400mg of EGTA.
  • Example 7 was repeated replacing the EDTA by 4800g of EGTA.
  • the mixture was filled and sealed into size 0 hard gelatin capsules with a full weight of 288mg. Each capsule contained 3.75mg triclosan and 120mg of EGTA.
  • Example 6 Following the procedure of Example 6, similar tablets were prepared containing 7.5mg of triclosan and 240mg of EGTA, or 3.75mg triclosan and 120mg of EGTA.
  • Example 6 Following the procedure of Example 6, similar tablets were prepared containing an amount of triclosan monophosphate to provide the equivalent of an amount of 7.5 mg of triclosan and 38.25 mg of EDTA-disodium salt dihydrate, or 3.75 mg of triclosan and 19.125 mg of EDTA-disodium salt dihydrate.
  • Example 11 Following the procedure of Example 11, similar tablets were prepared containing an amount of triclosan monophoshate to provide the equivalent of an amount of 7.5mg triclosan in place of the 7.5mg of triclosan.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
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  • Communicable Diseases (AREA)
  • Engineering & Computer Science (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Composition pharmaceutique sous la forme posologique d'unités administrées par voie orale et destinées au traitement des troubles gastro-intestinaux associés aux infections par Helicobacter pylori. Chaque unité comporte de 0,1 à 300 mg de triclosan ou de son dérivé, ou une certaine quantité d'un ester de triclosan ou de son dérivé, un sel cationique d'un ester de triclosan ou de son dérivé, ou un sel cationique de triclosan ou de son dérivé, afin d'obtenir 0,1 à 300 mg de triclosan ou de son dérivé, et de 1 à 600 mg d'EDTA ou de son sel, ou bien de 1 à 3600 mg d'EGTA ou de son sel, le rapport pondéral entre le triclosan et l'EDTA ou son sel dans chaque unité étant compris entre 1:2 et 1:60, ou le rapport pondéral entre le triclosan et l'EGTA ou son sel dans chaque unité étant compris entre 1:10 et 1:500.
PCT/GB1995/001544 1994-06-29 1995-06-29 Compositions pharmaceutiques renfermant du triclosan ou ses derives et de l'edta ou de l'egta WO1996000569A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP8502954A JPH11503404A (ja) 1994-06-29 1995-06-29 トリクロサンまたはその誘導体およびｅｄｔａまたはｅｇｔａを含有する医薬組成物
AU28016/95A AU686829B2 (en) 1994-06-29 1995-06-29 Pharmaceutical compositions containing triclosan or derivatives thereof and EDTA or EGTA
EP95923465A EP0768874A1 (fr) 1994-06-29 1995-06-29 Compositions pharmaceutiques renfermant du Triclosan ou ses derives et de l'Edta ou de l'Egta

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB9413072.1 1994-06-29
GB9413072A GB9413072D0 (en) 1994-06-29 1994-06-29 Pharmaceutical compositions
GB9505032.4 1995-03-13
GBPCT/GB95/00540 1995-03-13
GB9500540 1995-03-13
GBGB9505032.4A GB9505032D0 (en) 1995-03-13 1995-03-13 Improvements in or relating to organic compositions

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Publication Number Publication Date
WO1996000569A1 true WO1996000569A1 (fr) 1996-01-11

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AU (1) AU686829B2 (fr)
CA (1) CA2193104A1 (fr)
WO (1) WO1996000569A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2336999A (en) * 1998-05-05 1999-11-10 Reckitt & Colmann Prod Ltd High-dosage triclosan compositions
EP1208839A1 (fr) * 2000-11-16 2002-05-29 Director of National Institute of Agrobiological Resources Ministry of Agriculture Forestry and Fisheries Chélate pour le traitement d'infections causées par l'Hélicobacter pylori

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2202698A1 (fr) * 1972-10-13 1974-05-10 Beecham Group Ltd
EP0455475A2 (fr) * 1990-05-03 1991-11-06 Reckitt And Colman Products Limited Utilisation de triclosan pour traiter les affections du canal digestif

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2202698A1 (fr) * 1972-10-13 1974-05-10 Beecham Group Ltd
EP0455475A2 (fr) * 1990-05-03 1991-11-06 Reckitt And Colman Products Limited Utilisation de triclosan pour traiter les affections du canal digestif

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2336999A (en) * 1998-05-05 1999-11-10 Reckitt & Colmann Prod Ltd High-dosage triclosan compositions
WO1999056738A1 (fr) * 1998-05-05 1999-11-11 Reckitt & Colman Products Limited Utilisation de triclosan pour traiter des infections par helicobacter pylori
EP1208839A1 (fr) * 2000-11-16 2002-05-29 Director of National Institute of Agrobiological Resources Ministry of Agriculture Forestry and Fisheries Chélate pour le traitement d'infections causées par l'Hélicobacter pylori

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EP0768874A1 (fr) 1997-04-23
CA2193104A1 (fr) 1996-01-11
AU686829B2 (en) 1998-02-12
AU2801695A (en) 1996-01-25

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