WO2001074322A1 - Composition - Google Patents

Composition Download PDF

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Publication number
WO2001074322A1
WO2001074322A1 PCT/US2001/009880 US0109880W WO0174322A1 WO 2001074322 A1 WO2001074322 A1 WO 2001074322A1 US 0109880 W US0109880 W US 0109880W WO 0174322 A1 WO0174322 A1 WO 0174322A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
chlorhexidine
oral hygiene
composition according
orally acceptable
Prior art date
Application number
PCT/US2001/009880
Other languages
English (en)
Inventor
Robert M. Buch
Original Assignee
Smithkline Beecham Corporation
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 Smithkline Beecham Corporation filed Critical Smithkline Beecham Corporation
Priority to CA002404598A priority Critical patent/CA2404598A1/fr
Priority to AU2001247837A priority patent/AU2001247837A1/en
Priority to JP2001572068A priority patent/JP2003528902A/ja
Priority to US10/239,814 priority patent/US20030206876A1/en
Priority to EP01920823A priority patent/EP1267814A4/fr
Publication of WO2001074322A1 publication Critical patent/WO2001074322A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/43—Guanidines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

  • the present invention relates to oral hygiene compositions comprising the cationic antibacterial agent, chlorhexidine, for combating halitosis.
  • Cationic antibacterial agents such as chlorhexidine have long been recognised as useful therapeutic agents for treating various oral health conditions such as plaque, caries, periodontal diseases and halitosis due not only to their intrinsic in vitro antibacterial activity but also because of their substantivity to oral tissue. They are thus adsorbed onto oral surfaces and gradually released over a period of time, to produce a prolonged antibacterial effect.
  • EP-A-920857 describes an oral composition for the treatment of halitosis comprising a combination of 0.025 to 0.20% by weight of a chlorhexidine salt, 0.025 to 0.10% by weight of a quaternary ammonium salt such as cetylpyridinium chloride and a Zn or Cu salt providing 100 to lOOOppm of Zn or Cu ions.
  • WO-00/51559 (which was published on 8 September 2000 after the priority date of the present application) describes a mouthwash composition for the treatment of halitosis containing 0.005 to 0.05% w/v of an antibacterial agent selected from bis- guanides and quaternary ammonium compounds and 0.05 to 0.5% w/v of zinc acetate.
  • the present invention provides an oral hygiene composition comprising chlorhexidine or an orally acceptable addition salt thereof in a concentration not greater than 0.025% by weight of the total composition and an orally acceptable carrier or excipient with the proviso that when the oral hygiene composition is a mouthwash composition it does not contain from 0.05 to 0.5% w/v of zinc acetate.
  • the present invention provides the use of chlorhexidine or an orally acceptable addition salt thereof in the manufacture of an oral hygiene composition as hereinbefore described for combating halitosis.
  • the present invention provides a method of combating halitosis by administering to a patient in need thereof of an oral hygiene composition as hereinbefore described.
  • chlorhexidine or an orally acceptable addition salt thereof is present in an amount from 0.001 to 0.024%, preferably 0.002 to 0.020%, and more preferably 0.005 to 0.015% by weight of the oral hygiene composition.
  • the oral hygiene composition does not contain a Zn or Cu salt.
  • chlorhexidine or an orally acceptable addition salt thereof is present as the sole antibacterial agent.
  • Suitable such salts of chlorhexidine include those which have a solubility at 20°C of at least 0.005% w/v and include the digluconate, diformate, diacetate, dipropionate, dihydroiodide, dihydrochloride, dilactate, dinitrate, sulphate, and tartrate. Of these, the digluconate, diacetate and dihydrochloride are favoured.
  • Oral hygiene compositions of the present invention may also usefully contain an ionic fluorine-containing compound.
  • Suitable ionic fluorine-containing compounds include, for instance, fluoride salts such as amine fluorides and alkali metal fluoride salts, for example sodium fluoride, and monofluorophosphate salts such as alkali metal monofluorophosphate salts, for example sodium monofluorophosphate.
  • fluoride salts such as amine fluorides and alkali metal fluoride salts, for example sodium fluoride
  • monofluorophosphate salts such as alkali metal monofluorophosphate salts, for example sodium monofluorophosphate.
  • the ionic fluorine-containing compound is incorporated into the composition to provide between 100 and 3000ppm, preferably between 500 and 2000ppm of fluoride ions.
  • Oral hygiene compositions of the present invention maybe provided in any of the presentations normally used for such products, for instance, dentifrices including toothpastes and toothpowders, abrasive and non-abrasive gels, mouthwashes, gargles, irrigating solutions, mouthsprays and presentations for sucking or chewing by the user such as gums, pastilles, lozenges and wafers which can rapidly dissolve in the mouth.
  • dentifrices including toothpastes and toothpowders, abrasive and non-abrasive gels, mouthwashes, gargles, irrigating solutions, mouthsprays and presentations for sucking or chewing by the user such as gums, pastilles, lozenges and wafers which can rapidly dissolve in the mouth.
  • Components for the orally acceptable carrier or excipient will be selected according to the particular type of presentation involved.
  • abrasives capable of acting as a source of anions are preferably avoided in favour of compatible abrasives.
  • Suitable nonionic surfactants include, for example, polyethoxylated sorbitol esters, in particular polyethoxylated sorbitol monoesters, for instance, PEG(40) sorbitan di- isostearate, and the products marketed under the trade name Tween'by ICI; polycondensates of ethylene oxide and propylene oxide (poloxamers), for instance the products marketed under the trade name Pluronic' by B ASF-Wyandotte; condensates of propylene glycol; polyethoxylated hydrogenated castor oil, for instance, cremophors; and sorbitan fatty esters.
  • polyethoxylated sorbitol esters in particular polyethoxylated sorbitol monoesters, for instance, PEG(40) sorbitan di- isostearate, and the products marketed under the trade name Tween'by ICI
  • Suitable amphoteric surfactants include, for example, long chain imidazoline derivatives such as the product marketed under the trade name Miranol C2M' by Miranol; long chain alkyl betaines, such as the product marketed under the tradename ⁇ mpigen BB'by Albright + Wilson, and long chain alkyl amidoalkyl betaines, such as cocamidopropylbetaine, and mixtures thereof.
  • Suitable cationic surfactants include the D,L-2-pyrrolidone-5-carboxylic acid salt of ethyl-N-cocoyl-L-arginate, marketed under the trade name CAE by Ajinomoto Co. Inc.
  • the surfactant is present in the range 0.005 to 20%, preferably 0.1 to
  • Suitable nonionic thickening agents include, for example, (Cl-6)-alkylcellulose ethers, for instance methylcellulose, hydroxy(Cl-6)-alkylcellulose ethers, for instance hydroxypropylcellulose, (C2-6)-alkylene oxide modified (Cl-6)-alkylcellulose ethers, for instance hydroxypropyl methylcellulose, and mixtures thereof.
  • the nonionic thickening agent is present in the range 0.01 to 30%, preferably 0.1 to 15%, more preferably 1 to 5%, by weight of the composition.
  • Suitable abrasives include a sparingly soluble salt in combination with an agent to suppress anion formation or an essentially insoluble compound.
  • Suitable sparingly soluble salts that may be used as an abrasive include calcium carbonate, calcium phosphates, magnesium carbonate, insoluble sodium metaphosphate, and suitable mixtures thereof.
  • the agent to suppress anion formation typically comprises a water soluble salt containing a cation which may be same as the cation of the abrasive and which forms an essentially insoluble or sparingly soluble salt with the anion of the abrasive.
  • the sparingly soluble salt used as an abrasive is calcium carbonate, advantageously used in combination with dicalcium phosphate, which also usefully buffers the pH of the formulation. Suitable types of calcium carbonate include both natural and synthetic chalks.
  • the agent to suppress anion formation may be an alkaline earth metal salt, for instance calcium chloride. The agent is preferably present in from 0.0001 to 1%, more preferably 0.005 to 0.1% by weight of the dentifrice.
  • the term 'essentially insoluble compound' as used herein refers to a compound which is intrinsically insoluble in aqueous solution and includes those compounds which are listed as being 'insoluble' in cold water in the Handbook of Chemistry and Physics', 48th Edition, Chemical Rubber Company, Section B, Physical Constants of Inorganic Compounds. Furthermore, such compounds when used as an abrasive shall contain little if any contaminating anionic impurities.
  • the insoluble abrasive compound should contains less than 1%, preferably less than 0.5%, and more preferably less than 0.25% of anionic impurities, based on the weight of the abrasive.
  • Suitable essentially insoluble compounds for use as abrasives include, for example, silica, zinc orthophosphate, plastics particles, alumina, hydrated alumina, and calcium pyrophosphate or mixtures thereof.
  • the abrasive is silica.
  • Suitable silicas include natural amorphous silica, for instance diatomaceous earth; and synthetic amorphous silicas, for instance a precipitated silica, or a silica gel, such as a silica xerogel; or mixtures thereof.
  • the preferred synthetic amorphous silicas are those with a low-level of water soluble anionic impurities (hereinafter referred to as "low-anion silica"). These are obtainable from manufacturing process which are carefully controlled so that the level of anion impurities, particularly sulphate and silicate from sodium sulphate and sodium silicate, respectively, is kept to a minimum.
  • the level of anion impurities may be reduced to the required level by careful washing of the initially produced silica with, for instance, deionised or distilled water.
  • Suitable low- anion silicas contain less than 0.5%, preferably less than 0.25%, more preferably less than 0.1 % by weight of water soluble impurities such as sodium sulphate and/or sodium silicate.
  • the abrasive is advantageously present in the range 1 to 80%, preferably 5 to 70%, more preferably 5 to 60% by weight of the dentifrice.
  • each of the thickening agent, the surfactant and abrasive should be, at the level employed in the dentifrice, compatible with the cationic antibacterial agent, that is, each will not substantially reduce the availability of the cationic antibacterial agent, for instance, by more than 30%, preferably more than 20%. This may be confirmed by, for instance, determining the biological activity of the formulation, by conventional microbiological assay using, for instance, M. luteus as the assay organism in a standard agar diffusion method, in the presence and absence of each of the aforementioned thickening agent, surfactant and abrasive.
  • Mouthwashes according to the present invention will preferably comprise as components of the carrier a surfactant and a humectant in an aqueous or an aqueous/ethanol solution.
  • Gels according to the present invention will preferably comprise as components of the carrier a surfactant, humectant, thickening agent and optionally water.
  • Dentifrices according to the present invention will preferably comprise as components of the carrier a surfactant, humectant, thickening agent, abrasive and if necessary, water.
  • Suitable humectants for use in compositions of the invention include for instance glycerine, sorbitol, propylene glycol or polyethylene glycol, or mixtures thereof.
  • the humectant may be present in the range from 5 to 70%, preferably 5 to 30%, more preferably 10 to 30% by weight of the dentifrice.
  • compositions may be added to the compositions if required, for instance sweetening agents, flavouring agents, colouring and whitening agents, preservatives and emulsifiers.
  • the pH of a composition according to the invention will be orally acceptable and typically in the range pH 4 to 9.
  • Oral hygiene compositions according to the present invention may be prepared by mixing the ingredients thereof in the required proportions and in any order that is convenient and thereafter and if necessary adjusting the pH to the required value.
  • Cysteine challenge testing consisted of the obtaining of an initial baseline NSC determination, the subsequent introduction of the cysteine challenge substrate, measuring the NSC response over a 20 minute period, introducing the test rinse and at set times thereafter, repeating the cysteine challenge for up to 7 hours.
  • Inhibition was assessed quantitatively by the degree of inhibition of NSC production from cysteine by the test agent, chlorhexidine digluconate, as compared to NSC production from cysteine at baseline. Duration of the inhibition was assessed as the time it takes for VSC production with successive cysteine challenges to return to that seen at baseline.
  • a mouthrinse comprising chlorhexidine digluconate at a concentration of 0.025% (v/v) was found to significantly inhibit the production of VSCs. Most inhibition was seen two hours after the rinse, with inhibition being maintained at gradually decreasing levels for over 7 hours from the initial rinse. Similarly advantageous results are obtained at lower concentrations of chlorhexidine digluconate such as 0.020, 0.015, 0.0125 and 0.010 % by weight of the composition.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Cosmetics (AREA)
  • Confectionery (AREA)

Abstract

L'invention concerne des compositions d'hygiène buccale contenant de la chlorhexidine et servant à traiter la mauvaise haleine.
PCT/US2001/009880 2000-03-30 2001-03-29 Composition WO2001074322A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CA002404598A CA2404598A1 (fr) 2000-03-30 2001-03-29 Composition
AU2001247837A AU2001247837A1 (en) 2000-03-30 2001-03-29 Composition
JP2001572068A JP2003528902A (ja) 2000-03-30 2001-03-29 組成物
US10/239,814 US20030206876A1 (en) 2000-03-30 2001-03-29 Composition
EP01920823A EP1267814A4 (fr) 2000-03-30 2001-03-29 Composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0007762.8 2000-03-30
GB0007762A GB0007762D0 (en) 2000-03-30 2000-03-30 Composition

Publications (1)

Publication Number Publication Date
WO2001074322A1 true WO2001074322A1 (fr) 2001-10-11

Family

ID=9888785

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/009880 WO2001074322A1 (fr) 2000-03-30 2001-03-29 Composition

Country Status (7)

Country Link
EP (1) EP1267814A4 (fr)
JP (1) JP2003528902A (fr)
AU (1) AU2001247837A1 (fr)
CA (1) CA2404598A1 (fr)
GB (1) GB0007762D0 (fr)
WO (1) WO2001074322A1 (fr)
ZA (1) ZA200207594B (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015041523A1 (fr) 2013-09-18 2015-03-26 Glymur B.V. Compositions d'hygiène buccale
BE1022773B1 (fr) * 2015-03-16 2016-08-31 Medical Beyond Modern Care Composition de traitement ou d'inhibition d'une mauvaise haleine par voie orale sous la forme d'un spray
FR3033700A1 (fr) * 2015-03-16 2016-09-23 Medical Beyond Modern Care Composition de traitement ou d'inhibition d'une mauvaise haleine par voie orale sous la forme d'un spray
WO2021018596A1 (fr) * 2019-08-01 2021-02-04 MEDA Pharma S.p.A. Composition liquide pour soins buccodentaires
CN113226269A (zh) * 2019-01-11 2021-08-06 梅达公司 包括氯己定和精氨酸或它们的盐的口腔护理制剂

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4923685A (en) * 1987-07-30 1990-05-08 Henkel Kommanditgesellschaft Auf Aktien Antimicrobial flavored compositions having particular utility as mouth washes

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58109410A (ja) * 1981-12-24 1983-06-29 Lion Corp 口腔用組成物
JPS61268259A (ja) * 1985-05-24 1986-11-27 ライオン株式会社 消臭剤
IN168400B (fr) * 1987-01-30 1991-03-23 Colgate Palmolive Co
DE3928063A1 (de) * 1989-08-25 1991-02-28 Henkel Kgaa Belaghemmende zahnpaste
DE69024323T2 (de) * 1989-10-27 1996-10-17 Genencor Int Antimikrobielles Verfahren und Formulierung unter Verwendung von Endoglycosidase vom Typ II und antimikrobielles Mittel
JPH08268854A (ja) * 1995-03-31 1996-10-15 Sunstar Inc 口腔用組成物
US5804165A (en) * 1996-07-24 1998-09-08 Arnold; Michael J. Antiplaque oral composition
NO307168B1 (no) * 1999-03-01 2000-02-21 Orix As Oralt preparat som er effektivt mot halitose

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4923685A (en) * 1987-07-30 1990-05-08 Henkel Kommanditgesellschaft Auf Aktien Antimicrobial flavored compositions having particular utility as mouth washes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1267814A4 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015041523A1 (fr) 2013-09-18 2015-03-26 Glymur B.V. Compositions d'hygiène buccale
BE1022773B1 (fr) * 2015-03-16 2016-08-31 Medical Beyond Modern Care Composition de traitement ou d'inhibition d'une mauvaise haleine par voie orale sous la forme d'un spray
FR3033700A1 (fr) * 2015-03-16 2016-09-23 Medical Beyond Modern Care Composition de traitement ou d'inhibition d'une mauvaise haleine par voie orale sous la forme d'un spray
CN113226269A (zh) * 2019-01-11 2021-08-06 梅达公司 包括氯己定和精氨酸或它们的盐的口腔护理制剂
CN113226269B (zh) * 2019-01-11 2023-11-28 梅达公司 包括氯己定和精氨酸或它们的盐的口腔护理制剂
WO2021018596A1 (fr) * 2019-08-01 2021-02-04 MEDA Pharma S.p.A. Composition liquide pour soins buccodentaires

Also Published As

Publication number Publication date
CA2404598A1 (fr) 2001-10-11
EP1267814A1 (fr) 2003-01-02
ZA200207594B (en) 2003-12-22
GB0007762D0 (en) 2000-05-17
EP1267814A4 (fr) 2003-07-09
JP2003528902A (ja) 2003-09-30
AU2001247837A1 (en) 2001-10-15

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