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WO2003037284A1 - Composition pour hygiene buccale - Google Patents

Composition pour hygiene buccale Download PDF

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Publication number
WO2003037284A1
WO2003037284A1 PCT/EP2002/012100 EP0212100W WO03037284A1 WO 2003037284 A1 WO2003037284 A1 WO 2003037284A1 EP 0212100 W EP0212100 W EP 0212100W WO 03037284 A1 WO03037284 A1 WO 03037284A1
Authority
WO
WIPO (PCT)
Prior art keywords
coqo
oral hygiene
composition
periodontal disease
instance
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP2002/012100
Other languages
English (en)
Inventor
Donal Hynes
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
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 Ltd filed Critical SmithKline Beecham Ltd
Publication of WO2003037284A1 publication Critical patent/WO2003037284A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61K31/12—Ketones
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • A61K8/355—Quinones

Definitions

  • the present invention relates to oral hygiene compositions for use in the prophylaxis and/or treatment of halitosis and/or periodontal disease.
  • gingitosis includes any inflammatory disease of the periodontium (tooth - surrounding tissue).
  • Related disorders affecting the gingiva are also included herein.
  • Chronic adult periodontal disease is characterised by loss of gingival attachment and resorption of alveolar bone which, in extreme cases, can lead to loss of teeth. It is generally believed to be mediated by a complex interaction between the host immune system and specific oral microbial pathogens.
  • the micro flora of the periodontal pocket are extremely complex and are believed to be mainly comprised of gram-negative obligate anaerobes and various spirochaetes.
  • Porphyromonas gingivalis Prevotella intermedia, Bacteroides forsythus, Treponema denticola, Wolinella recta and Fusobacterium nucleatum are regarded as being important in the etiology of periodontal disease.
  • Such anaerobes are also implicated in the development of halitosis.
  • the ability of such organisms to survive in the periodontal pocket or anaerobic pit of the tongue is dependent, in part, on the existence of a low reduction potential (Eh).
  • the Eh is basically a measure of the oxidising or reducing power of a system. The more positive the Eh, the more oxidising the system; the more negative the Eh the more reducing the system.
  • the oral cavity has a diverse range of reduction potentials: a clean tooth surface which has a ready supply of molecular oxygen can be as high as +200mV, the gingival crevice may have values in the region of +70mN, and the periodontal pocket where there will be little, if any molecular oxygen and one which is rich in reduced bacterial metabolites can have values as low as -300mV.
  • Ubiquinones disclosed include Coenzyme Q 7 and Coenzyme Q 10 , Coenzyme Q 7 being particularly favoured.
  • WO 94/15595 describes topically applied medicaments comprising CoQio for use in a variety of complaints including angina pectoris, hypertension, muscular dystrophy and periodontal disease.
  • US Patent 4654373 describes pharmaceutical compositions comprising
  • Coenzyme Q 0 (CoQ 0 which is 2,3 di-methoxy- 5-methyl-l,4-benzoquinone) is surprisingly more effective than COQ I Q as a redox agent in the prophylaxis and/or treatment of halitosis, periodontal disease and related disorders.
  • the present invention provides an oral hygiene composition comprising CoQo and an orally acceptable carrier or excipient.
  • suitable oral hygiene compositions include conventional presentations such as dentifrices, gels, mouthwashes, gargles, irrigating solutions and presentations for sucking or chewing such as gums, pastilles and lozenges.
  • the oral hygiene composition is capable of delivering a controlled release of CoQo directly to the diseased area, in particular to the gingival sulcus or crevice or periodontal pocket.
  • the orally acceptable carrier or excipient is topically retainable so to control the release of CoQ 0 at the site of application.
  • Topically retainable carriers suitable for use in the present invention include bioadhesive agents.
  • bioadhesive agents include polymers of acrylic acid or acrylic acid derivatives, e.g. carbopol or polycarbophil, cellulose derivatives, e.g.
  • various polymers such as polyethylene oxide, polyvinylpyrrolidone, polyvinylalcohol or polyvmylpyrrolidone/maleic anhydride copolymers, or natural materials such as chitosan, xanfhan gum, sodium alginate/alginic acid, gelatin, zein, guar gum, carrageenan, gum acacia or gum karay
  • the bioadhesive agent can be incorporated into any of the oral hygiene presentations as hereinbefore described.
  • such oral hygiene composition is in the form of a gel or a solid matrix which can be applied directly to the gingival sulcus or crevice or periodontal pocket.
  • a gel formation can be applied for example by means of a syringe to the desired area. Examples of solid matrixes are described in
  • US Patent 5087451 and include plasters, strips or microspheres comprising a bioadhesive agent as hereinbefore described.
  • the CoQo is applied in sufficient quantity to raise the reduction potential of the diseased anaerobic environment so to prevent the survival of pathogenic anaerobic bacteria implicated in halitosis, periodontal disease and related diseases.
  • the oral hygiene composition therefore comprises from 0.01 to 10% of CoQo by weight of the total composition, preferably from 0.05 to 1% by weight of the total composition.
  • the oral hygiene composition is applied to provide from 0.01 to 4mg of CoQo per unit dose, preferably from 0.1 to 2mg of CoQo.
  • bioadhesive agent is present in the range 0.01 to 30%, preferably
  • compositions of the present invention will contain appropriate formulating agents such as abrasives, surfactants, humectants, thickening agents, flavouring agents, sweetening agents, opacifying or colouring agents, preservatives and water, selected from those conventionally used in the oral hygiene composition art for such purposes and which are compatible with CoQo.
  • Suitable surfactants for use in compositions according to the present invention include, for instance, anionic, nonionic, cationic and amphoteric surfactants or mixtures thereof.
  • Suitable anionic surfactants include alkali metal (Ci2-18) ai kyl sulphates, for instance sodium lauryl sulphate, and N-acyl sarcosinates and N-acyl taurines in which the acyl moiety has from 12 to 16 carbon atoms, for instance, N-lauroyl, N-myristoyl and N-palmitoyl sarcosine alkali metal salts.
  • Suitable nonionic surfactants include, for example, alkylpolyglucosides for instance the products marketed under the trade name 'Plantacare' by Henkel, polyethoxylated sorbitol esters, in particular polyethoxylated sorbitol monoesters, for instance, PEG(40) sorbitan di-zsostearate, 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 BASF-Wyandotte; condensates of propylene glycol; polyethoxylated hydrogenated castor oil, for instance, cremophors; and sorbitan fatty esters.
  • alkylpolyglucosides for instance the products marketed under the trade name 'Plantacare' by Henkel
  • polyethoxylated sorbitol esters in particular polye
  • 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 betames, such as the product marketed under the tradename 'Empigen 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., and cocamidopropyl PG dimonium chloride phosphate and lauramidopropyl PG dimonium chloride phosphate, available under the trade names Monaquat PTC and Monaquat PTL, respectively, from Mona Corporation.
  • the surfactant is present in the range 0.005 to 20%, preferably 0.1 to 10%, more preferably 0.1 to 5% by weight of the total composition.
  • Suitable thickening agents for gel or dentifrice formulations include, for instance, nonionic thickening agents such as, for example, (C[-6)alkylcellulose ethers, for instance methylcellulose; hydroxy(C ⁇ 6)a ⁇ kylce ⁇ lulose ethers, for instance hydroxyethylcellulose and hydroxypropylcellulose; (C2"6) a lkylene oxide modified (C ⁇ -6)alkylcellulose ethers, for instance hydroxypropyl methylcellulose; and mixtures thereof.
  • nonionic thickening agents such as, for example, (C[-6)alkylcellulose ethers, for instance methylcellulose; hydroxy(C ⁇ 6)a ⁇ kylce ⁇ lulose ethers, for instance hydroxyethylcellulose and hydroxypropylcellulose; (C2"6) a lkylene oxide modified (C
  • thickening agents such as natural and synthetic gums or gum like material such as Irish Moss, xanfhan gum, gum tragacanth, sodium carboxymethylcellulose, polyvinyl pyrrolidone, starch and thickening silicas may also be used.
  • the thickening agent is xanthan gum. It will be appreciated that certain thickening agents may also function as the bioadhesive agent.
  • the 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 total composition.
  • Suitable humectants for use in compositions of the invention include for instance, glycerine, xylitol, sorbitol, propylene glycol or polyethylene glycol, or mixtures thereof; which humectant may be present in the range from 5 to 30%, preferably 5 to 20%, more preferably 5 to 15% by weight of the total composition.
  • Suitable abrasives for use in dentifrice compositions of the present invention include calcium carbonate, calcium phosphates, calcium pyrophosphate, insoluble sodium metaphosphate, sodium aluminosilicate, alumina, hydrated alumina, zinc orthophosphate, plastic particles, and silica, of which silica is the preferred abrasive.
  • Suitable silicas include natural amorphous silicas, such as, for instance, diatomaceous earth, and synthetic amorphous silicas, such as precipitated silicas and silica gels, including silica xerogels. Suitable silica xerogels are described in US
  • Suitable grades of precipitated silicas have BET surface areas in the range 20 to 300, preferably 20 to 100 m ⁇ /g and median agglomerate sizes in the range 2 to 50, preferably 5 to 30m.
  • Suitable precipitated silicas and silica xerogels are those marketed under the trade names Sident and Syloblanc, by Degussa and W R Grace Corporation Davison Chemical Division, respectively.
  • the silica is a "low anion” silica.
  • the term “low-anion” silicas refers to those in which anionic impurities such as sodium sulphate and sodium silicate which normally arise during the course of the manufacturing process are kept to a minimum, through careful control of the manufacturing process.
  • "Low anion” silicas suitably have less than 1%, preferably less than 0.5% advantageously less than 0.25% by weight of anionic impurities.
  • Suitable such "low anion" silicas are described in EP 0 368 130 (Procter & Gamble), EP 0 315 503 and EP 0 396 459 (Rhone-Poulenc) and WO 90/05113 (J.M. Huber Corp).
  • grades of commercially available silica with ionic impurities may be rendered suitable by washing thereof with deionised water. Conductivity measurements on the water after washing may be used to monitor the efficacy of such washing. Suitably the conductivity of the water after washing is reduced to less than 200 ⁇ Siemens/cm.
  • Suitable "low anion" silicas include the grade RP93 available from Rhone-Poulenc.
  • dentifrice compositions will have from 5 to 80%, preferably from 10 to 60% by weight of the abrasive.
  • compositions according to the present invention will have a pH which is orally acceptable, typically ranging from about pH 4 to 10, e.g. 5.5 to 8.
  • compositions according to the present invention may be prepared by admixing the ingredients in the appropriate relative amounts in any order that is convenient and thereafter and if necessary adjusting the pH to give the final desired value.
  • Example 1 Effect of COQ NJ and CoQo on the Reduction Potential and Survival of Broth cultures of P.gingivalis CoQo and CoQio were prepared as 0.3 M stock solutions using DMSO
  • test compound stock solution 40 ⁇ l was added to the above prepared culture to give a final concentration of 3.0mM and then incubated anaerobically at 37°C for up to 48 hours. Either deionised water or 1% DMSO (final concentration) were used as controls. Samples were taken for viable counting and reduction potential measurements were determined at set time points.
  • Viable counts was determined by performing serial dilutions of culture down to 10 "8 by transferring lOO ⁇ l volumes sequentially into 4 x 9ml volumes of PBS. Miles and Misra counts were carried out on blood agar and incubated for 48 hours.
  • Example 2 MIC Determination of CoQo n the absence and presence of Dithiothreitol 100 ⁇ l of Wilkins-Chalgrin (WC) Broth was added to the wells of a 96 well microtitre plate either alone or in the presence of dithiothreitiol [(DTT) to give a final concentration of 2 mg/ml].
  • P. gingivalis W50 was grown over 48 hours in WC Broth supplemented with 5 ⁇ g/ml of haemin and 0.5 ⁇ g/ml of menadione, 20 ⁇ l of this culture was added to each well.
  • CoQo was prepared as a stock solution (2% w/v in DMSO) and titred out in doubling dilutions across the plate. Plates were incubated anaerobically for 48 hours.
  • CoQo inhibits the growth of P.gingivalis in the absence of DTT. However this inhibition was reversed in the presence of DTT suggesting that CoQo produces its antibacterial effect through a redox specific mechanism of action.
  • a gel formulation is made up to contain:
  • a mouthwash formulation is made up to contain:

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Cosmetics (AREA)

Abstract

Cette invention se rapporte à des compositions pour hygiène buccale, qui comprennent la co-enzyme Q0.
PCT/EP2002/012100 2001-10-31 2002-10-29 Composition pour hygiene buccale Ceased WO2003037284A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0126085A GB0126085D0 (en) 2001-10-31 2001-10-31 Composition
GB0126085.0 2001-10-31

Publications (1)

Publication Number Publication Date
WO2003037284A1 true WO2003037284A1 (fr) 2003-05-08

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Application Number Title Priority Date Filing Date
PCT/EP2002/012100 Ceased WO2003037284A1 (fr) 2001-10-31 2002-10-29 Composition pour hygiene buccale

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WO (1) WO2003037284A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2455625A (en) * 2007-12-13 2009-06-17 Syntopix Ltd The use of benzoquinones and hydroquinones as antibacterial agents in the treatment of periodontal diseases

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3534137A (en) * 1965-09-30 1970-10-13 Takeda Chemical Industries Ltd Method of systemic therapy for severe early destructive periodontal disease
EP0155812A2 (fr) * 1984-03-16 1985-09-25 Kuraray Co., Ltd. Compositions dentaires
JPH049330A (ja) * 1990-04-26 1992-01-14 Nippon Oil & Fats Co Ltd 抗白癬菌剤
WO1994015595A1 (fr) * 1993-01-06 1994-07-21 Jemo-Pharm A/S Preparation comprenant une substance active pharmacologique/biologique
JPH07136239A (ja) * 1993-09-24 1995-05-30 Toppan Printing Co Ltd 消臭剤
WO1997049662A1 (fr) * 1996-06-25 1997-12-31 The University Of Sheffield Inhibiteurs bacteriens a base de quinone
US5925335A (en) * 1997-06-12 1999-07-20 C.S. Bioscience Inc. Dental formulation
WO2002053148A1 (fr) * 2000-12-31 2002-07-11 Hans Michael Brecht Produits de soins dentaires contenant des derives d'ubiquinone

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3534137A (en) * 1965-09-30 1970-10-13 Takeda Chemical Industries Ltd Method of systemic therapy for severe early destructive periodontal disease
EP0155812A2 (fr) * 1984-03-16 1985-09-25 Kuraray Co., Ltd. Compositions dentaires
JPH049330A (ja) * 1990-04-26 1992-01-14 Nippon Oil & Fats Co Ltd 抗白癬菌剤
WO1994015595A1 (fr) * 1993-01-06 1994-07-21 Jemo-Pharm A/S Preparation comprenant une substance active pharmacologique/biologique
JPH07136239A (ja) * 1993-09-24 1995-05-30 Toppan Printing Co Ltd 消臭剤
WO1997049662A1 (fr) * 1996-06-25 1997-12-31 The University Of Sheffield Inhibiteurs bacteriens a base de quinone
US5925335A (en) * 1997-06-12 1999-07-20 C.S. Bioscience Inc. Dental formulation
WO2002053148A1 (fr) * 2000-12-31 2002-07-11 Hans Michael Brecht Produits de soins dentaires contenant des derives d'ubiquinone

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MATSUMURA T ET AL: "EVIDENCE FOR ENHANCED TREATMENT OF PERIODONTAL DISEASE BY THERAPY WITH COENZYME Q", INTERNATIONAL JOURNAL FOR VITAMIN & NUTRITION RESEARCH, HOGREFE AND HUBER, BERNE, CH, vol. 43, no. 4, April 1973 (1973-04-01), pages 537 - 548, XP000965181, ISSN: 0300-9831 *
PATENT ABSTRACTS OF JAPAN vol. 016, no. 156 (C - 0930) 16 April 1992 (1992-04-16) *
PATENT ABSTRACTS OF JAPAN vol. 1995, no. 08 29 September 1995 (1995-09-29) *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2455625A (en) * 2007-12-13 2009-06-17 Syntopix Ltd The use of benzoquinones and hydroquinones as antibacterial agents in the treatment of periodontal diseases
GB2455625B (en) * 2007-12-13 2010-02-24 Syntopix Ltd The use of benzoquinones and hydroquinones as antibacterial agents in the treatment of periodontal diseases

Also Published As

Publication number Publication date
GB0126085D0 (en) 2001-12-19

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