GB2395433A - Oral compositions comprising a halogenated hydroxydiphenyl ether, eg triclosan, and a delivery enhancing agent, eg a parahydroxybenzoate - Google Patents
Oral compositions comprising a halogenated hydroxydiphenyl ether, eg triclosan, and a delivery enhancing agent, eg a parahydroxybenzoate Download PDFInfo
- Publication number
- GB2395433A GB2395433A GB0326793A GB0326793A GB2395433A GB 2395433 A GB2395433 A GB 2395433A GB 0326793 A GB0326793 A GB 0326793A GB 0326793 A GB0326793 A GB 0326793A GB 2395433 A GB2395433 A GB 2395433A
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- United Kingdom
- Prior art keywords
- alkyl
- oral composition
- group
- composition according
- formula
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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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- 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
- A61K8/37—Esters of carboxylic acids
-
- 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
Abstract
An oral composition (eg a toothpaste) comprises a halogenated hydroxydiphenyl ether at from 0.01 to 0.4% by weight at the composition and from 0.1 to 3.5% by weight at the composition at a delivery enhancing agent for said halogenated hydroxydiphenyl ether, said delivery enhancing agent being a compound at Formula 1: <EMI ID=1.1 HE=49 WI=30 LX=698 LY=457 TI=CF> <PC>wherein: z takes a value of from 1 to 5 and the R groups are independently selected tram the group consisting of: H, F, Cl, Br, -OH, C1 to C5 alkyl, -C(O)H, and -C(O)-C1 to C15 alkyl; R' is selected tram the group consisting of: H, -OH, F, Cl, Br, I, and C1-C6 alkyl and n is an integer in the range from 0 to 12; wherein X is a group selected tram -C(O)-NH-R'', -R'', -C(O)-R'' , -C (O)O-R'', and -SO2-R'' , and R'' is an optionally substituted hydrocarbon (eg) -C1-16-alkyl or CH2C6H5). The halogenated hydroxydiphenyl ether compound, is preferably 2', 4, 4'-trichloro-2-hydroxy-diphenyl ether ie triclosan Preferred compounds of Formula 1 include 1-(4-hydroxy phenyl) nonan-1-one, 3-hydroxybenzoic acid octyl ester, 3,4-dihydroxybenzoic acid octyl ester and 3-chloro-4-hyroxy-benzoic acid octyl ester. The most preferred compounds is n-octyl parahydroxy benzoate. Delivery enhancement is confirmed by measuring the amount of triclosan delivered to salivary sediment in tests using a salivary sediment model.
Description
- 1 COMPOSITION
The present invention relates to an oral composition comprising a halogenated hydroxydiphenyl ether and a 5 delivery enhancing agent.
Alkyl hydroxybenzoates (parabens) are known in the art where the alkyl group is methyl. For example, methyl hydroxybenzoate is mentioned, albeit fleetingly, for use in 10 medicinal and oral care preparations as a preservative (WO 00/09507 and WO 00/69401).
We have found that there exists a range of compounds which improve the delivery of halogenated bisphenolic compounds 15 such as triclosan.
Accordingly the present invention provides in a first aspect, an oral composition comprises a halogenated hydroxydiphenyl ether at from 0.01 to 0.4% by weight of the 20 composition and from 0.1 to 3.5% by weight of the composition of a delivery enhancing agent for said halogenated hydroxydiphenyl ether, said delivery enhancing agent being a compound of Formula 1:
- 2 - zR /q (CHR')n Formula (1) wherein: 5 z takes a value of from 1 to 5 and the R groups are independently selected from the group consisting of: H. F. Cl, Br, -OH, Cl C5 alkyl, -C(0)H, and -C(O)-C1 Cl5 alkyl; R' is selected from the group consisting of: H. -OH, F. Cl, 10 Br, I, and Cl-C6 alkyl and n is an integer in the range from 0 to 12, preferably from 0 to 3; especially 0 or 1 and most preferably 0; wherein X is a group selected from -C(0)-NH-R'', -R'', -C(O R'',-C(0)0-R'', and -SO2-R'', and R'' is Cll6 alkyl or CH2C6H6.
In a second aspect the invention provides an oral composition comprising a halogenated hydroxydiphenyl ether 20 at from 0.01 to 0.4% by weight of the composition and a delivery enhancing agent for said halogenated diphenyl ether, said delivery enhancing agent comprising from 0.1 to 3.5% by weight of the composition and being a compound of Formula l:
- 3 OR X Formula (1), 10 wherein: z takes a value of 1 or 2 and the R groups are independently selected from Cl or -OH; 15 wherein X is a group selected from -C(0)-R'' or C(0)0-R'', and R'' is -Cll6or -alkyl.
According to Formula 1 R' is selected from -OH and/or C1.
20 Preferred compounds of Formula 1 that are used in the composition of the present invention include 1-(4-hydoxy phenyl) nonan-1-one, 3hydroxybenzoic acid ocLyl ester, 3-4 dihydoxybenzoic acid octyl ester and 3 chloro 4 hydorxy benzoic acid octyl ester. The most preferred compounds are 25 n-octyl parahydroxy benzoates.
In a preferred embodiment X is-C(0)0-R'', wherein R'' is a substituted or unsubstituted branched or straight chain hydrocarbon moiety.
- Preferably R'' is an aliphatic alkyl group, more preferably comprising from 1 to 16 and especially from 3 to 12 carbon atoms. Examples of suitable R'' groups include methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, benzyl, 5 heptyl, ocLyl, 2-ethyl hexyl, nonyl, decyl, undecyl, dodecyl or tridecyl. Of these the most preferred are the straight chain alkyls. The most preferred compound is where R'' is n-
ocLyl. 10 According to Formula 1 z ranges from 1 to 5 and is preferably 1 or 2, more preferably 1. It is preferred that at least one R group is in the pare or mete position, more preferably the pare position.
15 According to Formula 1 R' is selected from the group consisting of: H. -OH, F. Cl, Br, I, and C1-C6 alkyl.
Manufacture of such compounds as represented by Formula 1 would be a simple step for the man skilled in the art to 20 carry out.
The most preferred compound is n-ocLyl parahydroxy benzoate.
The compound according to Formula 1 is preferably present at 25 from 0.1 to 3.5% by weight of the composition. Preferably, in an amount ranging from 0.15 to 2.3% by weight and most preferably from 0.2 to 1.3% by weight of the composition.
The composition according to the invention also comprises a 30 halogenated hydroxydiphenyl ether compound, more preferably 2', 4, 4'trichloro-2-hydroxy-diphenyl ether, hereinafter
- 5 known as triclosan. Preferably the halogenated hydroxydiphenyl ether is present at from 0.01 to 0.4% by weight of the composition.
5 The composition according to the invention may also comprise a divalent metal salt. Preferably, the divalent metal salt is a salt selected from the group consisting of zinc- and stannous salts such as zinc citrate, zinc sulphate, zinc glycinate, sodium zinc citrate, stannous pyrophosphate and 10 mixtures thereof. The preferable divalent metal salt is zinc citrate. Suitably, the amount of divalent metal salt ranges from 0.01 to 10% by weight of the composition, preferably from 0.05 to 15 5% by weight, more preferably from 0.1 to 2% by weight and especially preferably from 0.3 to 0.9% by weight of the composition. The oral composition according to the invention comprise 20 further ingredients which are common in the art, such as: antimicrobial agents, e.g. chlorhexidine, sanguinarine extract, metronidazole, quaternary ammonium compounds, such as cetylpyridinium chloride; bis-guanides, such as 25 chlorhexidine digluconate, hexetidine, octenidine, alexidine; and halogenated bisphenolic compounds, such as 2,2' methylenebis-(4-chloro-6bromophenol); anti-inflammatory agents such as ibuprofen, flurbiprofen, 30 aspirin, indomethacin etc.;
- 6 anti-caries agents such as sodium- and stannous fluoride, aminefluorides, sodium monofluorophosphate, sodium trimeta phosphate and casein; 5 plaque buffers such as urea, calcium lactate, calcium glycerophosphate and strontium polyacrylates; vitamins such as Vitamins A, C and E; 10 plant extracts; desensitizing agents, e.g. potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate and strontium salts; anti-calculus agents, e.g. alkali-metal pyrophosphates, hypophosphite-containing polymers, organic phosphonates and phosphocitrates etc.; 20 biomolecules, e.g. bacteriocins, antibodies, enzymes, etc.; flavours, e.g. peppermint and spearmint oils; proteinaceous materials such as collagen; preservatives; opacifying agents; 30 colouring agents;
pH-adjusting agents; sweetening agents; 5 pharmaceutically acceptable carriers, e.g. starch, sucrose, water or water/alcohol systems etc.; surfactants, such as anionic, nonionic, cationic and zwitterionic or amphoteric surfactants; particulate abrasive materials such as silicas, aluminas, calcium carbonates, dicalciumphosphates, calcium pyrophosphates, hydroxyapatites, trimetaphosphates, insoluble hexametaphosphates and so on, including 15 agglomerated particulate abrasive materials, usually in amounts between 3 and 60% by weight of the oral care composition. Preferred abrasives are chalk and silica, more preferably fine ground natural chalk.
20 Humectants such as glycerol, sorbitol, propyleneglycol, xylitol, lactitol etch binders and thickeners such as sodium carboxymethyl-
cellulose, hydroxyethyl cellulose (Natrosol), xanthan gum, 25 gum arable etc. as well as synthetic polymers such as polyacrylates and carboxyvinyl polymers such as Carbopol; polymeric compounds which can enhance the delivery of active ingredients such as antimicrobial agents can also be 30 included;
- 8 buffers and salts to buffer the pH and ionic strength of the oral care composition; and other optional ingredients that may be included are e.g. 5 bleaching agents such as peroxy compounds e.g. potassium peroxydiphosphate, effervescing systems such as sodium bicarbonate/citric acid systems, colour change systems, and so on.
10 Liposomes may also be used to improve delivery or stability of active ingredients.
The oral compositions may be in any form common in the art, e.g. toothpaste, gel, mousse, aerosol, gum, lozenge, powder, 15 cream, etc. and may also be formulated into systems for use in dual-compartment type dispensers.
In a third aspect the invention provides the use of a compound according to Formula 1 as described herein as a 20 delivery enhancing agent in an oral care composition for a halogenated diphenyl ether, preferably triclosan.
Embodiments according to the invention shall now be discussed with reference to the following non-limiting 25 examples.
EXAMPLE 1
The following is a formulation according to the present 30 invention. It is made by known processes.
- 9 Ingredient %w/w 70% aq.sorbitol 45.0 Saccharin 0.2 5 Polyethylene glycol 2.0 Titanium dioxide 1.0 Sodium fluoride 0.32 Thickening silica 9. 0 Abrasive silica 10.0 10 Sodium lauryl sulphate 1.6 Sodium carboxymethylcellulose 0.8 Flavour 1.0 Zinc citrate trihydrate 0.75 nOctyl paraben 1.0 15 Triclosan 0.2 Water to 100 EXAMPLE 2
20 Toothpaste formulations (minus the abrasives) comprising 0.2% w/w triclosan and varying levels of n-ocLyl paraben were tested in a salivary sediment model similar to that described by R.L. Wijoijweera and I. Kleinberg in Archs.
Oral Biol., Vol. 34, No. 1, 1989, pages 43-53, using ex-vivo 25 samples and measuring the amount of triclosan delivered to the salivary sediment.
The values represent the amount (ppm per ml sediment suspension) of triclosan delivered.
- 10 Table 1
5(w/w) n-octyl paraben TCN delivered 0 7.4 0.4 9.8
0.6 10.3
0.8 11.6
5 As can be clearly seen the paraben increases the level of triclosan delivered. This is an unexpected effect.
Claims (11)
1. An oral composition comprises a halogenated hydroxydiphenyl ether at from 0.01 to 0.4% by weight of 5 the composition and from 0.1 to 3.5% by weight of the composition of a delivery enhancing agent for said halogenated hydroxydiphenyl ether, said delivery enhancing agent being a compound of Formula 1: zR /q (CHR')n X tar Formula wherein: z takes a value of from 1 to 5 and the R groups are 15 independently selected from the group consisting of: H. F. Cl, Br, -OH, Cl to C5 alkyl, -C(0)H, and C(O)-C1 to C5 alkyl; R' is selected from the group consisting of: H. -OH, F. 20 Cl, Br, I, and C1-C6 alkyl and n is an integer in the range from 0 to 12;
- 12 wherein X is a group selected from -C(0)-NH-R'', -R'', -
C(O-R'',-C(0)0-R'', and -SO2-R'', and R'' is -Cll6-alkyl or -CH2C6H6.
5
2. An oral composition comprising a halogenated hydroxydiphenyl ether at from 0.01 to 0.4% by weight of the composition and a delivery enhancing agent for said halogenated diphenyl ether, said delivery enhancing agent comprising from 0.1 to 3.5% by weight of the 10 composition and being a compound of Formula 1: X 20 Formula (1), wherein: z takes a value of 1 or 2 and the R groups are independently selected from Cl or -OH; wherein X is a group selected from -C(0)-R'' or - C(O)O R'', and R'' is -Cll6 or -alkyl.
3. An oral composition according to claim 1, wherein X is 30 C(0)0-R''.
[
4. An oral composition according to claim 1 or 2, wherein R'' is an aliphatic alkyl group.
5. An oral composition according to any preceding claim, 5 wherein R'' represents a straight chain alkyl group comprising from 5 to 12 carbon atoms.
6. An oral composition according to any preceding claim, wherein -R'' is C6-C12 alkyl.
7. An oral composition according to any preceding claim, wherein -R'' is C8 alkyl.
8. An oral composition according to any preceding claim, 15 wherein z is 1.
9. An oral composition according to any preceding claim, wherein the halogenated hydroxydiphenyl ether is triclosan.
10. An oral composition according to any preceding claim wherein the compound of Formula 1 is chosen from 1-(4 hyboxy phenyl) nonan-1-one, 3-hydroxybenzoic acid ocLyl ester, 3, 4-dihydoxybenzoic acid octal ester or 3 25 chloro, 4-hydroxy benzaic acid ocLyl ester.
11. Oral composition according to any preceding claim wherein the composition comprises an agent selected from the group consisting of anticaries agents, anti-tartar 30 agents, anti-oral malodour agents, tooth whitening agents, breath freshening agents and mixtures thereof.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02258069 | 2002-11-22 |
Publications (2)
Publication Number | Publication Date |
---|---|
GB0326793D0 GB0326793D0 (en) | 2003-12-24 |
GB2395433A true GB2395433A (en) | 2004-05-26 |
Family
ID=29762715
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB0326793A Withdrawn GB2395433A (en) | 2002-11-22 | 2003-11-18 | Oral compositions comprising a halogenated hydroxydiphenyl ether, eg triclosan, and a delivery enhancing agent, eg a parahydroxybenzoate |
Country Status (2)
Country | Link |
---|---|
FR (1) | FR2847463A1 (en) |
GB (1) | GB2395433A (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996019190A1 (en) * | 1994-12-22 | 1996-06-27 | The Procter & Gamble Company | Oral compositions containing dimethicone copolyols |
WO1996019192A1 (en) * | 1994-12-22 | 1996-06-27 | The Procter & Gamble Company | Oral compositions |
-
2003
- 2003-11-18 GB GB0326793A patent/GB2395433A/en not_active Withdrawn
- 2003-11-20 FR FR0313586A patent/FR2847463A1/en not_active Withdrawn
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996019190A1 (en) * | 1994-12-22 | 1996-06-27 | The Procter & Gamble Company | Oral compositions containing dimethicone copolyols |
WO1996019192A1 (en) * | 1994-12-22 | 1996-06-27 | The Procter & Gamble Company | Oral compositions |
Also Published As
Publication number | Publication date |
---|---|
GB0326793D0 (en) | 2003-12-24 |
FR2847463A1 (en) | 2004-05-28 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |