Title of Invention


Abstract The present invention relates to oral care compositions with an improved teeth whitening effect. This effect is achieved by inclusion in the oral care compositions of certain organic peroxy compounds as teeth whitening/bleaching agents, particularly peroxyamidophthalamides, sulphoperbenzoic acid, monoperoxyphthalic acid, and (per)acetylatedperboric acid with imine quaternary salts as catalysts for the peroxy compounds
Full Text FORM-2
THE PATENTS ACT, 1970 (39 OF 1970)
COMPLETE SPECIFICATION (See Section 10; rule 13)
HINDUSTAN LEVER LIMITED, a company incorporated under the Indian Companies Act. 1913 and having its registered office at Hindustan Lever house, 165/166, Backbay Reclamation, Mumbai -400 020, Maharashtra, India
The following specification particularly describes the nature of the invention and the

manner in which it is to be performed.

The present invention related to an oral composition with an improved teeth whitening effect. More particularly, it relates to an oral composition with an improved teeth whitening effect comprising a safe and effective amount of certain organic peroxy compounds and certain catalysts, which are capable of reacting with the organic peroxy compounds to generate more reactive oxygen species.
The use of peroxy compounds in oral care compositions has already been proposed in the prior art. Many peroxy compounds have been suggested for whitening/ bleaching human teeth, and representative examples of such peroxy compounds are hydrogen peroxide, urea peroxide, organic peracids such as perphathalic acid, diperoxycarboxylic acids, 1,12- dodecanedioic peroxy acid, peroxy acetic acid and systems comprising a peroxy compound and a peroxy acid precursor which generate peroxy acetic acid in situ, such as sodium perborate and tetraacetylethylene diamine (TAED). The use of peroxy acetic acid is suggested in particular in e.g. EP-A-0545,594 (Colgate), which also sets out the various prior proposals, made in the art for several peroxy compounds as bleaching/whitening agent for human teeth.
In our WO-A-96/05802 we have described the use of various organic peroxyacids as teeth whitening agents.
We have now found that certain organic peroxy compounds, which will be defined hereinafter, when used together with certain catalysts, defined hereinafter, are much more effective than the organic peroxy compounds above, even in

the absence of a peroxy acid precursor (bleach precursor) , producing a teethwhitening effect much more rapidly. These certain organic peroxy compounds are selected from the group consisting of:
1) peroxy amido phthalamides having the structural

in which R = hydrogen or
C1-C4 alkyl;
n = I to 5; and
X = C=0 or SO;
2) sulphoperbenzoic acid ("SPB"),
3) monoperoxyphthalic acid ("MPP"), and
4) (per)acetylperoxyboric acid
and/or salts thereof.
The peroxy amido phthalamides of formula 1) are known per se and have been described in EP-A-325,288 and EP-A-325,289^ A preferred compound of this formula is N-phthalimido hexanoic peroxy acid ("PAP") of formula 1), in which B = H, n = 5 and X = C=0. An example of a compound according to formula 1) wherein X - S02 is saccharin-perhexanoic acid ("saccharin PAP"), as described in EP-A-^85,927. The salts of these peroxyacids are preferably the alkalimetal salts.

The salts of sulphoperbenzoic are preferably the alkalimetal salts, particularly preferably the potassium salt ("KSPB"). This peroxyacid has been described in EP-A-124,968 and EP-A-212,913.
The salts of monoperoxyphthalic acid are preferably the alkalimetal and alkaline earth metal salts, particularly preferably the magnesium salt. The use of magnesium monoperoxyphthalate in oral care products has been described in US-A-4,670,252.
(Per)acetylperoxyboric acid and salts thereof are also known per se from EP-A-212,913.
Preferably, the peroxy compound is PAP and/or KSPB.
The amount of the peroxy compounds,used in the present invention, may vary from 0.01 to 99 % by weight of the oral composition, preferably from 0.1 to 30 % by weight, particularly preferably from 0.1-5 % by weight.
The catalysts, used in the present invention are imine quaternary salts as described in"US-A-5,360, 568 yand US-A-5,3 60,569, which are hereby incorporated by way of Reference. Suitable examples of these imine quaternary salts are of the formula:

(formula I)

wherein Ri is hydrogen or a Ci-C8 alkyl group, R2 is hydrogen, or a phenyl group or a keto group, R3/ R-i and R5 are hydrogen or -0-R1, whereby R1 is a C1-C4 alkyl group, R6 and R7 are hydrogen or a C\-Ct alkyl group and X is a counterion, stable in the presence of oxidizing agents, comprising Br", BF4", CI", CH3S A preferred catalyst is an imine quaternary salt of the above formula, in which Rj = methyl, and R2~R6 are all hydrogen, and X is tosylate ("Imine Quat 200").
The catalyst is used generally in an amount of 0.01 to 5 %
by weight, preferably 0.05 to 1.5 % by weight, and
particulary preferably 0.1 to 1 % by weight of the oral
care composition.
The oral compositions can be formulated in any suitable application form, such as gels, mouthwashes, toothpowders and toothpastes. They may be formulated into a single formulation or they may be formulated for multi compartment containers into different formulations, e.g. one containing the peroxy compound and ingredients compatible therewith, and another containing the remaining ingredients.
The oral care compositions of the present invention may furthermore comprise optional, conventional ingredients such as pharmaceutical^ acceptable carriers like starch, sucrose, water or water/alcohol "systems etc.. Small amounts of surfactants may also be included, such as anionic, nonionic and afliphotei£ic «surf actants. When formulated into a

dentifrice, such formulation may contain all the usual dentifrice ingredients.
Thus, they may comprise particulate abrasive materials such as silicas, aluminas, calcium carbonates, dicalciumphosphates, calcium pyrophosphates hydroxyapatites, trimetaphosphates, insoluble hexametaphosphates, agglomerated particulate abrasive materials and so on, usually in amounts between 5 and 60 % by weight.
Furthermore, the dentifrice formulations may comprise humectants such as glycerol, sorbitol, propyleneglycol, xylitol, lactitol and so on.
Binders and thickeners such as sodium carboxymethyl-cellulose, xanthan gum, gum arabic etc. may also be included, as well as synthetic polymers such as polyacrylates and carboxyvinyl polymers such as Carbopol®.
Flavours such as peppermint and spearmint oils may also be included, as well as preservatives, opacifying agents, colouring agents, pH-adjusting agents, sweetening agents and so on. Stabilising agents for the organic peroxy compounds such as dipicolinic acid or sodium stannate may also be usefully included.
Anti-bacterial agents may. also be included such" as Triclosan, chlorhexidine, copper-, zinc- and stannous salts such as zinc citrate, sodium zinc citrate and stannous pyrophosphate, sanguinarine extract, metronidazole. Further examples of anti-bacterial agents are quaternary ammonium

compounds such as cetylpyridinium chloride; bis-guanides such as chlorhexidine digluconate, hexetidine, octenidine, alexidine; halogenated bisphenolic compounds such as 2,2" methylenebis-(4-chloro-6-bromophenol) .
Polymeric compounds which can enhance the delivery of active ingredients such as anti-bacterial agents can also be included. Examples of such polymers are copolymers of polyvinylmethylether with maleic anhydride and other similar delivery enhancing polymers, e.g. those described in DE-A-3,942,643 (Colgate)
Furthermore anti-inflammatory agents such as ibuprofen, flurbiprofen, aspirin, indomethacin etc. may also be included.
Anti-caries agents such as sodium- and stannous fluoride, aminefluorides, monosodiumfluorophosphate", casein, plaque buffers such as urea, calcium lactate, calcium glycerophosphate, strontium polyacrylates may also be included. Other optional ingredients include vitamins sue. as Vitamin C, and plant extracts. Desensitising agents svr... as potassium citrate, potassium chloride, potasium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate as well as strontium salts may also be included.
Buffers and salts to buffer the pH and ionic strength of
the compositions may also be included. The pH of the
compositions usually ranges from 5-10, preferably 6-9 and
especially preferably 7-8.5.

Liposomes and other encapsulates may also be used to improve delivery or stability of active ingredients.
Furthermore, the oral compositions may comprise anti-calculus agents such as alkalimetal pyrophosphates, hypophosphite-containing polymers, organic phosphonates, phosphocitrates etc..
In addition, the compositions may comprise functional biomolecules such as bacteriocins, antibodies", enzymes and so on.
Other optional ingredients that may be included are e.g. effervescing systems such as sodium bicarbonate/citric acid systems, colour change systems, and so on.
Preferably, the compositions do not contain a bleach precursor.
When formulated as a mouthwash, the oral care composition usually comprises a water/alcohol solution, flavour, humectant, sweetener and colorant.
Since the peroxy compounds of the invention also have an anti-microbial property, the composition of the invention are also effective to combat plaque and caries.
The present invention will further be illustrated by way of Example.

Example I
PAP, KSPB and acetylated sodium perborate with and without Imine Quat 200 were evaluated as to their bleaching efficacy.
The bleaching agents were evaluated as follows:
(1) Synthetic hydroxyapatite discs were polished and placed in sterile saliva at 37°C overnight to form a pellicle.
(2) Discs were stained with tea/coffee/iron salts/saliva mixture for seven days at 37°C.
(3) Stained discs were immersed in bleaching solutions for desired time.
(4) The change in colour of the discs was measured using .-. Minolta chromameter CR-300 in L*a*b* mode. Using L*
(initial), L* (soiled), and L* (cleaned), the percentage of stain removed was calculated.
The concentration of the PAP and the KSPB was 3.6 x 10"2M in aqueous solution which also contained 0.5M sodium bicarbonate.
The amount of Imine Quat 200 was varied as indicated in the Table. The following results were obtained:
1) Percent stain removed with PAP (3.6 x 10"2M) in -0.5M
NaHCOj with different concentrations of IQ200

% s tain removed with
[IQ200] 1 (M) 0 min 1 min 3 min 5 min
3.6 x 10"J 0 67 86 91
1.8 x 10"J 0 62 83 89
0.9 x 10"J 0 58 71 89
3.6 x 10"4 0 46 59 68
1.8 x 10"4 0 40 69 76
0 0 24 55 67
Percent stain removed with potassium sulphoperbenzoic acid (KSPB) (3.6 x 10"2M)

% stain removed with
Time (mins) KSPB KSPB/ IQ200 NaHC03
0 0 0 0
0.5 22 42 3
r-t 34 55 3
3 54 73 3
Percent stain removed with acetylated sodium perborate (0.15 % w/w) in 0.5 M sodium bicarbonate solution with IQ200 (0.1 % w/w).

% stain removed with
Time Acetylated sodium Acetylated sodium
(sees) perborate perborate and

0 0 0
30 3 A
60 16 22
120 24 38
Example II
Bovine enamel blocks (5 x 5 x 2mm) were attached to partial or full dentures. These were worn in the mouth for 21 days in order to build up naturally stained pellicle. The blocks were removed from the dentures and treated for 15 x 1 minute v/ith one of the following mixtures:
A - 0.5 M NaHC03
B - 1% PAP/0.5M NaHC03
C - 1% PAP + 0.11% Imine Quat 200/0.5M NaHC03
The colour of the bovine blocks were measured using a Minolta Chromameter CR241 in the CIE L*a*b* mode. Colour measurements were made before any treatment and after 1, 3, 5, 10 and 15 one minute treatments.
These are expressed in change in L* and as I stain removed.


Treatment No. o Change in L* f 1 min treatments
1 3 5 10 15
A 0.2 0.5 0.8 0.9 0.8
B 0.1 0.5 1.1 2.5 3.3
C 1.6 4.7 6.9 7.6 8.8

% stain removed
1 3 5 10 15
A -2 3 5 3 7
B 1 4 8 19 26
C 10 31 44 51 58
These results illustrate that Imine Quat catalysed peracid bleaching gives a rapid increase in L* - i.e. toothwhitening benefits after only a very short exposure.
Example III
Example I was repeated, using different imine quaternary
salts as described below. The following results were

The imine quat was modified by extending the methyl chain to butyl, hexyl and octyl, i.e.


IQ200, R = methyl
IQ204, R = n-butyl
IQ206, R = n-hexyl
IQ208, R = n-octyl
) X" being tosylate"
and was tested in the in vitro stain model as described in Example I.
[PAP] = 3.6 x 10"2M, [IQ] = 3.6 x 10"3M in 0. 5M sodium ) bicarbonate solution.

% 1 min stain removed 3 mins
PAP/IQ200 43 56
PAP/IQ204 29 41
PAP/IQ206 23 36
PAP/IQ208 21 34
PAP 21 29
Repeating the experiment with PAP IQ206 gave the following results


% stain removed with
Time (mins) PAP (s.d.) PAP/IQ206 (s.d.)
0 0 0
0.5 9 (6) 26 (12)
1.0 34 (5) 4 8 (9.)
44 (.6)
64 (6)

The pH profile of IQ200 catalysts was investigated, using same concentrations as above in various phosphate and borate buffers.

% stain removed wi th
6.0 16 34
7.0 25 72
8.0 46 74
9.0 49 69
The pH profile of IQ208 was also investigated.

% stain removed wi th
6.0 32 78
7.0 49 76
8.0 45 59
9.0 72 71
The ketone and 3-raethyl, 3-phenyl derivatives were also evaluated under same concentrations as above.




IQ200 (3-Me, 3-ph)

% stain removed 0.5 min 1.0 mins (s.d.)
3.0 mi ns
PAP 3 (3) 23 (3) 50 (4)
PAP/IQ200 40 (5) 68 (2) 6 4 (3}
PAP/IQKetone 16 (4) 37 (5) 69 (3)
PAP/IQ200(3-Me, 3- -pH) 1^ (4) 42 (6) €7 (3)
IQ200-(5,7-dimethoxy-l-methyl) gives similar results.
Example IV
Example I was repeated using magnesium monoperoxyphth> (H48) (3.6 x 10-2M) with IQ200 (3.6 x 10-3M)
% stain removed
Time H48 (s.d.) H48 + IQ200 (s.d.)

0 0 0
0.5 27 (5) 89 (4)
1.0 62 (5) 97 (2)
2.0 80 (6) —
Example V
Bovine enamel slabs were stained with Stookey type stain and brushed with a conventional toothpaste (RDA = 100), with or without PAP/IQ200 (1 %/0.11 % w/w) in a brushing machine for 2,100 strokes. The increase in L* was measured

WE Claims
1. An oral composition with an improved teeth whitening effect, comprising a safe and effective amount of an organic peroxy compound, selected from the group consisting of:
1) peroxy amido phthalamides having the structural formula:

in which R = hydrogen or
N-(CHR)n-CChH Ci-C n = 1 to 5; and X = C=0 or S02

sulphoperbenzoic acid
3) monoperoxyphthalic acid, and
per)acetylperoxyboric acid, and/or salts thereof, characterised in that the composition further comprises an imine quaternary salt of the formula

(formula I)

wherein Ri is hydrogen or a Ci-Cs alkyl group, R2 is hydrogen, or a phenyl group or a keto group, R3, R4 and R5 are hydrogen or -O-R1, whereby R1 is a C1-C4 alkyl group and X is a counterion, stable in the presence of oxidizing agents, comprising Br"" BF4", CI", CH3SO4~, tosylate , PF6", F , fluorophosphate cations and Ci2_ alkylsulphate cations; and a humectant.
2. A composition according to claim 1, characterised in that the organic peroxy compound is N-phthalimido hexanoic peroxy acid or sulphoperbenzoic acid.
3. A composition according to claim 1 or 2, characterised in that the imine quaternary salt is a compound according to formula (I) wherein R1 is methyl, R2-R6 are all hydrogen and X is tosylate



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Patent Number 208772
Indian Patent Application Number IN/PCT/2001/00318/MUM
PG Journal Number 35/2007
Publication Date 31-Aug-2007
Grant Date 09-Aug-2007
Date of Filing 22-Mar-2001
# Inventor's Name Inventor's Address
PCT International Classification Number A61K 7/20, A61K 7/16
PCT International Application Number PCT/EP99/07379
PCT International Filing date 1999-09-20
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 98307835.3 1998-09-25 EUROPEAN UNION