WO2021094156A1

WO2021094156A1 - A film and a kit for whitening teeth

Info

Publication number: WO2021094156A1
Application number: PCT/EP2020/080906
Authority: WO
Inventors: Sameer Keshav Barne; Srikala KUMARAN; Praful Gulab Rao LAHORKAR; Ashish Anant Vaidya
Original assignee: Unilever Ip Holdings B.V.; Unilever Global Ip Limited; Conopco, Inc., D/B/A Unilever
Priority date: 2019-11-11
Filing date: 2020-11-04
Publication date: 2021-05-20

Abstract

The present invention relates to an oral care film for whitening teeth and to a method of obtaining such whitening. The first aspect of the present invention relates to a tooth whitening film comprising (i) at least one photosensitizer which is selected from a xanthene class of dye; (ii) a polymer A selected from a polysaccharide or a modified polysaccharide; and (iii) a polymer B selected from a water soluble film forming synthetic polymer. The method of the invention relates to whitening teeth comprising the steps of: (i) applying a film of the first aspect on to teeth; and (ii) exposing said film so applied, to a source of actinic light.

Description

A FILM AND A KIT FOR WHITENING TEETH

Field of the Invention

The present invention relates to an oral care film for whitening teeth and to a method of obtaining such whitening. More specifically, the invention relates to such a film and a kit that contains this film having a photosensitizer and a source of light that ensures whitening of teeth.

Background of the Invention

The colour of our teeth is influenced by a combination of their intrinsic colour and the presence of any extrinsic stains that may form thereon. Staining is linked to the adsorption of materials into the pellicle on the surface of enamel. Factors that influence extrinsic stain formation include poor brushing techniques, smoking, dietary intake of coloured foods (e.g. red wine), age and the use of certain cationic agents such as chlorhexidine or metallic salts of tin and iron. Consumers have strong desire for whiter teeth and some individuals are dissatisfied with the inherent colour of their teeth or with the stains. This desire for whiter teeth has given rise to a growing trend of whitening products which range from toothpastes to mouthwashes and chewing gums.

Toothpastes meant for whitening rely on an optimization of abrasive and chemical components for removal of stains. During brushing, these abrasive particles get temporarily trapped between the toothbrush and the stained surface (of teeth) to abrade away the stains. Chemical components may also be used, usually in conjunction with abrasive particles, and these include calcium chelators, polymers, surfactants, enzymes and oxidising agents.

One of the more prevalent methods involves the use of dentifrices which contain a bleaching agent such as hydrogen peroxide with one or more other bleaching agents. Examples of such disclosures are US2002122776A and W00018366A1 (Both Unilever).

US2003194383 AA (Unilever) discloses a kit and method for whitening teeth which utilizes a U-shaped dental tray fittable over a person's teeth and a bleaching composition formed from a combination of first and second compositions, which prior to use, are stored separately from one another but need to be mixed just prior to use. The first composition includes a peroxide and the second composition includes an alkaline material.

It is known to photobleach stained teeth by applying a photobleaching composition containing a photosensitizer (chromophores/dyes), followed by exposure to light such as UV, visible, LED light. Sometimes an applicator (tray) is used to facilitate the application and contact with teeth. Usually such compositions contain a bleach/peroxide, or the compositions are meant to be pre-mixed with a bleach before application.

In the past, people used photoactivatable compositions containing per-compounds. In this case, a user needs to first apply the composition (usually a gel) containing the percompound. Thereafter (s)he needs to activate the percompound by exposing it (i.e. the composition) to radiation which may be UV or visible. The light decomposes the percompound quickly to release free radicals which act against the stains to bleach them.

The present inventors have in the past tried to get away from compositions and methods which involve bleaching agents as they involve release of free radicals which are sometimes not liked by consumers as they believe that free radicals can, under some conditions, be harmful to the body. The present applicants have filed a patent application which is published as WO2018224311. The invention therein relates to an aqueous gel composition for whitening teeth, comprising at least one photosensitizer which is selected from a xanthene class of dye; maximum of 10 wt% organic solvent; less than 0.1 wt% oxidising agent; and, a polymeric gelling agent other than those containing galactose, galactomannan or glucosamine units in their chemical structure. The method as per this published patent application involves applying such a gel on to the desired tooth surface and exposing it to actinic light.

The present inventors have tried to improve the efficacy of such types of compositions and after extensive experimentation arrived at the present invention. They realized that it is not straightforward to arrive at the desired efficacy in a relatively dry format like a film as compared to a gel which has a higher quantity of water. High water containing compositions enable the ingredients dissolved therein to diffuse to the desired substrate e.g. the surface of the teeth to interact with the molecules thereon to provide the desired benefit. In a relatively dry format like a film the diffusion of for example the dye is limited and therefore the solution to the problem is not simple. To the utter surprise of the present invention they found that if they entrapped the desired dye in a film comprising two different types of polymers, this could be achieved. The present invention involves applying the film to the tooth surface and then shining actinic light on to it. The present invention has the advantage over the earlier invention in that it does not involve the use of gels which have to be subsequently removed from the mouth by rinsing, which some users may consider as a little messy. The present invention simply involves stripping off the film after use and throwing it away.

It is thus an object of the present invention to provide for a user friendly article like a film which can be applied on to teeth followed by shining actinic light on it to deliver whiteness to teeth.

Summary of the Invention

The first aspect of the present invention relates to a tooth whitening film comprising:

(i) at least one photosensitizer which is selected from a xanthene class of dye;

(ii) a polymer A selected from a polysaccharide or a modified polysaccharide; and

(iii) a polymer B selected from a water soluble film forming synthetic polymer.

The second aspect of the present invention relates to a kit-of-parts comprising:

(i) a film as per the first aspect of the present invention;

(ii) a source of actinic light; and

(iii) optionally, a set of instructions for use of said kit-of-parts.

The third aspect of the present invention relates to a method of whitening teeth comprising:

(i) applying a film of the first aspect on to teeth; and

(ii) exposing said film so applied, to a source of actinic light.

The fourth aspect of the present invention relates to use of a film of the first aspect for whitening teeth.

The fifth aspect of the present invention relates to a process to prepare the film of the first aspect comprising the steps of: (i) dissolving the photosensitizer, polymer A and polymer B in water to form a premix;

(ii) casting said premix into film solutions of desired thickness; and

(iii) drying said film solutions to desired moisture content, to prepare said film.

Detailed Description of the Invention

Any feature of one aspect of the present invention may be utilized in any other aspect of the invention. The word “comprising” is intended to mean “including” but not necessarily “consisting of” or “composed of.” In other words, the listed steps or options need not be exhaustive. Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word “about”. Numerical ranges expressed in the format "from x to y" are understood to include x and y. When for a specific feature multiple preferred ranges are described in the format "from x to y", it is understood that all ranges combining the different endpoints are also contemplated.

As per this invention the term ‘A derivative of xanthene’ is meant one or more dye selected from the ‘Xanthene class of dyes’. The two terms are used interchangeably.

All references to the terms wt% or % by weight shall be construed as referring to the % of the concerned ingredient by weight of the film composition, unless indicated to the contrary.

The term "actinic light" is intended to mean light energy emitted from a specific light source (e.g. visible, UV, lamp, LED, or laser) and capable of being absorbed by matter (e.g. the chromophore or photoactivator defined below). It is preferred that the actinic light is visible light.

The term "photosensitizer" refers to any agent capable of absorbing the actinic light. The photosensitive agent undergoes photoexcitation and transfers its energy. This may be in the form of emitted light (e.g. fluorescence) and/or energy transferred to molecules. This energy may initiate chemical reactions. Photosensitizers may enhance and/or accelerate the dispersion of light energy, or otherwise enhance and/or activate the decomposition of an oxidizing agent. The term “chromophore” means a chemical compound or a part of a chemical compound, which when contacted by light irradiation, is capable of absorbing the light. The chromophore readily undergoes photoexcitation and then emits energy such as by transferring its energy to other molecules or by emitting light.

“Substantially free of, as used herein, means comprising less than 1.5%, and preferably less than 1.0%, and more preferably less than 0.75% and more preferably still less than 0.5%, and even more preferably less than 0.1 % and most preferably from 0.0 to 0.01 % by weight, based on total weight of the film composition, including all ranges subsumed therein.

The whitening film of the Invention

A tooth whitening film composition of the invention comprises at least one photosensitizer which is selected from a xanthene class of dye; and a polymer A selected from a polysaccharide or a modified polysaccharide; and a polymer B selected from a water soluble film forming synthetic polymer.

The composition of the invention is meant for whitening teeth which implies that it is useful for maintaining the whiteness of teeth. Alternatively, the composition of the invention is useful for removing or lightening, at least partly, some of the common stains such as tea or coffee stain.

The compositions of the invention include at least one photosensitizer which is selected from a xanthene class of dye. Alternatively, the compositions of the invention include more than one, i.e. , a combination of such photosensitizers.

One of the general structures of xanthene class of dye is as follows:

Where R1 , R2, R3, R4, R5 and R6 are functional groups such as -OH, H, Br, I, Cl, amines, ketones, 0-M⁺( where M is metal ion) and R7 is an organic moiety / derivative such as a substituted aromatic or benzofuran.

It is preferred that the xanthene class of dye is at least one of Acid Red 52, Acid Red 289, Gallein, Bromopyrogallol Red, 2',7'-Dichlorofluorescein Sodium Salt, 9-(4'- Dimethylaminophenyl)-2,6,7-trihydroxyfluorone Sulfate Hydrate, Dibromofluorescein, Uranine K, Fluorescein, Uranine, Pyrogallol Red, Rhodamine 6G, Rhodamine B, Sulfonfluorescein, Tetrabromofluorescein Potassium Salt, Acid Red 91 ( Eosin Bluish), Acid Red 94 (Rose Bengal), Acid Red 87( Eosin), Acid Red 92 (Phloxine B ), 3, 4,5,6- Tetrachlorofluorescein, Tetraiodofluorescein (Erythrosin B or Erythrosine B) and Phenylfluorone.

It is particularly preferred that the dye is at least one of Rose Bengal, Eosin, Phloxine B or Erythrosine, more preferably Phloxine B or Rose Bengal.

It is also preferred that the film of the invention comprises 0.001 to 5 wt% photosensitizer by weight of the film. Where a combination of photosensitizers is included in the film, the above mentioned range applies to the total amount thereof. It is further particularly preferred that the film of the invention comprises 0.01 to 2.5 wt% of the photosensitizer, further preferably 0.01 to 1.0 wt% of the photosensitizer.

General structure of a preferred form of xanthene dye is shown below:

Referring to the chemical structure indicated above, in Fluorescein the X=H and Y=H; in Eosin the X = Br and Y=H; in Erythrosine the X=l and Y=H and in Rose Bengal the X=l and Y=CI.

The structures of the various types of preferred photosensitizers of the xanthene class are:

Acid Red 52

Acid Red 289

Bromopyrogallol Red

2',7'-Dichlorofluorescein Sodium Salt

2',7'-Dichlorofluorescein Sodium Salt, 9-(4'-Dimethylaminophenyl)-2,6,7- trihydroxyfluorone Sulfate Hydrate

Dibromofluorescein

Acid Red 91 (Eosin Bluish)

Uranine ( Fluorescein Sodium Salt)

Pyrogallol Red

Rhodamine 6G

Rhodamine B

Rhodamine 800

Tetrabromofluorescein Potassium Salt

Acid Red 87 (Eosin) (Tetrabromofluorescein Sodium Salt)

3,4,5,6-Tetrachlorofluorescein

Tetraiodofluorescein(iodoeosine)- Eryth rosin B

Phenylfluorone

Acid red 92 (Phloxine B)

The photosensitizer molecule is included in a film comprising two polymers - Polymer A and Polymer B. Polymer A is a polymer derived from natural sources. Suitable examples of polymer A are one or more of modified cellulose, guar gum or xanthan gum. Of these modified cellulose is most preferred. Suitable examples of modified cellulose for inclusion in the film of the invention are hydroxyethyl cellulose (HEC), methyl cellulose, hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (SCMC), preferably HEC.

Polymer B is a synthetic polymer. It is preferably selected from one or more of polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycol, propylene glycol and polyacrylates preferably polyvinylpyrrolidone.

It is preferred that the film is formed from the two polymers in a specific weight ratio. The weight ratio of of polymer A to polymer B is preferably in the range of 20:80 to 90: 10, more preferably in the range of 40:60 to 60:40.

In the case of conventional compositions that contain a bleach, it is believed that photosensitizers, when exposed to actinic light, accelerate the dispersion of light energy which consequently leads to photochemical activation of the oxidizing agent within the composition. However, in the case of the present invention, when the photosensitizer is exposed to actinic light, it produces reactive excited species which in turn interact with the stains on teeth to thereby lighten the stains. The film matrix that is formed as a combination of the two polymers used in the composition of the present invention allows effective contact of the dye molecules with the surface of the teeth. It also prevents unwanted quenching of the radicals formed thereby increasing the effectiveness of the dye concentration used. This results is better whitening of teeth.

The tooth whitening film composition of the invention comprise less than 0.1 wt% oxidising agent. This means that when such an agent is present, the amount thereof, in the aggregate, is less than 0.1 wt%. Preferably the amount is less than 0.05 wt% and more preferably the amount is less than 0.025 wt%, even more preferably less than 0.01 wt%. The oxidising agent which is preferably substantially absent may be one or more of chlorine dioxide or sodium chlorite or a peroxide, a peroxyacid, a percarbonate, a perborate, a persulphate, a perphosphate or a monoperoxyphthalate.

The film is preferably in a dry state. By a dry state is meant that the film does not present any perceptible wetness when touched. Most solid materials when stated to be dry do not have zero amount of moisture. Rather it has a low amount of moisture content which is generally in equilibrium with the humidity of the ambient air. In the present invention the film may contain a certain amount of low moisture which is generally less than 10 wt%, preferably less than 5 wt%, more preferably less than 1 wt%.

The film of the invention comprises a maximum of 15 wt% of one or more organic solvents. In other words, the presence of organic solvents is optional. Whenever present, the compositions of the invention preferably comprise 0.5 to 10 wt%, furthermore preferably 5 to 10% of organic solvent. The amount refers to the amount of the solvent in the aggregate, even if there is more than solvent. Preferably the organic solvent is at least one of glycerine, sorbitol, propyleneglycol, polyethyleneglycol or ethyleneglycol.

The composition in accordance with the invention needs to be used in conjunction with a suitable source of actinic light.

Any suitable source of actinic light can be used so long as the light is able to activate the photosensitizer belonging to xanthene group. The primary characteristic of suitable sources of actinic light will be that they emit light in a wavelength (or wavelengths) appropriate for photosensitization of the photosensitizer present in the composition.

Preferably the source of actinic light is halogen bulb, LED or plasma arc lamp, or laser such as an argon laser, potassium-titanyl phosphate (KTP) laser, or LED photocuring device. The radiation is preferably of the visible range but it may be UV or IR. It is preferred that the actinic light has a wavelength in the range from about 400 nm to about 700 nm. In a preferred embodiment, the actinic light has wavelength in the range from about 420 nm to about 560 nm, more preferably 435 nm to about 550 nm.

The present invention also relates to a kit-of-parts comprising a film of the first aspect; a source of actinic light; and optionally, a set of instructions for use of the kit-of-parts.

The set of instructions is preferably in the form of a pamphlet containing useful information about the contents and step-by-step instructions for use of the film composition and light source of the invention.

In accordance with another aspect is disclosed a method of whitening teeth comprising applying a film of the first aspect on to teeth; and exposing the film so applied, to a source of actinic light. The film may be so shaped that it is contoured to sit flush with the curved surface of the teeth. The film is applied on to the teeth and then exposed to actinic light preferably for 5 to 45 minutes, more preferably for less than 10 minutes. Alternatively, the exposure lasts less than 5 minutes, such as 4, 3, 2, or 1 minute. The application may be repeated as often as desired, e.g. 2 to 3 times a day and 3 to 4 days in a fortnight. The method preferably results in at least one unit of shade difference on the Vita® Shade card, preferably at least 2 units and more preferably at least 3 units. The method is relatively free of post-treatment sensitivity. In some other cases, there is minimal or acceptable level of post-treatment sensitivity. The whitening effect may diminish over time following a treatment. In that case, repeat of the treatment is advisable.

The method for whitening the teeth may be performed in a dentist's office or a clinic under ordinary or supervised conditions. Alternatively, and more preferably the method is performed by an informed user at home or in other words, without any medical supervision when the method is non-therapeutic. The film and method of the invention is useful to whiten teeth. This means that the composition is useful to preserve the white appearance of teeth or to restore the appearance periodically. Alternatively, invention is useful to lighten the teeth which are discoloured due to extrinsic or intrinsic stains (e.g., tobacco, coffee, tea and/or food or wine stains), fluorosis, developmental disturbances, bacteria, genetics, tetracycline antibiotics, trauma, blood decomposition, pigments present during development of teeth.

In one aspect, the method is non-therapeutic. Preferably such a method is a cosmetic method. A therapeutic treatment starts from a pathological state, whereas a non- therapeutic treatment starts from a normal, healthy state. Application of such a method to a person is to improve his bodily appearance (cosmetic treatment).

In another aspect the method is therapeutic in nature. Treatment by therapy is defined as any treatment which is designed to cure, alleviate, remove or lessen the symptoms of, or prevent or reduce the possibility of contracting any disorder or malfunction of the human body, in this case it is teeth.

In accordance with yet another aspect is disclosed use of a film composition of the first aspect for whitening teeth.

In one aspect the use is for non-therapeutic purpose. Alternatively, the use is for therapeutic purpose. The part of the description related to the method of the invention is also applicable mutatis mutandis to this aspect of the invention.

It has been further found that the film composition of the present invention is useful in oral biofilm removal.

The following examples will more fully illustrate the embodiments of this invention. All parts, percentages and proportions referred to herein and in the appended claims are by weight unless otherwise illustrated. Examples

Example 1: LAB and □E values of stained HAP disks treated with a film of the invention over many cycles:

The experiments were performed on Hydroxyapatite (HAP) discs because they are most suited for this purpose. In the first step the discs were stained with a staining solution (tea) by incubating the discs in an aqueous solution of tea for four days. All the discs turned dark brown in colour.

A film with composition as shown in Tablel was prepared as follows:

Pre- mix solutions of the two polymers were made by dissolving the polymer powder in waster using overhead stirrer. The film was cast from the solution to get the desired film composition. The premixes were mixed into homogeneous solution and then spread on a petri dish. The petri dish was kept in oven at 50°C for drying.

Table 1

The stained HAP disks were treated with the film as in Table 1 above as follows:

70 to 80 mg of film samples was placed on stained HAP disc. It was moistened with water and were exposed to Light source = Spectrum LED lamp 14 B 22 at distance of 1 5cm. The total exposure time was 30 mins. Above treatment was repeated four times. The discs were brushed with regular toothpaste after every cycle to removes leftover film.

A photograph to determine visual impact of the samples was taken and the L*, a* and b* values were measured after 4 cycles. The colour of the disks were measured using the following method:

Absorbance measurement over the entire visible color spectrum were obtained using the CIELAB color scale (Commission International de L'Eclairage, 1978 and 1986) with a SpectroShade® Micro spectrophotometer (MHT, Italy). This scale quantifies color according to three parameters, L* (lightness-darkness); a* (red-green); and b* (yellow- blue) with increasing L* indicating a more aesthetically pleasing and desirable colour (whiter teeth). The □E value is then calculated using the formula given below:

Subscript 1 & 2 represent the values before and after photobleach treatment

The L* a* and b* values obtained after every cycle is as given in the Table 2 below

Table 2

The data in the Table 2 above indicates high tooth whitening using the film of the invention as compared to control.

Examples A-C, 2: Effect of various treatments on biofilm removal Example - A: Control

Example - B: Treatment with a film of Example 1 without shining light on it Example - C: Treatment by only shining light

Example - 2: Treatment with film of Example 1 and then shining light on it. The samples were tested for biofilm removal using the following procedure:

Oral biofilm formed on salivary pellicle coated HAP disc (24 hold biofilm) were immersed in test suspension for 5 h with exposure to light every 30mins with gap of 10 mins before each contact time. At the end of contact the biofilm on the HAP disc was extracted and serially diluted in neutralizing media and plated in BHI agar. The plates were incubated anaerobically for 4- 5 days in Anaerobic Jar at 37’C. At the end of incubation colonies were counted and multiplied by the dilution factor to determine the number of CFU/mL in the original sample.

While removing the photosensitizer film it may also remove the preformed biofilms. Hence photosensitizer solution (0.02%) was added according to above procedure.

The data is summarized in Table 3 below.

Table 3

The data in table 3 above indicates the efficacy of the film composition of the invention (Example - 2) using the method to get excellent biofilm removal.

Examples D, E and 3-8: Effect of various ratios of polymer A to polymer B:

Films with the compositions as shown in Table 4 below were prepared using the same procedure as for Example 1. Table 4

The film compositions as in Table 4 above were measured for relative photobleach efficacy and for the sensory effect on the tooth using the following procedure:

A □E value of >15 unit is considered Very Good (VG), a □E in the range of 10-15 is considered Good (G) and a □E of <10 is considered Poor (P).

Sensory is based on visual assessment of the film property such as transmittance, homogeneity, flexibility, and on the stability of casting solution. The composition were rated by a panel of three people and graded as Very Good (VG), Good (G), or Poor

(P)·

The average of the results are summarized in Table 5 below:

Table 5

Table 5 above indicates that of the compositions of the invention (Examples 3 to 8), the compositions 3 to 6 provide good or very good sensory and photobleach efficacy while compositions 4 is the best on both counts.

Claims

1. A tooth whitening film comprising:

(ii) a polymer A selected from a polysaccharide or a modified polysaccharide; and a polymer B selected from a water soluble film forming synthetic polymer wherein said polymer A is selected from one or more of modified cellulose, guar gum orxanthan gum.

2. A film as claimed in claim 1 wherein the composition comprises less than 0.1 wt% oxidising agent.

3. A film as claimed in any of claim 1 or 2 wherein said photosensitiser is present in an amount of 0.001 to 5 wt%, preferably 0.01 to 2.5% by weight of the film.

4. A film as claimed in any of the preceding claims wherein the xanthene class of dye is at least one of Acid Red 52, Acid Red 289, Gallein, Bromopyrogallol Red, 2', 7'- Dichlorofluorescein Sodium Salt, 9-(4'-Dimethylaminophenyl)-2,6,7- trihydroxyfluorone Sulfate Hydrate, Dibromofluorescein, Uranine K, Fluorescein, Uranine, Pyrogallol Red, Rhodamine 6G, Rhodamine B, Sulfonfluorescein, Tetrabromofluorescein Potassium Salt, Acid Red 91 ( Eosin Bluish), Acid Red 94 (Rose Bengal), Acid Red 87( Eosin), Acid Red 92 (Phloxine B), 3, 4,5,6- Tetrachlorofluorescein, Tetraiodofluorescein (Erythrosin B or Erythrosine B) and Phenylfluorone.

5. A film as claimed in claim 4 wherein said dye is at least one of Rose Bengal, Eosin, Phloxine B or Erythrosine, more preferably Phloxine B or Rose Bengal.

6. A film as claimed in any one of the preceding claims wherein said modified cellulose is one or more of hydroxyethyl cellulose (HEC), methyl cellulose, hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (SCMC), preferably HEC.

7. A film as claimed in any one of the preceding claims wherein said polymer B is selected from one or more of polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycol, propylene glycol and polyacrylates preferably polyvinylpyrrolidone.

8. A film as claimed in any one of the preceding claims wherein the weight ratio of polymer A to polymer B is in the range of 20:80 to 90:10 preferably in the range of 40:60 to 60:40.

9. A kit-of-parts comprising:

(i) a film as claimed in any of the preceding claims;

(ii) a source of actinic light; and

(iii) optionally, a set of instructions for use of said kit-of-parts.

10. A method of whitening teeth comprising:

(i) Applying a film as claimed in any one of the preceding claims 1 to 8 on to teeth; and

(ii) exposing said film so applied, to a source of actinic light.

11. A method as claimed in claim 10 wherein said method in non-therapeutic.

12. Use of a film as claimed in any one of the preceding claims 1 to 8 for whitening teeth.

13. A process to prepare the film as claimed in any one of the preceding claims 1 to 8 comprising the steps of

(i) dissolving the photosensitizer, polymer A and polymer B in water to form a premix;

(ii) casting said premix into film solutions of desired thickness; and