EP4281190A1

EP4281190A1 - Oral care composition

Info

Publication number: EP4281190A1
Application number: EP21844300.0A
Authority: EP
Inventors: Nandini Sachin Dabholkar; Alison Katharine Green; Sayandip MUKHERJEE; Sandip Bhanudas Pathak; Glyn Roberts; Maya Treesa Saji
Original assignee: Unilever Global IP Ltd; Unilever IP Holdings BV
Current assignee: Unilever Global IP Ltd; Unilever IP Holdings BV
Priority date: 2021-01-22
Filing date: 2021-12-22
Publication date: 2023-11-29
Also published as: WO2022156990A1

Abstract

The present application relates to a composition having a pH at 20°C from 4 to 6 and comprising: i) a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), ii) a PEG hydrogenated castor oil; in which the quaternary ammonium compound and the PEG hydrogenated castor oil are present as a co-micelles.

Description

ORAL CARE COMPOSITION

Field of the Invention

The present invention is concerned with oral care compositions. More particularly, the present invention is concerned with mouthwash compositions.

Background of the Invention

The benefit associated with oral care products are many including prevention and treatment of gingivitis, tooth whitening, breath freshness mitigation of tooth decay and mitigation of tooth sensitivity.

The present invention has found that certain oral care compositions are stable on storage and are effective in the for use in the reduction of transmission and treatment of bacterial and viral infections.

Summary of the Invention

The present invention relates to a composition having a pH at 20°C from 4 to 6 and comprising: i) a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), ii) a PEG hydrogenated castor oil;

In which the quaternary ammonium compound and the PEG hydrogenated castor oil are present as a co-micelles.and in which the weight ratio of PEG hydrogenated castor oil ii) to quaternary ammonium compound i) is from 19:1 to 10:1

The invention also relates to a composition as described above for use in the reduction of transmission of enveloped viruses preferably coronaviruses and orthomyxoviruses more preferably SARS-CoV-2 (covid 19), hCoV 229E, HcoV OC43, influenza A viruses.

A further aspect of the invention is a composition as described above for use in the control of oral bacteria, preferably Streptococcus mutans, ATCC 251751 DSM 20523, Streptococcus sanguinis, ATCC 10556 / DSM 20567, Streptococcus salivarius, ATCC 13419 / DSM 205Q0Streptococcus mitis, ATCC 6249 .Neisseria subflava ATCC 49275 / DSM 17610, Actinomyces viscosus ATCC 15987. Detailed Description of the Invention

Water-insoluble, refers to the solubility of a material in water at 25°C and atmospheric pressure being 0.1 % by weight or less.

Except in the 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 may optionally be understood as modified by the word “about’.

All amounts are by weight of the composition, unless otherwise specified.

It should be noted that in specifying any ranges of values, any upper value can be associated with any particular lower value.

Where a feature is disclosed with respect to a particular aspect of the invention (for example a composition of the invention), such disclosure is also to be considered to apply to any other aspect of the invention (for example a method of the invention) mutatis mutandis.

In the context of the present application transmission incudes infecting others with virus/bacteria and becoming infected yourself with the virus.

The critical micelle concentration (CMC) is the concentration of surfactants above which micelles will form and all additional surfactants added to the system will form micelles. The term co-micelles in the context of the present invention relates to a mixture of components that are both present at levels above their CMC.

Compositions according to the invention comprise cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), or mixtures thereof. Preferably the ammonium material comprises cetylpyridinium chloride (CPC).

Preferably the level of quaternary ammonium compound is from 0.001 to 1wt% of the total composition, more preferably from 0.01 to 0.5 wt%, most preferably from 0.03 to 0.2wt%.

Compositions according to invention comprise PEG hydrogenated castor oil, preferably PEG40 hydrogenated castor oil. It is preferred if the level of PEG hydrogenated castor oil, preferably PEG40 castor oilis from 0.6 to 1 ,4wt% of the total composition, more preferably from 0.7 to 1.2 wt% most preferably from 0.8 to 1 wt%.

Preferably the molar ratio of PEG hydrogenated castor oil to quaternary ammonium compound is preferably from 8: 1 to 10: 1 , more preferably 0.8: 1 to 5: 1.most preferably 0.8: 1 to 2: 1. It is particularly advantageous if the molar ratio of PEG hydrogenated castor oil to quaternary ammonium is from 0.9:1 to 1.5:1 most preferably 1.1:1.

It is preferable if compositions of the invention are in the form of a mouthwash or spray, mouthwashes being particularly preferred. The term “mouthwash” generally denotes liquid formulations which are used to rinse the surfaces of the oral cavity and provide the user with a sensation of oral cleanliness and refreshment. The mouthwash is an oral composition that is not intentionally swallowed for purposes of systemic administration of therapeutic agents, but is applied to the oral cavity, used to treat the oral cavity and then expectorated.

Compositions according to the invention preferably comprise an aqueous base, particularly if it is a mouthwash will usually contain an aqueous continuous phase. The amount of water generally ranges from 70 to 99% by weight based on the total weight of the mouthwash.

A mouthwash composition according to the invention will generally contain further ingredients to enhance performance and/or consumer acceptability, such as the humectants and surfactants. The amount of humectant generally ranges from 1 .0 to 20%, more preferably from 1 .5 to 5% by weight based on the total weight of the mouthwash. Preferred humectants that are present at the above levels include polyols, more preferred is sorbitol and/or glycerol, glycerol is particularly preferred.

It is preferable if the level of ethanol in the total composition is less than 0.1 wt%.

Compositions of the invention may comprise a preservative, preferred preservatives are benzyl alcohol, and phenoxyethanol. Preferably the level of preservative is from 0.1 to 1 wt% of the total composition.

The composition of the invention may comprise a deposition aid. The term “deposition aid” in the context of this invention generally means a material which aids deposition of anti-bacterial agents from the composition. Suitable deposition aids for use in the invention will generally dissolve or disperse in water at a temperature of 25°C.

Preferred deposition aids for use in the invention are water soluble. The term “water-soluble” in this particular context generally means that the deposition aid has an aqueous solubility of at least 10g/L at 25°C, and more preferably at least 30g/L at 25°C (where the solubility is determined in unbuffered distilled water). It is particularly preferable that the deposition aid remains water soluble after drying, so that it can be re-dissolved. This prevents undesirable build-up of the deposition aid on the teeth after repeated usage of the composition.

Suitable deposition aids for use in the invention include polymeric materials, preferably polymeric materials which are water soluble as defined above.

Polymeric materials for use as deposition aids in the invention may be naturally or synthetically- derived, and may be ionic or nonionic in nature.

Preferably such polymeric materials are high molecular weight. The term “high molecular weight’ in this particular context generally means that the polymeric material has a molecular weight of at least 50,000, more preferably at least 500,000 g/mol. A suitable method to determine the molecular weight of such polymeric materials is gel permeation chromatography against a polyethylene glycol standard.

Specific examples of suitable classes of polymeric material for use as deposition aids in the invention include:

Water-soluble, high molecular weight linear homopolymers of ethylene oxide characterised by the general formula H(OCH2CH2)_nOH. These materials are generally termed polyethyleneoxides (or alternatively, polyoxyethylenes, or polyethylene glycols). In the general formula, n usually has an average value of at least 2000, preferably at least 50,000.

Water-soluble, high molecular weight cellulose ethers such as methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxybutyl methylcellulose, hydroxyethyl ethylcellulose, sodium carboxymethylcellulose, and sodium carboxymethyl hydroxyethylcellulose. A preferred class of polymeric material for use as deposition aids in the invention includes water- soluble, high molecular weight polymers having anionic side groups along the polymer main chain.

Specific examples of such materials include poly(carboxylic acid) polymers. Poly (carboxylic acid) polymers are typically polymers which include -COOH groups in their structure, or groups which are derived from -COOH groups such as salt, ester or anhydride groups.

For example, the poly(carboxylic acid) polymers may include:

-[C(R¹)(COOH)-]- units in their structure, in which R¹ is selected from hydrogen, C1.3 alkyl, C1.3 alkoxy or

C1.3 hydroxyalkyl. Preferably R¹ is hydrogen.

A preferred type of poly (carboxylic acid) polymer includes adjacent:

-[C(R¹)(COOH)-]- units in its structure (where R¹ is as defined above), for example polymers based on maleic acid, which typically include: -CH(C00H)-CH(C00H)-]- units, and/or salts or esters of such units, or such units in anhydride form in which -COOH groups on adjacent carbon atoms are cyclised to form a ring system.

For example, the poly(carboxylic acid) polymers may comprise units with pairs of carboxylic acid groups on adjacent polymer chain carbon atoms, for example polymers comprising:

-[-C(R¹)(R²)-C(R³)(R⁴)-C(R⁵)(COOH)- C(R⁶)(COOH)-]- units in its structure (and/or salts or esters of such units, or such units in anhydride form in which - COOH groups on adjacent carbon atoms are cyclised to form a ring system); in which R¹,R²,R³,R⁴,R⁵ and R⁶ are each independently selected from hydrogen, C1.3 alkyl or C1.3 alkoxy. Preferably R¹ and R² are hydrogen, R³ is hydrogen and R⁴ is methoxy and R⁵ and R⁶ are hydrogen. Such a poly(carboxylic acid) polymer may be described as the polymer based on a copolymer of methyl vinyl ether and maleic anhydride, and is commercially available for example under the trade name Gantrez®.

A particularly preferred example of such a polymer comprises:

-[-CH2-CH(OCH₃)-CH(COOH)-CH(COOH)-]- units in its structure, in which the -COOH groups are in free acid form. Such polymers may be linear or cross-linked. More preferably the polymer is linear. Polymers of this type are commercially available for example under the trade name Gantrez® S. Most preferably such a polymer has a molecular weight of at least 500,000 g/mol (e.g. Gantrez® S-96), ideally at least 1 ,000,000 g/mol (e.g. Gantrez® S-97).

Alternative polymers which may be used comprise the units as described above in anhydride form, i.e. in which the two adjacent -COOH groups are cyclised to form a ring system. Such polymers are commercially available under the tradename Gantrez® AN, e.g. Gantrez® AN- 119, Gantrez® AN-903, Gantrez® AN- 139 and Gantrez® AN-169.

Other alternative polymers which may be used comprise the units as described above in partial salt form, for example in which some of the free -COOH groups are converted into a metal salt of a Group I or Group II metal such as either sodium or calcium, or a mixed sodium-calcium salt. Such polymers are commercially available under the tradename Gantrez® MS, e.g. Gantrez® MS-955.

Other alternative polymers which may be used comprise the units as described above in partial ester form, for example in which some of the free -COOH groups are esterified with Ci-6 alkyl, e.g. ethyl or n-butyl. Such polymers are commercially available under the tradename Gantrez® ES, e.g. Gantrez® ES-225 or Gantrez® ES-425.

Mixtures of any of the above described materials may also be used.

The amount of deposition aid (as defined above) in compositions of the invention suitably ranges from 0.001 to 5.0%, preferably from 0.005 to 4.0%, more preferably from 0.01 to 2.0% by total weight deposition aid (as defined above) based on the total weight of the composition. Preferably the composition comprises an acid anhydride polymers, particularly preferred are copolymers of maleic anhydride with methyl vinylether, in which the anhydride moiety may be in a partially or fully hydrolysed or alcoholysed form.

The composition may contain low levels of surfactant based on the total weight of the composition. If present, the surfactant is preferably present at levels of less than 3.0 wt% of the total composition, more preferably at levels less than 2.0 wt%, most preferably at levels of less than 1 .5 wt%.

Suitable surfactants for use in the invention comprises nonionic surfactants, such as polyethoxylated fatty acid sorbitan esters, ethoxylated fatty acids, esters of polyethylene glycol, ethoxylates of fatty acid monoglycerides and diglycerides, and ethylene oxide/propylene oxide block polymers. Preferred nonionic surfactants are ethoxylated polyethylene glycol esters of castor oil, particularly PEG 40 hydrogenated castor oil.

Other suitable surfactants include amphoteric surfactants, such as betaines or sulphobetaines. Mixtures of any of the above described materials may also be used.

Preferably the composition is free of anionic surfactants.

Compositions of the present invention may also contain further optional ingredients customary in the art such as fluoride ion sources, anticalculus agents, buffers, flavouring agents, stability agents such as EDTA, sweetening agents, colouring agents, opacifying agents, antisensitivity agents and antimicrobial agents.

Use of the composition in the context of this invention typically involves application of the composition to the oral cavity, for a recommended time period before being expectorated. Preferred application times are from 10 to 60 seconds.

The invention is further illustrated with reference to the following, non-limiting Examples. Examples according to the invention are illustrated by a number, comparative Examples are illustrated by a letter. EXAMPLES

Formulations

Mouthwash compositions having the ingredients shown in Table 1 below were prepared.

All ingredients are expressed by weight percent of the total formulation, and as level of active ingredient.

Table 1

The Examples were evaluated for virucidal activity against Severe Acute Respiratory Syndrome- Related Coronavirus 2 (SARS-CoV-2 isolate USA-WA1/2020) following a standard suspension ‘time to kill’ protocol (30s) based upon ASTM International Standard E1052-20. The mean Iog10 reduction was calculated as the difference in logioPFU per ml between the MW product treatments and virus control. 3 replicates were completed.

The results are shown in Table 2

Table 2 The stability of the mouth washes was assessed, and the results shown in Table 3

Table 3

Microbiology data for the above Examples was generated using standard method ASTM 2783. and multiple bacterial species (Streptococcus mutans, ATCC 251751 DSM 20523, Streptococcus sanguinis, ATCC 10556 / DSM 20567, Streptococcus salivarius, ATCC 13419 / DSM 20560 Streptococcus mitis, ATCC 6249 .Neisseria subflava ATCC 49275 / DSM 17610, Actinomyces viscosus ATCC 15987. The results are shown in T able 4 the higher the number greater the efficacy. The time is period of MW treatment.

Table 4

The Example according to the invention has good anti-viral activity, antibacterial activity, and stability. Comparative Examples falling outside this claim do not have this total combination of attributes.

Claims

1. A composition having a pH at 20°C from 4 to 6 and comprising: i) a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), ii) a PEG hydrogenated castor oil; in which the quaternary ammonium compound and the PEG hydrogenated castor oil are present as a co-micelles.and in which the weight ratio of PEG hydrogenated castor oil ii) to quaternary ammonium compound i) is from 19:1 to 10:1

2. A composition according to any preceding claim in which the PEG hydrogenated castor oil ii) is PEG40 hydrogenated castor oil.

3. A composition according to any preceding claim in which the level of PEG hydrogenated castor oil ii) is from 0.6 to 1 ,4from 0.7 to 1.3 wt% of the total composition.

4. A composition according to any preceding claim in which the quaternary ammonium compound comprises cetylpyridinium chloride (CPC).

5. A composition according to any preceding claim in which the level of quaternary ammonium compound i) is from 0.001 to 1 wt% of the total composition.

6. A composition according to any preceding claim which is an oral care composition.

7. A composition according to any preceding claim that is a mouth wash.

8. A composition according to any preceding claim that further comprises glycerol.

9. A composition according to any preceding claim that further comprises an acrylamide based polymer.

10. A composition according to any preceding claim that is in an aqueous base. A composition as described in any preceding claim for use in the reduction of transmission of enveloped viruses preferably coronaviruses and orthomyxoviruses more preferably SARS- CoV-2 (covid 19), hCoV 229E, HcoV OC43, influenza A viruses. A composition as described in any of claims 1 to 10 for use in the control of oral bacteria, preferably Streptococcus mutans, ATCC 251751 DSM 20523, Streptococcus sanguinis, ATCC 10556 / DSM 20567, Streptococcus salivarius, ATCC 13419 / DSM 205Q0Streptococcus mitis, ATCC 6249 .Neisseria subflava ATCC 49275 / DSM 17610, Actinomyces viscosus ATCC 15987.