WO2022053194A1

WO2022053194A1 - Oral care compositions

Info

Publication number: WO2022053194A1
Application number: PCT/EP2021/067261
Authority: WO
Inventors: Glyn Roberts
Original assignee: Unilever Global IP Ltd; Unilever IP Holdings BV; Conopco Inc
Current assignee: Unilever Global IP Ltd; Unilever IP Holdings BV; Conopco Inc
Priority date: 2020-09-08
Filing date: 2021-06-23
Publication date: 2022-03-17
Anticipated expiration: 2023-03-08
Also published as: BR112023001199A2; CN116157113A; EP4210662A1

Abstract

A composition comprising a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), or mixtures thereof for use in the reduction of transmission of SARS-CoV-2 (covid 19).

Description

ORAL CARE COMPOSITIONS

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 can be effective in the for use in the reduction of transmission of SARS-CoV-2 (covid 19).

Summary of the Invention

The present invention relates to a composition comprising a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), or mixtures thereof for use in the reduction of transmission of SARS-CoV-2 (covid 19).

The invention further relates to the use of a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), or mixtures thereof in a composition for the reduction of transmission of SARS-CoV-2 (covid 19).

A further aspect of the invention relates to the use of a composition comprising a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC) and mixtures thereof in the reduction of transmission of SARS-CoV-2 (covid 19).

The invention also discloses the use of a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC) in the manufacture of a medicament for the reduction of transmission of SARS-CoV-2 (covid 19). 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 human coronavirus SARS-CoV-2 (covid 19) and becoming infected yourself with the virus.

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 2 wt% of the total composition, more preferably from 0.01 to 1 wt%.

Compositions according to the invention preferably comprise at least one extract selected from Aloe Barbadensis leaf, Quercus alba bark, Abies Siberica Juniperus communis fruit, turpentine oil and mixtures thereof. Preferably these extracts are aqueous based extracts or carbon dioxide extracts. In the context of the present application aqueous based extracts include water and steam based extractions. It is preferable if the aqueous and carbon dioxide based extracts are included from 0.01 to 1 wt% of the total composition. The material listed above were sourced form Russian or European sources. Compositions according to the invention preferably comprises llrtica Dioica Leaf Extract, Chamomilla Recutita Flower Extract, Chelidonium Majus Extract (whole plant), Hypericum Perforatum Flower / Leaf / Stem Extract, Achillea Millefolium Extract (whole plant) and mixtures thereof. Preferred extracts are propylene glycol based extracts. Preferably the level of propylene glycol based extract is from 0.1 to 5 wt% of the total composition. The material listed above were sourced from Russian or European sources.

Preferably the total weight ratio of natural extract to CPC is from 1 : 1 to 20: 1 , more preferably from 2:1 to 15:1.

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 50 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. EXAMPLE

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 - Example 1

The ASTM (American Society for Testing and Measurement) have produced recommendations on SARS-CoV-2 surrogates, these include the Human Corona virus Strain 229E (ATCC #VR-740), This surrogate was used to demonstrate the effectiveness of the present invention.

Example 1 and a commercial mouthwash (Comparative Example A) comprising 15.7 wt% alcohol were evaluated for virucidal activity against Human Coronavirus Strain CoV-229E (ATCC #VR-740) following a standard suspension ‘time to kill’ protocol based upon ASTM International Standard E1052-20. The mean Iog10 reduction was calculated as the difference in TCID50 between the test product treatment and virus recovery control. % reduction was calculated using TCID50 for the test treatment and virus recovery control. 3 replicates were completed.

Table 2

In a standard contact ‘time to kill’ viral suspension test, Example 1 of the invention applied for 30 and 60 seconds, resulted in greater than 3 log reduction of viral count of a SARS-CoV-2 surrogate, CoV- SARS 229E. In contrast, under the same 30- and 60-second contact times, a comparative Example containing 15.7% ethanol demonstrated poor virucidal action with only 0.17 and 0.33 log reductions, respectively.

Claims

1 . A composition comprising a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), or mixtures thereof for use as a medicament in the reduction of transmission of SARS-CoV-2 (covid 19).

2. A composition for use according to claim 1 in which the quaternary ammonium compound comprises cetylpyridinium chloride (CPC).

3. A composition for use according to any preceding claim in which the level of quaternary ammonium compound is from 0.01 to 1 wt% of the total composition.

4. A composition for use according to any preceding claim that further comprises from 0.01 to 1 wt% of the total composition of a aqueous or carbon dioxided based extract selected from Aloe Barbadensis leaf, Quercus alba bark, Abies Siberica Juniperus communis fruit, turpentine oil and mixtures thereof.

5. A composition for use according to any preceding claim that comprises from 0.1 to 5 wt% of the total composition of a propylene glycol based extract selected from Urtica Dioica Leaf Extract, Chamomilla Recutita Flower Extract, Chelidonium Majus Extract (whole plant), Hypericum Perforatum Flower / Leaf / Stem Extract, Achillea Millefolium Extract (whole plant) and mixtures thereof.

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

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

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

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

10. A composition for use according to any preceding claim that comprises polyethylene glycol hydrogenated castor oil. A composition for use according to any preceding claim that is in an aqueous base. Use of quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), and mixtures thereof in a composition for the reduction of transmission of SARS-CoV-2 (covid 19). Use of a composition comprising a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC) in the reduction of transmission of SARS-CoV-2 (covid 19). The use of a quaternary ammonium compound selected from cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC) in the manufacture of a medicament for the reduction of transmission of SARS-CoV-2 (covid 19).