EP4593791A1

EP4593791A1 - Oral care composition comprising hyaluronic acid and a panax ginseng root extract

Info

Publication number: EP4593791A1
Application number: EP23764286.3A
Authority: EP
Inventors: Ying LE; Yiwen Sun
Original assignee: Unilever Global IP Ltd; Unilever IP Holdings BV
Current assignee: Unilever Global IP Ltd; Unilever IP Holdings BV
Priority date: 2022-09-29
Filing date: 2023-08-30
Publication date: 2025-08-06
Also published as: CN119968194A; WO2024068168A1

Abstract

An oral care composition is disclosed comprising a hyaluronic acid and/or its derivatives and a Panax Ginseng root extract, wherein the weight ratio of the hyaluronic acid and/or its derivatives to the Panax Ginseng root extract ranges from 50:1 to 10000:1; and wherein the hyaluronic acid derivatives are hyaluronate in the form of a salt with a cation selected from sodium, potassium, zinc, ammonium, mono-, di-, tri-alkanolamine and combinations thereof.

Description

ORAL CARE COMPOSITION COMPRISING HYALURONIC ACID AND A PANAX GINSENG ROOT EXTRACT

Field of the Invention

The present invention relates to an oral care composition such as toothpastes, gums, mouthwashes and the like, which comprises a Panax Ginseng root extract and a hyaluronic acid and/or its derivatives. This invention also relates to the use of such compositions to provide oral care benefits (particularly oral mucosa care benefits) in the oral cavity of an individual.

Background of the Invention

The oral mucosa is the term used to describe the soft tissue lining of the oral cavity including the buccal mucosa and the gum (gingivae). It has many different functions and consists of a distinct layered structure that is similar to the structure and function of skin. Oral mucosa primarily acts as a barrier against the external harmful environments. Loss of its barrier function due to diseases or injury will cause significant dysfunction within the oral cavity. The oral mucosa can be commonly affected by a variety of conditions, such as periodontitis, gingivitis, mucositis, recurrent aphthous, stomatitis, herpes, and candidiasis. These diseases can cause major damage to the oral mucosa.

Hyaluronic acid (also called as hyaluronan) is a straight chain, glycosaminoglycan polymer of the extracellular matrix composed of repeating units of the disaccharide [-D-glucuronic acid- pi ,3-N-acetyl-D-glucosamine-pi,4-]n, and is identified via CAS number 9004-61-9, and it can be found in all tissues and body fluids of vertebrates as well as in some bacteria. It is a linear polymer of exceptional molecular weight, especially abundant in loose connective tissue.

Recent studies have shown that hyaluronic acid is an important component of the extracellular matrix of periodontal tissue in the oral cavity.

US2020/0390677A1 (The Procter & Gamble Company) discloses leave-on oral care compositions having good spreadability and improved retention property are provided for promoting gum health of a user. Said leave-on oral care compositions comprise a hyaluronic acid or a salt thereof, a polyacrylic acid as a mucoadhesive polymer and an additional polymer.

US2020/0390801 A1 (The Procter & Gamble Company) discloses leave-on oral care compositions comprising a hyaluronic acid, and a gum-strengthening polyol are provided for promoting gum health of a user. CN107536725A (Guangzhou Weimeizi Ind Co Ltd) discloses a multiple-effect oral cavity composition containing a hyaluronic acid mixture. The multiple-effect oral cavity composition contains 0.1-5.0 part of hyaluronic acid mixture and 0.5-2.0 parts of zinc citrate, wherein the hyaluronic acid mixture contains low molecular weight hyaluronic acid and high molecular weight hyaluronic acid, the weight ratio of the low molecular weight hyaluronic acid to the high molecular weight hyaluronic acid is 1: (0.5-2.0).

CN115154501A (YUNNAN BAIYAO GROUP CO LTD) discloses a composition for oral cavity repair, a prepared gel preparation and application. The composition comprises a pseudoginseng extract, a periplaneta americana extract and a mangnolia officinalis extract. The prepared gel preparation comprises the pharmaceutical composition, a gel adhesive and an additive. The gel adhesive is prepared from the following components in parts by mass: 0.02 to 1 part of low molecular weight sodium hyaluronate, 0.02 to 1 part of high molecular weight sodium hyaluronate and 0.06 to 1 part of tremella fuciformis extract.

KR20170141034A (LG HOUSEHOLD & HEALTH CARE LTD) discloses a composition for preventing, treating or alleviating dental diseases comprising an extract of Panax ginseng.

There remains a need to develop an oral care composition which provides oral mucosa care benefits in the oral cavity of an individual.

Summary of the Invention

In a first aspect, the present invention is directed to an oral care composition comprising:

(a) a hyaluronic acid and/or its derivatives; and

(b) a Panax Ginseng root extract; wherein the weight ratio of the hyaluronic acid and/or its derivatives to the Panax Ginseng root extract ranges from 50:1 to 10000:1 ; and wherein the hyaluronic acid derivatives are hyaluronate in the form of a salt with a cation selected from sodium, potassium, zinc, ammonium, mono-, di-, tri-alkanolamine and combinations thereof.

In a second aspect, the present invention is directed to a packaged oral care product comprising the oral care composition of the first aspect of this invention.

In a third aspect, the present invention is directed to use of an oral care composition of any embodiment of the first aspect to provide oral mucosa care benefits in the oral cavity of an individual. Preferably, the present invention is directed to use of an oral care composition of any embodiment of the first aspect to provide oral mucosa repair benefits in the oral cavity of an individual. The use is preferably for non-therapeutic benefits.

All other aspects of the present invention will more readily become apparent upon considering the detailed description and examples which follow.

Detailed Description of the Invention

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

For the avoidance of doubt, 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.

The disclosure of the invention as found herein is to be considered to cover all embodiments as found in the claims as being multiply dependent upon each other irrespective of the fact that claims may be found without multiple dependency or redundancy.

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.

Hyaluronic acid and/or its derivatives

The oral care composition of the present invention comprises a hyaluronic acid and/or its derivatives. Hyaluronic acid (HA) is a linear polysaccharide consisting of a repeating disaccharide of (1-3) and (1-4)-linked p-d-glucuronic acid and /V-acetyl-p-d-glucosamine units. It can be found in all tissues and body fluids of vertebrates as well as in some bacteria. It is a linear polymer of exceptional molecular weight, especially abundant in loose connective tissue. Recent studies have shown that hyaluronic acid is an important component of the extracellular matrix of periodontal tissue in the oral cavity. The hyaluronic acid derivatives are hyaluronates in the form of a salt with a cation selected from sodium, potassium, zinc, ammonium, mono-, di-, tri-alkanolamine and combinations thereof. Mixtures of such ions may also be employed. Preferably the cation is selected from sodium, potassium, zinc and combinations thereof. Sodium hyaluronate is particularly preferred.

In another embodiment of the invention, the hyaluronic acid derivatives are modified hyaluronic acid with substituents of bisphosphonate, amine, cystamine, hydrazide, dopamine, thiol or mixtures thereof. Examples of suitable modified hyaluronic acid include HA-bisphosphonate, HA-amine, HA-cystamine, HA-hydrazide, HA-dopamine, HA-thiol or mixtures thereof.

Preferably the hyaluronic acid and/or its derivatives has a molecular weight ranging from 50,000 to 2,000,000 Dalton, more preferably from 100,000 to 1 ,000,000 Dalton, even more preferably from 150,000 to 800,000 Dalton and most preferably from 200,000 to 600,000 Dalton. The term “molecular weight” as used in the context of the present invention refers to the viscosity average molecular weight of hyaluronic acid and/or its derivatives herein is measured by using an Ubbelohde viscometer to obtain an intrinsic viscosity [q], and the molecular weight is calculated by the equation:

Preferably the hyaluronic acid and/or its derivatives suitable for use in the present invention comprises a combination of (i) low molecular weight hyaluronic acid and/or its derivatives; and (ii) high molecular weight hyaluronic acid and/or its derivatives. The term “low molecular weight hyaluronic acid and/or its derivatives” as used in the context of the present invention means a hyaluronic acid and/or its derivatives having a molecular weight less than 1 ,000,000 Dalton, preferably less than 800,000 Dalton, more preferably less than 600,000 Dalton and even more preferably less than 400,000 Dalton. The term “high molecular weight hyaluronic acid and/or its derivatives” as used in the context of the present invention means a hyaluronic acid and/or its derivatives having a molecular weight greater than 1 ,000,000 Dalton, preferably from 1 ,000,000 to 2,000,000 Dalton, more preferably from 1 ,000,000 to 1 ,800,000 Dalton and even more preferably from 1 ,200,000 to 1 ,500,000 Dalton.

It is preferred that the hyaluronic acid and/or its derivatives suitable for use in the present application is sodium hyaluronate. An example is commercially available under the trade name Biomoist® from Bloomage Biotechnology Corp Ltd. The oral care composition of the present invention preferably comprises from 0.0001 to 10% by weight of hyaluronic acid and/or its derivatives, more preferably from 0.001 to 5%, even more preferably from 0.001 to 1%, and most preferably from 0.005 to 0.5%, based on the total weight of the oral care composition and including all ranges subsumed therein.

Panax Ginseng root extract

Panax Ginseng (also called Asian Ginseng, Korean Ginseng, Chinese Ginseng, and true Ginseng) belongs to “Ginseng” plant family. Panax Ginseng root extract is an extract obtained from the root of Panax Ginseng.

The Panax Ginseng root extract may be provided in any suitable form, for example, a solid or a liquid. The Panax Ginseng root extract can be a solid, preferably in the form of a powder. When the Panax Ginseng root extract is a solid, it preferably comprises less than 10% by weight of water, more preferably less than 7%, even more preferably less than 5% and most preferably less than 1 % by weight of water. In other words, the Panax Ginseng root extract preferably comprises 0 to 10% by weight of water, more preferably from 0 to 7%, even more preferably from 0 to 5% and most preferably from 0 to 1% by weight of water.

Preferably the Panax Ginseng root extract is a liquid. The Panax Ginseng root extract suitable for use in the present invention may be prepared by a method comprising the steps of: i) washing, drying and crushing the Panax Ginseng root; ii) extracting the Panax Ginseng root with ethanol by reflux and concentrating the extract; iii) fermenting the concentrate of step (ii) with microorganisms (enzymes and strains); iv) filtering the fermentation liquid of step (iii); v) optionally dispensing the resulting filtrate of step (iv) in water or other solvents to obtain a Panax Ginseng root extract.

Preferably the ethanol in step (ii) has a concentration from 70 to 95wt%, more preferably from 75 to 85wt%. Preferably the extract of step (ii) is filtered before concentration. Suitable solvent for step (v) is butylene glycol.

A suitable method of preparing the Panax Ginseng root extract is disclosed in CN112852621 B.

The weight of Panax Ginseng root extract, as used in the context of the present invention, refers to the dry weight of the Panax Ginseng root extract. “Dry weight” as used herein, refers to the weight of material remaining after removing water and/or solvent from the Panax Ginseng root extract. The remaining material comprises less than 1.5% by weight of water and/or solvent, preferably less than 1.0%, more preferably less than 0.75%, 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 of water and/or solvent.

Preferably the Panax Ginseng root extract comprises ginsenosides. Ginsenosides are a group of glycosylated triterpenes, also known as saponins, that represents the active compounds found in the root Panax. Ginsenosides preferably comprise prototype ginsenoside, rare ginsenosides or mixtures thereof. Prototype ginsenosides refers to ginsenosides directly extracted from the “Ginseng” plant family. Examples of prototype ginsenosides include, but not limited to, Ra, Rb1 , Rb2, Rb3, Rc, Rd, Re, Rf, Rg, Ro or mixtures thereof. Rare ginsenosides derived from prototype ginsenosides through biological enzyme transformation or metabolism. Examples of rare ginsenosides include, but not limited to, Rk1 , Rk2, Rk3, Rg3, Rg5, Rh1 , Rh2, Rh3, Rh4, aPPT, aPPD or mixtures thereof.

Preferably the Panax Ginseng root extract comprises rare ginsenosides selected from Rk1 , Rk2, Rk3, Rg3, Rg5, Rh1 , Rh2, Rh3, Rh4, aPPT, aPPD and combinations thereof. It is preferred that the Panax Ginseng root extract comprises ginsenoside Rg3, ginsenoside Rh2 or mixtures thereof, preferably a combination of ginsenoside Rg3 and ginsenoside Rh2. The ginsenoside Rg3 is preferably present in the Panax Ginseng root extract in an amount of 0.001 to 10%, more preferably from 0.01 to 5%, even more preferably 0.05 to 1% and most preferably 0.1 to 0.2%. The ginsenoside Rh2 is preferably present in the Panax Ginseng root extract in an amount of from 0.001 to 10%, more preferably from 0.005 to 5%, even more preferably from 0.01 to 1% and most preferably from 0.02 to 0.1 %.

Suitable Panax Ginseng root extract is commercially available, for example, from Guangzhou COFINE Biotechnology Co., under the tradename Cotuline MixGSG.

The Panax Ginseng root extract is preferably present in an amount of from 0.00001 to 1% by weight of the composition, more preferably from 0.0001 to 0.5%, and most preferably from 0.0005 to 0.1%, based on total weight of the composition and including all ranges subsumed therein.

The weight ratio of the hyaluronic acid and/or its derivatives to the Panax Ginseng root extract in the composition ranges from 50:1 to 10000:1 , preferably from 80:1 to 8000:1, more preferably from 100:1 to 6000:1 , and most preferably from 150:1 to 5000:1. Carrier

The composition of the present invention may comprise a physiologically acceptable carrier. The carrier preferably comprises at least surfactant, thickener, humectant or a combination thereof.

Preferably the composition comprises a surfactant. Preferably the composition comprises at least 0.01% surfactant by weight of the composition, more preferably at least 0.1% and most preferably from 0.5 to 7%. Suitable surfactants include anionic surfactants, such as the sodium, magnesium, ammonium or ethanolamine salts of Cs to C alkyl sulphates (for example sodium lauryl sulphate), Cs to C alkyl sulphosuccinates (for example dioctyl sodium sulphosuccinate), Cs to C alkyl sulphoacetates (such as sodium lauryl sulphoacetate), Cs to Cis alkyl sarcosinates (such as sodium lauryl sarcosinate), Cs to Cis alkyl phosphates (which can optionally comprise up to 10 ethylene oxide and/or propylene oxide units) and sulphated monoglycerides. The preferred anionic surfactants are sodium lauryl sulphate and/or sodium dodecylbenzene sulfonate. Other suitable surfactants include nonionic surfactants. Other suitable surfactants include nonionic surfactants, such as optionally polyethoxylated fatty acid sorbitan esters, ethoxylated fatty alcohols (such as C8 to C18 alkyl alcohol ethoxylates with an average of from 3 to 20 moles of ethylene oxide per mole of alcohol), ethoxylated fatty acids, esters of polyethylene glycol, ethoxylates of fatty acid monoglycerides and diglycerides (such as coconut fatty acid esters, palm oil fatty acid esters and palm kernel oil fatty acid esters), and ethylene oxide/propylene oxide block polymers, fatty acid amides, alkyl polyglycosides (such as decyl glucoside). 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 surfactant comprises sodium lauryl sulphate, decyl glucoside, cocamidopropyl betaine, or mixtures thereof. More preferably, the surfactant comprises decyl glucoside, cocamidopropyl betaine, or mixtures thereof.

Thickener may also be used in this invention. Illustrative examples of the types of thickeners that may be used in this invention include, sodium carboxymethyl cellulose (SCMC), hydroxyl ethyl cellulose, methyl cellulose, ethyl cellulose, gum tragacanth, gum arabic, gum karaya, sodium alginate, carrageenan, guar, xanthan gum, Irish moss, starch, modified starch, silica based thickeners including silica aerogels, magnesium aluminum silicate (e.g., Veegum), Carbomers (cross-linked acrylates) and mixtures thereof. Typically, xanthan gum and/or sodium carboxymethyl cellulose and/or a Carbomer is/are preferred. When a Carbomer is employed, those having a weight-average molecular weight of at least 700,000 are desired, and preferably, those having a molecular weight of at least 1 ,200,000, and most preferably, those having a molecular weight of at least about 2,500,000 are desired. Mixtures of Carbomers may also be used herein.

In an especially preferred embodiment, the Carbomer is Synthalen PNC, Synthalen KP or a mixture thereof. It has been described as a high molecular weight and cross-linked polyacrylic acid and identified via CAS number 9063-87-0. These types of materials are available commercially from suppliers like Sigma.

In another especially preferred embodiment, the sodium carboxymethyl cellulose (SCMC) used is SCMC 9H. It has been described as a sodium salt of a cellulose derivative with carboxymethyl groups bound to hydroxy groups of glucopyranose backbone monomers and identified via CAS number 9004-32-4. The same is available from suppliers like Alfa Chem.

In another especially preferred embodiment, the thickener is xanthan gum.

Thickener typically makes up from 0.01 to about 15%, more preferably from 0.1 to 10%, and most preferably, from 0.1 to 9% by weight of the composition, based on total weight of the composition and including all ranges subsumed therein.

Suitable humectants are preferably used in the composition of the present invention and they include, for example, glycerin, sorbitol, propylene glycol, dipropylene glycol, diglycerol, triacetin, mineral oil, polyethylene glycol (preferably, PEG-400), alkane diols like butane diol and hexanediol, ethanol, pentylene glycol, or a mixture thereof. Glycerin, polyethylene glycol, sorbitol or mixtures thereof are the preferred humectants.

The humectant may be present in the range of from 10 to 90% by weight of the composition. More preferably, the carrier humectant makes up from 25 to 80%, and most preferably, from 30 to 60% by weight of the composition, based on total weight of the composition and including all ranges subsumed therein.

Fluoride source

The composition may comprise a fluoride source. Preferred fluoride source includes sodium fluoride, stannous fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride or mixtures thereof. Preferably, the fluoride source is stannous fluoride, sodium fluoride, sodium monofluorophosphate or mixtures thereof. Sodium fluoride is particularly preferred. The fluoride source may be present at a level from 0.01 to 10%, more preferably from 0.03 to 5% and most preferably from 0.05 to 2% by weight of the composition, based on total weight of the composition and including all ranges subsumed therein.

Antimicrobial agents

The composition may comprise antimicrobial agents. Antimicrobial agents may be selected from one or more of metal salts where the metal is selected from zinc, copper, silver or a mixture thereof, chlorhexidine, sanguinarine extract, metronidazole, quaternary ammonium compounds, such as cetylpyridinium chloride; cetylpyridium chloride clay complex, bis-guanides, such as chlorhexidine digluconate, hexetidine, octenidine, alexidine; and halogenated bisphenolic compounds, such as 2,2' methylenebis-(4-chloro-6-bromophenol).

Preferably the antimicrobial agents are zinc salts. Examples of suitable zinc salts include, but not limited to, zinc oxide, zinc chloride, zinc acetate, zinc ascorbate, zinc sulphate, zinc nitrate, zinc citrate, zinc lactate, zinc peroxide, zinc fluoride, zinc ammonium sulfate, zinc bromide, zinc iodide, zinc gluconate, zinc tartarate, zinc succinate, zinc formate, zinc phenol sulfonate, zinc salicylate, zinc glycerophosphate, zinc monoglycerolate, zinc pyrophosphate, zinc maleate or a mixture thereof. Preferably the antimicrobial agent is zinc citrate, zinc sulfate or mixtures thereof. Zinc citrate is particularly preferred.

The antimicrobial agent is preferably present in an amount of from 0.01 to 5% by weight of the composition, more preferably from 0.05 to 4%, and most preferably from 0.1 to 3% by weight of the composition, based on total weight of the composition and including all ranges subsumed therein.

The composition of the present invention may contain a variety of other ingredients which are common in the art to enhance physical properties and performance. These ingredients include opacifying agents, colouring agents, anti-inflammatory agents (such as ibuprofen, flurbiprofen, aspirin, indomethacin), anti-caries agents (sodium trimeta phosphate and casein), plaque buffers (such as urea, calcium lactate, calcium glycerophosphate and strontium polyacrylates), vitamins (such as Vitamins A, C and E), plant extracts, plant-derived antioxidants (such as flavonoid, catechin, polyphenol, and tannin compounds and mixtures thereof), desensitizing agents (such as potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate and strontium salts), anti-calculus agents (such as alkali-metal pyrophosphates, hypophosphite-containing polymers, organic phosphonates and phosphocitrates), biomolecules (such as bacteriocins, antibodies, enzymes), flavours (such as peppermint and spearmint oils), proteinaceous materials (such as collagen), preservatives, amino acids (such as arginine), pH-adjusting agents, sweetening agents, polymeric compounds, buffers and salts to buffer the pH and ionic strength of the compositions, and mixtures thereof.

Such ingredients typically and collectively make up less than 20% by weight of the composition, and preferably, from 0.0 to 15% by weight, and most preferably, from 0.01 to 12% by weight of the composition, including all ranges subsumed therein.

Form of compositions

The oral care composition may be in any form common in the art. Preferred forms are dentifrices, toothpastes, gels, mouthwashes, medicaments, oral films, serums, chewing gums and lozenges, more preferably a toothpaste, a gel or a mouthwash. When the oral care composition is a toothpaste or gel, the same typically has a viscosity from about 30,000 to 300,000 mPa.s (centipoise), and preferably, from 60,000 to 280,000 mPa.s (centipoise), and most preferably, from 65,000 to 250,000 mPa.s (centipoise), taken at room temperature (25°C) with a Brookfield Viscometer, Spindle No.93/94 and at a speed of 5 rpm for 1 minute. Typically the composition will be packaged. In toothpaste or gel form, the composition may be packaged in a conventional plastic laminate, metal tube or a single compartment dispenser. The same may be applied to dental surfaces by any physical means, such as a toothbrush, fingertip or by an applicator directly to the sensitive area. In liquid mouthwash form the composition may be packaged in a bottle, sachet or other convenient container.

It is preferred that the oral care composition is a toothpaste composition, which may further comprise abrasives. Preferred abrasives include silicas, aluminas, calcium carbonates, dicalcium phosphates, calcium pyrophosphates, hydroxyapatites, trimetaphosphates, insoluble hexametaphosphates or mixtures thereof, including agglomerated particulate abrasives.

Calcium carbonate and silica are particularly preferred, especially silica. The abrasives may be present in the range of from 0.01 to 60%, more preferably from 0.1 to 30%, and most preferably from 1 to 15% by weight of the oral care composition, based on total weight of the composition and including all ranges subsumed therein. Preferably, the toothpaste composition comprises at least 5% by weight of water, more preferably at least 10%, even more preferably at least 15%. It is preferable that the water content is from 1.5 to 95% by weight of the tooth paste composition, more preferably from 10 to 80%, even more preferably from 15 to 60% and most preferably from 20 to 50% by weight of the toothpaste composition, based on total weight of the composition and including all ranges subsumed therein.

It is also preferred that the oral care composition is a mouthwash composition, which may further comprise at least 20% by weight of a liquid medium selected from water, alcohol and combinations thereof. Preferably, the mouthwash composition comprises at least 20% by weight of water, more preferably at least 30%, even more preferably at least 40% by weight of water. It is preferable that the water content is from 20 to 99% by weight of the mouthwash composition, more preferably from 30 to 95%, even more preferably from 40 to 95% and most preferably from 50 to 90% by weight of the mouthwash composition, based on total weight of the composition and including all ranges subsumed therein. Preferably the mouthwash composition comprises less than 0.5% by weight of alcohol, more preferably less than 0.1 % by weight of alcohol. The mouthwash composition preferably comprises from 0.1 to 20% by weight of sweeteners, more preferably from 1 to 15%, and most preferably from 3 to 10% by weight of sweeteners, based on total weight of the composition and including all ranges subsumed therein. The sweeteners in the mouthwash composition are preferably sugar substitutes. Examples of suitable sweeteners include, but not limited to, stevia, aspartame, sucralose, neotame, acesulfame potassium, saccharin, advantame, sorbitol, lactitol, xylitol or mixtures thereof. Preferably the sweeteners in the mouthwash composition are selected from sucralose, saccharin, sorbitol, xylitol and combinations thereof. The mouthwash composition of the present invention preferably comprises one or more preservatives selected from benzyl alcohol, phenoxyethanol, sodium benzoate, methyl paraben, zinc and combinations thereof. Preferably the preservatives comprise benzyl alcohol, phenoxyethanol or mixtures thereof.

Use

The oral care composition of this invention can be used in a method for providing oral mucosa care benefits in the oral cavity of an individual. The term “oral mucosa” as used in the context of the present invention means the soft tissue lining of the oral cavity including the buccal mucosa and the gum (gingivae). The term “oral mucosa care benefits” as used in the context of the present invention refers to benefits provided to oral mucosa (particularly the gum tissue), which includes relief of red, swollen, bleeding or tender oral mucosa, repair of oral mucosa (such as improve oral mucosa would healing). Preferably the oral care composition of the present invention is used in a method for providing oral mucosa repair benefits in the oral cavity of an individual. Preferably, the method is non-therapeutic. Additionally or alternatively, the present invention is directed to an oral care composition for use in providing oral mucosa care benefits in the oral cavity of an individual, preferably for use in providing oral mucosa repair benefits in the oral cavity of an individual.

Additionally or alternatively, the present invention is directed to use of an oral care composition for providing oral mucosa care benefits in the oral cavity of an individual. Preferably, the present invention is directed to use of an oral care composition for providing oral mucosa repair benefits in the oral cavity of an individual. The use is preferably non-therapeutic.

Additionally or alternatively, the present invention is directed to use of an oral care composition in the manufacture of a medicament in providing oral mucosa care benefits in the oral cavity of an individual. Preferably, the present invention is directed to use of an oral care composition in the manufacture of a medicament in providing oral mucosa repair benefits in the oral cavity of an individual.

The composition can be effective even when used in an individual’s daily oral hygiene routine. The oral care composition of the present invention is preferably applied at least once a day in the oral cavity. More preferably the oral care composition is applied between 1 and 4 times per day in the oral cavity, and most preferably the oral care composition is applied 2 to 3 times per day in the oral cavity. The oral care composition of the present invention is preferably applied on the tooth surfaces, the oral mucosa (particularly the gum tissue) and combinations thereof.

When the oral care composition is a toothpaste, the composition is preferably brushed onto the teeth. The composition may, for example, be contacted with the teeth for a time period of one second to 20 hours. More preferably from 1 second to 10 hours, more preferably still from 10 seconds to 1 hour and most preferably from 30 seconds to 5 minutes. The composition may be used daily, for example for use by an individual once, twice or three times per day.

When the oral care composition is a mouthwash, the oral care composition may be applied in the oral cavity by ingesting said composition and keeping the composition in the mouth for at least 10 seconds. More preferably the composition is kept in the mouth for 15 to 120 seconds, and most preferably the composition is kept in the mouth for 20 to 60 seconds. The composition is preferably removed from the oral cavity after at least 30 seconds after application of the composition in the oral cavity, wherein at least 80% by weight of the composition is removed from the oral cavity. More preferably at least 90% by weight of the composition is removed from the oral cavity. Most preferably at least 95% by weight of the composition is removed from the oral cavity. The removal of the composition from the oral cavity involves spitting out, optionally after washing the oral cavity with rinse water.

When the oral care composition is a leave-on composition such as a gel, the composition is preferably applied in the oral cavity after brushing teeth, or as the last step of daily oral hygiene routine. The term “leave-on” as used in the context of the present invention means a composition is applied onto a surface for a time period of more than 1 minute, preferably more than 2 minutes. Preferably a “leave-on” composition means a composition which is intent not to be rinsed off or spitted out. Preferably the composition is applied to the oral mucosa (particularly the gum tissue) of the oral cavity of an individual, leaving on for more than 2 minutes, preferably more than 10 minutes, more preferably more than 30 minutes, even more preferably more than 60 minutes or longer. The leave-on composition is preferably applied in the oral cavity using a delivery carrier, wherein the delivery carrier may comprise strip, film of material, dental tray, aligner, sponge material applicator, or mixtures thereof.

Examples

Example 1

This example demonstrates the effects of the composition of the present invention on oral mucosa repair.

Samples were prepared as shown in Table 1. All ingredients are expressed by weight percent of the total formulation.

Table 1

1. Commercially available under the trade name Biomoist, from Bloomage Biotechnology Co. Ltd. 2. Commercially available under the trade name Cotuline MixGSG (active level 0.5%), from Shanghai Saifu Chemical Development Co. Ltd.

3. DMEM (Dulbecco's Modified Eagle Medium, Gibco) and 2% (v/v) fetal bovine serum (FBS, Gibco).

Methods

Cell scratch method is used to assess oral mucosa repair in vitro. It is a method to determine the migration and repair ability of cells.

Cell Culture and Scratch Process

Human Gingival Fibroblast (HGF) cells were cultured in complete medium consisting of DMEM (Dulbecco's Modified Eagle Medium, Gibco) and 10% (v/v) fetal bovine serum (FBS, Gibco) at 37°C and 5% CO₂.

Cell suspension was diluted to a concentration of 5x10⁵ cell/mL with medium and spread to 6-well culture plates for cell culture. After 48h of cell culture, cells were scratched using a sterile pipette tip to simulate wound formation, and rinsed with phosphate buffered saline (PBS) twice to remove the scraped cell debris. Cells were then immediately treated with samples Oh after scratching and cultured at 37°C for 24 hours. For negative control (NC), cells were treated with low nutrition medium under the same condition at Oh. Plates were photographed at Oh and 24h after scratching to record scratch recovery.

Wound Closure Rate Test

Oral mucosa repair ability of the test samples can be assessed by their ability to enhance the growth and migration of the cells for wound healing. Quantitative analyses were conducted on the photographs covering the blank areas at Oh and 24h after scratching, using the image analysis software Imaged. Wound closure rates of the NC (Wound Closure Rate_Nc) and each sample (Wound Closure Rate_x) were calculated according to the following formula.

Area_oh - Area₂₄h

Wound Closure Rate % = - x 100%

Area_oh

The relative wound closure rate (RWCR) of each sample (Relative Wound Closure Rate_x) was calculated by comparing the wound closure rate of each sample (Wound Closure Rate_x) to the wound closure rate of the NC (Wound Closure Rate_Nc). Wound Closure Rate_x

Relative Wound Closure Rate_x % = - , — ₅ - x 100%

Wound Closure Rate_NC

Results

The relative wound closure rates (RWCRs) of the samples were set forth in Table 2.

Table 2 It can be seen from the results that the experimental relative wound closure rates of cells treated by samples 1 , 2, and 3 in accordance with the present invention are higher compared to their calculated relative wound closure rates, indicating improved oral mucosa repair ability.

Claims

1. An oral care composition comprising:

(a) a hyaluronic acid and/or its derivatives; and

2. The oral care composition according to claim 1, wherein the hyaluronic acid derivative is sodium hyaluronate.

3. The oral care composition according to claim 1, wherein the hyaluronic acid derivatives are modified hyaluronic acid with substituents of bisphosphonate, amine, cystamine, hydrazide, dopamine, thiol or mixtures thereof.

4. The oral care composition according to any of the preceding claims, wherein the molecular weight of the hyaluronic acid and/or its derivatives ranges from 50,000 to 2,000,000 Dalton, preferably from 100,000 to 1 ,000,000 Dalton.

5. The oral care composition according to any of the preceding claims, wherein the Panax Ginseng root extract comprises ginsenosides comprising prototype ginsenosides, rare ginsenosides or mixtures thereof, preferably rare ginsenosides.

6. The oral care composition according to claim 5, wherein the rare ginsenosides comprise Rk1 , Rk2, Rk3, Rg3, Rg5, Rh1 , Rh2, Rh3, Rh4, aPPT, aPPD or mixtures thereof, preferably Rg3, Rh2 or mixtures thereof.

7. The oral care composition according to any of the preceding claims, wherein the Panax Ginseng root extract comprises a combination of ginsenoside Rg3 and ginsenoside Rh2. The oral care composition according to any of the preceding claims, wherein the hyaluronic acid and/or its derivatives are present in an amount of from 0.0001 to 10% by weight of the composition, preferably from 0.001 to 5%. The oral care composition according to any of the preceding claims, wherein the Panax Ginseng root extract is present in an amount of from 0.00001 to 1% by weight of the composition, preferably from 0.0001 to 0.5%. The oral care composition according to any of the preceding claims, wherein the weight ratio of the hyaluronic acid and/or its derivatives to the Panax Ginseng root extract ranges from 80:1 to 8000:1 , preferably from 100:1 to 6000:1. The oral care composition according to any of the preceding claims, wherein the oral care composition is a toothpaste, a gel, or a mouthwash, preferably a toothpaste composition or a mouthwash composition. The oral care composition according to any of the preceding claims, wherein the oral care composition is a mouthwash and further comprises at least 20% by weight of liquid medium selected from water, alcohol and combinations thereof. Use of an oral care composition according to any of the preceding claims to provide oral mucosa care benefits in the oral cavity of an individual, preferably providing oral mucosa repair benefits. The use according to claim 13, wherein the composition is applied at least once a day in the oral cavity.