WO2023187028A1 - Mouthwash composition comprising one or more strontium salt - Google Patents
Mouthwash composition comprising one or more strontium salt Download PDFInfo
- Publication number
- WO2023187028A1 WO2023187028A1 PCT/EP2023/058235 EP2023058235W WO2023187028A1 WO 2023187028 A1 WO2023187028 A1 WO 2023187028A1 EP 2023058235 W EP2023058235 W EP 2023058235W WO 2023187028 A1 WO2023187028 A1 WO 2023187028A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- oral care
- care composition
- strontium
- strontium salt
- present
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 113
- 159000000008 strontium salts Chemical class 0.000 title claims abstract description 90
- 239000002324 mouth wash Substances 0.000 title description 25
- 229940051866 mouthwash Drugs 0.000 title description 22
- 239000012876 carrier material Substances 0.000 claims abstract description 17
- 150000005846 sugar alcohols Chemical class 0.000 claims abstract description 15
- 208000024693 gingival disease Diseases 0.000 claims description 29
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 28
- 229940127557 pharmaceutical product Drugs 0.000 claims description 28
- AHBGXTDRMVNFER-UHFFFAOYSA-L strontium dichloride Chemical group [Cl-].[Cl-].[Sr+2] AHBGXTDRMVNFER-UHFFFAOYSA-L 0.000 claims description 26
- 229910001631 strontium chloride Inorganic materials 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 17
- 230000005764 inhibitory process Effects 0.000 claims description 17
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 17
- 239000000811 xylitol Substances 0.000 claims description 17
- 235000010447 xylitol Nutrition 0.000 claims description 17
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 17
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- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 3
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- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- DHEQXMRUPNDRPG-UHFFFAOYSA-N strontium nitrate Chemical compound [Sr+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O DHEQXMRUPNDRPG-UHFFFAOYSA-N 0.000 description 2
- IATRAKWUXMZMIY-UHFFFAOYSA-N strontium oxide Chemical compound [O-2].[Sr+2] IATRAKWUXMZMIY-UHFFFAOYSA-N 0.000 description 2
- UBXAKNTVXQMEAG-UHFFFAOYSA-L strontium sulfate Chemical compound [Sr+2].[O-]S([O-])(=O)=O UBXAKNTVXQMEAG-UHFFFAOYSA-L 0.000 description 2
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
Definitions
- the present invention relates to an oral care composition.
- the present invention relates to an oral care composition having an effect against oral diseases and diseases emerging from oral diseases.
- Biofilm is a structure scaffolded with extracellular polysaccharide substances (EPS), created by microorganisms, in which the microorganisms are embedded. Biofilm can be difficult to clean or remove, and dental plaque is a form of biofilm. Dental plaque biofilm is a slightly viscous liquid film, which forms on teeth between cleanings, e.g. by brushing.
- EPS polysaccharide substances
- plaque on teeth is undesirable, because the bacteria, such as Streptococcus mutans or Porphyromonas gingivalis, which grow in plaque biofilm, and are among the most potent bacteria responsible for oral diseases/gum diseases, such as caries and gingivitis.
- Oral plaque is also believed to be associated with other diseases related to the gum disease such as diabetes, Alzheimer's Disease, and cardiovascular disease.
- a mouthwash may be provided.
- mouthwashes are antiseptic solutions intended to reduce the microbial load in the mouth, although other mouthwashes might be given for other reasons such as for their analgesic, anti-inflammatory or anti-fungal action. Additionally, some rinses act as saliva substitutes to neutralize acid and keep the mouth moist in xerostomia (dry mouth).
- an improved oral care composition having strong antibacterial activity which is effective and reliable in inhibiting and/or removing plaque form the mouth, gums and the teeth without the need for physical removal of germs, and/or plaque biofilm.
- it is desirable to provide an oral care composition having strong antibacterial activity with a reduced number side effects or even without any side effects would be advantageous and highly desirable.
- an object of the present invention relates to an oral care composition having an effect against oral diseases and diseases emerging from oral diseases.
- an object of the present invention to provide an oral care composition that solves the problems of the prior art with and having strong antibacterial activity, which is effective and reliable in inhibiting and/or removing plaque form the mouth, gums and the teeth without the need for physical removal of germs, and/or plaque biofilm and preferably without any side effects.
- one aspect of the invention relates to an oral care composition
- an oral care composition comprising a carrier material, at least one strontium salt, a sugar alcohol, wherein the composition comprises a moisture content above 15% (w/w).
- Another aspect of the present invention relates to an oral care composition
- an oral care composition comprising a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w/w).
- An additional aspect of the present invention relates to a mouthwash comprising a carrier material and at least one strontium salt.
- a further aspect of the present invention relates to a mouthwash comprising a carrier material, at least one strontium salt, and a sugar alcohol.
- the pharmaceutical product for use in inhibition, reduction, treatment or prophylaxis of a gum disease or a disease related to the gum disease
- the pharmaceutical product comprises an oral care composition comprising at least one strontium salt, wherein the concentration of the strontium salt is in the range of 1-10% (w/w) of the pharmaceutical product.
- Still another aspect of the present invention relates to a pharmaceutical product according to the present invention for the inhibition, reduction, treatment or prophylaxis of a disease relating to the gum disease
- a disease relating to the gum disease include diabetes, in particular Type-II diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; premature low-weight babies; lung infections, like bronchitis; pneumonia; or emphysema; or a combination hereof.
- Another aspect of the present invention relates to a pharmaceutical product according to the present invention for the inhibition, reduction, treatment or prophylaxis of Type-II diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; premature low-weight babies; lung infections, like bronchitis; pneumonia; or emphysema; or a combination hereof.
- an oral care composition in particular a mouthwash, comprising a strontium salt was highly effective against the development of biofilm in the mouth and on the teeth, reducing the incidence and risk of plaque, oral diseases and gum diseases, such as caries, gingivitis or periodontitis and avoiding loss of teeth, ligament destruction, jawbone destruction and receding gums.
- the oral care composition according to the present invention may promote regeneration of ligaments, jawbone and gums which has suffered from oral diseases and gum diseases.
- a preferred embodiment of the present invention relates to an oral care composition
- an oral care composition comprising a carrier material, at least one strontium salt, a sugar alcohol, wherein the composition comprises a moisture content above 15% (w/w).
- a further preferred embodiment of the present invention relates to an oral care composition comprising a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w/w).
- the oral care composition according to the present invention comprising a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w/w), further comprises a sugar alcohol.
- Sugar alcohols may be organic compounds, typically derived from sugars, containing one hydroxyl group (-OH) attached to each carbon atom in the molecule. They may traditionally be white, water-soluble solids and may occur naturally in nature or be produced industrially by hydrogenation of sugars. Since sugar alcohols contain multiple OH-groups, sugar alcohols may be classified as polyols.
- Sugar alcohols are used widely in the food industry and pharma industry, e.g. as thickeners and/or sweeteners and are well known to the skilled person.
- the sugar alcohol may be xylitol.
- the carrier material may be a material capable of dissolving and/or suspending the at least one strontium salt and the sugar alcohol.
- the carrier material may be water.
- Xylitol is a five-carbon sugar polyol and may be used in the oral care composition as a non-fermentable agent that assist in regulating and restoring the pH balance in the mouth.
- the properly balanced pH creates an inhospitable environment for destructive bacteria that are responsible for plaque formation and gum diseases.
- Xylitol may also be responsible for reducing, or even reversing, dental caries.
- the oral care composition comprises a moisture content above 20% (w/w), e.g. above 30% (w/w), such as above 40% (w/w), e.g. above 50% (w/w), such as above 60% (w/w), e.g. above 70% (w/w), such as above 75% (w/w), e.g. above 80% (w/w), such as above 85% (w/w) , e.g. above 90% (w/w), such as above 92% (w/w), e.g. in the range of 20-98% (w/w), such as in the range of 40- 95% (w/w), e.g. in the range of 60-92% (w/w), such as in the range of 75-90% (w/w), e.g. in the range of 80-85% (w/w).
- the content of a sugar alcohol, in particular xylitol may be in the range of 0.05-20% (w/w), such as in the range of 0.1-15% (w/w), e.g. in the range of 0.5-10% (w/w), such as in the range of 1-7.5% (w/w), e.g. in the range of 1.5-5% (w/w), such as in the range of 2-4.5% (w/w), e.g. in the range of 3-4% (w/w).
- the oral care composition further comprises a sweetener.
- the sweetener may be a compound different from the organic compound.
- the sweetener may be a sugar compound or a sugar substitute.
- the sweetener may be a sugar substitute.
- the sugar substitute may be selected from aspartame, sucralose, neotame, acesulfame potassium, saccharin, advantame, stevia, or a combination hereof.
- the sugar substitute may be stevia.
- the oral care composition further comprises a preservative agent and/or a flavouring agent.
- the flavouring agent may be selected from menthol, eucalyptol or thymol.
- the flavouring agent may be mentha piperita oil, mentha spicata flower extract, or a combination hereof.
- a preservative agent may be added to the oral care composition.
- Addition of a preservative agent to the oral care composition may have the effect of preventing decomposition of the oral care composition, e.g. by microbial growth and/or by undesirable chemical changes.
- the preservative agent added to the oral care composition may be sodium benzoate, potassium sorbate, benzoic acid or a combination hereof.
- preservative agents may be the preferred preservative agents, the skilled person would know other relevant preservative agents that may be used in combination or alone in an oral care composition according to the present invention.
- the oral care composition comprises less than 10% (w/w) alcohol, such as less than 7.5% (w/w), e.g. less than 5% (w/w), such as less than 2.5% (w/w), e.g. less than 1% (w/w).
- the oral care composition according to the present invention comprises no alcohol.
- the alcohol according to the present invention may preferably be ethanol.
- the oral care composition further comprises one or more fluoride compounds.
- the at least one strontium salt may include at least one water soluble strontium salt. Even more preferably, the at least one water soluble strontium salt may be strontium chloride.
- the amount of strontium obtained from a specific amount of strontium salt may depend on the molecular weight of the compound, relative to the number of strontium molecules therein, thus a salt with low molecular weight per strontium molecule maybe preferred.
- the effective ratio (ER) of the salt may be expressed as the effective ratio (ER) of the salt.
- the higher effective ratio (ER) the smaller amount of the salt is required for obtaining the desired effect.
- ER effective ratio
- a strontium salt with a high effective ratio is preferred.
- the ER of the strontium salt present in the oral care composition may be more than 0.40, or more than 0.45 or 0.50, such as more than 0.53 such as more than 0.55, such as in the range of 0.40-0.70, e.g. in the range of 0.45-0.65, such as in the range of 0.50-0.60, e.g. in the range of 0.55-0.59.
- the at least one strontium salt comprises at least one water-soluble strontium salt.
- the at least one water-soluble strontium salt present in the composition according to the present invention has a solubility in water at room temperature of at least 25 g/L, such as at least 50 g/L, e.g. at least 75 g/L, such as at least 100 g/L, e.g. at least 150 g/L, such as at least 200 g/L, e.g. at least 250 g/L, such as at least 300 g/L, e.g. at least 350 g/L, such as at least 400 g/L, e.g. at least 450 g/L, such as at least 500 g/L, e.g.
- At least 525 g/L such as in the range of 25-750 g/L, e.g. in the range of 100-700 g/L, such as in the range of 200-650 g/L, e.g. in the range of 300-625 g/L, such as in the range of 400-600 g/L, e.g. in the range of 500-550 g/L.
- the one or more water soluble strontium salt may be selected from the group consisting of strontium chloride, strontium bromide, strontium nitrate, strontium hydroxide, strontium oxide, strontium acetate, strontium glutamate, strontium aspartate, strontium malonate, strontium pyruvate, strontium alpha-ketoglutarate, strontium maleate, strontium succinate, strontium fumarate, strontium ascorbate, strontium tartate, strontium glutarate, strontium methanesulfonate, strontium benzenesulfonate, strontium sulphide, and a combination hereof. More preferably, the at least one water soluble strontium salt may be strontium chloride.
- the at least one strontium salt may be strontium chloride.
- the oral care composition according to the present invention wherein the strontium chloride may be selected from the group consisting of SrCI 2 , SrCI 2 -2-H 2 0, SrCI 2 -6-H 2 0, or a combination hereof.
- the at least one strontium salt in particular strontium chloride, may be anhydrous, specifically strontium chloride may be strontium chloride anhydrous or strontium chloride hexahydrate.
- the at least one strontium salt includes at least one water soluble strontium salt, preferably, the at least one water soluble strontium salt is strontium chloride.
- the content of the at least one strontium salt in the oral care composition according to the present invention may be dependent on e.g. the formulation of the oral care composition, the condition of the mouth of the subject to be treated, the condition of the subject to be treated, and/or the age of the subject to be treated, in particular the age of the subject to be treated.
- the oral care composition comprises in the range of 0.5-15% (w/w) of the at least one strontium salt (in particular the strontium salt may be strontium chloride), such as in the range of 0.6-14% (w/w) of the at least one strontium salt, e.g. in the range of 0.7-13% (w/w) of the at least one strontium salt, such as in the range of 0.8-12% (w/w) of the at least one strontium salt, e.g. in the range of 0.9-11% (w/w) of the at least one strontium salt, such as in the range of 1.0-10% (w/w) of the at least one strontium salt, e.g.
- the at least one strontium salt in the range of 1.25-9% (w/w) of the at least one strontium salt, such as in the range of 1.5-8% (w/w) of the at least one strontium salt, e.g. in the range of 1.75-7% (w/w) of the at least one strontium salt, such as in the range of 2-6% (w/w) of the at least one strontium salt, e.g. in the range of 2.5-5% (w/w) of the at least one strontium salt, such as in the range of 3-4% (w/w) of the at least one strontium salt, e.g. about 3.5% (w/w).
- the oral care composition may preferably comprise in the range of 0.25-8% (w/w) of strontium ions in the oral care composition, such as in the range of 0.5-5% (w/w), e.g. in the range of 1.0-4% (w/w), such as in the range of 1.5-3% (w/w), e.g. in the range of 1.75-2.5% (w/w), such as about 2.0% (w/w).
- the at least one strontium salt or the oral care composition may comprise a water insoluble strontium salt or a combination of a water- soluble strontium salt and a water insoluble strontium salt.
- the water insoluble strontium salt may be selected from the group consisting of strontium carbonate and strontium sulphate. Even more preferably, the water insoluble strontium salt may be strontium carbonate.
- the oral care composition comprise at least 45% (w/w) strontium in the form of a water-soluble strontium salt, such as at least 50% (w/w) strontium in the form of a water-soluble strontium salt, e.g. at least 60% (w/w) strontium in the form of a water-soluble strontium salt, such as at least 70% (w/w) strontium in the form of a water-soluble strontium salt, e.g. at least 80% (w/w) strontium in the form of a water-soluble strontium salt, such as at least 90% (w/w) strontium in the form of a water-soluble strontium salt, e.g.
- At least 95% (w/w) strontium in the form of a water-soluble strontium salt such as at least 98% (w/w) strontium in the form of a water- soluble strontium salt, e.g. at least 99% (w/w) strontium in the form of a water-soluble strontium salt, such as about 100% (w/w) strontium in the form of a water-soluble strontium salt, e.g. in the range of 45-100 % of strontium in the form of a water-soluble strontium salt, such as in the range of 60-99 % strontium in the form of a water-soluble strontium salt, e.g. in the range of 75-98 % strontium in the form of a water-soluble strontium salt, such as in the range of 85-95 % strontium in the form of a water soluble strontium salt.
- the oral care composition may be a mouthwash composition.
- the oral care composition or the mouthwash, comprises
- a carrier material preferably water
- An active ingredient e.g. an API, provided by at least one strontium salt, preferably strontium chloride;
- a pH regulator/sugar substitute preferably xylitol;
- a sweetener preferably stevia
- a preservative preferably sodium benzoate; and Flavouring/aroma agent, preferably Mentha Piperita Oil and/or Mentha Spicata flower Extract.
- the concentration of strontium chloride in the oral care composition was as described above, preferably about 3.5% (on a weight-by-weight basis - (w/w)) of the oral care composition and the concentration of xylitol was as described above, preferably, about 3% (on a weight-by-weight basis - (w/w)).
- the mouthwash according to the present invention may be provided as a gel or as a liquid.
- the mouthwash according to the present invention may be formulated into a gel.
- the gel may be applied to the teeth and/or to the gums (the soft tissue lining of the mouth which also surrounds the teeth and provide a seal around them).
- the gel may be rubbed onto the teeth and/or into the gums.
- the mouthwash according to the present invention may be a liquid which is held in the mouth passively or swilled around the mouth by contraction of the perioral muscles and/or movement of the head, and may be gargled, where the head is tilted back and the liquid bubbled at the back of the mouth.
- the oral care composition according to the present invention is not a toothpaste.
- Some of the disadvantages of a toothpaste may be that:
- Toothpaste may apply wear on the tooth enamel and/or on the gum, whereas the oral care composition or the mouthwash according to the present invention are much gentler;
- Toothpaste may not come into all the difficult places and voids of the mouth, e.g. along the gumline (the gumline may be the line along the top of the gums, where the gums meet the surface of the teeth), whereas the mouthwash gets better distributed around the surfaces of the mouth;
- the oral care composition or the mouthwash according to the present invention also clean the gums and the oral mucosa,, in addition to cleaning the teeth;
- re. plaque, the oral care composition or the mouthwash according to the present invention also show improved activity against development and treatment of canker sores and other kind of ulcer in the mouth.
- mouthwash may give a good breath that is not possible with a toothpaste.
- the inventors of the present invention found that it was possible to stabilise the mouthwash without addition of magnesium salt. Since magnesium is consumed from many different food and beverages products it is undesirably, to add magnesium salt to the mouthwash according to the present invention, as too high intake of magnesium can lead to gastrointestinal problems, such as diarrhoea, nausea, or cramping.
- the mouthwash according to the present invention does not comprise a magnesium salt, such as a water-soluble magnesium salt.
- the mouthwash according to the present invention comprises a pH value in the range of pH 5-8, such as in the range of pH 6-7.5, e.g. about pH 7.
- a preferred embodiment of the present invention relates to a pharmaceutical product for use in inhibition, reduction, treatment or prophylaxis of a gum disease or a disease related to the gum disease
- the pharmaceutical product comprises an oral care composition comprising at least one strontium salt, wherein the concentration of the strontium salt is in the range of 1-10% (w/w) of the pharmaceutical product.
- the pharmaceutical product comprises a moisture content above 20% (w/w), e.g. above 30% (w/w), such as above 40% (w/w), e.g. above 50% (w/w), such as above 60% (w/w), e.g. above 70% (w/w), such as above 75% (w/w), e.g. above 80% (w/w), such as above 85% (w/w) , e.g. above 90% (w/w), such as above 92% (w/w), e.g. in the range of 20-98% (w/w), such as in the range of 40- 95% (w/w), e.g. in the range of 60-92% (w/w), such as in the range of 75-90% (w/w), e.g. in the range of 80-85% (w/w).
- the pharmaceutical product may be an oral composition according to the present invention.
- the pharmaceutical product may be a mouthwash composition.
- the gum disease may be gingivitis and periodontitis in the mouth.
- Gingivitis and periodontitis are both types of gum disease, which are inflammation of the gums and tissues surrounding the teeth. Gingivitis may relate to the early stage of gum disease, and periodontitis may relate to the advanced stage of gum disease. Gingivitis may lead to bleeding gums whereas periodontitis may lead to tooth loss, ligament destruction, jawbone destruction and receding gums.
- the gum disease may include gum infection, in particular caused by bacterial infection of the gum and/or the disease resulting from a bacterial infection of the mouth.
- the bacterial infection of the mouth may relate to the action of one or more bacterial species present in the mouth that causing decay of gum and/or teeth.
- Gum diseases generally occurs due to bacterial infection in the mouth.
- Unhygienic mouth may permit bacterial to deposit and growth in voids in the gums and in the mouth causing inflammation.
- the bacteria may also release small amounts of toxins that may break down gum tissue and thereby pushing to the progress of infection.
- the bacterial growth results (in combination with saliva and food residues) in the formation of a sticky biofilm on the surface of the teeth, creating plague.
- plague formed along the gum-line can be one indication leading to the gum disease. If the plague may not be treated and removed, plague at or below the gumline hardens into tartar and becomes harder to treat.
- the pharmaceutical composition may be used for the treatment, reduction or the prophylaxis of bacterial infections in the mouth.
- gum diseases may also lead to one or more of other serious health problems.
- the one or more of other serious health problems may include diabetes, in particular Type-II diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; premature low-weight babies; bronchitis; pneumonia; emphysema or a combination hereof.
- the disease relating to the gum disease include diabetes, in particular Type-II diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; premature low-weight babies; lung infections, like bronchitis; pneumonia; or emphysema; or a combination hereof.
- the effect of the gum disease on the one or more of other serious health problems may arise from bacteria from the mouth which first attack the bones and gums in the mouth and then enter the blood stream small cracks in the gums whereby the bacteria or metabolites from the bacteria may cause the one or more of other serious health problems.
- the one or more of other serious health problems relates to diabetes, and in particular to Type-II diabetes. Studies have shown that when people suffering from type-II diabetes also are affected by periodontitis, the risk of early death may be significantly increasing, if not treated in time.
- the inventor of the present invention submits that the oral care composition according to the present invention, or the pharmaceutical product according to the present invention may be suitable for the treatment or alleviation of diabetes, in particular Type-II diabetes.
- treatment of periodontitis according to the present invention may significantly decrease the blood sugar level in patients with between 0.10-1.5%, such as between 0.20-1%, e.g. between 0.30-0.65%. It is expected that a reduction in blood sugar level of 0.2% may reduce mortality by about 10%.
- the treatment of periodontitis according to the present invention may significantly decrease the mortality rate of diabetes patients, in particular in Type II diabetes patients, by at least 10%, such as at least 20%, e.g. at least 30%, such as at least 40%, e.g. at least 50%.
- the present invention relates to a pharmaceutical product and/or an oral care composition for the prophylaxis and/or alleviation of diabetes, such as prophylaxis and/or alleviation of mortality of diabetes patients, in particular for Type-II diabetes.
- the one or more of other serious health problems may be Alzheimer disease. Studies have shown that bacteria may travel from the mouth to the brain and that the bacteria, and/or their metabolites degrades not only the gums, but also nerve cells in the brain, which may also be associated with the development of Alzheimer disease and related dementias, especially vascular dementia.
- the oral care composition and/or the pharmaceutical product according to the present invention may be used for the prophylactic treatment and/or avoid and/or postpone development of Alzheimer disease or related dementias.
- the present invention relates to a pharmaceutical product and/or an oral care composition for the prophylactic treatment and/or avoid and/or postpone development of Alzheimer disease or related dementias.
- the one or more of other serious health problems may be cardiovascular diseases.
- cardiovascular diseases cardiovascular diseases.
- the oral care composition and/or the pharmaceutical product according to the present invention may be used for reducing the risk (prophylaxis) of cardiovascular diseases, in particular stroke, heart attack, and/or heart failure.
- the treatment of periodontitis according to the present invention may significantly decrease the risk for cardiovascular diseases, in particular stroke, heart attack, and/or heart failure, compared to people having a healthy gum.
- the risk for cardiovascular diseases, in particular stroke, heart attack, and/or heart failure, compared to people having a healthy gum may be reduced to be below 45% higher than the risk of people having a healthy gum to develop cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; such as below 40% higher; e.g. below 35% higher; such as below 30% higher; e.g. below 25% higher, such as below 20% higher; e.g. below 15% higher; such as below 10% higher; e.g. in the range of 10-45% higher; such as in the range of 15-40% higher; e.g. in the range of 20- 35% higher; such as in the range of 25-30% higher.
- the present invention relates to a pharmaceutical product and/or an oral care composition for the prophylactic treatment (reducing the risk) of cardiovascular diseases, in particular stroke, heart attack, and/or heart failure.
- the inventor of the present invention believes that by controlling the development of gum diseases by administrating the oral care composition according to the present invention or the pharmaceutical product according to the present invention, it may be possible to treat, alleviate, reducing the risk or incidence of developing one or more of other serious health problems.
- Bacterial infections in the mouth may be the caused by oral bacteria which includes streptococci, lactobacilli, staphylococci, porphyromonas, and corynebacteria.
- the bacterial infection of the mouth and/or gum may be caused by Streptococcus mutans, Streptococcus pneumonia, Streptococcus aureus, Streptococcus pyogenes, Helicobactor pylori, Porphyromonas gingivalis or a combination hereof.
- a major group of oral bacteria may include Streptococcus mutans, Streptococcus pneumonia, Streptococcus aureus, Streptococcus pyogenes, Helicobactor pylori, and Porphyromonas gingivalis, which may be the cause of caries.
- Streptococcus mutans has strong effects in the oral cavity, e.g. by breaking down the enamel of teeth and causing tooth decay. If not treated in time, Streptococcus mutans may cause great pain in the teeth and jaw. Streptococcus mutans
- Staphylococcus aureus is an usual member of the microbiota of the body, frequently Staphylococcus aureus may be found in the upper respiratory tract and the mouth and may cause pain and development of diseases.
- Streptococcus pyogones may be found in the mouth and in the pharynx and may be one of the most common bacteria in laryngitis and otitis media.
- Helicobactor Pylori may cause infection in the gastrointestinal tract and may come from food and water (and thus into the mouth).
- Helicobactor Pylori may be linked to the development of diabetes and to elevated haemoglobin levels.
- Porphyromonas gingivalis may be the major microorganism involved in chronic periodontitis.
- the bacterial species in particular Streptococcus mutans (S. /nutans), may use dietary sugars to produce acid that results in demineralization associated with dental caries. S. mutans may also produce extracellular polysaccharides early in the process of biofilm formation, in effect forming a "glue" for the biofilm.
- the oral care composition according to the present invention comprising strontium salt and xylitol may be capable of strengthen the enamel of the teeth and even rebuilding the enamel of the teeth.
- the strengthening effect and/or the rebuilding of the enamel of the teeth may be observed after a period of 5 days or more, such as 1 week or more, e.g. 2 weeks or more, such as 3 week or more, e.g. 5 weeks or more, such as 8 week or more, e.g. 10 weeks or more, such as 12 week or more, e.g. 14 weeks or more.
- the oral care composition or the pharmaceutical product may be administered to a human.
- the human is above 12 years old, such as above 15 years old, e.g. above 16 years old, such as above 18 years old.
- the oral care composition or the pharmaceutical product may not comprise alcohol, such as ethanol.
- the oral care composition or the pharmaceutical product may by administered to human below the age of 18 years old, e.g. below 16 years old, such as below 15 years old, e.g. below 12 years old, such as below 10 years old.
- the oral care composition or the pharmaceutical product may not be administered to a human below 2 years old, such as below 4 years old, e.g. below 6 years old.
- the daily oral dosage regimen will generally be from about 0.001 to about 80 mg strontium salt/kg of total body weight, such as from about 0.01 to about 60 mg strontium salt/kg total body weight, e.g. from about 0.1-40 mg strontium salt/kg total body weight, such as from about 1 to about 30 mg strontium salt/kg total body weight, e.g. from about 3-20 mg strontium salt/kg total body weight, such as from about 5 to about 15 mg strontium salt/kg total body weight, e.g. from about 10-12 mg strontium salt/kg total body weight.
- One dosage may be administered one to two times daily.
- the dose administered should be an "effective amount" or an amount necessary to achieve the desired effect in a subject to be treated.
- the subject to be treated may be a human.
- 10-100 ml such as in the range of 25-75 ml of the oral care composition or the pharmaceutical composition according to the present invention is held in the mouth, swilled around the mouth, and/or gargled in the mouth for a period of 10-120 seconds, e.g. for a period of 20-60 seconds, such as in a period of 25- 45 seconds, e.g. for about 30 seconds.
- the procedure of holding, swilling, and/or gargling the oral care composition or the pharmaceutical composition according to the present invention in the mouth may be performed at least one time a day, preferably 1-2 times a day, more preferably two times a day.
- Example 1 Preparation of an oral care composition.
- An oral care composition was prepared including the following ingredients, which were mixed in 1 litre water (as carrier material) :
- Strontium chloride and Xylitol Strontium chloride and Xylitol.
- concentration of strontium chloride in the oral care composition was 3.5% (on a weight-by-weight basis - (w/w)) of the oral care composition and the concentration of xylitol was 3% (on a weight-by-weight basis - (w/w)).
- the strontium chloride and the xylitol were easily soluble in the carrier material (water).
- Example 2 The oral care composition according to the present invention was tested on inhibiting the growth of Streptococcus mutans
- the medium was inoculated with the Streptococcus mutans from the appropriate dilution to obtain a concentration of approximately 10 4 CFU/ml.
- step 9 was repeated for each dilution.
- step 9 was repeated for each dilution.
- step 9 was repeated for each dilution.
- the liquids were allowed diffusing into the agar at room temperature for 1 hour before incubation at appropriate temperature and oxygen conditions for about 18 hours.
- the inhibition zones were measured with a precision of 0.1 mm using a Kaefler zone measuring instrument.
- Example 1 the oral care composition prepared in Example 1 - Comprising 3.5% (w/w) strontium chloride (the strontium salt was 100% strontium chloride) and 3% (w/w) xylitol (providing sample (b));
- Table 1 The cell density of Streptococcus mutans on the plates are 2.0xl0 4 CFU/ml
- Example 2 demonstrates that a significant increase in the inhibition of the development and growth of Streptococcus mutans.
- Example 3 The oral care composition according to the present invention (prepared following the same procedure as described in Example 2) was tested for the effect on inhibiting growth of Streptococcus pneumonia
- Example 3 demonstrates that a significant increase in the inhibition of the development and growth of Streptococcus pneumonia.
- Example 4 The oral care composition according to the present invention (prepared following the same procedure as described in Example 2) was tested for the effect on inhibiting growth of Streptococcus aureus and Streptococcus pyogenes.
- Table 3 The results from testing the effect of the oral care compositions according to the present invention on Streptococcus aureus and Streptococcus pyogenes relative to a prior art composition are shown in table 3 below: Table 3: The cell density of Streptococcus aureus and Streptococcus pyogenes on the plates are 3.6xl0 4 CFU/ml
- Example 4 demonstrates a significant increase in the inhibition of the development and growth of Streptococcus aureus and Streptococcus pyogenes.
- Example 5 The oral care composition according to the present invention (prepared following the same procedure as described in Example 2) was tested for the effect on inhibiting growth of Helicobactor pylori
- Table 4 The cell density of Helicobactor pylori on the plates are 3.6xl0 4 CFU/ml
- Example 5 demonstrates that a significant increase in the inhibition of the development and growth of Helicobactor pylori.
- Example 6 Various concentrations of strontium in oral care compositions according to the present invention was tested for the effect on inhibiting growth of Streptococcus mutans.
- the oral care compositions were prepared including the following ingredients, which were mixed in 1 litre water (as carrier material) :
- Various concentrations of strontium chloride in the oral care composition were prepared having 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, and 3.5% (on a weight-by-weight basis - (w/w)) of the oral care composition and the concentration of xylitol was 3% (on a weight- by-weight basis - (w/w)).
- the strontium chloride and the xylitol were easily soluble in the carrier material (water).
- Example 6 demonstrates that a certain amount of strontium salt is necessary to promote inhibition of the development and growth of Streptococcus mutans and it is demonstrated that that increasing amount of strontium salt, in particular strontium chloride results in an increased inhibition of the development and growth of Streptococcus mutans.
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Abstract
The present invention relates to an oral care composition comprising a carrier material, at least one strontium salt, a sugar alcohol, wherein the composition comprises a moisture content above 15% (w/w) and in the range of 0.5-15% (w/w) of the at least one strontium salt.
Description
MOUTHWASH COMPOSITION COMPRISING ONE OR MORE STRONTIUM SALT
Technical field of the invention
The present invention relates to an oral care composition. In particular, the present invention relates to an oral care composition having an effect against oral diseases and diseases emerging from oral diseases.
Background of the invention
Biofilm is a structure scaffolded with extracellular polysaccharide substances (EPS), created by microorganisms, in which the microorganisms are embedded. Biofilm can be difficult to clean or remove, and dental plaque is a form of biofilm. Dental plaque biofilm is a slightly viscous liquid film, which forms on teeth between cleanings, e.g. by brushing.
The presence of plaque on teeth is undesirable, because the bacteria, such as Streptococcus mutans or Porphyromonas gingivalis, which grow in plaque biofilm, and are among the most potent bacteria responsible for oral diseases/gum diseases, such as caries and gingivitis.
Oral plaque is also believed to be associated with other diseases related to the gum disease such as diabetes, Alzheimer's Disease, and cardiovascular disease.
While many dentifrices claim reductions in plaque and gingivitis, most dentifrices do not effectively removal plaque from the mouth and from the teeth. Indeed, for such dentifrices, physical removal of plaque is believed to be mostly achieved by the toothbrush bristles themselves interacting with the tooth surface during the physical act of brushing.
This interaction may have implications since it may cause wear on the teeth enamel, difficulties in cleaning "hidden" cavities, damages to the oral mucosa, proper cleaning for the gumline etc.
In order to meet these difficulties a mouthwash may be provided.
Usually mouthwashes are antiseptic solutions intended to reduce the microbial load in the mouth, although other mouthwashes might be given for other reasons such as for their
analgesic, anti-inflammatory or anti-fungal action. Additionally, some rinses act as saliva substitutes to neutralize acid and keep the mouth moist in xerostomia (dry mouth).
However, the challenges with the mouthwashes presently available is that they are not sufficiently effective in removing plaque (oral plaque), it still leaves a high number of viable bacteria capable of causing oral diseases/gum diseases, such as caries and gingivitis.
Hence, there is a need for an improved oral care composition having strong antibacterial activity, which is effective and reliable in inhibiting and/or removing plaque form the mouth, gums and the teeth without the need for physical removal of germs, and/or plaque biofilm. In particular, it is desirable to provide an oral care composition having strong antibacterial activity with a reduced number side effects or even without any side effects would be advantageous and highly desirable.
Summary of the invention
Thus, an object of the present invention relates to an oral care composition having an effect against oral diseases and diseases emerging from oral diseases.
In particular, it is an object of the present invention to provide an oral care composition that solves the problems of the prior art with and having strong antibacterial activity, which is effective and reliable in inhibiting and/or removing plaque form the mouth, gums and the teeth without the need for physical removal of germs, and/or plaque biofilm and preferably without any side effects.
Thus, one aspect of the invention relates to an oral care composition comprising a carrier material, at least one strontium salt, a sugar alcohol, wherein the composition comprises a moisture content above 15% (w/w).
Another aspect of the present invention relates to an oral care composition comprising a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w/w).
An additional aspect of the present invention relates to a mouthwash comprising a carrier material and at least one strontium salt.
A further aspect of the present invention relates to a mouthwash comprising a carrier material, at least one strontium salt, and a sugar alcohol.
Yet an aspect of the present invention relates to a pharmaceutical product for use in inhibition, reduction, treatment or prophylaxis of a gum disease or a disease related to the gum disease, the pharmaceutical product comprises an oral care composition comprising at least one strontium salt, wherein the concentration of the strontium salt is in the range of 1-10% (w/w) of the pharmaceutical product.
Still another aspect of the present invention relates to a pharmaceutical product according to the present invention for the inhibition, reduction, treatment or prophylaxis of a disease relating to the gum disease include diabetes, in particular Type-II diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; premature low-weight babies; lung infections, like bronchitis; pneumonia; or emphysema; or a combination hereof.
Another aspect of the present invention relates to a pharmaceutical product according to the present invention for the inhibition, reduction, treatment or prophylaxis of Type-II diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; premature low-weight babies; lung infections, like bronchitis; pneumonia; or emphysema; or a combination hereof.
The present invention will now be described in more detail in the following.
Detailed description of the invention
Accordingly, the inventors of the present invention surprisingly found that an oral care composition, in particular a mouthwash, comprising a strontium salt was highly effective against the development of biofilm in the mouth and on the teeth, reducing the incidence and risk of plaque, oral diseases and gum diseases, such as caries, gingivitis or periodontitis and avoiding loss of teeth, ligament destruction, jawbone destruction and receding gums. The inventors of the present invention surprisingly found that the oral care composition according to the present invention may promote regeneration of ligaments, jawbone and gums which has suffered from oral diseases and gum diseases.
Thus, a preferred embodiment of the present invention relates to an oral care composition comprising a carrier material, at least one strontium salt, a sugar alcohol, wherein the composition comprises a moisture content above 15% (w/w).
A further preferred embodiment of the present invention relates to an oral care composition comprising a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w/w).
Preferably, the oral care composition according to the present invention comprising a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w/w), further comprises a sugar alcohol.
Sugar alcohols may be organic compounds, typically derived from sugars, containing one hydroxyl group (-OH) attached to each carbon atom in the molecule. They may traditionally be white, water-soluble solids and may occur naturally in nature or be produced industrially by hydrogenation of sugars. Since sugar alcohols contain multiple OH-groups, sugar alcohols may be classified as polyols.
Sugar alcohols are used widely in the food industry and pharma industry, e.g. as thickeners and/or sweeteners and are well known to the skilled person.
In an embodiment of the present invention the sugar alcohol may be xylitol.
The carrier material may be a material capable of dissolving and/or suspending the at least one strontium salt and the sugar alcohol. Preferably, the carrier material may be water.
Xylitol, is a five-carbon sugar polyol and may be used in the oral care composition as a non-fermentable agent that assist in regulating and restoring the pH balance in the mouth. The properly balanced pH creates an inhospitable environment for destructive bacteria that are responsible for plaque formation and gum diseases. Xylitol may also be responsible for reducing, or even reversing, dental caries.
In an embodiment of the present invention wherein the oral care composition comprises a moisture content above 20% (w/w), e.g. above 30% (w/w), such as above 40% (w/w), e.g. above 50% (w/w), such as above 60% (w/w), e.g. above 70% (w/w), such as above 75% (w/w), e.g. above 80% (w/w), such as above 85% (w/w) , e.g. above 90% (w/w), such as above 92% (w/w), e.g. in the range of 20-98% (w/w), such as in the range of 40- 95% (w/w), e.g. in the range of 60-92% (w/w), such as in the range of 75-90% (w/w), e.g. in the range of 80-85% (w/w).
Preferably, the content of a sugar alcohol, in particular xylitol, may be in the range of 0.05-20% (w/w), such as in the range of 0.1-15% (w/w), e.g. in the range of 0.5-10%
(w/w), such as in the range of 1-7.5% (w/w), e.g. in the range of 1.5-5% (w/w), such as in the range of 2-4.5% (w/w), e.g. in the range of 3-4% (w/w).
In an embodiment of the present invention the oral care composition further comprises a sweetener.
Preferably, the sweetener may be a compound different from the organic compound.
Preferably the sweetener may be a sugar compound or a sugar substitute. Preferably, the sweetener may be a sugar substitute. Preferably, the sugar substitute may be selected from aspartame, sucralose, neotame, acesulfame potassium, saccharin, advantame, stevia, or a combination hereof. Preferably, the sugar substitute may be stevia.
In an embodiment of the present the oral care composition further comprises a preservative agent and/or a flavouring agent.
Preferably, the flavouring agent may be selected from menthol, eucalyptol or thymol. Preferably, the flavouring agent may be mentha piperita oil, mentha spicata flower extract, or a combination hereof.
Even some of the other ingredients of the oral care composition may comprise a preservative activity of the oral care composition a preservative agent may be added to the oral care composition.
Addition of a preservative agent to the oral care composition may have the effect of preventing decomposition of the oral care composition, e.g. by microbial growth and/or by undesirable chemical changes.
In an embodiment of the present invention the preservative agent added to the oral care composition may be sodium benzoate, potassium sorbate, benzoic acid or a combination hereof.
Even the mentioned preservative agents may be the preferred preservative agents, the skilled person would know other relevant preservative agents that may be used in combination or alone in an oral care composition according to the present invention.
In an embodiment of the present invention the oral care composition comprises less than 10% (w/w) alcohol, such as less than 7.5% (w/w), e.g. less than 5% (w/w), such as less than 2.5% (w/w), e.g. less than 1% (w/w). Preferably, the oral care composition according to the present invention comprises no alcohol.
The alcohol according to the present invention may preferably be ethanol.
In an embodiment of the present invention the oral care composition further comprises one or more fluoride compounds.
Preferably, the at least one strontium salt may include at least one water soluble strontium salt. Even more preferably, the at least one water soluble strontium salt may be strontium chloride.
The amount of strontium obtained from a specific amount of strontium salt may depend on the molecular weight of the compound, relative to the number of strontium molecules therein, thus a salt with low molecular weight per strontium molecule maybe preferred.
This may be expressed as the effective ratio (ER) of the salt. The effective ratio (ER) may be defined as, ER = (strontium (mg))/(strontium salt (mg))
The higher effective ratio (ER) the smaller amount of the salt is required for obtaining the desired effect. As a relatively large amount of the active ingredient is required a strontium salt with a high effective ratio is preferred.
In an embodiment of the present invention, it may be preferred that the ER of the strontium salt present in the oral care composition may be more than 0.40, or more than 0.45 or 0.50, such as more than 0.53 such as more than 0.55, such as in the range of 0.40-0.70, e.g. in the range of 0.45-0.65, such as in the range of 0.50-0.60, e.g. in the range of 0.55-0.59.
In an embodiment of the present invention the at least one strontium salt comprises at least one water-soluble strontium salt.
Preferably, the at least one water-soluble strontium salt present in the composition according to the present invention has a solubility in water at room temperature of at least 25 g/L, such as at least 50 g/L, e.g. at least 75 g/L, such as at least 100 g/L, e.g. at least 150 g/L, such as at least 200 g/L, e.g. at least 250 g/L, such as at least 300 g/L, e.g. at least 350 g/L, such as at least 400 g/L, e.g. at least 450 g/L, such as at least 500 g/L, e.g. at least 525 g/L, such as in the range of 25-750 g/L, e.g. in the range of 100-700 g/L, such as in the range of 200-650 g/L, e.g. in the range of 300-625 g/L, such as in the range of 400-600 g/L, e.g. in the range of 500-550 g/L.
Preferably, the one or more water soluble strontium salt may be selected from the group consisting of strontium chloride, strontium bromide, strontium nitrate, strontium hydroxide, strontium oxide, strontium acetate, strontium glutamate, strontium aspartate, strontium malonate, strontium pyruvate, strontium alpha-ketoglutarate, strontium maleate, strontium succinate, strontium fumarate, strontium ascorbate, strontium tartate, strontium glutarate, strontium methanesulfonate, strontium benzenesulfonate, strontium sulphide, and a combination hereof. More preferably, the at least one water soluble strontium salt may be strontium chloride.
Thus, preferably the at least one strontium salt may be strontium chloride.
The oral care composition according to the present invention wherein the strontium chloride may be selected from the group consisting of SrCI2, SrCI2 -2-H20, SrCI2 -6-H20, or a combination hereof.
Preferably, the at least one strontium salt, in particular strontium chloride, may be anhydrous, specifically strontium chloride may be strontium chloride anhydrous or strontium chloride hexahydrate.
In an embodiment of the present invention the at least one strontium salt includes at least one water soluble strontium salt, preferably, the at least one water soluble strontium salt is strontium chloride.
The content of the at least one strontium salt in the oral care composition according to the present invention may be dependent on e.g. the formulation of the oral care composition, the condition of the mouth of the subject to be treated, the condition of the subject to be treated, and/or the age of the subject to be treated, in particular the age of the subject to be treated.
Preferably, the oral care composition comprises in the range of 0.5-15% (w/w) of the at least one strontium salt (in particular the strontium salt may be strontium chloride), such as in the range of 0.6-14% (w/w) of the at least one strontium salt, e.g. in the range of 0.7-13% (w/w) of the at least one strontium salt, such as in the range of 0.8-12% (w/w) of the at least one strontium salt, e.g. in the range of 0.9-11% (w/w) of the at least one strontium salt, such as in the range of 1.0-10% (w/w) of the at least one strontium salt, e.g. in the range of 1.25-9% (w/w) of the at least one strontium salt, such as in the range of 1.5-8% (w/w) of the at least one strontium salt, e.g. in the range of 1.75-7% (w/w) of the at least one strontium salt, such as in the range of 2-6% (w/w) of the at least one
strontium salt, e.g. in the range of 2.5-5% (w/w) of the at least one strontium salt, such as in the range of 3-4% (w/w) of the at least one strontium salt, e.g. about 3.5% (w/w).
The oral care composition may preferably comprise in the range of 0.25-8% (w/w) of strontium ions in the oral care composition, such as in the range of 0.5-5% (w/w), e.g. in the range of 1.0-4% (w/w), such as in the range of 1.5-3% (w/w), e.g. in the range of 1.75-2.5% (w/w), such as about 2.0% (w/w).
In an embodiment of the present invention the at least one strontium salt or the oral care composition may comprise a water insoluble strontium salt or a combination of a water- soluble strontium salt and a water insoluble strontium salt.
Preferably, the water insoluble strontium salt may be selected from the group consisting of strontium carbonate and strontium sulphate. Even more preferably, the water insoluble strontium salt may be strontium carbonate.
In one embodiment of the present invention the oral care composition comprise at least 45% (w/w) strontium in the form of a water-soluble strontium salt, such as at least 50% (w/w) strontium in the form of a water-soluble strontium salt, e.g. at least 60% (w/w) strontium in the form of a water-soluble strontium salt, such as at least 70% (w/w) strontium in the form of a water-soluble strontium salt, e.g. at least 80% (w/w) strontium in the form of a water-soluble strontium salt, such as at least 90% (w/w) strontium in the form of a water-soluble strontium salt, e.g. at least 95% (w/w) strontium in the form of a water-soluble strontium salt, such as at least 98% (w/w) strontium in the form of a water- soluble strontium salt, e.g. at least 99% (w/w) strontium in the form of a water-soluble strontium salt, such as about 100% (w/w) strontium in the form of a water-soluble strontium salt, e.g. in the range of 45-100 % of strontium in the form of a water-soluble strontium salt, such as in the range of 60-99 % strontium in the form of a water-soluble strontium salt, e.g. in the range of 75-98 % strontium in the form of a water-soluble strontium salt, such as in the range of 85-95 % strontium in the form of a water soluble strontium salt.
In an embodiment of the present invention the oral care composition may be a mouthwash composition.
Preferably, the oral care composition, or the mouthwash, comprises
A carrier material, preferably water
An active ingredient, e.g. an API, provided by at least one strontium salt, preferably strontium chloride;
A pH regulator/sugar substitute, preferably xylitol;
A sweetener, preferably stevia;
A preservative, preferably sodium benzoate; and Flavouring/aroma agent, preferably Mentha Piperita Oil and/or Mentha Spicata flower Extract.
Preferably the concentration of strontium chloride in the oral care composition was as described above, preferably about 3.5% (on a weight-by-weight basis - (w/w)) of the oral care composition and the concentration of xylitol was as described above, preferably, about 3% (on a weight-by-weight basis - (w/w)).
In an embodiment of the present invention the mouthwash according to the present invention may be provided as a gel or as a liquid.
The mouthwash according to the present invention may be formulated into a gel.
Preferably, the gel may be applied to the teeth and/or to the gums (the soft tissue lining of the mouth which also surrounds the teeth and provide a seal around them). The gel may be rubbed onto the teeth and/or into the gums.
The mouthwash according to the present invention may be a liquid which is held in the mouth passively or swilled around the mouth by contraction of the perioral muscles and/or movement of the head, and may be gargled, where the head is tilted back and the liquid bubbled at the back of the mouth.
Preferably, the oral care composition according to the present invention is not a toothpaste. Some of the disadvantages of a toothpaste may be that:
Toothpaste may apply wear on the tooth enamel and/or on the gum, whereas the oral care composition or the mouthwash according to the present invention are much gentler;
Toothpaste may not come into all the difficult places and voids of the mouth, e.g. along the gumline (the gumline may be the line along the top of the gums, where the gums meet the surface of the teeth), whereas the mouthwash gets better distributed around the surfaces of the mouth;
Whereas toothpaste is mainly focussed on cleaning the teeth and removing plaque on the surface of the teeth, the oral care composition or the mouthwash according to the present invention also clean the gums and the oral mucosa,, in addition to
cleaning the teeth;
For the same reason as above, re. plaque, the oral care composition or the mouthwash according to the present invention also show improved activity against development and treatment of canker sores and other kind of ulcer in the mouth.
Further differences between using the oral care composition or the mouthwash according to the present invention and not toothpaste may be that mouthwash may give a good breath that is not possible with a toothpaste.
The inventors of the present invention found that it was possible to stabilise the mouthwash without addition of magnesium salt. Since magnesium is consumed from many different food and beverages products it is undesirably, to add magnesium salt to the mouthwash according to the present invention, as too high intake of magnesium can lead to gastrointestinal problems, such as diarrhoea, nausea, or cramping.
Thus, in an embodiment of the present invention the mouthwash according to the present invention does not comprise a magnesium salt, such as a water-soluble magnesium salt.
Preferably, the mouthwash according to the present invention comprises a pH value in the range of pH 5-8, such as in the range of pH 6-7.5, e.g. about pH 7.
A preferred embodiment of the present invention relates to a pharmaceutical product for use in inhibition, reduction, treatment or prophylaxis of a gum disease or a disease related to the gum disease, the pharmaceutical product comprises an oral care composition comprising at least one strontium salt, wherein the concentration of the strontium salt is in the range of 1-10% (w/w) of the pharmaceutical product.
In an embodiment of the present invention, the pharmaceutical product comprises a moisture content above 20% (w/w), e.g. above 30% (w/w), such as above 40% (w/w), e.g. above 50% (w/w), such as above 60% (w/w), e.g. above 70% (w/w), such as above 75% (w/w), e.g. above 80% (w/w), such as above 85% (w/w) , e.g. above 90% (w/w), such as above 92% (w/w), e.g. in the range of 20-98% (w/w), such as in the range of 40- 95% (w/w), e.g. in the range of 60-92% (w/w), such as in the range of 75-90% (w/w), e.g. in the range of 80-85% (w/w).
Preferably, the pharmaceutical product may be an oral composition according to the present invention.
Preferably, the pharmaceutical product may be a mouthwash composition.
In an embodiment of the present invention the gum disease may be gingivitis and periodontitis in the mouth.
Gingivitis and periodontitis are both types of gum disease, which are inflammation of the gums and tissues surrounding the teeth. Gingivitis may relate to the early stage of gum disease, and periodontitis may relate to the advanced stage of gum disease. Gingivitis may lead to bleeding gums whereas periodontitis may lead to tooth loss, ligament destruction, jawbone destruction and receding gums.
The gum disease may include gum infection, in particular caused by bacterial infection of the gum and/or the disease resulting from a bacterial infection of the mouth. In an embodiment of the present invention the bacterial infection of the mouth may relate to the action of one or more bacterial species present in the mouth that causing decay of gum and/or teeth.
Gum diseases, generally occurs due to bacterial infection in the mouth.
Unhygienic mouth may permit bacterial to deposit and growth in voids in the gums and in the mouth causing inflammation. The bacteria may also release small amounts of toxins that may break down gum tissue and thereby pushing to the progress of infection. The bacterial growth results (in combination with saliva and food residues) in the formation of a sticky biofilm on the surface of the teeth, creating plague.
If the plague is not removed, plague formed along the gum-line can be one indication leading to the gum disease. If the plague may not be treated and removed, plague at or below the gumline hardens into tartar and becomes harder to treat.
In an embodiment of the present invention the pharmaceutical composition may be used for the treatment, reduction or the prophylaxis of bacterial infections in the mouth.
In addition to bleeding gums, tooth loss, ligament destruction, jawbone destruction and receding gums that may be the consequence of a gum disease, gum diseases may also lead to one or more of other serious health problems.
In an embodiment of the present invention the one or more of other serious health problems may include diabetes, in particular Type-II diabetes; Alzheimer disease;
cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; premature low-weight babies; bronchitis; pneumonia; emphysema or a combination hereof.
In yet an embodiment of the present invention the disease relating to the gum disease include diabetes, in particular Type-II diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; premature low-weight babies; lung infections, like bronchitis; pneumonia; or emphysema; or a combination hereof.
The terms "one or more of other serious health problems" and "disease relating to the gum disease" may be used interchangeably and relates both to indications and consequences and diseases resulting from the gum disease.
The effect of the gum disease on the one or more of other serious health problems may arise from bacteria from the mouth which first attack the bones and gums in the mouth and then enter the blood stream small cracks in the gums whereby the bacteria or metabolites from the bacteria may cause the one or more of other serious health problems.
In an embodiment of the present invention the one or more of other serious health problems relates to diabetes, and in particular to Type-II diabetes. Studies have shown that when people suffering from type-II diabetes also are affected by periodontitis, the risk of early death may be significantly increasing, if not treated in time.
Based on this, the inventor of the present invention submits that the oral care composition according to the present invention, or the pharmaceutical product according to the present invention may be suitable for the treatment or alleviation of diabetes, in particular Type-II diabetes. In an embodiment of the present invention treatment of periodontitis according to the present invention may significantly decrease the blood sugar level in patients with between 0.10-1.5%, such as between 0.20-1%, e.g. between 0.30-0.65%. It is expected that a reduction in blood sugar level of 0.2% may reduce mortality by about 10%. Thus, in an embodiment of the present invention the treatment of periodontitis according to the present invention may significantly decrease the mortality rate of diabetes patients, in particular in Type II diabetes patients, by at least 10%, such as at least 20%, e.g. at least 30%, such as at least 40%, e.g. at least 50%.
Thus, the present invention relates to a pharmaceutical product and/or an oral care composition for the prophylaxis and/or alleviation of diabetes, such as prophylaxis and/or alleviation of mortality of diabetes patients, in particular for Type-II diabetes.
In an embodiment of the present invention the one or more of other serious health problems may be Alzheimer disease. Studies have shown that bacteria may travel from the mouth to the brain and that the bacteria, and/or their metabolites degrades not only the gums, but also nerve cells in the brain, which may also be associated with the development of Alzheimer disease and related dementias, especially vascular dementia.
Thus, based on this the inventor of the present invention submit that the oral care composition and/or the pharmaceutical product according to the present invention may be used for the prophylactic treatment and/or avoid and/or postpone development of Alzheimer disease or related dementias.
Thus, the present invention relates to a pharmaceutical product and/or an oral care composition for the prophylactic treatment and/or avoid and/or postpone development of Alzheimer disease or related dementias.
In an embodiment of the present invention the one or more of other serious health problems may be cardiovascular diseases. Studies have shown that the more severe the gum disease the higher the risk for a cardiovascular disease. Again, the degradation or damage of the gums may allow bacteria and metabolites to enter the blood stream an causing dangerous and harmful changes for the blood vessels. Up to about 49% of people suffering from periodontitis showed increased risk for cardiovascular diseases, in particular stroke, heart attack, and/or heart failure, compared to people having a healthy gum.
Thus, based on this the inventor of the present invention submit that the oral care composition and/or the pharmaceutical product according to the present invention may be used for reducing the risk (prophylaxis) of cardiovascular diseases, in particular stroke, heart attack, and/or heart failure.
In an embodiment of the present invention the treatment of periodontitis according to the present invention may significantly decrease the risk for cardiovascular diseases, in particular stroke, heart attack, and/or heart failure, compared to people having a healthy gum. Preferably, the risk for cardiovascular diseases, in particular stroke, heart attack, and/or heart failure, compared to people having a healthy gum may be reduced to be below 45% higher than the risk of people having a healthy gum to develop cardiovascular diseases, in particular stroke, heart attack, and/or heart failure; such as below 40% higher; e.g. below 35% higher; such as below 30% higher; e.g. below 25% higher, such as below 20% higher; e.g. below 15% higher; such as below 10% higher; e.g. in the
range of 10-45% higher; such as in the range of 15-40% higher; e.g. in the range of 20- 35% higher; such as in the range of 25-30% higher.
Thus, the present invention relates to a pharmaceutical product and/or an oral care composition for the prophylactic treatment (reducing the risk) of cardiovascular diseases, in particular stroke, heart attack, and/or heart failure.
The inventor of the present invention believes that by controlling the development of gum diseases by administrating the oral care composition according to the present invention or the pharmaceutical product according to the present invention, it may be possible to treat, alleviate, reducing the risk or incidence of developing one or more of other serious health problems.
Bacterial infections in the mouth may be the caused by oral bacteria which includes streptococci, lactobacilli, staphylococci, porphyromonas, and corynebacteria.
In an embodiment of the present invention the bacterial infection of the mouth and/or gum may be caused by Streptococcus mutans, Streptococcus pneumonia, Streptococcus aureus, Streptococcus pyogenes, Helicobactor pylori, Porphyromonas gingivalis or a combination hereof.
A major group of oral bacteria may include Streptococcus mutans, Streptococcus pneumonia, Streptococcus aureus, Streptococcus pyogenes, Helicobactor pylori, and Porphyromonas gingivalis, which may be the cause of caries.
Streptococcus mutans has strong effects in the oral cavity, e.g. by breaking down the enamel of teeth and causing tooth decay. If not treated in time, Streptococcus mutans may cause great pain in the teeth and jaw. Streptococcus mutans
Staphylococcus aureus is an usual member of the microbiota of the body, frequently Staphylococcus aureus may be found in the upper respiratory tract and the mouth and may cause pain and development of diseases.
Streptococcus pyogones may be found in the mouth and in the pharynx and may be one of the most common bacteria in laryngitis and otitis media. When intubating heart patients before surgery, through the mouth and pharynx, there may be a high risk of bacteria from the mouth and the pharynx being transported into the lungs. Therefore, there is an interest in removing these strains from the patient before intubating or the tubes may be treated with a composition according to the present invention before use.
Helicobactor Pylori may cause infection in the gastrointestinal tract and may come from food and water (and thus into the mouth). Helicobactor Pylori may be linked to the development of diabetes and to elevated haemoglobin levels.
Porphyromonas gingivalis may be the major microorganism involved in chronic periodontitis.
The bacterial species, in particular Streptococcus mutans (S. /nutans), may use dietary sugars to produce acid that results in demineralization associated with dental caries. S. mutans may also produce extracellular polysaccharides early in the process of biofilm formation, in effect forming a "glue" for the biofilm.
The inventors of the present invention found that the oral care composition according to the present invention comprising strontium salt and xylitol may be capable of strengthen the enamel of the teeth and even rebuilding the enamel of the teeth. The strengthening effect and/or the rebuilding of the enamel of the teeth may be observed after a period of 5 days or more, such as 1 week or more, e.g. 2 weeks or more, such as 3 week or more, e.g. 5 weeks or more, such as 8 week or more, e.g. 10 weeks or more, such as 12 week or more, e.g. 14 weeks or more.
The oral care composition or the pharmaceutical product may be administered to a human. Preferably, the human is above 12 years old, such as above 15 years old, e.g. above 16 years old, such as above 18 years old.
Preferably, the oral care composition or the pharmaceutical product may not comprise alcohol, such as ethanol. In the event the oral care composition or the pharmaceutical product does not comprise ethanol the oral care composition or the pharmaceutical product may by administered to human below the age of 18 years old, e.g. below 16 years old, such as below 15 years old, e.g. below 12 years old, such as below 10 years old. In an embodiment of the present invention the oral care composition or the pharmaceutical product may not be administered to a human below 2 years old, such as below 4 years old, e.g. below 6 years old.
The daily oral dosage regimen will generally be from about 0.001 to about 80 mg strontium salt/kg of total body weight, such as from about 0.01 to about 60 mg strontium salt/kg total body weight, e.g. from about 0.1-40 mg strontium salt/kg total body weight, such as from about 1 to about 30 mg strontium salt/kg total body weight, e.g. from about 3-20 mg strontium salt/kg total body weight, such as from about 5 to about 15 mg
strontium salt/kg total body weight, e.g. from about 10-12 mg strontium salt/kg total body weight. One dosage may be administered one to two times daily.
The dose administered should be an "effective amount" or an amount necessary to achieve the desired effect in a subject to be treated.
Preferably, the subject to be treated may be a human.
In an embodiment of the present invention 10-100 ml, such as in the range of 25-75 ml of the oral care composition or the pharmaceutical composition according to the present invention is held in the mouth, swilled around the mouth, and/or gargled in the mouth for a period of 10-120 seconds, e.g. for a period of 20-60 seconds, such as in a period of 25- 45 seconds, e.g. for about 30 seconds.
Preferably, the procedure of holding, swilling, and/or gargling the oral care composition or the pharmaceutical composition according to the present invention in the mouth may be performed at least one time a day, preferably 1-2 times a day, more preferably two times a day.
It should be noted that embodiments and features described in the context of one of the aspects of the present invention also apply to the other embodiments and aspects of the invention.
The invention will now be described in further details in the following non-limiting examples.
Examples
Example 1 - Preparation of an oral care composition.
An oral care composition was prepared including the following ingredients, which were mixed in 1 litre water (as carrier material) :
Strontium chloride and Xylitol.
The concentration of strontium chloride in the oral care composition was 3.5% (on a weight-by-weight basis - (w/w)) of the oral care composition and the concentration of xylitol was 3% (on a weight-by-weight basis - (w/w)).
The strontium chloride and the xylitol were easily soluble in the carrier material (water).
Example 2 - The oral care composition according to the present invention was tested on inhibiting the growth of Streptococcus mutans
The effect was evaluated using a zone of inhibition test according to the following procedure:
1) a suspension comprising Streptococcus mutans in 0.9% NaCI. The cell concentration at OD550 is about lx lO8 CFU/ml.
2) the suspension is diluted to dilution IO-8 and 1 ml is poured into a plate comprising a growth medium (from each dilution 10-4 - IO-8).
3) the plates are incubated at 37°C for 24 hours.
4) the colonies are counted and the CFU/ml is calculated.
5) the medium was inoculated with the Streptococcus mutans from the appropriate dilution to obtain a concentration of approximately 104 CFU/ml.
6) approximately 25 ml of the inoculated medium was allowed to solidify in Petri dishes of 9 cm in diameter.
7) 4 wells per dish were prepared in the solidified medium.
8) a prior art strontium tablet comprising 360 mg strontium carbonate per gram tablet (a content in the tablet of 36% (w/w)) was ground aseptically and diluted in 0.9% NaCI 1 : 1, 1 :5 and 1 : 10 using Maximum Recovery Diluent pH 7 (providing sample (a)).
9) 0.2 g of the sample (tested in triplets and a blind control of Maximum Recovery Diluent) were transferred to the wells of the medium in a dish.
10) step 9 was repeated for each dilution.
11) the liquids were allowed diffusing into the agar at room temperature for 1 hour before incubation at appropriate temperature and oxygen conditions for about 18 hours.
12) the inhibition zones were measured with a precision of 0.1 mm using a Kaefler zone measuring instrument.
Similar test was performed using:
- the oral care composition prepared in Example 1 - Comprising 3.5% (w/w) strontium chloride (the strontium salt was 100% strontium chloride) and 3% (w/w) xylitol (providing sample (b));
- 2.8% (w/w) strontium chloride and 0.7% strontium carbonate (the strontium salt was 80% strontium chloride and 20% strontium carbonate) and 3% (w/w) xylitol (providing sample (c)), and
- 2.1% (w/w) strontium chloride and 1.4% strontium carbonate (the strontium salt was 60% strontium chloride and 40% strontium carbonate) and 3% (w/w) xylitol (providing sample (d)).
Results
The results from testing the effect of the oral care compositions according to the present invention on Streptococcus mutans relative to a prior art composition are shown in table 1 below:
Example 2 demonstrates that a significant increase in the inhibition of the development and growth of Streptococcus mutans.
Example 3 - The oral care composition according to the present invention (prepared following the same procedure as described in Example 2) was tested for the effect on inhibiting growth of Streptococcus pneumonia
The effect was evaluated using a zone of inhibition test according to the procedure described in Example 2.
Results
The results from testing the effect of the oral care compositions according to the present invention on Streptococcus pneumonia relative to a prior art composition are shown in table 2 below:
Example 3 demonstrates that a significant increase in the inhibition of the development and growth of Streptococcus pneumonia.
Example 4 - The oral care composition according to the present invention (prepared following the same procedure as described in Example 2) was tested for the effect on inhibiting growth of Streptococcus aureus and Streptococcus pyogenes.
The effect was evaluated using a zone of inhibition test according to the procedure described in Example 2.
Results
The results from testing the effect of the oral care compositions according to the present invention on Streptococcus aureus and Streptococcus pyogenes relative to a prior art composition are shown in table 3 below:
Table 3: The cell density of Streptococcus aureus and Streptococcus pyogenes on the plates are 3.6xl04 CFU/ml
Example 4 demonstrates a significant increase in the inhibition of the development and growth of Streptococcus aureus and Streptococcus pyogenes.
Example 5 - The oral care composition according to the present invention (prepared following the same procedure as described in Example 2) was tested for the effect on inhibiting growth of Helicobactor pylori
The effect was evaluated using a zone of inhibition test according to the procedure described in Example 2.
Results
The results from testing the effect of the oral care compositions according to the present invention on Helicobactor pylori relative to a prior art composition are shown in table 4 below:
Example 5 demonstrates that a significant increase in the inhibition of the development and growth of Helicobactor pylori.
Example 6 - Various concentrations of strontium in oral care compositions according to the present invention was tested for the effect on inhibiting growth of Streptococcus mutans.
The oral care compositions were prepared including the following ingredients, which were mixed in 1 litre water (as carrier material) :
Strontium chloride and
Xylitol.
Various concentrations of strontium chloride in the oral care composition were prepared having 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, and 3.5% (on a weight-by-weight basis - (w/w)) of the oral care composition and the concentration of xylitol was 3% (on a weight- by-weight basis - (w/w)).
The strontium chloride and the xylitol were easily soluble in the carrier material (water).
The effect was evaluated using a zone of inhibition test according to the procedure described in Example 2.
Results
The results from testing the effect of the oral care compositions according to the present invention on Streptococcus mutans relative to a prior art composition are shown in table 5 below:
Example 6 demonstrates that a certain amount of strontium salt is necessary to promote inhibition of the development and growth of Streptococcus mutans and it is demonstrated
that that increasing amount of strontium salt, in particular strontium chloride results in an increased inhibition of the development and growth of Streptococcus mutans.
Claims
1. An oral care composition comprising a carrier material, at least one strontium salt, a sugar alcohol, wherein the composition comprises a moisture content above 15% (w/w) and in the range of 0.5-15% (w/w) of the at least one strontium salt.
2. An oral care composition comprising a carrier material, at least one strontium salt, wherein the composition comprises a moisture content above 50% (w/w).
3. The oral care composition according to anyone of claims 1-2, wherein the oral care composition comprises a sugar alcohol.
4. The oral care composition according to anyone of claims 1 or 3, wherein the sugar alcohol is xylitol.
5. The oral care composition according to anyone of the preceding claims, wherein the composition further comprises a sweetener, a preservative agent and/or a flavouring agent.
6. The oral care composition according to anyone of the preceding claims, wherein the oral care composition further comprises one or more fluoride compounds.
7. The oral care composition according to anyone of the preceding claims, wherein the at least one strontium salt includes at least one water soluble strontium salt, preferably, the at least one water soluble strontium salt is strontium chloride.
8. A pharmaceutical product for use in inhibition, reduction, treatment or prophylaxis of a gum disease or a disease related to the gum disease, the pharmaceutical product comprises an oral care composition comprising at least one strontium salt, wherein the concentration of the strontium salt is in the range of 1-10% (w/w) of the pharmaceutical product.
9. The pharmaceutical product according to claim 8, wherein the pharmaceutical composition is used for the treatment, reduction or the prophylaxis of bacterial infections in the mouth.
10. A pharmaceutical product according to anyone of claims 8 or 9, wherein disease relating to the gum disease include diabetes, in particular Type-II diabetes; Alzheimer disease; cardiovascular diseases, in particular stroke, heart attack, and/or heart failure;
premature low-weight babies; lung infections, like bronchitis; pneumonia; or emphysema; or a combination hereof.
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WO1997004742A1 (en) * | 1995-07-29 | 1997-02-13 | The Procter & Gamble Company | Oral compositions |
WO2009098531A1 (en) * | 2008-02-07 | 2009-08-13 | Italmed S.R.L. | Dental composition for desensitization and disinfection of exposed dentin |
WO2012023936A1 (en) * | 2010-08-18 | 2012-02-23 | Colgate-Palmolive Company | Oral care product and methods of use and manufacture thereof |
WO2013144247A1 (en) * | 2012-03-28 | 2013-10-03 | Arla Foods Amba | Nanoparticle aggregates containing osteopontin and calcium- and/or strontium-containing particles |
US20190099338A1 (en) * | 2017-09-29 | 2019-04-04 | 3M Innovative Properties Company | Aqueous oral care fluoride treatment compositions, and methods |
CN111437216A (en) * | 2020-04-22 | 2020-07-24 | 苏州清馨健康科技有限公司 | Anti-allergy toothpaste |
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2023
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WO1997004742A1 (en) * | 1995-07-29 | 1997-02-13 | The Procter & Gamble Company | Oral compositions |
WO2009098531A1 (en) * | 2008-02-07 | 2009-08-13 | Italmed S.R.L. | Dental composition for desensitization and disinfection of exposed dentin |
WO2012023936A1 (en) * | 2010-08-18 | 2012-02-23 | Colgate-Palmolive Company | Oral care product and methods of use and manufacture thereof |
WO2013144247A1 (en) * | 2012-03-28 | 2013-10-03 | Arla Foods Amba | Nanoparticle aggregates containing osteopontin and calcium- and/or strontium-containing particles |
US20190099338A1 (en) * | 2017-09-29 | 2019-04-04 | 3M Innovative Properties Company | Aqueous oral care fluoride treatment compositions, and methods |
CN111437216A (en) * | 2020-04-22 | 2020-07-24 | 苏州清馨健康科技有限公司 | Anti-allergy toothpaste |
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