WO2023041357A1 - A plant extract and its use - Google Patents
A plant extract and its use Download PDFInfo
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- WO2023041357A1 WO2023041357A1 PCT/EP2022/074548 EP2022074548W WO2023041357A1 WO 2023041357 A1 WO2023041357 A1 WO 2023041357A1 EP 2022074548 W EP2022074548 W EP 2022074548W WO 2023041357 A1 WO2023041357 A1 WO 2023041357A1
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- extract
- plant
- solvent
- composition
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- 230000036347 tooth sensitivity Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 235000019801 trisodium phosphate Nutrition 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
-
- 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
-
- 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
-
- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
Definitions
- the present invention relates to an extract of a plant of the species Rubus fruticosus or of any part of this plant. Furthermore, it relates to a composition comprising this extract and at least one orally acceptable carrier and optionally at least one orally acceptable ingredient. Furthermore, it relates to this extract or this composition for use in a method for treatment of the human or animal body by therapy, including prophylaxis. Furthermore, it relates to this extract or this composition for use in a method for treating or preventing caries of a human or of an animal.
- Another embodiment of the present invention is the extract according to the present invention, wherein the extraction is carried out at a temperature of 15 °C to 115 °C.
- Another embodiment of the present invention is the extract according to the present invention, wherein the extract is an extract of a part of the plant and wherein this part is selected from the group consisting of a fruit and a leave.
- Another subject of the present invention is the extract according to the present invention or the composition according to the present invention for use in a method for preventing or suppressing dental plaque formation in a human or in an animal.
- the present invention provides a method of providing oral care benefits in a living animal, including a human, by means of inhibiting glucansucrase, inhibition of the adhesion of oral pathogens, comprising the step of administering to the oral cavity of a living animal, including a human, an amount of a water soluble and/or organic solvent soluble and/or liquid carbon dioxide soluble extract preparation which is effective to provide an oral care benefit.
- One embodiment of the present invention is a process for manufacturing an extract preparation comprising a. contacting the plant material with water-organic mixtures: i. wherein a water-miscible organic solvent is selected from C1-C4 alcohols, acetone and/or their combination, ii. wherein the pH of the water and/or water/organic solvent mixture is kept in the range 1-14 by means of appropriate base, acid, salt or buffer, iii. wherein the ratio of water to organic solvents is in a range from 100:0 to 1 :99, iv. wherein the extraction is carried out at temperatures in a range from 0°C to at boiling point; v.
- a water-miscible organic solvent is selected from C1-C4 alcohols, acetone and/or their combination
- the pH of the water and/or water/organic solvent mixture is kept in the range 1-14 by means of appropriate base, acid, salt or buffer, iii. wherein the ratio of water to organic solvents is in a range from
- the extract according to the present invention preferably is a water soluble and/or organic solvent and/or liquid carbon dioxide soluble extract with glucansucrase inhibition activity derived from water soluble and/or organic solvent soluble and/or liquid carbon dioxide soluble components of plant material and fractions of this extract.
- the extract according to the present invention can be used as such according to the present invention. Furthermore, fractions and compounds from the extracts possessing beneficial oral care properties, remineralization properties, anti-adhesion activity including inhibitory activity towards to glucansucrase can be used.
- One embodiment of the present invention is a method of providing oral care benefits in a living animal, including a human, by means of inhibiting glucansucrase, inhibiting adhesion of oral pathogens, comprising the step of administering to the oral cavity of a living animal, including a human, an amount of an extract according to the present invention which is effective to provide an oral care benefit.
- the extract preparation can be selected for its inhibitory activity towards glucansucrase.
- the beneficial effect of the extract preparation may be further enhanced by incorporation of fractions, and compounds of the extract possessing beneficial oral care properties including inhibitory activity towards to glucansucrase, anti-microbial activity against oral pathogens, remineralization properties, anti-adhesion activity, inhibitory activity towards cyclooxygenases and lipoxygenases, breath freshening properties, anti-oxidant properties, and/or antiinflammatory properties.
- beneficial oral care properties including inhibitory activity towards to glucansucrase, anti-microbial activity against oral pathogens, remineralization properties, anti-adhesion activity, inhibitory activity towards cyclooxygenases and lipoxygenases, breath freshening properties, anti-oxidant properties, and/or antiinflammatory properties.
- the pH of the water can be kept in the range of 4 to 8.
- the pH of the water can be kept in the range of 5 to 7.
- the ratio of water to organic solvents can be 100:0.
- the ratio of METHYL-T-BUTYL ETHER to MeOH can be 50:50.
- orally acceptable carrier denotes a carrier made from materials that are safe and acceptable for oral use in the amounts and concentrations intended, for example materials as would be found in conventional toothpaste and mouthwash. Such materials include water or other solvents that may contain a humectant such as glycerin, sorbitol, xylitol and the like. In some aspects, the term “orally acceptable carrier” encompasses all of the components of the oral care composition.
- the carrier is typically a water/humectant system that provides a major fraction by weight of the composition.
- the carrier component of a toothpaste composition may comprise water, one or more humectants, and other functional components other than the hydrolyzed wheat protein or hydrolyzed rice protein.
- the carrier is typically a water/alcohol liquid mixture in which the hydrolyzed wheat protein or hydrolyzed rice protein is dissolved or dispersed.
- the carrier typically comprises a solid matrix material that dissolves slowly in the oral cavity.
- the carrier typically comprises a gum base, while in an edible strip, the carrier typically comprises one or more film forming polymers.
- the oral care compositions for use in accordance with the present disclosure may further comprise one or more additional ingredients selected from abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, anti-calculus or tartar control agents, sweeteners, flavorants, colorants and preservatives. These ingredients may also be regarded as carrier materials. Non-limiting examples are provided below.
- insoluble phosphates useful as abrasives are orthophosphates, polymetaphosphates and pyrophosphates.
- Illustrative examples are dicalcium orthophosphate dihydrate, calcium pyrophosphate, [beta]- calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate and insoluble sodium polymetaphosphate.
- One or more abrasives are optionally present in the oral care compositions of the present invention in an amount of 1 weight % to 5 weight % by total weight of the composition.
- the average particle size of an abrasive, if present, is generally 0.1 to 30pm, and preferably, 5 to 15pm.
- Any orally acceptable pH modifying agent can be used, including, without limitation, carboxylic, phosphoric and sulfonic acids, acid salts (for example, monosodium citrate, disodium citrate, monosodium malate), alkali metal hydroxides such as sodium hydroxide, carbonates such as sodium carbonate, bicarbonates, borates, silicates, phosphates (for example, monosodium phosphate, trisodium phosphate, pyrophosphate salts) imidazole and the like.
- acid salts for example, monosodium citrate, disodium citrate, monosodium malate
- alkali metal hydroxides such as sodium hydroxide
- carbonates such as sodium carbonate, bicarbonates, borates, silicates
- phosphates for example, monosodium phosphate, trisodium phosphate, pyrophosphate salts
- imidazole imidazole and the like.
- One or more pH modifying agents are optionally
- an oral care composition for use in accordance with the present disclosure comprises at least one foam modulator, useful, for example, to increase the amount, thickness or stability of foam generated by the composition upon agitation.
- foam modulator can be used including, without limitation, polyethylene glycols (PEGs).
- PEGs polyethylene glycols
- One or more PEGs are optionally present in a total amount of from 0.1 weight % to 10 weight by total weight of the composition.
- an oral care composition for use in accordance with the present disclosure at least one humectant which may be used to prevent hardening of a toothpaste upon exposure to air, or in the case of a mouthwash, to provide improved moisturizing and mouthfeel and enhance the miscibility of poorly soluble components such a flavoring oils.
- Any orally acceptable humectant can be used, including, without limitation, polyhydric alcohols such as glycerin, sorbitol, xylitol or low molecular weight PEGs. Most humectants also function as sweeteners.
- One or more humectants are optionally present in a total amount of 1 weight % to 50 weight % by total weight of the composition.
- an oral care composition for use in accordance with the present disclosure comprises at least one sweetener which enhances taste of the composition.
- Any orally acceptable natural or artificial sweetener can be used including, without limitation, dextrose, sucrose, maltose, dextrin, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup, partially hydrolyzed starch, hydrogenated starch hydrolysate, sorbitol, mannitol, xylitol, maltitol, isomalt, aspartame, neotame, saccharin and salts thereof, dipeptide-based intense sweeteners, cyclamates and the like.
- One or more sweeteners are optionally present in a total amount of 0.005 weight % to 5 weight % by total weight of the composition.
- an oral care composition for use in accordance with the present disclosure comprises at least one flavorant which enhances the taste of the composition.
- Any orally acceptable natural or synthetic flavorant can be used including, without limitation, vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, oil of Wintergreen (methylsalicylate), peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, citrus oils, fruit oils and essences, and the like.
- ingredients that provide fragrance and/or other sensory effects in the mouth including cooling or warming effects.
- Such ingredients illustratively include menthol, menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol, eugenol, cassia, oxanone, a-irisone, thymol, linalool, benzaldehyde, cinnamaldehyde, N-ethyl- p-menthan-3-carboxamine, N,2,3-trimethyl-2-isopropylbutanamide, 3 -(1 -menthoxy)-propane- 1 ,2-diol, cinnamaldehyde glycerol acetal (CGA), menthone glycerol acetal (MGA) and the like.
- One or more flavorants are optionally present in a total amount of 0.01 weight % to 5 weight %, by total weight of the composition.
- an oral care composition for use in accordance with the present disclosure comprises at least one colorant.
- a colorant can serve a number of functions. These include providing a white or light-colored coating on a dental surface, indicating locations on a dental surface that have been effectively contacted by the composition, and/or modifying the appearance of the composition to enhance attractiveness to the consumer.
- Any orally acceptable colorant can be used including, without limitation, talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, magnesium aluminum silicate, silica, titanium dioxide, zinc oxide, iron oxide, ferric ammonium ferrocyanide, manganese violet, titaniated mica, bismuth oxychloride and the like.
- One or more colorants are optionally present in a total amount of 0.001 weight % to 20 weight % by total weight of the composition.
- Dry plant material was ground and extracted with water for 16 hours at 20 °C.
- the extract was filtered to eliminate microbial contamination (0.22 pm).
- the water was evaporated from the filtered solution to obtain the dry extract.
- Extracts were used as a dry starting powder. Different concentrations of these dry powders were dissolved in water. To promote dissolution the solutions were left agitated at 37 °C for 3 hours. Undissolved particles were removed by centrifugation.
- Weight of biofilm (mg) Weight of rod + biofilm (mg) - Weight of rod (mg)
- the TVC data is given below:
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Abstract
The present invention relates to an extract of a plant of the species Rubus fruticosus or of any part of this plant. Furthermore, it relates to a composition comprising this extract and at least one orally acceptable carrier and optionally at least one orally acceptable ingredient. Furthermore, it relates to this extract or this composition for use in a method for treatment of the human or animal body by therapy, including prophylaxis. Furthermore, it relates to this extract or this composition for use in a method for treating or preventing caries of a human or of an animal.
Description
A Plant Extract and its Use
The present invention relates to an extract of a plant of the species Rubus fruticosus or of any part of this plant. Furthermore, it relates to a composition comprising this extract and at least one orally acceptable carrier and optionally at least one orally acceptable ingredient. Furthermore, it relates to this extract or this composition for use in a method for treatment of the human or animal body by therapy, including prophylaxis. Furthermore, it relates to this extract or this composition for use in a method for treating or preventing caries of a human or of an animal.
The aims of oral care are to prevent and/or treat dental diseases as well as provide cosmetic benefits.
Dental caries is an oral disease caused by bacterial pathogens and it affects hundreds of millions of people worldwide.
A spatiotemporal model of oral bacterial colonization shows a recognition of salivary pellicle receptors by initial colonizing bacteria and coaggregations between initial colonizers, fusobacteria and late colonizers of the tooth surface. Collectively, these interactions represent the development of dental plaque. Starting at the bottom, initial colonizers, e.g. Streptococcus gordonii, Streptococcus mitis, Streptococcus oralis and Streptococcus sanguinis, bind to complementary salivary receptors (sialylated mucins, proline-rich protein, a-amylase, salivary agglutinin and bacterial cell fragments) in the acquired pellicle coating the tooth surface. Late colonizers bind to previously bound bacteria. Sequential binding results in the appearance of nascent surfaces that bridge with the next coaggregating partner cell. Coaggregation is different from aggregation that occurs between genetically identical cells and from agglutination of cells through interaction of cells with soluble molecules, for example, antibodies. Most coaggregations are between cells of different genera; Fusobacterium nucleatum strains, for example, coaggregate intergenerically with representatives of all oral bacterial species. However, intrageneric coaggregation among fusobacterial strains is only rarely observed. In sharp contrast, streptococci exhibit broad intrageneric coaggregation partnerships (for example, S. gordonii and S. oralis) as well as intraspecies partnerships (for example, S. gordonii DL1 and S. gordonii 38). Each bacterial strain exhibits specificity in partners. For example, some streptococci are capable of coaggregating with certain Veillonella spp., whereas other streptococci cannot coaggregate with those veillonellae but do coaggregate with a separate group of veillonellae (NATURE REVIEWS, MICROBIOLOGY, VOLUME 8, 2010, 471).
Caries results from the accumulation of plaque on the teeth and production of organic acids (plaque acids) when plaque bacteria ferment sugars and starches in food residue left behind in the oral cavity. Before being washed away by saliva, the acids accumulate in the plaque long enough to lower the pH and to cause some of the enamel, a calcium-phosphorous mineral known as hydroxyapatite, to dissolve, that is, demineralize, which can lead to dental caries (tooth decay), and tooth sensitivity.
Another factor of cariogenesis is the accumulation of plaque bacteria which extracellularly produce glucansucrase enzymes, which catalyze formation of glucans from sucrose. These glucans cover tooth surfaces and serve as the backbone and primary layer of dental plaque. Plaque formation also involves the participation of a number of other opportunistic bacteria which are capable of attaching to the glucans and colonizing the tooth surface. Glucansucrases are expressed and secreted by oral pathogens such as Streptococcus mutans and Streptococcus sobrinus. The glucansucrase enzymes share a high degree of homology and consist of two functional domains - catalytic and glucan binding, (Monchois V. et al, 1999 "Glucansucrases: mechanism of action and structure-function relationships" FEMS Microbiology Reviews 23:131-151). It is known that some low molecular weight inhibitors of glucansucrase, such as 6-deoxysucrose, act through interfering with the catalytic domain of glucansucrase. To inhibit glucansucrase activity, it may be desirable to obtain/identify new substances which are capable of binding/inhibiting glucansucrase and may be effective for preventing or reducing cariogenesis.
A method of preventing the formation of dental plaque by inhibition of glucansucrase activity is disclosed in U.S. Patent 5,204,089 to Hara, et al. Inhibition of glucansucrase activity is demonstrated with selected polyphenols derived from tea.
Inhibition of glucansucrase activity by polyphenol compounds derived from the fruits of the rosaceae family is disclosed in U.S. Patent 5,853,728 to Tanabe, et al. Polyphenols are disclosed to hinder the activity of glucansucrase produced by oral Streptococcus, specifically inhibiting the formation of deposit which is an important factor of dental caries. The disclosed function of the polyphenols also includes antiallergic activity, ultraviolet light absorbing activity and free radical erasing activity for skin cosmetic material, and anticariogenic activity and deodorant activity for toothpaste.
Thus, a strategy for managing oral infections, besides mechanical removal of the formed plaque, may be based on application of antimicrobial agents, agents capable of inhibition of glucansucase, or their combination.
WO 2006/078699 relates to water dispersible extract preparations derived from water soluble components of Labiatae family plant material, including plant material hay and previously extracted or spent hay, which possesses beneficial oral care properties, methods of their manufacturing and application of the preparations in oral care products.
WO 2006/027248 discloses compositions comprising a combination of following extracts, and methods of preparing and using the same: use of an extract from the orders Fucales, Ericales, Saxifragales, Malpighiales, Malvales, Lamiales, Rosales, Fagales, Asterales, Myrtales, Apiales, Zingiberales, Magnoliales, Piperales, Laurales, Coniferales, Sapindales for inhibition of dextran sucrase to inhibit bacterial biofilm formation.
The problem underlying the present invention is to provide a substance that can be used to prevent dental plaque formation in humans or in animals and/or to prevent caries in humans or in animals.
This problem is solved by the extract of a plant of the species Rubus fruticosus or of any part of this plant. This extract is a subject of the present invention.
One embodiment of the present invention is the extract according to the present invention, wherein the extract is obtainable by contacting the plant or the part of the plant with a solvent so that the extract dissolves in the solvent, separating the solvent with the extract dissolved in it from the remaining plant or the remaining part of the plant so that a solvent-extract- combination is obtained, and removing the solvent from the solvent-extract-combination so that the extract is obtained, and wherein the solvent is preferably selected from the group consisting of water, a C1- to C4-alcohol, an ether comprising 1 to 8 C-atoms, a hydrocarbon comprising 1 to 10 C-atoms, supercritical carbon dioxide, and mixtures thereof.
Removing the solvent can be done by any method for removing solvents known to the person skilled in the art, e. g. be distillation, evaporation or freeze-drying. After removing the solvent it is possible that small amounts or traces of solvent are still present in the extract.
Another embodiment of the present invention is the extract according to the present invention, wherein the solvent is selected from the group consisting of water, ethanol and a mixture of methyl-t-butyl-ether and methanol.
Another embodiment of the present invention is the extract according to the present invention, wherein the extraction is carried out at a temperature of 15 °C to 115 °C.
Another embodiment of the present invention is the extract according to the present invention, wherein the extract is an extract of a part of the plant and wherein this part is selected from the group consisting of a fruit and a leave.
Another subject of the present invention is a composition comprising the extract according to the present invention, preferably in an amount of 0.1 to 20 % by weight, more preferably 0.1 to 10 % by weight, especially 0.1 to 1 % by weight, and at least one orally acceptable carrier and optionally at least one orally acceptable ingredient, wherein this composition preferably is selected from the group consisting of a toothpaste, a dentifrice and a mouthwash.
Another subject of the present invention is the extract according to the present invention or the composition according to the present invention for use in a method for treatment of the human or animal body by therapy, including prophylaxis.
Another subject of the present invention is the extract according to the present invention or the composition according to the present invention for use in a method for preventing caries of a human or of an animal.
Another subject of the present invention is the extract according to the present invention or the composition according to the present invention for use in a method for preventing or suppressing dental plaque formation in a human or in an animal.
Another subject of the present invention is a method for treating the human or animal body by therapy, including prophylaxis comprising contacting the extract according to the present invention or the composition according to the present invention with the oral cavity of the human or of the animal.
Another subject of the present invention is a method for preventing caries of a human or of an animal comprising contacting the extract according to the present invention or the composition according to the present invention with the oral cavity of the human or of the animal.
Another subject of the present invention is a method for preventing or suppressing dental plaque formation of a human or of an animal comprising contacting the extract according to the present invention or the composition according to the present invention with the oral cavity of the human or of the animal.
Further preferred embodiments or aspects of the present invention are described in the following paragraphs.
The present invention provides a method of providing oral care benefits in a living animal, including a human, by means of inhibiting glucansucrase, inhibition of the adhesion of oral pathogens, comprising the step of administering to the oral cavity of a living animal, including a human, an amount of a water soluble and/or organic solvent soluble and/or liquid carbon dioxide soluble extract preparation which is effective to provide an oral care benefit.
It furthermore provides a method wherein the extract preparation is contacted with the oral cavity in the form of a chewing gum, a breath freshening strip, a confectionary product, a food product, a beverage, a toothpaste/dentifrice, a mouthwash/rinse or a floss, pet food, pet snack, and pet chewing material, selected from pig's ears and raw hides.
One embodiment of the present invention is a process for manufacturing an extract preparation comprising a. contacting the plant material with water-organic mixtures: i. wherein a water-miscible organic solvent is selected from C1-C4 alcohols, acetone and/or their combination, ii. wherein the pH of the water and/or water/organic solvent mixture is kept in the range 1-14 by means of appropriate base, acid, salt or buffer, iii. wherein the ratio of water to organic solvents is in a range from 100:0 to 1 :99, iv. wherein the extraction is carried out at temperatures in a range from 0°C to at boiling point; v. wherein the extraction may include microwave assisted water extractions and/or subcritical extraction with water, including high temperature and high pressure; b. contacting the plant material with organic solvents or mixtures: i. wherein the organic solvent is methyl-t-butyl ether, THF or acetonitrile and/or combinations with organic solvents selected from C1-C4 alcohols, acetone; ii. wherein the extraction is carried out at temperatures in a range from 0°C to at boiling point; iii. wherein the extraction may include microwave assisted extractions and/or subcritical extraction, including high temperature and high pressure; c. contacting the plant material with liquid carbon dioxide at 5 - 95 °C under pressure of 5- 100 MPa; d. removing the extract from insoluble material; e. optionally repeating the extraction step using the same or different solvent/mixture;
f. optional fractionation of the extracted material by means of precipitation i. wherein precipitation is achieved by increasing the content of the organic solvent chosen from C1-C4 alcohols, acetone, and/or their combination, ii. wherein precipitation is achieved by decreasing pH, iii. wherein precipitation is achieved through complexation with multicharged cations, iv. wherein precipitation is achieved by increasing ionic strength of the solution, and/or v. wherein precipitation is further aided by decreasing the temperature; g. optional purification of the extracts by means of liquid - liquid extraction, solid-phase extraction, chromatographic methods, membrane-based filtration or combinations of thereof; and h. stabilizing the obtained preparations by means of addition of anti-spoiling agents, or preferably by vacuum drying, or spray drying methods using appropriate carriers.
Plant material according to the present invention can be any plant material. It can be leaves, fruits or plant material hay.
Plant material can be any part of a plant, not limited to foliage, blossoms, stems, roots, and any other plant parts. Moreover, this material may be fresh plant matter, plant matter which has been subjected to drying or to steam distilling.
The extract according to the present invention preferably is a water soluble and/or organic solvent and/or liquid carbon dioxide soluble extract with glucansucrase inhibition activity derived from water soluble and/or organic solvent soluble and/or liquid carbon dioxide soluble components of plant material and fractions of this extract.
One embodiment of the present invention is a method of providing beneficial oral care by means of preventing dental plaque accumulation. These described effects may be achieved by contacting the oral cavity with products containing effective amounts of the extract according to the present invention or fractions thereof.
The extract according to the present invention can be used as such according to the present invention. Furthermore, fractions and compounds from the extracts possessing beneficial oral care properties, remineralization properties, anti-adhesion activity including inhibitory activity towards to glucansucrase can be used.
One embodiment of the present invention is a method of providing oral care benefits in a living animal, including a human, by means of inhibiting glucansucrase, inhibiting adhesion of oral pathogens, comprising the step of administering to the oral cavity of a living animal, including a human, an amount of an extract according to the present invention which is effective to provide an oral care benefit.
In this method the extract preparation can be selected for its inhibitory activity towards glucansucrase.
In this method the extract can be contacted with the oral cavity in the form of a chewing gum, a breath freshening strip, a confectionary product, a food product, a beverage, a toothpaste/dentifrice, a mouthwash/rinse or a floss, pet food, pet snack, and pet chewing material, e.g. selected from pig's ears and raw hides.
The beneficial effect of the extract preparation may be further enhanced by incorporation of fractions, and compounds of the extract possessing beneficial oral care properties including inhibitory activity towards to glucansucrase, anti-microbial activity against oral pathogens, remineralization properties, anti-adhesion activity, inhibitory activity towards cyclooxygenases and lipoxygenases, breath freshening properties, anti-oxidant properties, and/or antiinflammatory properties.
The beneficial effect of the extract according to the present invention may be further enhanced by incorporation of fractions, and compounds of the extract and mixtures of these.
One embodiment of the present invention is a process for manufacturing a Rubus fruticosus plant material extract preparation comprising a. contacting Rubus fruticosus plant material with water-organic mixtures: i. wherein a water- miscible organic solvent is selected from C1-C4 alcohols, acetone, and/or their combination, ii. wherein the pH of the water and/or water/organic solvent mixture is kept in the range 1- 14 by means of appropriate base, acid, salt or buffer, iii. wherein the ratio of water to organic solvents is in a range from 100:0 to 1 :99, iv. wherein the extraction is carried out at temperatures in a range from 0 °C to at boiling point; v. wherein the extraction may include microwave assisted water extractions and/or subcritical extraction with water, including high temperature and high pressure; or b. contacting Rubus fruticosus plant material with organic solvents or mixtures:
i. wherein the organic solvent is METHYL-T-BUTYL ETHER, THF or Acetonitrile and/or combinations with organic solvents selected from C1-C4 alcohols, acetone; ii. wherein the extraction is carried out at temperatures in a range from 0 °C to at boiling point; iii. wherein the extraction may include microwave assisted extractions and/or subcritical extraction, including high temperature and high pressure; or c. contacting the Rubus fruticosus plant material with supercritical carbon dioxide: i. wherein the extraction is carried out at temperatures in a range from 35-95°C; ii. wherein the extraction is carried out under pressure of 7.5-100 MPa; after extraction (a. or b. or c.): d. removing the extract from insoluble material; e. optionally repeating the extraction step using the same or different solvent mixture; f. optional fractionation of the extracted material by means of precipitation i. wherein precipitation is achieved by increasing the content of the organic solvent chosen from C1- C4 alcohols, acetone, and/or their combination, ii. wherein precipitation is achieved by decreasing pH, iii. wherein precipitation is achieved through complexation with multicharged cations, iv. wherein precipitation is achieved by increasing ionic strength of the solution, and/or v. wherein precipitation is further aided by decreasing the temperature; g. optional purification of the extracts by means of liquid - liquid extraction, solid-phase extraction, chromatographic methods, membrane-based filtration or combinations of thereof; and h. stabilizing the obtained preparations by means of addition of anti-spoiling agents, or preferably by vacuum drying, or spray drying methods using appropriate carriers.
In this process the pH of the water can be kept in the range of 4 to 8.
In this process the pH of the water can be kept in the range of 5 to 7.
In this process In this process the ratio of water to organic solvents can be 100:0.
In this process the organic solvent can be EtOH.
In this process the ratio of METHYL-T-BUTYL ETHER to MeOH can be 50:50.
The following paragraphs describe orally acceptable carriers and orally acceptable ingredients than can be used in the composition according to the present invention.
The expression “orally acceptable carrier” as used herein denotes a carrier made from materials that are safe and acceptable for oral use in the amounts and concentrations intended, for example materials as would be found in conventional toothpaste and mouthwash. Such
materials include water or other solvents that may contain a humectant such as glycerin, sorbitol, xylitol and the like. In some aspects, the term “orally acceptable carrier” encompasses all of the components of the oral care composition.
Orally acceptable carriers for use in accordance with the present disclosure include conventional and known carriers used in making mouth rinses or mouthwashes, toothpastes, tooth gels, tooth powder, lozenges, chewing gums, beads, edible strips, tablets and the like. Carriers should be selected for compatibility with each other and with other ingredients of the composition.
The following non-limiting examples are provided. In a toothpaste composition, the carrier is typically a water/humectant system that provides a major fraction by weight of the composition. Alternatively, the carrier component of a toothpaste composition may comprise water, one or more humectants, and other functional components other than the hydrolyzed wheat protein or hydrolyzed rice protein. In a mouth rinse or a mouthwash formulation, the carrier is typically a water/alcohol liquid mixture in which the hydrolyzed wheat protein or hydrolyzed rice protein is dissolved or dispersed. In a dissolvable lozenge, the carrier typically comprises a solid matrix material that dissolves slowly in the oral cavity. In chewing gums, the carrier typically comprises a gum base, while in an edible strip, the carrier typically comprises one or more film forming polymers.
The oral care compositions for use in accordance with the present disclosure may further comprise one or more additional ingredients selected from abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, anti-calculus or tartar control agents, sweeteners, flavorants, colorants and preservatives. These ingredients may also be regarded as carrier materials. Non-limiting examples are provided below.
In one embodiment a composition for use in accordance with the present disclosure comprises at least one abrasive, useful, for example, as a polishing agent. Any orally acceptable abrasive can be used, but the type, fineness (particle size) and amount of abrasive should be selected so that tooth enamel is not excessively abraded during normal use of the composition. Suitable abrasives include, without limitation, silica, for example in the form of silica gel, hydrated silica or precipitated silica, alumina, insoluble phosphates, calcium carbonate, resinous abrasives such as urea-formaldehyde condensation products and the like. Among insoluble phosphates useful as abrasives are orthophosphates, polymetaphosphates and pyrophosphates. Illustrative examples are dicalcium orthophosphate dihydrate, calcium pyrophosphate, [beta]- calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate and insoluble
sodium polymetaphosphate. One or more abrasives are optionally present in the oral care compositions of the present invention in an amount of 1 weight % to 5 weight % by total weight of the composition. The average particle size of an abrasive, if present, is generally 0.1 to 30pm, and preferably, 5 to 15pm.
In a further embodiment an oral care composition for use in accordance with the present disclosure comprises at least one bicarbonate salt, useful, for example, to impart a "clean feel" to teeth and gums due to effervescence and release of carbon dioxide. Any orally acceptable bicarbonate can be used, including, without limitation, alkali metal bicarbonates such as sodium and potassium bicarbonates, ammonium bicarbonate and the like. One or more bicarbonate salts are optionally present in a total amount of 1 weight % to 10% by weight of the composition.
In a still further embodiment, an oral care composition for use in accordance with the present disclosure comprises at least one pH modifying agent. Such agents include acidifying agents to lower pH, basifying agents to raise pH and buffering agents to control pH within a desired range. For example, one or more compounds selected from acidifying, basifying and buffering agents can be included to provide a pH of 2 to 10, or in various illustrative embodiments a pH of 2 to 8, 3 to 9, 4 to 8, 5 to 7, 6 to 10, or 7 to 9. Any orally acceptable pH modifying agent can be used, including, without limitation, carboxylic, phosphoric and sulfonic acids, acid salts (for example, monosodium citrate, disodium citrate, monosodium malate), alkali metal hydroxides such as sodium hydroxide, carbonates such as sodium carbonate, bicarbonates, borates, silicates, phosphates (for example, monosodium phosphate, trisodium phosphate, pyrophosphate salts) imidazole and the like. One or more pH modifying agents are optionally present in a total amount effective to maintain the composition in an orally acceptable pH range.
In a still further embodiment an oral care composition for use in accordance with the present disclosure comprises at least one surfactant, useful, for example, to provide enhanced stability to the composition and the components contained therein, to aid in cleaning a dental surface through detergent action, and to provide foam upon agitation (for example, during brushing with a dentifrice composition of the invention). Any orally acceptable surfactant, including those which are anionic, nonionic or amphoteric, can be used. Suitable anionic surfactants include, without limitation, water-soluble salts of Cs-2o alkyl sulfates, sulfonated monoglycerides of Cs-2o fatty acids, sarcosinates, taurates and the like. Suitable nonionic surfactants include, without limitation, poloxamers, polyoxyethylene sorbitan esters, fatty alcohol ethoxylates, alkylphenol ethoxylates, tertiary amine oxides, tertiary phosphine oxides, dialkyl sulfoxides and the like.
Suitable amphoteric surfactants, without limitation, derivatives of Cs-20 aliphatic secondary and tertiary amines having an anionic group such as carboxylate, sulfate, sulfonate, phosphate or phosphonate. A suitable example is cocoamidopropyl betaine. One or more surfactants are optionally present in a total amount of 0.01 weight % to 10 weight %, for example, from 0.05 weight % to 5 weight % or from 0.1 weight % to 2 weight % by total weight of the composition. In a still further embodiment, an oral care composition for use in accordance with the present disclosure comprises at least one foam modulator, useful, for example, to increase the amount, thickness or stability of foam generated by the composition upon agitation. Any orally acceptable foam modulator can be used including, without limitation, polyethylene glycols (PEGs). One or more PEGs are optionally present in a total amount of from 0.1 weight % to 10 weight by total weight of the composition.
In a still further embodiment, an oral care composition for use in accordance with the present disclosure comprises at least one thickening agent, useful, for example, to impart a desired consistency and/or mouth feel to the composition. Any orally acceptable thickening agent can be used including, without limitation, carbomers (carboxyvinyl polymers), carrageenans, cellulosic polymers such as hydroxyethylcellulose, carboxymethylcellulose (CMC) and salts thereof, natural gums such as karaya, xanthan, gum arabic and tragacanth, colloidal magnesium aluminum silicate, colloidal silica and the like. One or more thickening agents are optionally present in a total amount of 0.01 weight % to 15 weight %, by total weight of the composition.
In a still further embodiment, a composition for use in accordance with the present disclosure comprises at least one viscosity modifier, useful, for example, to inhibit settling or separation of ingredients or to promote re-dispersion of ingredients upon agitation of a liquid composition. Any orally acceptable viscosity modifier can be used including, without limitation, mineral oil, petrolatum, clays, silica and the like. One or more viscosity modifiers are optionally present in a total amount of 0.01 weight % to 10 weight %, by total weight of the composition.
In a still further embodiment, an oral care composition for use in accordance with the present disclosure at least one humectant which may be used to prevent hardening of a toothpaste upon exposure to air, or in the case of a mouthwash, to provide improved moisturizing and mouthfeel and enhance the miscibility of poorly soluble components such a flavoring oils. Any orally acceptable humectant can be used, including, without limitation, polyhydric alcohols such as glycerin, sorbitol, xylitol or low molecular weight PEGs. Most humectants also function as sweeteners. One or more humectants are optionally present in a total amount of 1 weight % to 50 weight % by total weight of the composition.
In a still further embodiment, an oral care composition for use in accordance with the present disclosure comprises at least one sweetener which enhances taste of the composition. Any orally acceptable natural or artificial sweetener can be used including, without limitation, dextrose, sucrose, maltose, dextrin, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup, partially hydrolyzed starch, hydrogenated starch hydrolysate, sorbitol, mannitol, xylitol, maltitol, isomalt, aspartame, neotame, saccharin and salts thereof, dipeptide-based intense sweeteners, cyclamates and the like. One or more sweeteners are optionally present in a total amount of 0.005 weight % to 5 weight % by total weight of the composition.
In a still further embodiment, an oral care composition for use in accordance with the present disclosure comprises at least one flavorant which enhances the taste of the composition. Any orally acceptable natural or synthetic flavorant can be used including, without limitation, vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, oil of Wintergreen (methylsalicylate), peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, citrus oils, fruit oils and essences, and the like. Also encompassed within flavorants are ingredients that provide fragrance and/or other sensory effects in the mouth, including cooling or warming effects. Such ingredients illustratively include menthol, menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol, eugenol, cassia, oxanone, a-irisone, thymol, linalool, benzaldehyde, cinnamaldehyde, N-ethyl- p-menthan-3-carboxamine, N,2,3-trimethyl-2-isopropylbutanamide, 3 -(1 -menthoxy)-propane- 1 ,2-diol, cinnamaldehyde glycerol acetal (CGA), menthone glycerol acetal (MGA) and the like. One or more flavorants are optionally present in a total amount of 0.01 weight % to 5 weight %, by total weight of the composition.
In a still further embodiment, an oral care composition for use in accordance with the present disclosure comprises at least one colorant. A colorant can serve a number of functions. These include providing a white or light-colored coating on a dental surface, indicating locations on a dental surface that have been effectively contacted by the composition, and/or modifying the appearance of the composition to enhance attractiveness to the consumer. Any orally acceptable colorant can be used including, without limitation, talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, magnesium aluminum silicate, silica, titanium dioxide, zinc oxide, iron oxide, ferric ammonium ferrocyanide, manganese violet, titaniated mica, bismuth oxychloride and the like. One or more colorants are optionally present in a total amount of 0.001 weight % to 20 weight % by total weight of the composition.
In a still further embodiment, an oral care composition for use in accordance with the present disclosure comprises a preservative. The preservative may be selected from parabens, potassium sorbate, benzyl alcohol, phenoxyethanol, polyaminopropyl biguanide, caprylic acid,
sodium benzoate and cetylpyridinium chloride. In some embodiments, the preservative is present at a concentration of from about 0.001 to about 1 weight %, by total weight of the composition.
The following examples illustrate compositions for use in accordance with the present disclosure. The exemplified compositions are illustrative and do not limit the scope of the disclosure.
Examples
EXAMPLE 1 : aqueous extraction of plant material of a selected genus at 20 °C
Dry plant material was ground and extracted with water for 16 hours at 20 °C. The extract was filtered to eliminate microbial contamination (0.22 pm). The water was evaporated from the filtered solution to obtain the dry extract.
EXAMPLE 2: aqueous extraction of plant material of a selected genus at 110 °C
Dry plant material was extracted with water for 10 minutes under pressure (1.5 bar) at a temperature of 110 °C. Potential microbial contamination was removed by filtration (0.22 pm). The water was evaporated from the filtered solution to obtain the dry extract.
EXAMPLE 3: organic solvent extraction of plant material of a selected genus using a mixture of methyl-t-butyl ether and methanol
Dry plant material was ground and sieved (3 mm sieve). Extraction was carried out with a mixture of methyl-t-butyl ether and methanol 1 :1 for 60 minutes at room temperature, followed by separation of undissolved particles by a glass fiber filter and a 0.45 pm PTFE filter. Finally the solvent was removed by freeze drying.
EXAMPLE 4: organic solvent extraction of plant material of a selected genus using ethanol Dry plant material was ground and sieved (3 mm sieve). Extraction was carried out with ethanol for 30 minutes at room temperature, followed by separation of undissolved particles by a glass fiber filter. The extraction step was repeated with the undissolved plant material with ethanol for 30 minutes at room temperature. The undissolved plant material was separated by a glass fiber filter. The supernatants were combined and filtered through a 0.45 pm PTFE filter. Finally, the solvent was removed by freeze drying.
EXAMPLE 5: extraction of plant material with supercritical carbon dioxide
Prior to the extraction, the plant materials of a selected genus was grinded using a percussive mill, thus obtaining a grain break-up below 0.75 mm. After placing a weighed amount of the broken-up plant material (100 g) in the extractor (pressure vessel having a volume of 150 cm3) the supercritical carbon dioxide was incubated at 35 - 60 °C for 24 hours in order to extract bioactive components. The experiments were carried out under a pressure of 40 MPa. The supercritical carbon dioxide was displaced by inert gas (N2) to an evaporator in which the extract was deposited, the carbon dioxide was gasified. The dry and powdery extract was left and could be dissolved in an appropriate buffer solution and used in final applications.
Extraction temperature: 35 °C
Extraction temperature: 40 °C
Extraction temperature: 60 °C
EXAMPLE 6: inhibition of plaque formation by plant extracts.
The biological effect of plant extracts on the inhibition of plaque formation was investigated using a glass rod model. This ex vivo model for human dental plaque is based on an incubation of pooled human saliva with glass rods in the presence of plant extracts containing selected active ingredients.
Efficacy Measures:
• dry biofilm weight on glass rods
• Total Viable Count (TVC) of aerobes
Dental plaque, seeded from pooled human saliva, was grown on roughened glass rods inside an incubator for 3 days. Bacterial growth was promoted by the presence of Tryptic Soya Broth (TSB) and dissolved sucrose. The developing biofilms were also continuously exposed to each of the test extracts and after 3 days the biofilms were analyzed for weight and Total Viable Count of aerobes (TVC).
Sample Preparation
Sample preparation involved making a suitable substrate for the biofilm to grow on, and a means of holding this substrate in a growth medium (whilst preventing contamination), and the preparation of suitable growth media. a. G/ass Rod Substrate
Glass rods, 6 mm in diameter and 10 cm in length, were roughened using a bench grinder with 400 grit paper. The rods were rinsed thoroughly with deionized water before being left to air dry.
The rods were rubbed with clean tissue to remove any loose debris, then sterilized in 70 % isopropanol for 2 hours before being left to dry in a microbiological safety cabinet.
b. Saliva and 0.1 % Sucrose
Stimulated saliva (using flavorless gum) was collected and pooled. When a sufficient volume of saliva was collected 0.1 % sucrose (w/w) was added. c. Nutrient Broth
The nutrient broth consisted of a 3 % Tryptic Soya Broth (TSB) solution, with 10 % sucrose (w/w) and 6.5 % whole saliva (w/w). The broth and sucrose solution were made prior to commencement of the study, and the saliva was added at the beginning of each day.
T reatments
Extracts were used as a dry starting powder. Different concentrations of these dry powders were dissolved in water. To promote dissolution the solutions were left agitated at 37 °C for 3 hours. Undissolved particles were removed by centrifugation.
Procedure
On the afternoon of day 1 , the sterilized glass rods were inserted into 10 ml of treatment sample and saliva solution. The containers were placed in a rack and transferred to an incubator for approximately 18 hours at 37 °C. The solutions were agitated on a plate shaker set to 250 rpm. On days 2 and 3 the rods were placed in a fresh solution of nutrient broth and treatment and transferred back into the incubator. After 6 hours in broth the rods were transferred into the saliva containing 0.1 % sucrose and treatment and placed in the incubator for a further 18 hours.
On day 4 the containers containing the glass rods were removed from the incubator; 2 rods from each treatment group were used for TVC analysis. The remaining 2 rods were used to determine dry weight of biomass.
After the rods had air dried, they were removed from the container lids and weighed on a 4- decimal place analytical balance. After re-hydration by soaking in deionized water, the biofilm was harvested using sterile instruments into pre-labelled Eppendorfs and the rods were reweighed after drying.
Dry weight of biofilm was determined from the following equation:
Weight of biofilm (mg) = Weight of rod + biofilm (mg) - Weight of rod (mg)
TVC
Measurement of TVC (aerobes) was evaluated immediately (two rods per treatment group).
Photographs of each set of rods were taken immediately. The rods were then dip-washed 3 times in sterile saline and the original sample pots rinsed. The sample pots were refilled with 20 ml sterile saline and the rods scraped until visibly clean using sterile instruments. The material was mixed by vortexing to obtain a homogenous suspension and photographs were taken again. The suspension was plated out on Columbia blood agar and Potato Dextrose agar.
Serial dilutions were also plated out using Tryptone Soy agar to achieve a countable level. The plates were incubated at 37 °C.
Results a. Dry biofilm weights
Data for dry biofilms weights are given below:
Set 1 :
Rubus fruticosus EtOH extract 0.1 mg/ml 3.9 mg
0.5 mg/ml 1.3 mg
Buffer (negative control) 6.5 mg
Positive control (antimicrobial - 0.2 % chlorhexidine) 0.7
Set 2:
Rubus fruticosus METHYL-t-BUTYL ETHER/MeOH extract
1 mg/ml 1.3
Buffer (negative control) 2.7
Positive control (antimicrobial - 0.2 % chlorhexidine) 0.5
Set 3:
Rubus fruticosus H2O extract 2 mg/ml 1.3
Rubus fruticosus H2O under pressure extract 2 mg/ml 1.2
Buffer (negative control) 3.9
Positive control (antimicrobial - 0.2% chlorhexidine) 1.1
The extracts exhibit some anti-plaque activity resulting in a significant reduction of the biofilm weight in relation to the control.
b. TVC
The TVC data is given below:
Set 1
Rubus fruticosus EtOH extract 0.1 mg/ml 6,500,000
0.5 mg/ml 1 ,120,000
Buffer 5,900,000
Positive control (antimicrobial - 0.2 % chlorhexidine) 1
Set 2:
Rubus fruticosus METHYL-t-BUTYL ETHER/MeOH extract
1 mg/ml 20,500
Buffer 3,050,000
Positive control (antimicrobial - 0.2 % chlorhexidine) 11
Set 3:
Rubus fruticosus H2O extract 2 mg/ml 10,450,000
Rubus fruticosus H2O under pressure extract 2 mg/ml 10,550,000
Buffer 40,550,000
Positive control (antimicrobial - 0.2 % chlorhexidine) 118
Compared to the buffer control, the treatments with extracts caused a significant reduction in aerobes.
CONCLUSIONS
The experiments demonstrate that extracts of selected plant materials could be prepared. In addition, it was demonstrated that these extracts have a significant beneficial oral care property including prevention of dental caries through suppression of dental plaque formation and deposition via inhibition of enzyme glucansucrase activity.
The high activity of the extracts, as evidenced by the tests reported, showed that they are useful when applied to human beings as well as to domesticated animals, particularly dogs and cats.
Claims
1. The extract of a plant of the species Rubus fruticosus or of any part of this plant.
2. The extract according to claim 1 , wherein the extract is obtainable by contacting the plant or the part of the plant with a solvent so that the extract dissolves in the solvent, separating the solvent with the extract dissolved in it from the remaining plant or the remaining part of the plant so that a solvent-extract-combination is obtained, and removing the solvent from the solvent- extract-combination so that the extract is obtained, and wherein the solvent is preferably selected from the group consisting of water, a C1- to C4-alcohol, an ether comprising 1 to 8 C-atoms, a hydrocarbon comprising 1 to 10 C-atoms, supercritical carbon dioxide, and mixtures thereof.
3. The extract according to claim 2, wherein the solvent is selected from the group consisting of a C1- to C4-alcohol, an ether comprising 1 to 8 C-atoms, a hydrocarbon comprising 1 to 10 C-atoms, supercritical carbon dioxide, and mixtures thereof.
4. The extract according to claim 2, wherein the solvent is selected from the group consisting of water, ethanol and a mixture of methyl-t-butyl-ether and methanol.
5. The extract according to any of claims 2 to 4, wherein the extraction is carried out at a temperature of 15 °C to 115 °C.
6. The extract according to any of claims 1 to 5, wherein the extract is an extract of a part of the plant and wherein this part is selected from the group consisting of a fruit and a leave.
7. A composition comprising the extract according to any of claims 1 to 6, preferably in an amount of 0.1 to 20 % by weight, more preferably 0.1 to 10 % by weight, especially 0.1 to 1 % by weight, and at least one orally acceptable carrier and optionally at least one orally acceptable ingredient, wherein this composition preferably is selected from the group consisting of a toothpaste, a dentifrice and a mouthwash.
8. The extract according to any of claims 1 to 6 or the composition according to claim 7 for use in a method for treatment of the human or animal body by therapy, including prophylaxis.
The extract according to any of claims 1 to 6 or the composition according to claim 7 for use in a method for preventing caries of a human or of an animal. The extract according to any of claims 1 to 6 or the composition according to claim 7 for use in a method for preventing or suppressing dental plaque formation in a human or in an animal. The extract according to any of claims 1 to 6 or the composition according to claim 7 for use in a method for inhibiting glucansucrase.
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| EP21197167 | 2021-09-16 | ||
| EP21197167.6 | 2021-09-16 |
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| WO2023041357A1 true WO2023041357A1 (en) | 2023-03-23 |
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