WO2006117029A1 - Utilisation de polylysine associee a des extraits de the vert ou des extraits d'olive ou les deux dans le traitement de l'halitose - Google Patents

Utilisation de polylysine associee a des extraits de the vert ou des extraits d'olive ou les deux dans le traitement de l'halitose Download PDF

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WO2006117029A1
WO2006117029A1 PCT/EP2006/000973 EP2006000973W WO2006117029A1 WO 2006117029 A1 WO2006117029 A1 WO 2006117029A1 EP 2006000973 W EP2006000973 W EP 2006000973W WO 2006117029 A1 WO2006117029 A1 WO 2006117029A1
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polylysine
ingredients
green tea
formulations
extracts
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Lucas Huybrechts
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Lucas Huybrechts
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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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/88—Polyamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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

  • This invention is about oral care formulations, such as mouth rinse-, mouth spray- and gel formulations, lozenges, tablets for dissolution in the oral cavity, candies and chewing gums, that contain (epsilon)-polylysine and other anti-bacterial ingredients, for use in the treatment against halitosis.
  • oral care formulations such as mouth rinse-, mouth spray- and gel formulations, lozenges, tablets for dissolution in the oral cavity, candies and chewing gums, that contain (epsilon)-polylysine and other anti-bacterial ingredients, for use in the treatment against halitosis.
  • VSC sulfur containing gases
  • Some diseases such as, mouth cancer, diabetics, parodontitis, liver- and kidney diseases and sinusitis can agravate the problem, but the bacterial colonies in the oral cavity remain the dominant factor.
  • Good oral hygienic practises do contribute to improving the condition of breath but are seldomly sufficient to solve halitosis.
  • ingredients & formulations against halitosis can be determined by measurment of the sulfur containing gases in the oral cavity from volunteers who are using either blanco's or formulations with such ingredients. This can be achieved with sophisticated gas chromatographic equipment as well as with the less sophisticated devices that can pick up the simple sulfur containing VSC gases. Such equipment is available and registered under the name Halimeter.
  • Several products have been developed for treatment of halitosis: metal salts, oxidizing agents, bactericides, chitosan and natural extracts.
  • metal salts mostly zinc-, stannic- and bismut salts are used, but their efficacy is limited (US 5833952, US6426085,US6702999,US50053556); in some cases they are used in the form of complexes in order to increase solubility (polyamines: US5587147, inuline: US6511679, glycine: US6607711); however due to their toxicological profile, long term use is not adviced.
  • Oxidizing agents too have antiseptic competence; several agents are used such as hydrogen peroxide (US40234463), but especially also chlorinedioxide (US6582682, US 6696047) and chlorite (US 6375933, US 02114851, US 030129144). Oxidizing agents act in a non-selective way, they may create resistant bacteria after long-term use and appear to have a relatively unattractive, low LD50 value. They are rather unstable in formulations, influence the function of other ingredients, and often they provide an unwanted taste that is typical for oxidizing and chlorinated agents.
  • bactericides such as cetylpyridinium chloride (US5972312, US 6344184), salicylaldehyde (US40258733), or phenolic components such as triclosan (US5882631), but their efficacy is limited and short lived.
  • chlorohexidine (US20030165411) is used; it has a broad spectrum activity, creates resistant bacteria after the long-term use, discolours teeth, has a rather unpopular taste, requires alcohol for dissolution and may burden the stomach. It's long term use is not adviced.
  • v ⁇ u ⁇ iLu ⁇ i c s ave een sugges e suc as ex rac s a contain piieno ic compounds, quinones, flavones, tannines, coumarines, terpenoides, alcaloides or essential oils.
  • Patent application refers to the use of a "synergistic" mixture of epsilon-polylysine and inactive siloxane against bacterial plaque, caries, paradontitis and halitosis.
  • the patent emphasizes the unsatisfactory efficacy of pure e-polylysine against a build-up of plaque and does not claim nor does it provide any experimental prove that 5 the peptide may work against halitosis; in fact siloxanes, which may be beneficial for use as abrasive in toothpastes that act in the vicinity and on teeth, cannot be used in a meaningful way in formulations ( mouth rinses, oral sprays, dissolving tablets) that act closer to the tongue area, which is an essential condition for the treatment of halitosis. Siloxanes do not degrade, as is the case with peptides, and are problematic for use in 0 dosing concepts (mouth washes, rinses, tablets....) that enter the body system more readily.
  • lysozyme is limited to gum formulations (CN1318314) and it's anti-halitosis competence is marginal; this is also the case for lactoferrin that has only been patented in 5 combination with other ingredients: lactoferrin and epigallocatechin (WO2004012522), lactoferrin or lysozyme and polyvinylalcohol (JP2002322088), lactoferrin or lysozyme and immunoglobulines (JP2003137809).
  • polylysine exp. 3: degree of polymerisation 5-7
  • e-polylysine epsilon-polylysine
  • a-polylysine another peptide-polymer based on lysine
  • the degree of polymerisation can vary between 5 and 10000 lysine units.
  • spray dried mixtures can be used for convenience, such as e-polylysine/dextrin mixtures.
  • the reduction in sulfur gas content in the oral cavity after use of a formulation with e- polylysine in comparison to the bianco (oral cavity which is not treated with the product nor with hygienic products such as toothpaste) is between 60% and 80% when using a dosage between 0.5% and 1%.
  • (Epsilon)-polylysine can be dosed at between 0.01% to 10% and more in formulations, but preferably 0.1 to 1% in liquid formulations and preferably between 0.5% and 3% in dry formulations (tablet), whereby the daily intake of epsilon polylysine should be limited to below the accepted safe daily intake dosage of 10 mg/kg bodyweigth. They can be used and will be effective under acid, neutral and basic pH conditions.
  • extracts from white tea sourced from the same plant as green tea extracts: camellia sinensis
  • red tea sourced from the Rooibos plant
  • Oleuropein and hydroxytyrosol which are structurally related, belong to the most important polyhydroxyphenolic compounds in olive leaf and fruit extracts. Their dosage can vary according to the extraction procedure.
  • Olive extracts exhibit an equal modest reduction of sulfur gas content ,of -3% to -6%. They can be used at a dosage of between 0.01% and with no upper limit set for safety reasons.
  • Experiment 1 demonstrates the synergistic effect that results from the combined use of polylysines or epsilon-polyly sines with polyhydroxyphenolic compounds such as olive extracts (with hydroxytyrosol) or green tea extracts (with BCCG).
  • polyhydroxyphenolic compounds such as olive extracts (with hydroxytyrosol) or green tea extracts (with BCCG).
  • the sulfur gas content reduction in comparison to the bianco is between 70% and 87%.
  • the beneficial effect of the reduction of sulfur gasses persists after long-term use (experiment 2).
  • the duration of the remaining effect after terminating the use of the product will be between more than 12hours to several days.
  • the main advantages in comparison to existing antihalitosis products include: high efficacy and long duration time, extreem low toxicity (compared to synthetic cationic antiseptics such as chlorohexidine), no discoloration of teeth, no need for dissolution in alcohol, no bad taste, no known risk for creating resistant bacteria.
  • extreem low toxicity compared to synthetic cationic antiseptics such as chlorohexidine
  • no discoloration of teeth no need for dissolution in alcohol, no bad taste, no known risk for creating resistant bacteria.
  • the difficulty in mixing green tea extracts and (epsilon) polylysine in the basic form They immediately form a precipitate that may reduce it's effectiveness.
  • precipitation can be avoided if the products are mixed at a slight acid pH, preferably in the range of 5 to 6.9, more preferable around 5.5 to 5.8. This can be achieved for example by using (e) polylysine that has been adjusted to slightly acidic pH in solution before addition of the green tea extract.
  • the new active ingredients can be used with other ingredients, known in the field, in different forms of end formulations for use in the oral cavity: mouth refreshing solutions, mouth rinses, mouth sprays, gels, chewing gum, candies, dissolving tablets and other food systems, artificial saliva and medical products for the treatment against halitosis.
  • mouth refreshing solutions mouth rinses, mouth sprays, gels, chewing gum, candies, dissolving tablets and other food systems, artificial saliva and medical products for the treatment against halitosis.
  • Experiment 4 provides data on tablets, alike mint tablets, that dissolve in the oral cavity.
  • the end formulations can also contain components for the protection against caries: fluorides (US 2946725 and US 3678154; for example sodium fluoride, sodium monofluorophosphate and stannous fluoride or encapsulated fluoride ingredients (for protection against deactivating components such as calcium or orthophosphates). Fluorides are used at a concentration between 0.1% to 1% w/w, preferably between 0.25 and 0.5 % on weight basis.
  • the end formulation can contain also other protecting anticavity compounds such as natural bactericides, synthetic bactericides, plant extracts, peptides with immunological activity, antibodies against S.
  • Mutans, bacteriophages, sugars to reduce the production of acid xylitol, erythritol
  • enzymes e.g. glucanases and dextranases
  • Mutans antigen I/H ingredients for repair work (eg. calcium, phosphate, casein,, non- denaturated casein, casein hydrolysates (CPP), buffering components such as chitosan, polyethyleneimine fluorofosfaat, arginine and arginine containing peptides (with 2-4 amino acids).
  • Calcium salts can include calcium chloride, calcium acetate, calcium citrate, calcium butylate, calcium lactate, calcium salicylate or another non toxic anorganic or organic calcium salt at a concentration between 0.1 % to 5% w/w. , -, -, -, zwitterionic detergents as described in US 3988433, US 4051234, US 3959458.
  • Non ionic detergents are condensates from hydrophilic alkylene oxide groups with hydrophobic organic components.
  • poloxamers sold under the name Pluronic
  • polyoxyethylene sorbitan esters Teween
  • polyethylene oxide condensates of alkyl phenols condensates of ethylene oxide with reaction products from propylene oxide and ethylene diamine
  • ethylene oxide condensates from aliphatic alcohols tertiary amine oxides with a long chain
  • tertiary phosphine oxide with a long chain dialkylsulfoxides with a long chain and mixtures.
  • Amphoteric detergents are aliphatic secondary and tertiary amines, with an aliphatic chain and with the presence of an anionic group (e.g. carboxylate, sulfonate, sulfate, phoshate, phosphonate).
  • Anionic detergents are salts of alkylsulfates with 8 to 20 carbon atoms (for example sodium alkyl sulfate) and salts of sulfonated monoglycerides from fatty acids with 8 to 20 carbon atoms.
  • alkylsulfates with 8 to 20 carbon atoms
  • salts of sulfonated monoglycerides from fatty acids with 8 to 20 carbon atoms examples: sodium lauryl sulfate and sodium coconut monoglyceride sulfonate, sarcosinates such as sodium lauroyl sarcosinate, sodium lauryl sulfoacetate, sodium lauroyl isethionate, sodium laureth carboxylate, sodium dodecylbenzenesulfoiiate or mixtures.
  • the dosage of an anionic detergent is between 0.025% to 9% and preferably between 0.1% and 5% w/w.
  • Thickeners can be used in the end formulation to provide the desired rheological profile: guar gum, carboxyvinyl polymers, carageenan, Ko ⁇ jac, scleroglucan, carboxymethyl cellulose, hydroxyethyl cellulose, polyoxyethylene polyoxypropylene glycol copolymers, gum karaya, gum arabic, gum tragacanth and xanthan in a concentration of 0.1 % to 15%.
  • Cross-linked polymers from acrylic acid, such as Carbopol from BF Goodrich are known in the sector.
  • the end formulation can contain a humidifier.
  • Polyalcohols provide a wet feeling and prevent the product from becoming hard upon contact with air.
  • sorbitol examples include glycerin, sorbitol, butylene glycol, polyethylene glycol, sorbitol.
  • the end formulation can contain products against tooth-stone such as pyrophosphate salts such as Na.sub.4 P.sub.2 O.sub.7, K.sub.4 P.sub.2 O.sub.7, Na.sub.2 K.sub.2 P.sub.2 O.sub.7, Na.sub.2 H.sub.2 P.sub.2 O.sub.7 and K.sub.2 H.sub.2 P.sub.2 O.sub.7, sodium hexamethaphosphate, sodium tripolyphosphate and cyclic phoshphates such as sodium trimetaphosphate.
  • the dosage is about 0.5% to 10% w/w.
  • Anionic polycarboxylates or carboxylated chitosan could be used eventually in order to increase the anti-tooth stone effect.
  • Copolymers of maleic anhydride with other ethylenic monomers such as methyl vinyl ether with a molecular weight between 30.000 and 1.000.000 and preferably between 30.000 and 500.000 are known under the name Gantrez (US4627977).
  • the concentration in the end formulation is between 0.5% and 5%.
  • Other possibilities include zinc citrate trihydrate, polyphosphates, diphosphonates (EHDP).
  • the end formulation can contain aroma's, often at a concentration between 0.001% and 5% and preferably between 0.5% and 1.5% w/w.
  • Examples are: spearmint, peppermint, menthol, anethole, methyl salicylate, cassia, 1-menthyl acetate, eugenol, parsley oil, oxanone, alpha-irisone, marjoram, propenyl guaethol, vanillin, thymol, linalool, cinnamaldehyde glycerol acetal, wintergreen, sassfras clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, orange.
  • the end formulation can also contain sweeteners; besides the known anticariogenic sweeteners the following products are valuable: sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts, thaumatin, aspartame, D-tryptophan, dihydrochalcone, acesulfame and cyclamate salts.
  • sweeteners besides the known anticariogenic sweeteners the following products are valuable: sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts, thaumatin, aspartame, D-tryptophan, dihydrochalcone, acesulfame and cyclamate salts.
  • the end formulation can also contain ingredients against over-sensitivity (for example potassium nitrate or potassium citrate), whitening agents (hydrogen peroxide, calcium peroxide, urea peroxide), preservatives, cooling agents (carboxamides, menthol, ketals), anti-inflammatory ingredients (aspirin, ibuprofen, naproxen.).
  • compositions of end formulations are known and are added for reference: for example for mouthrinses US3988433, for candies US 4083955, for chewing gum US 4083955.
  • Mouth rinses and sprays often contain water (45% to 95%), ethanol (0% to 25%), a humidifier (0% to 50%), a tensio-active agent (0.01% to 7%), an aroma (0.04% to 2%), a sweetener (0.1% to 3%) a coloring agent (0.001% to 0.5%) and eventually an anticariogenic product (fluoride; 0.05% to 0.3%) or a product against tooth stone (0.1% to 3%).
  • Another formulation concerns non-abrasive gels (subgingival gels). They contain a thickener (0.1% to 20%), a humidifier (0.1% to 910%), an aroma
  • Chewing gum formulations often contain gum (50% to 99%), an aroma (0.4% to 2%), a sweetener (0.01% to 20%) and optionally an anticariogenic product.
  • Candies, mints, capsules, tablets and other food systems have been described in US 4642903, US 4946684, US 4305502, US 4371516, US 5188825, US 5215756, US 5298261, US 3882228, US 4687662, US 4642903.
  • Epsilon polylysine (so-called e-polylysine; degree of polymerisation; dp 30) and epsilon polylysine/dextrin spray dried powder are available from Chisso Corporation (Japan).
  • Polylysine with a dp of 2-7 can be obtained from Solabia (France).
  • Green tea extract can be sourced from companies such as Shanghai Lithy Foods Material Corp. (China), Ningbo Hanpharm Biotech Co. (China) or Shaanxi Jiahe Phytochem Co (China) with varying levels of polyphenolic compounds and EGCG (epigallocatechmgallate); DSM corp. (The Netlierlands) offers a tea extract with 94% EGCG.
  • Olive leaf extracts with more than 20% of oleuropein can be obtained from Guilin Layn Natural Ingredients corp. (China) and Genosa (Spain) offers olive fruit extracts with 45% hydroxytyrosol (Brandname: Hytolive).
  • Egg based lysozyme and lactoferrin are sourced respectively from Belovo corp. (Belgium) and DMV corp. (The Netherlands).
  • Xylitol and sorbitol are sourced from Roquette (France).
  • Histatin dh-5 is the synthetic fungicidal histatin analogue from the C-terminal part, residues 11-24, and sourced from the Vrije Universiteit Amsterdam (The Netherlands).
  • the menthol/thymol/eucalyptol alcohol mouth rinse can be obtained on the market under the trade name Listerine (Pfizer). Products such as glycine and lactic acid can be purchased from Aldrich (USA). Mint aroma's are from Firmenich (Germany).
  • VSC volatile sulfur compounds
  • the Halimeter does not respond equally to all three compounds, nor are all three compounds present in the same proportion in all patients — or even in the same patient — at all times.
  • the relative amounts of these compounds are affected by diet, and the extent of anaerobic bacterial growth. Elucidating the precise breakdown of the three compounds in an oral malodor sample requires a gas chromatograph.
  • the additive reading provided by the Halimeter correlates extremely well with organoleptic panels of trained human evaluators, and compares admirably with chromatographic testing.
  • the Halimeter reads out in parts-per-billion (ppb) of volatile sulfur compounds. Normal readings, for subjects with no oral malodor, are generally in the range of 80-140 parts per billion (ppb).
  • oral malodor is noticeable by an observer standing close to the patient.
  • the odor is noticeable by an observer standing several feet away from the patient.
  • the odor is more noticeable not because it is "stronger,” but because it is more foul.
  • the odor will linger for several minutes after the patient leaves the room. In many of these cases, odor will continue to emanate from the tongue during the entire sampling process, and the Halimeter reading will keep climbing, and may not truly peak, as the sample pump seems to draw more VSCs off the tongue surface.
  • the volunteer abstains from using hygienic products such as toothpaste over a period of several days, untill the average reading (of at least 3 measurements) is above 400 ppb. This is considered to be the "bianco" situation.
  • the measurements are mostly carried out just after wakening up, before breakfast. This avoids contamination with the varying paramaters that could affect readings during or at the end of the day (foods, drinks, tobacco.).
  • the volunteer is using the experimental product twice per day, in the morning after breakfast and in the evening just before going asleep.
  • the measurement of sulfur gases is carried out about twelve hours after use of the product (the next morning). Each time 3 measurements are taken and the average is used.
  • a volunteer was deprived for several days from using hygienic products (toothpaste's, moutwashes,...) in order to stimulate production of bad breath gases in the oral cavity and this untill the gas level was above 400 ppb (average of 3 measurements in the morning, just after wakening up on an empty stomach).
  • This value was established three times, each time before the use of the formulation with polyhydroxyphenolic ingredient, or with e-polylysine or with a mixture of both; the average of the three values is set to be the "bianco".
  • the volunteer used an oral pump spray formulation after breakfast ( 4 x 0.14 ml dosage) and repeated the treatment a second time just before going to bed in the evening.
  • the measurement of sulfur-gases was carried out after a residence time of above 12 hours (overnight; this is the time between the use of the product and the measurement); the measurement was done just after wakening up the following morning (on an empty stomach). The measurement was carried out three consecutive times (at the same moment) per day and was repeated daily over a period of 4 days (the given data are an average of 12 gas determinations over 4 days).
  • the aqueous solutions contained also 3% weight percent of erythritol and 3 drops of Mint-aroma per 40 gr of water.
  • Formulations where made respectively with the following active ingredients: natural extracts that contain a polyhydroxyphenolic component, such as olive extract (with 40% hydroxytyrosol) or green tea extract, or epsilon-polylysine (dp 30) or a mixture of epsilon polylysine with such natural extracts. 0.2% Glycine was also added to all formulations which contained e-polylysine.
  • natural extracts that contain a polyhydroxyphenolic component, such as olive extract (with 40% hydroxytyrosol) or green tea extract, or epsilon-polylysine (dp 30) or a mixture of epsilon polylysine with such natural extracts.
  • dp 30 epsilon-polylysine
  • Glycine was also added to all formulations which contained e-polylysine.
  • the pH was adjusted with lactic acid to 6.8-7.0 in all formulations except those that contained a mixture of e-polylysine and a green tea extract ( pH:5.75) Active ingredient(s) in the formulation / dosage of active ingredient weight %/ measurement of Sulfur-gases in ppb (Avg of 3 determinations) / variation with the bianco/ pH: bianco / 0%/ 474 / -% / - olive extract (hytolive) / 0.5% / 440 / -7.2% / 6.8-7.0 e-polylysine dp30 / 0.5% / /172 / -63.7% / 6.8-7.0 e-polylysine dp30 + olive extract (hytolive) / 0.5% + 0.5% / -77.4% / 6.8-7.0 bianco /0%/ 402/-%/ - green tea extract A / 0.5% / 392 / -2.5% / 6.8-
  • Number of the day / volunteer 1 determination of sulfur gases in the morning ppb/ volunteer 2: determination of sulfur gases in the morning / volunteer 1: determination of gases in the evening / volunteer 2: determination of gases in the evening: 0 1 / - / - /296.3/-
  • Average of number of days / volunteer 1 average of determination of sulfur gases in the 0 morning (stand, dev.) / volunteer 2: average of determination of sulfur gases in the morning (stand, dev.) / volunteer 1: average of determination of gases in the evening (stamd. dev.)/ volunteer 2: average of determination of gases in the evening (stand, dev.):
  • a volunteer was deprived for several days from using hygienic products (toothpaste's, moutwashes,...) in order to stimulate production of bad breath gases in the oral cavity 5 and this untill the gas level was above 400 ppb (average of 3 measurements in the morning, just after wakening up on an empty stomach); the average of the three values is selected as the "bianco".
  • the volunteer used an oral pump spray formulation after breakfast ( 4 x 0.14 ml dosage) and repeated the treatment a second time just before going to bed in the 0 evening.
  • the measurement of sulfur containing gases was carried out after a residence time of above 12 hours (overnight; this is the time between the use of the product and the measurement); the measurement was done just after wakening up the following morning (on an empty stomach). The measurement was carried out three consecutive times (at the 5 same moment) per day and was repeated daily over a period of 4 days (the given data are an average of 12 gas determinations over 4 days).
  • polylysine is active in a variety of forms, either as e-polylysine with a degree of polymerisation of dp 30 or polylysine with a dp of 5-7 or as an spray dried e-polylysine / dextrin 50/50 mixture; the activity is dose dependant.
  • a variety of olive extracts can be used, such as one containing 20% oleuropein or +40% hydroxytyrosol. It is evident that not all antibacterial peptides demonstrate antihalitosis competence; as opposted to e-polylysine, the activity of lysozym, lactoferrin and histatin hv-5 is modest. Equally, the effect of a mixtures of etheric oils such as thymol in the presence of ethanol is limited. Formulation 5 has been stored for + 3 months before use, demonstrating it's resistance against degradation.
  • Experiment 4 Determination of sulfur containing gases in the oral cavit y after the use of e-polylvsine and Dolvhvdroxvphenolic compounds in Mint-tablets After establishing the sulfur gas content of above 400 ppb for the determination of the bianco, as in experiment 3, the volunteer used one tablet in the morning, after breakfast and one tablet after evening dinner. The gas measurement was conducted before breakfast.
  • Peptide mix the use of epsilon-polylysine, or a mixture of e-polylysine and another antimicrobial peptide, such a lysozyme. Lozenge & mint 0.28 gram
  • Peptide mix epsilon-polylysine, or a mixture of e-polylysine and another antimicrobial peptide, such a lysozyme.

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Abstract

L'invention concerne des ingrédients et des préparations présentant une efficacité accrue et un effet longue durée dans le traitement de l'halitose (mauvaise haleine indésirable), résultant de l'effet synergique de l'utilisation dans cette préparation d'un mélange d'(epsilon)-polylysine et de composés polyhydroxyphénoliques, tels que des extraits de thé vert (contenant des composés polyphénoliques et/ou de l'épigallocatéchingallate) ou des extraits d'olive (contenant de l'oléuropéine et/ou de l'hydroxytyrosol) ou une combinaison de ceux-ci. L'invention concerne également un nouveau procédé de production destiné à empêcher la précipitation lors du mélange d'(epsilon)-polylysine et des extraits de thé vert. Les ingrédients et préparations selon l'invention peuvent être utilisés en bains de bouche, sprays buccaux, gels, comprimés se dissolvant dans la cavité buccale, chewing-gums, bonbons, salive artificielle.
PCT/EP2006/000973 2005-04-29 2006-02-03 Utilisation de polylysine associee a des extraits de the vert ou des extraits d'olive ou les deux dans le traitement de l'halitose WO2006117029A1 (fr)

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WO2007061912A3 (fr) * 2005-11-23 2008-01-31 Coca Cola Co Composition d'edulcorant tres puissant avec un agent anti-inflammatoire et compositions sucrees avec celle-ci
FR2922445A1 (fr) * 2007-10-19 2009-04-24 Oreal Compositions cosmetiques pour le traitement des fibres keratiniques comprenant une polylysine et un agent alcalin
FR2922446A1 (fr) * 2007-10-19 2009-04-24 Oreal Composition comprenant au moins une polylysine et au moins un agent alcalin particulier, procede de coloration et/ou de decoloration des fibres keratiniques
US8017168B2 (en) 2006-11-02 2011-09-13 The Coca-Cola Company High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith
EP2465361A1 (fr) 2010-12-16 2012-06-20 PURAC Biochem BV Procédé pour inhiber l'activité de la levure
DE102011077055A1 (de) * 2011-06-07 2012-12-13 Beiersdorf Ag Wirkstoffkombinationen aus å-Polylysin (Epsilon-Polylysin) und einem oder mehreren aromatischen Estern
WO2013010709A3 (fr) * 2011-07-21 2013-11-07 Henkel Ag & Co. Kgaa Agent de traitement capillaire alcoolique contenant de la poly-l-lysine
WO2012167936A3 (fr) * 2011-06-07 2013-11-21 Beiersdorf Ag Combinaisons de principes actifs comprenant de l'є-polylysine (epsilon-polylysine) et un ou plusieurs terpènes
CN104305203A (zh) * 2014-11-12 2015-01-28 解青 一种用于龋齿预防的制剂
US9101160B2 (en) 2005-11-23 2015-08-11 The Coca-Cola Company Condiments with high-potency sweetener
CN104971082A (zh) * 2014-04-08 2015-10-14 上海交通大学 橄榄树叶在制备或筛选治疗口臭的药物中的用途
JP2016023142A (ja) * 2014-07-16 2016-02-08 株式会社ロッテ 口臭抑制剤
JP2016147869A (ja) * 2016-02-25 2016-08-18 サンスター株式会社 メチルメルカプタン発生抑制用口腔用組成物
GB2535989A (en) * 2015-02-26 2016-09-07 Dr Heff's Products Ltd Dental product, use of a dental product and methods of use of a dental product
US9561168B2 (en) 2011-12-15 2017-02-07 Colgate-Palmolive Company Oral care compositions
JP2018058887A (ja) * 2017-12-07 2018-04-12 サンスター株式会社 メチルメルカプタン発生抑制用口腔用組成物
JP2019194264A (ja) * 2019-08-13 2019-11-07 サンスター株式会社 メチルメルカプタン発生抑制用口腔用組成物
US10470459B2 (en) 2014-05-28 2019-11-12 Ipabc Ltd Antimicrobial preparations, methods for preparing the same and uses thereof to combat microorganisms
GB2578147A (en) * 2018-10-18 2020-04-22 Oraldent Ltd Bioflavonoid compositions and their use
WO2022079498A1 (fr) * 2020-10-13 2022-04-21 Magi Euregio Scs Composition pour la prévention de l'infection par le sars-cov-2
CN114983872A (zh) * 2022-05-30 2022-09-02 浙江大学 一种具有优异血液相容性的可吞咽爆珠漱口水及其制备方法
CN115607488A (zh) * 2022-09-26 2023-01-17 喜德县元升农业科技有限公司 一种含有油橄榄提取物的漱口水
US11980185B2 (en) 2018-10-18 2024-05-14 Citrox Biosciences Limited Bioflavonoid compositions and their use for water purification and food preservation

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Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007061912A3 (fr) * 2005-11-23 2008-01-31 Coca Cola Co Composition d'edulcorant tres puissant avec un agent anti-inflammatoire et compositions sucrees avec celle-ci
US9101160B2 (en) 2005-11-23 2015-08-11 The Coca-Cola Company Condiments with high-potency sweetener
US8017168B2 (en) 2006-11-02 2011-09-13 The Coca-Cola Company High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith
FR2922445A1 (fr) * 2007-10-19 2009-04-24 Oreal Compositions cosmetiques pour le traitement des fibres keratiniques comprenant une polylysine et un agent alcalin
FR2922446A1 (fr) * 2007-10-19 2009-04-24 Oreal Composition comprenant au moins une polylysine et au moins un agent alcalin particulier, procede de coloration et/ou de decoloration des fibres keratiniques
EP2465361A1 (fr) 2010-12-16 2012-06-20 PURAC Biochem BV Procédé pour inhiber l'activité de la levure
WO2012080302A1 (fr) 2010-12-16 2012-06-21 Purac Biochem Bv Procédé pour l'inhibition de l'activité de levures
DE102011077055A1 (de) * 2011-06-07 2012-12-13 Beiersdorf Ag Wirkstoffkombinationen aus å-Polylysin (Epsilon-Polylysin) und einem oder mehreren aromatischen Estern
WO2012167936A3 (fr) * 2011-06-07 2013-11-21 Beiersdorf Ag Combinaisons de principes actifs comprenant de l'є-polylysine (epsilon-polylysine) et un ou plusieurs terpènes
WO2013010709A3 (fr) * 2011-07-21 2013-11-07 Henkel Ag & Co. Kgaa Agent de traitement capillaire alcoolique contenant de la poly-l-lysine
US9561168B2 (en) 2011-12-15 2017-02-07 Colgate-Palmolive Company Oral care compositions
CN104971082A (zh) * 2014-04-08 2015-10-14 上海交通大学 橄榄树叶在制备或筛选治疗口臭的药物中的用途
US10470459B2 (en) 2014-05-28 2019-11-12 Ipabc Ltd Antimicrobial preparations, methods for preparing the same and uses thereof to combat microorganisms
JP2016023142A (ja) * 2014-07-16 2016-02-08 株式会社ロッテ 口臭抑制剤
CN104305203A (zh) * 2014-11-12 2015-01-28 解青 一种用于龋齿预防的制剂
GB2535989A (en) * 2015-02-26 2016-09-07 Dr Heff's Products Ltd Dental product, use of a dental product and methods of use of a dental product
JP2016147869A (ja) * 2016-02-25 2016-08-18 サンスター株式会社 メチルメルカプタン発生抑制用口腔用組成物
JP2018058887A (ja) * 2017-12-07 2018-04-12 サンスター株式会社 メチルメルカプタン発生抑制用口腔用組成物
GB2578147A (en) * 2018-10-18 2020-04-22 Oraldent Ltd Bioflavonoid compositions and their use
US11980185B2 (en) 2018-10-18 2024-05-14 Citrox Biosciences Limited Bioflavonoid compositions and their use for water purification and food preservation
JP2019194264A (ja) * 2019-08-13 2019-11-07 サンスター株式会社 メチルメルカプタン発生抑制用口腔用組成物
WO2022079498A1 (fr) * 2020-10-13 2022-04-21 Magi Euregio Scs Composition pour la prévention de l'infection par le sars-cov-2
CN114983872A (zh) * 2022-05-30 2022-09-02 浙江大学 一种具有优异血液相容性的可吞咽爆珠漱口水及其制备方法
CN114983872B (zh) * 2022-05-30 2023-11-28 浙江大学 一种具有优异血液相容性的可吞咽爆珠漱口水及其制备方法
CN115607488A (zh) * 2022-09-26 2023-01-17 喜德县元升农业科技有限公司 一种含有油橄榄提取物的漱口水

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