BE1016514A6 - PRODUCTS FOR USE AGAINST HALITOSIS. - Google Patents

Description

Products for use against halitosis ~ "

Technical field

This invention relates to the use of oral care formulations, pastes, gels, powders, chewing gums, candies, mints, mouthwashes, mouth sprays, artificial saliva, containing one or more antibacterial products, for the treatment of halitosis.

State of the art

Bad mouth odor, also known as "halitosis" is an unwanted physical condition that affects many people. Approximately thirty percent of the population is confronted with it. It is well known that the undesirable mouth odor is caused by volatile sulfur gases (VSC), among which hydrogen sulphide, methyl mercaptan and methyl sulphide occupy an important place, which occur when dead cells are broken down and are produced by, mainly, anaerobic bacteria that mainly occur in the posterior tongue area. Some diseases such as oral cancer, diabetes, liver and kidney diseases and sinusitis can contribute to the development of halitosis, but it is known in the scientific world that the bacterial flora in the area of the tongue is the dominant cause. Good oral hygiene can contribute to an improvement, but is rarely sufficient to resolve halitosis.

A number of product groups have been developed that influence the bacterial flora and that can reduce the occurrence of halitosis: metal salts, oxidizing agents, bactericides, chitosan and natural extracts. Primarily zinc, tin and bismuth salts are used but their efficiency against halitosis is limited (US5833952, US6426085, US6702999, US50053556); sometimes complexes are used to increase solubility (polyamines: US5587147, inulin: US6511679, glycine: US6607711); Due to the toxicity to human cells, long-term use is less appropriate.

Oxidizing substances also have an antiseptic effect. In addition to hydrogen peroxide (US40234463), chlorine dioxide (US6582682, US6696047,) and chlorite (US6375933, US02114851, 030129144) are mainly used. Oxidants have a non-selective effect that affects the entire mouth flora; they create resistant bacteria after prolonged use, have a relatively high toxicity & LD50 value, are relatively unstable in oral care formulations and offer, on several occasions, a very undesirable taste that is typical for oxidizing and chlorinated products.

Bactericides are also used, including the cetylpyridine (US5972312, US6344184), salicylic aldehyde (US4025'TO3) phenophic bactericides such as triclosan (US5882631, which all have only limited efficiency, but especially also have chloro-hexidine (US20030165411); a broad spectrum of activity, creates resistant bacteria after prolonged use, discolor the teeth, burden the stomach and have a previously undesirable taste.It is generally accepted that the prolonged use of this product is less appropriate.

In the case of natural products, mention is made primarily of extracts containing one of the following active ingredients: phenols, quinones, flavones, tannins, coumarins, terpenoids, essential oils and alkaloids; mostly essential oils are used (US5401496, US5891422, US6348187, US6350435, US6379652, US 6555093, US6689342, US20054859, US40253192) they offer limited efficiency against halitosis. Also extracts from Mouton Bark (US40224287) and from the citrus Vitus plant (US6706256), as well as enzymes (oxidoreductases, US6074631), calcium hydroxide (US60715X)) and living organisms (yeast: US5866116).

The use of natural, non-degraded, high molecular weight chitosan against halitosis is mentioned in (US4512968); however, chitosan hydrolysates, also called chitosan oligosaccharides, with a molecular weight between 100 and 35000 daltons, are not mentioned in the patent. (US20050042184) does mention the use of chitosan oligosaccharides, but only for use against tartar and for the care of mucosa, not against halitosis.

The use of cationic antibacterial peptides against halitosis is limited. The use of antibacterial substances, more specifically antibacterial peptides, against the bacteria that cause caries does not automatically imply efficient usability against halitosis. Caries is caused by other bacteria, the best known of which is Streptococcus mutans. Caries and periodontitis are clinical conditions that occur around and around the teeth and that can result in the loss of teeth; whereas halitosis is caused by anaerobic bacteria and which, according to scientific research, mainly reside on the posterior part of the tongue (ref. S Roldan et al., Clin.Oral Investig. 2003 Dec; 7 (4): 189-97; ref M.

Tanaka, Microbes Infect. 2004 Oct; 6 (12): 1078-83; ref. WJ. Loesche, Curr Infect. Dis Rep. 2003 Jun; 5 (3): 220-226; ref. DV Messadi, Dermatol Clin 2003 Jan; 21 (1): 147-55; ref. U Cicek, Pediatric Int. 2003 Dec; 45 (6): 719-23).

There are also many people who are in charge of halibsis but have no periodontitis. There are several reasons why some antimicrobial products have a defective effect against halitosis. Some have a limited intrinsic competence, or their action due to other substances present in the mouth area or do not reach the bacteria hidden deep in the craters of tongue and environment, or the duration of their presence in the mouth area is too limited to to be effective. Preventing caries and periodontitis requires a force around and around the teeth, while halitosis requires an efficient antibacterial effect in the area of the tongue. The effect of an antibacterial product against halitosis should therefore also be evaluated specifically for this application.

(JP1993 310544A) only mentions the use of epsilon-polylysine against caries (anti-cavity) and periodontitis, but not against halitosis. The experiments report the use of S. Mutans but not of bacteria that are relevant for halitosis. Patent report (JP 2004107310) mentions the use of the epsilon-polylysine and inactive siloxane mixture against bacterial plaque control on teeth, caries, periodontitis and halitosis. The patent refers to an allegedly insufficient effect of epsilon-polylysine itself for control of bacterial plaque. No experimental data is provided that could demonstrate the efficiency of the epsilon-polylysine and halitosis siloxane mixture and the use of epsilon-polylsine without the presence of halitosis siloxane is not mentioned in the patent. It is clear that these formulations are more suitable for combating caries and periodontitis. Siloxanes are useful ingredients (abrasives) in toothpastes and gels for dental treatment but are not suitable in formulations for treatment of the tongue area and in formulations that the user swallows more (mouthwashes, spray pumps, mints, gums). After all, unlike peptides, they are not degradable in the human organism. The necessity of the presence of siloxane in formulation against halitosis has not been demonstrated experimentally. No experimental data has been reported with the use of bacteria relevant to halitosis.

It is therefore appropriate to develop a formulation for halitosis that contains only substances that are readily degradable by the human organism and the use of syloxane against halitosis is not recommendable.

The use of lysozyme against halitosis is limited to gum formulations (CN1318314). The antibacterial competence is limited. The same applies to lactoferrin that is only patented for halitosis in combination with other substances: lactoferrin and epigallocatechin (WO2004012522), lactoferrin or lysozyme with an adhesive such as polyvinyl alcohol (JP2002322088), lactoferrin or lysozyme with an immunoglobulin concentrate (JP2003137809). The use of lactoferrin and lysozyme alone or in combination with each other is safe for oral use but € # 05/0222 competence and therefore the effect on halitosis is limited.

(EP2004013549) claims the useful use of epsilon-polylysine (siloxane-free) for halitosis and demonstrates by means of bacteriological tests that epsilon-polylysine exhibits a selective action against anaerobic bacteria (70% and 11% of anaerobic and aerobic bacteria respectively are inhibited with the same dosage), which makes the product very suitable for use against halitosis; the efficient effect against halitosis is proven experimentally with gas measurements in the mouth area. However, there is still a great need for products that combine an even higher degree of safety with oral use with a high and even longer lasting efficiency against halitosis.

Invention

We have unexpectedly determined that hydrolyzed chitosan (also called chitosan oligosaccharide) is alctive to halitosis and that the antimicrobial competence of the polyamines, both epsilon-polylysine and chitosan oligosaccharide, can be improved and enhanced synergistically against halitosis by its use in combination with one or more other natural antimicrobial products, either an antimicrobial peptide or an antimicrobial plant extract. The effect of the mixture is better than the sum of the competences of the ingredients.

Without being bound by any explanation, the synergy is attributed to a difference in the mechanism of action of the antimicrobial products, whereby the action of one product can reinforce that of the other product. Epsilon-polylysine has a broad spectrum activity on gram + and gram bacteria with preference for anaerobic bacteria while nisin is able to drill holes in the bacterial wall and is more effective against gram + bacteria; lysozyme specifically hydrolyses beta 1,4-glucosidic bonds between N-acetyl muramate and N-acetyl glucosamine. Defensins and Cathelicidins are cationic peptides that interact with the bacterial wall. They have a broad operating spectrum. Lactoferrin is bacteriostatic because it is capable of complexing with Fe ions and the activity of the related cationic lactoferricin is not dependent on Fe complexation. Histatins are a group of peptides that are rich in histidine amino acids. They are very active against C. Albicans, especially the histatin-5.

It is of great importance that antimicrobial peptides and saccharides, in comparison with other product groups used against halitosis, combine a very low toxicity with a high efficiency. This allows efficient use during a prolonged period. This is due to the fact that these products act on specific structural components of the bacterial wall (such as anionic lipids) that occur less on the walls of human cells; as a result, the difference in toxicity of the product to the bacterium and the human cell is very high compared to existing antihalitosis products and its long-term use is indicated. In addition, the use of one or more antimicrobial peptides rarely leads to resistance formation.

We have unexpectedly determined that hydrolyzed chitosan, with a molecular weight of 35 kDa or lower, is active against halitosis. This is not self-evident since a decrease in molecular weight can weaken or destroy the antimicrobial effect. Example Chitosan hydrolysates used with a molecular weight of between 2000 and 20000 Daltons. The chitosan hydrolyzate is more suitable for use against halitosis compared to the non-hydrolyzed chitosan (only soluble at acidic pH), because of its good water solubility in a wide pH range (at acidic, neutral and basic pH). The product combines efficiency with user-friendly usability in oral care formulations against halitosis.

In an additional aspect of the innovation, it was unexpectedly found that the activity of chitosan oligosaccharide or epsilon-polylysine against halitosis is synergistically enhanced by the concomitant use of one or more other antimicrobial peptides, including the lysozyme (of egg or other origin), the lactorferrin and its structurally related peptides (e.g. Fe-poor lactoferrin), lactoferricin, histatin and derivatives such as dh-5 (amino sequence 11-24 trom histatin-5, ref. EJ Helmerhorst, Biochem. J. (1997) 326 ( 39-45)), nisin, subtilin, protamine, defensin and structurally related peptides, cathelicidin and related peptides. All these peptides belong to the group of cationic peptides. The experimental confirmation of the synergistic action of some of them illustrates the finding that peptides from this group can induce a synergistic action with epsilon-polylysine (also called e-polylysine) and hydrolyzed chitosan.

In an additional aspect of the innovate, it was unexpectedly established that a natural antimicrobial plant extract can also be used to synergistically enhance the anti-halitosis effect of epsilon-polylysine or hydrolysed chitosan. The extracts contain phenol-like structures, polyphenols, flavones, tannins or coumarins that react with bacterial components via the hydroxyl groups, or complex with saccharides, proteins and with the bacterial wall and inhibit enzymes; quinones form radicals and complex with nucleophele amino acids; essential oils are rich in terpenes that are thought to react with the hydrophobic bacterial wall. Terpenes are active against bacteria, fungi and viruses. The following natural plant extracts are eligible for generating synergy with hydrolyzed chitosan or with epsilon-polylysine:

Eucalyptus globulus, Menthol extract, Echinaceae angustifolia, Withania Somniferum, Laurus nobilis, Rhamnus purshiana, Ricinus communis, Erythroxylum coca, coriandrum sativum, Garcinia hanburyi, Gloriosa superba, Green tea, Peganum harmala, Armhereaia genus, Armorea erea peaumera, Rustic piperaceaumea, Olea peaumera , Licorice root, vinifera, Thymus vulgaris ,, Umbelliferae, Teetree oil, salicjylate oii, eugenol extract. Some examples illustrate the synergistic effect between products from the group of plant extracts with hydrolyzed chitosan and with epsilon-polylysine.

The antihalitosis effect can be demonstrated experimentally by means of a halimeter (RH-17 series, InterScan corp) that measures the presence of some sulfur gases (hydrogen sulfide, methyl mercaptan, methyl sulfide) in the mouth area.

To this end, the device sucks an air sample from the mouth area via a straw in the device, the gas dose being indicated in ppb. A dose of 80 to 150 ppb is considered normal for a user who does not suffer from halitosis. The length of time elapsed between the moment the antihalitosis agent is used and the moment the measurement takes place gives an indication of the duration within which the product exhibits an antihalitosis effect.

Hydrolyzed chitosan, epsilon-polylysine or a mixture thereof in combination with other microbial peptides can be used in any concentration depending on the type of formulation, preferably a concentration of 0.001% to 20% and even more preferably between 0.1% and 10%. Natural plant extracts can be used at any dosage depending on the type of formulation, preferably in a dosage between 0.001% and 10%, more preferably between 0.1% and 2%.

Epsilon-polylysine and hydrolyzed chitosan can be used in basic form or in salt form. In the latter case, an acid is added to the polyamine; for example: hydrochloric acid, sulfuric acid, phosphoric acid, or any other inorganic acid; or also acetic acid, propionic acid, fumaric acid, maleic acid, citric acid, adipic acid, gluconic acid or lactic acid or any other organic acid. One or more amino acids can also be added to enhance the antihalitosis effect. Including, glycine, alanine, valine, leucine, aspartic acid, glutamic acid, lysine, arginine and the like ...

Other ingredients in final formulations

The new tooth-protecting polymers can be used in known end formulations of various kinds for oral hygiene and antihalitosis applications: pastes, mouth-refreshing solution, mouthwash, mouth spray, gels, chewing gum, candies, mints and other foods,

An overview of the ingredients of this final formulation2 ^ 00§ÿi0222 mentioned in US 6,238,648, which is attached for reference.

The final formulations against halitosis may also contain other components: fluorides (US 2,946,725 and US 3,678,154; for example, fluoride salts of alkali metals of tin such as sodium fluoride, sodium monofluorophosphate or tin fluoride or encapsulated fluoride derivatives (to protect against deactivating agents) Fluoride components are used in a concentration of about 0.1 to 1% w / w and preferably between 0.25 and 0.5% by weight The final formulation may also contain other agents such as synthetic bactericides, zinc metal salts, bismuth or tin, sugars such as xylitol, erythritol and sorbitol, enzymes such as dextranase, calcium, phosphates, casein, undenatured casein, casein hydrolyzates (CPP), polyethylene imine fluorophosphate, arginine and arginine peptides (2-4).

Some ingredients (eg calcium salts) can be encapsulated with a micelle-forming substance or a water-resistant coating, to avoid interference with fluoride during the storage period.

Calcium chloride, calcium acetate, calcium butylate, calcium citrate, calcium lactate, calcium salicylate, or other non-toxic inorganic or organic calcium salt at a concentration of 0.1% to 5% w / w can be used.

The final formulation may also contain surfactants including non-ionic, anionic, amphoteric, cationic, zwitterionic and synthetic detergents described in various patents: US 3,988,433, US 4,051,234, US 3,959,458.

Non-ionic detergents are condensates of hydrophilic alkylene oxide groups with hydrophobic organic components. Examples of non-ionic are: poloxamers (sold under the name Pluroric), polyoxyethylene sorbitan esters ("Tween"), polyethylene oxide condensates of allcyl phenols, condensates of ethylene oxide with reaction products of propylene oxide and ethylene diamine, ethylene oxide condensates of aliphatic alcohols, tertiary amine oxides with chain, tertiary phosphine oxide with chain, dialkyl sulfoxides with chain and mixtures.

Amphoteric detergents are aliphatic secondary and tertiary amines where the aliphatic component is a straight or branched chain with the presence of an anionic group (e.g., carboxylate, sulfonate, sulfate, phosphate, phosphonate).

Anionic detergents are salts of alkyl sulfates with 8 to 20 carbon atoms (e.g. sodium alkyl sulfate) and salts of sulfonated monoglycerides of fatty acids with 8 to 20 carbon atoms.

A few examples: sodium lauryl sulphate and sodium colloxyl sulphonate, sarcosinates such as sodium lauroyl sarcosize, sodium lauryl sulphoacetate, sodium lauroyl isethionate, sodium laureth carboxylate, sodium dodecyl benzenesulphonate or mixtures. Usually an amount of anionic detergent is used from 0.025% to 9% and preferably 0.1% to 5% w / w.

Thickeners are used in final formulations to obtain a suitable Theological profile: guar gum, carboxyvinyl polymers, carageenan, carboxymethylcellulose, polyoxyethylene polyoxypropylene glycol copolymers, gum karaya, scleroglucan, gum arabic, gum tragacanth and xanthan gum are used in a concentration of 0.1% to 15%. Carbopol from BF Goodrich, cross-linked polymers of acrylic acid are known in the sector.

The final formulation may also contain a humidifier. This relates, for example, to polyalcohols which prevent the formulation from hardening upon air contact and which offer a soft, moist mouthfeel. More specifically, it concerns glycerin, sorbitol, butylene glycol, polyethylene glycol, sorbitol.

The final formulation may also contain abrasives that are well known for this application: silica such as amorphous hydrated silica, siloxanes such as, for example, cetyl dimethicone or polyoxyethylene polysiloxane copolymer, sodium methaphosphate, potassium metaphosphate, tri-calcium phosphate, calcium phosphate two-hydrate, calcium phosphate, calcium pyrophosphate, sodium bicarbonate, calcium bicarbonate, hydrated alumina.

Sometimes polymers are used as abrasives (US 3,070,510): melamines, polyphenols, melamine, ureas, urea formaldehyde .... Silica abrasives are described in US 3,538,230 and US 3,862,307 (attached for reference). "Syloid" (from W.R. Grâce & Company) and "Zeodent" from (J.M.Huber corporation) are well-known names. Toothpaste usually contains 10% to 70% abrasive. A mixture of abrasives can also be used.

The final formulation may also contain anti-tartar ingredients 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.4 K.sub.2 P.sub.2 O.sub.7, Na.sub.4 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 phosphates such as sodium trimethaphosphate.

The usage dose is around 0.5 to 10% w / w. If necessary, anionic polycarboxylates or carboxylated chitosan can be used to enhance the anti-tartar effect. Copolymers of maleic acid (anhydride) with other ethylenic monomers such as m / 10 / S2 / O222 ether / maleic anhydride with a molecular weight of JO.TfuC up to 1,000,000 and preferably between 30,000 and 500,000 are known under the name Gantrez. The usual concentration is between 0.5% and 5%. Other options are zinc citrate trihydrate, polyphosphates, diphosphonates (EHDP) and polypeptides.

The final formulation may also contain flavoring agents, usually at a concentration between 0.1% and 5% and preferably between 0.5% and 1.5% w / w. Examples of available oils are: spearmint, peppermint, menthol, anethole, methyl salicylate, cassia, 1-menthyl acetate, eugenol, parsley oil, oxanone, alpha-irisone, marjoram, propenyl guaethol, vanillin, thymol, linalool, cinnamaldéhyde glycerol acetal , wintergreen, sassafras clove, sage, eucaluptus, marjoram, cinnamon, lemon, lime, grapefruit, orange.

The final formulation may also contain sweeteners; In addition to the known anticariogenic sweeteners, the following products are also useful: sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maitose, xylitol, saccharin salts, thaumatin, aspartame, D-typthophan, dihydrochalconen, acesulfame and cyclamate salts, sodium Saccharin.

The final formulation may also contain anti-caking agents such as magnesium stearate.

The final formulation may also contain ingredients against hypersensitivity (for example potassium nitrate or potassium citrate), whitening products (for example hydrogen peroxide, calcium peroxide, urea peroxide), preservatives, a cooling agent (eg carboxamides, menthol, lcetals), anti-inflammatory ingredients (aspirin, ibuprofen, naproxen ...).

The final formulation may also contain known preservatives.

The formulation can be offered in one or two phases; in the case of two-phase formulation, the ingredients are in two separate compartments and they are mixed just before use, by means of co-extrusion.

The composition of the various final formulations is well known and is included for reference: for pastes and gels, for example US3988433, for mouthwashes for example US3988433, for candies for example US 4,083,955, for chewing gum for example US 4,083,955 and for subgingival treatment for example US 5,198. 220.

Pastes and gels often contain an abrasive (10% detergent (0.5% to 10%), a thickening agent (0.1% to J>%), a humidifier (10% to 55%), a flavor (0.04% to 2%), a sweetener (0.1% to 3%), a colorant (0.01% to 0.5%), water (2% to 45%) and optionally an anti-carcinogenic or anti-bacterial product with antihalitosis effect (0.05% to 10%) or an anti-tartar product (0.1% to 13%)

Mouthwashes and sprays often contain the following products: water (45% to 95%), ethanol (0% to 25%), a humidifier (0% to 50%), a surfactant (0.01% to 7%), a flavoring agent (0.04% to 2%), a sweetener (0.1% to 3%) and a coloring agent (0.001% to 0.5%) and optionally an anti-carcinogenic product (fluoride; 0.05% to 0.3%), or an antibacterial product, if any with antihalitosis effect (0.01% to 10%) and an anticalculus agent (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 90%), a flavor (0.04% to 2%), a sweetener (0.1% to 3%), a color (0.01% to 0.5%) ), water (2% to 45%) and optionally an anti-carcinogen, an anti-bacterial product if appropriate with an antihalitosis effect or an anti-calculus product.

Chewing gum formulations usually contain a gum (30% to 99%), a flavoring agent (0.4% to 2%) and a sweetening agent (0.01% to 20%), and possibly also an anti-carcinogenic product or an anti-bacterial product, possibly with antihalitosis effect , contain.

Candies, lozenges, tokens, capsules, tablets, and similar food vehicles are described in the following patents: US 4,642,903, US 4,946,684, US 4,305,502, US 4,371,516, US 5,188,825, US 5,215,756, US 5,298. 261, US 3,882,228, US 4,687,662, US 4,642,903.

Claims (7)

1. The use of hydrolyzed chitosan and the use of at least one of the antimicrobial polyamines epsilon-polylysine and hydrolyzed chitosan, in combination with one or more ingredients selected from the group of natural antimicrobial products consisting of lysozyme, lactoferrin, lactoferricin, nisin , subtilin, protamine, histatin and peptides that are structurally related such as dh-5, defensin, cathelicidin and antibacterial plant extracts from eucalyptus globulus, Menthol extract, Echinaceae angustifolia, Green tea, Withania Somniferum, Laurus nobilis, Rhamnus purshiana, Ricinus communxylum, Erythropus communisylum coca coriandrum sativum, Garcinia hanburyi, Gloriosa superba, Peganum harmala, Armoracia rusticana, Olea europaea, mentha piperita, Gaultheria procumbens, Licorice root, mouton bark, Vitis vinifera, Thymus vulgaris ,, Umbelliferae, Teetree oil and salyl extract in formulations for use in the treatment of halitosis. The use of ingredients according to claim 1 wherein hydrolyzed chitosan has a molecular weight between 100 and 35,000 dalton. The use of the ingredients according to claim 1 wherein epsilon polylysine is present in the base or salt form. 4: The use of the ingredients according to claim 1 in combination with one or more amino acids, selected from all available types of amino acids and preferably glycine or alanine. The use of the ingredients according to claim 1 wherein the formulation contains epsilon-polylysine, lysozyme, lactoferrin, lactic acid, glycine and an anti-carcinogenic sugar such as erithrytol, mannitol and / or sorbitol. 6. The use of the ingredients according to claim 1 in formulations such as pastes and gels, mouthwashes, spray pumps, artificial saliva, lozenges, chewing gums, mints and candies. 7. The use of ingredients according to claims 1. to 5. in combination with known ingredients in the formulations of claim 6. such as those mentioned in this document, and for example, fluorides, synthetic bactericides, saccharides, phosphates, complexing substances and peptides and proteins, cäl ^ umzfruier ^ detergents, thickeners, wetting agents, abrasive products, anti-calculus products, flavors, sweetening agents, anti-cacking ingredients, whitening ingredients, anti-sensitivity products, preservatives and anti-inflammation ingredients Methods & materials Epsilon- polylysine, lactoferrin and lysozyme were obtained from Chisso Corp. (Japan), DMV corporation (The Nether lands) and Belovo (Belgium). Xylitol was obtained from Roquette (France) and lactic acid and glycine from Sigma Corp. The mint concentrate comes from the company Firmenich (Ag). The halimeter is from InterScan Corp (USA). Experiment 1: formulation with e-polylysine, lactoferrin and lysozyme The production of sulfur gases was measured with the aid of the halimeter in the mouth of two test persons over a period of sixteen days. The measurement was performed twice a day: in the morning just after getting up and before eating, and in the evening before eating. After sixteen days, the following anti-halitosis product is started daily (dosage in% by weight relative to the total formulation weight): epsilon-polylysine 1% lactoferrin 0.2% egg lysozyme 0.1% xylitol 3% glycine 0.2% mint concentrate 2 drops of lactic acid concentrate to pH 6.5 - 7 water 30 ml The pH was adjusted to 7 with lactic acid. From the 17th day onwards, the product is administered in the evening after eating (before bedtime) and in the morning after eating with a spray can (spray dose: 5 x spraying; dose volume 0.1 ml / spray). The spray head (with extension tube of approximately 4 cm) is placed in the mouth area and aimed at the center of the tongue). After spraying, swallowing is dispensed with for 0.5 to 1 minute so that the product is well dispersed in the mouth area. 'No alcohol is used within a period of 6 hours before the gas measurement. There is no eating within a two-hour period that precedes the gas measurement. The time between the use of the product and the gas measurement is therefore approximately 12 hours each. The gases are measured in ppb.

All gas values are expressed in ppb. * A-morning: Test person A, gas measurements taken in the morning before dinner. ** A-evening: Test person A, gas measurements taken in the evening before eating. 0 Avg day 1-16: the average of the daily values for the 2005/0222 Every day measurement is an average value of 3 gasmeters. The following formulations are added for illustration. For other formulations, reference is also made to the known formulations described in the literature and mentioned in this document. The ingredients of these innovative ingredients can be used in all known variants of oral care formulations. The dosage of the ingredients is stated in percent by weight (%) relative to the weight of the entire formulation. chewing eraser

* Peptide mix & chitosan: the use of hydrolyzed chitosan with a Mw of maximum 35 kDa, or of epsilon-polylysine, or of a combination thereof with one or more other antimicrobial peptides. Lozenge & mint 0.5 gram

mouthwash & mouth spray

Pasta & dentriflce