SK751089A3 - Assembly comprising dosing tank and content thereof - Google Patents

Abstract

A composition containing an effective anti-plaque proportion of a substantially water insoluble non-cationic antibacterial agent packaged in a dispensing container which includes a solid polymeric material, which solid polymeric material is compatible with the antibacterial agent. Also the composition contains a stabilising proportion of a terpene or flavouring agent which stabilises the antibacterial agent in the presence of less preferred plastic material.

Description

The invention relates to a kit comprising a dispensing container and its contents, comprising formulations containing 2 ', 4,4'-trichloro-2-hydroxydiphenyl ether (THDE) as an effective antibacterial agent against the formation of a dental plaque. Polymeric plastic which is in contact with the oral composition and is compatible with the antibacterial agent in the composition.

BACKGROUND OF THE INVENTION

Although various plastics may reduce the effectiveness of antibacterial agents against coating, some plastics such as polyfluoroethylene and polyvinyl chloride are THDE compatible and have been shown not to cause too much loss of antibacterial or dental plaque storage properties at room temperature. or even at a higher temperature. Although part of the container is a plastic that is not fully compatible and antibacterial, compatibility can be improved by adding a stabilizing amount of an antibacterial stabilizer, such as terpene, for example limonene or natural or synthetic oil, to the oral composition. at the same time a flavoring agent for oral compositions. The stabilizer should be included in a sufficient proportion to maintain the effectiveness of the anti-dental coating compositions during packaging and distribution. The invention also encompasses a toothbrush which comprises an effective proportion of a cleaning composition with an anti-dental coating effect.

The coating on the teeth is considered to be the cause of undesirable toothing conditions and, moreover, is a precursor of tartar. It can form on various parts of the tooth surface, including the gingiva margin. The appearance of the tooth becomes dull and can cause tartar and gum inflammation. It is therefore desirable

- 26.05.1999 oral composition containing a dental plaque-active ingredient.

Although it has been known that antimicrobial agents in oral compositions can reduce dental plaque formation and their effectiveness increases in combination with some other agents, various antibacterial agents have disadvantageous properties that limit their use in oral compositions. For example, cationic antibacterial agents, such as quaternary ammonium halides, may stain teeth differently and may be inactivated by anionic materials such as wetting agents in the same composition.

Especially water-insoluble halogenated and often also hydroxylated diphenyl ethers, such as THDE (triclosan) and 2,2'-dihydroxy-5,5'-dibromophenyl ether (DDDE), are particularly effective antifoam agents, but these may be inactivated by nonionic wetting agents and a variety of plastics. It is therefore an object of the present invention to use halogenated diphenyl ethers, in particular THDE and DDDE and similar dental plaque agents, in oral compositions so that they can be stored in packages and delivered for consumption without much loss of antibacterial storage performance prior to use. In the known triclosan-containing cleaners, it was not possible to provide effective amounts of antibacterial agent to prevent dental plaque formation once or twice a day at 1.5 g for brushing, a total of 1 minute, which is probably an average cleaning time after delivery to the consumer teeth. The compositions should cause at least a 25% reduction in coating formation after 3 weeks of use compared to using the control toothpaste in the same manner.

The most preferred antibacterial anti-tartar component is

THDE, ie. triclosan. This material was disclosed in U.S. Pat. 4 022

880 as an antibacterial agent in combination with a tartar-releasing agent that releases zinc ions and in DE 35 32 860 in combination with a copper compound. The same substance is also disclosed in European Patent Publication Nos. 161,898 and 161,899. No. 220,890 discloses dentifrice compositions which in addition contain polyethylene glycol and an essential flavoring oil.

Various compositions for oral administration or brushing of the teeth are known, such as pastes, gels, powders, liquid formulations, tablets, lozenges, liquid and tablet mouthwashes and, in addition, professional aids such as curing agents teeth containing, for example, fluoride ions. These products are usually packaged in deformable tubes, cartridges, equipped with dispensing equipment, pressurized cartridges, packages, bottles and other types of cartridges. Although the deformable tubes were originally made of metals such as lead and aluminum, and bottles were made of glass, in recent years these types of containers have often been made of synthetic organic polymeric plastics or laminates containing these plastics. Interactions are known between the oral composition and the material from which the container is made, for example, the reactions between toothpastes and aluminum containers. In order to avoid these reactions, the containers are processed in a special way or other materials are used. To date, however, it has probably not been known that some plastic coatings could adversely affect the efficacy of halogenated diphenyl ethers as antibacterial agents against the formation of dental plaques in oral compositions when placed in containers. Also, it was not known that some plastics could be used which would not cause loss of performance of halogenated diphenyl ethers or that such loss could be prevented by incorporating terpenes such as limonene or other essential oils into the composition.

The invention thus relates to an oral composition which, as an active ingredient, contains a water-insoluble non-cationic antibacterial agent and is contained in a container of a solid polymeric material, for example a synthetic organic polymeric plastic material which is compatible with the antibacterial agent. · T

A dental coating in an oral composition when stored in a container, for example at a temperature of 20 to 40 ° C for several weeks, preferably a year or more.

*

The packaged oral composition is typically a toothpaste, a dentifrice gel or a mouthwash in a deformable tube, dispenser container, or bottle, and the container does not contain any plastic component adversely affecting the effect of the antibacterial agent, preferably a halogenated diphenyl ether such as triclosan, the oral composition may also contain a component that prevents adverse "reactions" between the antibacterial substance and any part of the container made of plastic that would otherwise adversely affect the effectiveness of the anti-tooth coating compositions.

plastic material adversely incapable of incorporating into the means for oral effectivity of THD or other

In addition to oral compositions such as dentifrice gel compositions and the like, dental care compositions such as fluoride and phosphate enamel-hardening compositions, antibacterial pharmaceutical compositions, dye-coating solutions and other means for oral administration. An aerosol package may also be used under pressure, usually using compressed nitrogen gas, provided that the parts of the plastics that come into contact with the oral composition are made of a material that does not cause a significant loss of effectiveness of the antibacterial composition against toothpaste formation in the toothpaste. or other oral composition.

In addition to the various containers shown in the drawings and described above, it is also possible to use compressible bottles, capsules, spongy media and various other types of containers for mechanical metering. Since some halogenated diphenyl ether-type antibacterials are light sensitive, it may be desirable in some cases for the container walls to be coated or laminated with chemical or physical substances that prevent light transmission. Many of these substances are known, for example, to inactivate ultraviolet light. For the same reason, containers will often be opaque to prevent radiation from passing to the device, such as toothpaste.

The causes of the inactivation of THDE and other substantially non-cationic antibacterial agents against dental plaque formation in oral compositions by the action of plastics are not yet fully understood.

So far, studies have not shown a mechanism of loss of efficacy, but so far it appears to be neither a chemical reaction nor a physical absorption. Experiments with mouthwashes containing THDE have shown that if these materials β

stored in containers at room temperature, 38 and 49 ° C for up to 12 weeks, there will be high losses above 25% of the initial THDE concentration if the mouthwash has been in contact with a container wall made of low or high density polyethylene, polyethylene terephthalate, polypropylenes, nylons, polyalomers and polymethylpentenes. Similarly, high losses also occur when the walls are made of elastomeric copolymers of polyesters and polyethers previously used in conventional dispensing systems. Conversely, it has been shown that polyfluoroethylenes such as polytetrafluoroethylene, polyvinyl chlorides, polycarbonates and polysuifones do not absorb or react to a greater extent with HTDE. However, polycarbonates and polysuiphones are brittle and therefore simply unsuitable for the above use. Polyvinyl chlorides often cause the foreign flavor of an oral composition, such as a toothpaste, and are therefore unsuitable, except in certain cases where the altered taste is compatible with the flavor in the toothpaste. This means that of all compatible polymeric plastics, the preferred materials for this use are polyfluoroethylenes. However, as mentioned above, if a stabilizer, for example terpenes such as limonene, or also essential oils, which also often contain terpenes, or other flavoring agents with stabilizing properties, is added to the oral composition containing the antibacterial agent, reduce efficacy losses even when the antibacterial substance comes into contact with the parts of the cartridges that are made of plastic causing a substantial loss of efficacy. For this reason, it is not necessary to use polyfluoroethylene as a container material, provided that the oral composition also contains a stabilizing amount of "terpene" or other suitable stabilizer. When the stabilizer is included in the formulation or when polyfluoroethylene (or polyvinyl chloride, polycarbonate or polysulfone) is used as the only polymeric material to come into contact with the oral formulation, the storage efficiency losses are less than 25% preferably less than 20% even after storage at a relatively high temperature, for example 20 to 40 ° C for several weeks to a year or even longer. The most stable oral compositions are those containing stabilizing amounts of terpene or t

other suitable stabilizer and also comprise parts which are in contact with the composition only of polyfluoroethylene or other non-reactive plastic. Although the primary stabilizers are terpenes and essential oils, some other flavor components also have a stabilizing effect on the coating material either by interfering with the destabilization reaction or by causing inhibition of the absorption of halogenated diphenyl ether by plastic or other unknown mechanisms. It is theorized that some components that solubilize THDE may also inhibit the migration of this substance into the plastic. On the other hand, it is also claimed that this solubilizing effect could in turn cause the migration of solubilized THDE into the plastic. Since this problem has not yet been resolved, it is not possible to refer to any of these theories. However, it is preferred that the terpenes and other stabilizers be equally palatable in the composition, but this is not necessary and the stabilizers can only be used for their stabilizing effect.

Although it is preferred that the containers of the invention have internal walls that come into contact with or lined with the composition of a solid organic polymeric plastic, these materials may also be used if they are not synthetic, organic or plastic . For example, it is also possible to use polyethylene glycols and methoxypolyethylene glycols, for example Carbowax-type agents, for example Carbowax 4000 or Carbowax 6000, often as lining of the inner wall of the container. In addition, silicon-containing organic polymers such as siloxanes and non-synthetic organic film-forming materials such as essential oils such as carrageenan, tragacanth, karaya and the like can be used for the same purpose. It is furthermore possible to use solid polymeric materials such as cellulose and starch and derivatives thereof as materials for the manufacture of a container that comes into contact with the antibacterial component of the oral composition.

The most commonly manufactured packaged compositions of the invention for oral use are toothpastes, gel toothpastes and mouthwashes. The first two of these compositions are commonly referred to as dentifrices. These compositions comprise three main components, the vehicle, the polishing material, and the surfactant or wetting agent. An antibacterial agent, such as a halogenated diphenyl ether, is usually present in a carrier composition, which usually constitutes 10 to 80% by weight of the composition. The carrier comprises 0-40% water, 7-77% water retention agent such as glycerol, sorbitol, propylene glycol or mixtures thereof and 0.5-10% gel agent such as sodium carboxymethylcellulose, carrageenan, iota-carrageenan or hydroxyethylcellulose and the like, including mixtures thereof. The polishing material is usually 10 to 75% of the gel or paste or 50 to 99% of the powder. These may be colloidal or precipitated silica, sodium aluminosilicate, insoluble sodium metaphosphate, hydrated or calcined alumina, dibasic calcium phosphate dihydrate, anhydrous dibasic calcium phosphate or calcium carbonate, or other known materials and mixtures thereof may be used. The surfactant may have an anionic, nonionic, cationic or amphoteric nature, but the nonionic agent is not suitable due to the adverse effect on the antibacterial, e.g. THDE, and the use of the cationic and amphoteric agent is often unsuitable as they tend to color or darken your teeth. That is, a synthetic organic anionic surfactant is preferred, and sodium lauryl sulfate and other higher alkylsulfates containing from 10 to 18 carbon atoms in the alkyl moieties are preferred, although other well known sulfate or sulfone-type surfactants, at least as a proportion of the total quantity. Other active ingredients, such as fluoride ion source compounds, such as sodium fluoride or sodium monofluorophosphate, can be used to prevent caries, usually in an amount that provides 0.001 to 1% fluoride ions, and further contain formulations usually excipients. , for example, sweeteners and flavoring agents in an amount of 0.1 to 10%. In addition, a polycarboxylate such as polyvinylmethyl ether copolymerized with maleic anhydride (PVM / MA) may be used, such as a Gantrez copolymer, typically used in amounts of 0.5 to 4% based on the amount of the composition. These polycarboxylates have been shown to significantly improve the effectiveness of the antibacterial agent against coating. The use of these polycarboxylates in oral compositions is described in U.S. Pat. 4,627,977.

In mouthwashes, the vehicle is preferably a mixture of water and an alcohol, the alcohol usually being ethanol or isopropanol. The vehicle generally comprises 90 to 99.9% of the composition, of which 5 to 30% is alcohol and often 2 to 10% propylene glycol. The remainder of the composition, e.g. 0.1 to 10% may be a flavoring, wetting, sweetening, coloring, anti-dental, and other adjuvants for specific purposes. In a dentifrice and mouthwash composition, an effective amount of anti-dental antibacterial agent is usually in the range of 0.02-0.2, preferably 0.03-0.1% in mouthwashes, and typically 0.25-1.1. preferably 0.25 to 0.5 or 0.6% in dentifrices, at most 0.8% for THDE in toothpastes and at most 0.2% in a certain substance in the mouthwash, since higher concentrations cause a sensation of numbness of the mucosa, however, it is not possible to use below the indicated amounts, since then the effectiveness against the coating would be insufficient. Preferably, the composition is to contain the amounts mentioned above, but if the initial concentration is within that range, a loss of up to 25% is expected, so that the final concentration is still sufficiently effective.

In order to stabilize the oral composition intended to be placed in a container with plastic walls or other parts in the event that the plastics material somehow reacts with the antibacterial agent, it is desirable that the oral composition contains 0.1 to 2% of terpene or other stabilizer, preferably 0, 05 to 1, in particular 0.1 to 0.5% of this stabilizer. The stabilizer may be present in the flavoring agent of the composition and then constitutes at least 5%, preferably at least 10, more preferably at least 25 and particularly preferably at least 50% of the additive.

Although the above description relates in particular to dentifrices and mouthwashes, other compositions of the invention for oral administration, for example, chewing gum, may have a similar composition, depending on the form of the composition, the liquid compositions will contain minor amounts. of this substance, as well as mouthwashes and denser compositions, larger quantities, as well as toothpastes, will often contain other specific ingredients for the particular purposes for which the compositions are intended. For example, dentifrices may contain fluorides and phosphates such as sodium or potassium fluoride and sodium fluorophosphate in the form of dentifrices or mouthwashes, typically in the range of 1 to 5%. Color coating solutions may contain suitable colorants, usually red at a concentration of 0.001 to 0.1% in the mouthwash base. Other means may be treated in a manner similar to those skilled in the art.

The antibacterial is a non-cationic material that is water insoluble or substantially insoluble, its water solubility at 25 ° C is less than 10 g / l and often less than 1 or 0.1 g / l. These materials are soluble or dispersible in a dentifrice vehicle containing glycerol, sorbitol and / or propylene glycol and in the resultant base-based products. They are also soluble or dispersible in the aqueous-alcoholic mouthwash environment.

Of the antibacterial substances, the halogenated diphenyl ethers usually contain bromine and / or chlorine, preferably chlorine. These are preferably substituted with one to three hydroxyl groups and 1 to 4 halogen atoms, preferably 1 to 2 hydroxyl groups and 2 or 3 halogen atoms, preferably 4 substituents, two on each ring. Among the preferred compounds, in particular 2,2'-dihydroxy-5,5'-dibromodiphenyl ether and 2 ', 4,4'-trichloro-2-hydroxyphenyl ether (THDE) may be used, the latter being most preferred. A variety of halogenated phenolic, non-cationically substantially water-insoluble antibacterial anti-dental coatings, for example those listed on pages 2 to 8 of U.S. Patent Application Serial No. 07/398566, Aug. 25, 1989, may be used as a whole or in part instead of halogenated diphenyl ethers.

The term "terpenes" refers to terpene hydrocarbons and their oxygenated derivatives, including dl-limonene, menthol, diterpenes, polyterpenes and derivatives thereof, many of which are essential oils and other flavorings. Except for

they are suitable as stabilizers for halogenated diphenyl ethers, and are often also desirable flavorings for oral compositions. Zterpenes and derivatives thereof have the best properties of limonene, although other terpenes, including tasteless ones, can also be used, other emulsifiable lipophilic essential oils and flavoring agents with stabilizing ingredients can also be used.

The various plastics which have already been described as constituents of the various containers and / or their portions have been mentioned briefly, since their chemical nature and degree of polymerization are well known, so there is no need to list them in detail. Further details can be found in the Modem Plastics Encyclopedia, published annually by McGraw-Hil Inc., New York, New York.

As described in U.S. Pat. No. 07 / 398,566, the oral composition may comprise a fluoride ion source capable of delivering 25-5000 ppm of fluoride ions, preferably 300-2000 and especially 800-1500 ppm in the oral cavity. Further data on suitable fluorides and their proportions can be found in U.S. Pat. Fluorides cause a primary hardening of the teeth, but also serve to stabilize polyphosphates as an anti-tartar agent, if present in the composition. The polyphosphate is usually a mixture of sodium and potassium pyrophosphates and is also stabilized with Gantrez S-97. Corresponding proportions are disclosed in U.S. Pat. No. 07 / 398,605, Aug. 25, 1989, and U.S. Pat. 4,627,977 and 4,806,340.

Further details regarding the compositions, ingredients, excipients, manufacture and use are also given in the aforementioned applications and files.

The production of the described oral compositions is accomplished by standard methods. For example, the THDE is dispersed and / or dissolved in a portion of the vehicle environment of a dentifrice composition in which terpene is present as a flavoring agent. In the manufacture of a dentifrice, a vehicle containing glycerol, sorbitol and propylene glycol, a gel agent and suitable adjuvants including Gantrez S-97 and triclosan is prepared, and then the carrier medium and the aqueous anionic wetting agent, preferably sodium lauryl sulfate or a mixture of lauryl sulfate are mixed. sodium and sodium methylcocoyl taurate, and a polishing agent is mixed with the resulting mixture. Finally, the ethanol-soluble flavor, including terpene, is added and the pH is adjusted. In making mouthwash, the various ingredients are simply mixed with alcohol or a mixture of water and alcohol and mixed until the ingredients are dissolved. In the mouthwash, a mixture of sodium lauryl sulphate (SLS) and sodium methyl cocoyltaurate in a ratio of 1: 4 to 4: 1 is preferably used as the anionic wetting agent, the taurate allowing a correspondingly desirable reduction in the SLS content. Other oral compositions may be prepared in a similar manner.

When storing compositions for oral use, it is desirable to avoid contact with plastic parts made of an elastomeric copolymer of polyester and polyether, as well as to avoid contact of a composition that does not contain a stabilizing agent such as terpene or essential oil thereof to parts made of plastic. a composition which has been mentioned above as a composition reactive with THDE and other antibacterial agents effective against dental plaque formation. It is particularly important to exclude the aforementioned plastics from materials for mixing equipment and any other containers, pipes, pumps or other equipment in which the composition may be stored for a longer period of time or for a shorter period of time at a higher temperature.

Although the packaged composition of the invention containing THDE or other halogenated diphenyl ether type antibacterial agent is kept away from unsuitable plastics, it is desirable to reduce the effect of heat and light to the greatest possible extent, since both factors accelerate the loss of efficacy against dental plaque formation. Thus, the compositions are preferably stored and packaged in opaque containers at a temperature in the range of 10-38 ° C and are also stored at that temperature. Alternatively, the packaged compositions may be stored and used in the conventional manner to achieve the desired anti-dental plaque. This effect was verified by laboratory experiments and evaluation on the teeth of volunteers using various packaged formulations of the invention and control means. A statistically significant improvement in f

The anti-tooth coating properties of the compositions packaged by the method of the present invention as compared to the compositions containing the plastics material were " reactive " to halogenated diphenyl ether as an antibacterial agent when the packs did not contain a stabilizer in the oral composition. An improvement could also be observed when the containers were made of a reactive plastic but not of an elastomeric copolymer of polyester and polyether, the composition containing terpene. Control compositions that did not contain terpenes or terpene-containing flavor components had a significantly higher loss of anti-dental plaque performance. .

means n

effect

With a dental coating in the preferred composition, it can be stored in a container, for example at a temperature of 20 ° C to 0 ° C, for a few weeks, preferably / or more. A packaged oral / coexistence device is usually a toothpaste / gel brushing or oral votfa in a deformable tube, dispenser / bottle dispenser, or bottle, and the dispenser contains no plastic part adversely affecting non-bacterial / agents, with The advantage of the halogenated diphenyl ether as an oral composition may also comprise a component which prevents adverse "reactions" between the arithibacterial substance and any part of the container sprained from plastic that would otherwise adversely affect the effectiveness of the anti-tooth coating compositions.

_ / ^z

In FIG. 1 is a view of the toothpaste tube with the cap removed, with the toothpaste pushed out of the toothbrush tube.

In FIG. 2 is an enlarged cross-sectional view of a laminated tube wall, for example of FIG. First

In FIG. 3 is a vertical sectional view of a container with a pump for dispensing toothpaste or gel.

In FIG. 4 is a side view of disposable toothpaste pads sealed by heat.

In FIG. 5 is a side view of a mouthwash bottle provided with a closure.

In FIG. 1, a dental plaque assembly 11 is shown in an appropriate package. The assembly 11 is formed by a deformable tube 13 which contains toothpaste 15 intended to be extruded in amounts of 0.8 to

2.0 g per toothbrush 17. The tube 13 is opaque and is made of or lined with a synthetic organic polymeric plastic material, such as polyfluoroethylene, for example, in the form of a laminate, so that the toothpaste performance against the dental plaque during storage is not adversely affected. The tube 13 may also be lined with a plastics material that reduces the effectiveness of the antibacterial agent, but in this case it is necessary to prevent this adverse effect by the presence of a stabilizing agent such as terpene, for example limonene or other effective essential oil. In a preferred embodiment, neither the tube nor the closure nor any other part of the tube coming into contact with the toothpaste, such as the interior of the closure, should be made of a copolymer of polyester and polyether or other plastic material that substantially reduces the effectiveness of the oral composition even in the presence of a stabilizer. . It is also appropriate to exclude the presence of other elastomers, such as isobutadienes, polychloropropenes, butadiene and nitrile resins, which could react with or absorb THDE. It is desirable that these parts be made of a plastics material that does not adversely affect the presence of terpenes or other stabilizers, but some destabilizing plastics can be used in the presence of a toothpaste stabilizer to prevent the inactive effect of the plastics (except elastomeric copolymers). polyesters and polyethers and other unsuitable elastomers).

In FIG. 2 shows a laminate consisting of a polyfluoroethylene film 21, an aluminum foil 23 and a polyethylene film 25, wherein the polyfluoroethylene film 21 forms the inside of the tube in contact with the toothpaste. The unclosure of the closure 19 of FIG. 1 may also be made of polyfluoroethylene so that all surfaces in contact with the toothpaste when stored are compatible with halogenated diphenyl ether as an antibacterial component of the toothpaste and will not cause loss of effectiveness of this component against the dental plaque during storage. The polyfluoroethylene film 21 may also be replaced by polyethylene or another suitable polymer.

In FIG. 3 shows a container for dispensing toothpaste, which is the subject of U.S. Pat. No. 4,776,496, issued by Guala S.p.A.,

Italy. The ready-to-use cartridge 27 contains toothpaste in the compartment 29 defined by the bottom wall 31 and the membrane 33. Pressing the control lever 35 compresses the diaphragm 33 downwardly, pushing the toothpaste through the conduit 37 into the outlet opening 39. The pressure on the control lever compresses the diaphragm 33, which is elastic, so that once the pressure on the control lever 35 ceases, it returns to your original location. At the same time, the lower wall 31 returns upwardly under atmospheric pressure. All of the inner parts of the cartridge that are in contact with the toothpaste are preferably made of plastics which do not inactivate halogenated diphenyl ether as a dental plaque. However, if it is not possible to use plastics having the desired physical properties for some parts and at the same time being compatible with the antibacterial agent, other plastics may be used provided the toothpaste or gel contains a stabilizing agent such as limonene or other effective terpene or essential oil. However, it is most preferable to avoid the use of any elastomeric material of the polyester-polyether copolymer type, especially in the case of the membrane 33, since said platinum compositions particularly adversely affect the effectiveness of the antibacterial in the oral composition.

In FIG. 4, a cushion 41 is shown, heat sealed on three sides 43 and 45. The fourth side 47 is only folded and does not need to be sealed. Inside the pad is a composition (not shown), for example toothpaste, the inner surface of the pad being a plastic that does not cause a significant loss of effectiveness of the antibacterial in the oral composition. As with other containers for such formulations, a laminate may be used, the inner layer of which is a plastics material which does not adversely affect the antibacterial agent and, if it does, it is necessary to add a suitable stabilizer, preferably one which forms at the same time the flavoring agent of the composition.

In FIG. 5 shows an opaque bottle 45 with a closure 51. Both the bottle and the seal cartridge (not shown) in the closure 51 are made of THDE-compatible plastic contained in mouthwash 53 in the bottle 49. As in previous cartridges, it is necessary to In cases where the plastic adversely affects the efficacy of the antibacterial composition, incorporate a stabilizer into the oral composition to prevent excessive loss of THDE or other halogenated diphenyl ether.

ŕ ft Λ M k e ipt ipt y * *.

Practical embodiments will be illustrated by the following examples, which are not intended to limit the invention. Unless otherwise indicated, all percentages and all parts in the example section are by weight and all temperature data are in ° C.

Example 1 component percentage deionized water47.84 sorbitol (70% solution) 20.00 ethanol (95% aqueous solution) 12.50 glycerol10.00 propylene glycol7.00 ^x Gantrez S-97 (13% solution) 1.92 sodium hydroxide (50%) % aqueous solution) 0.12 sodium lauryl sulphate 0.25

Tauranol WSHP0,20 ^ flavor mixture0,12 ^ riclosan (Irgasan DP 300,0,05

100.0 * copolymer of polyvinylmethyl ether and maleic anhydride (GAF

Corp.).

”Sodium methylcocoyltaurate

Terpene content of at least 25%, including at least 25% limonene.

THDE (2 ', 4,4'-trichloro-2-hydroxydiphenyl ether).

The mouthwash is obtained from the above ingredients by mixing them in any suitable order by conventional means, but preferably by first dissolving triclosan in propylene glycol and ethanol, then mixing the resulting mixture with an aqueous solution of sorbitol, glycerol and anionic surfactants, and finally a mixture of flavorings is added. The sodium hydroxide solution is used to neutralize the resulting acidic mixture to a pH of 6.84 since it is desirable to adjust the pH to neutral or approximately neutral values.

The resulting mouthwash has very good cosmetic stability and acceptable taste, with the flavors and triclosan dissolving well, probably at least in part due to the presence of Tauronal WSHP. When only 0.25% SLS is used as an anionic surfactant, the dissolution of the flavor and triclosan is not as satisfactory. Although dissolution can be improved by using a larger amount of SLS, the highest acceptable amount of this substance in the mouthwash is 0.25%, with a mixture of Tauranol WSHP and SLS in that ratio being safe and acceptable. The described mouthwash was tested in vitro for the bioavailability of triclosan compared to a similar mouthwash without tauranol WSHP in one case and in another case by substituting half of the non-ionic wetting agent Pluronic F-127. In experiments measuring the binding of triclosan to saliva-coated hydroxyapatite disks and protein binding in the "inhibition zone", the presence of an anionic surfactant mixture has been shown to provide a comparable bioavailability of triclosan compared to that of a composition containing only SLS. availability is significantly higher than in compositions that do not contain a nonionic surfactant than in compositions that contain a Pluronic F-127 ionic surfactant.

If the mouthwash of this example has aged at a higher temperature of 41 ° C for 3 to 5 weeks, which is considered to be aging, equivalent to at least> 6 months and 1 year at room temperature, these tests were carried out in conventional polyvinyl chloride glass packaging. and polyethylene terephthalate, or when the containers are unloaded with plastic. Chemical analysis of the mouthwash after this period showed no loss of triclosan in the case of glass, but there were losses in the case of polyethylene terephthalate or polyvinyl chloride but these losses were less than 25% of the original concentration (this loss is tolerated) and may be less than 5-10 %.

When using dl-limonene in an amount of 0.1, 0.2 and 0.4% instead of a mixture of flavorings, an even better stabilization of triclosan can be achieved, the same result can be obtained using other essential oils or flavorings substances in similar amounts. These good results can also be achieved if the container or its liner is made of polymethylpentene, polyalomer, polypropylene, high and low density polyethylene and nylon, although these materials cause substantial triclosan losses in the absence of terpene-containing flavorings. from mouthwash during storage, especially at higher temperatures.

Example 2 Component Percent Deionized Water84.42 Ethanol (95%) 10.00 Propylene Glycol5.0 Sodium Laural Sulphate 0.50 Triclosan0.06 Saccharin Sodium 0.02

100.00

The mouthwash of the above composition was tested for the availability of triclosan after storage for 3 weeks in containers made of or lined with different platinum materials. The experiments were carried out at room temperature and at higher temperatures of 38 and 49 ° C, with a higher temperature simulating a longer storage time, a year or more at room temperature. Losses greater than 25% of triclosan could be observed when the containers were made of polymethylpentene, polyalomer, polypropylene, low and high density polyethylene and nylon, particularly adverse results were obtained using polypropylene, polyethylene and nylon, results with the latter substance. were the worst.

When the container material or container liner was polyvinyl chloride, polycarbonate, polysulfone, or polyfluoroethylene, such as polytetrafluoroethylene or teflon, there was essentially no loss of triclosan. Losses of triclosan from mouthwash stored in reservoirs of polymethyl terpene type polymers and the like. can be reduced in the same way as in Example 1, i.e. by adding limonene, other terpenes or essential oils containing terpenes to the mouthwash with a terpene content of at least 0.1%, preferably 0.2 or 0.4%. In some cases, the use of a flavoring agent which does not contain any significant amount of terpenes has a positive effect, although such an effect would not be expected.

Example 3 component propylene glycol iota careagenone sodium fluoride sorbitol (70%) saccharin sodium titanium dioxide sodium hydroxide (50% aqueous solution) deionized water ^x Luviform (35 5 solution) 'Zeident 113' Sident 22S percent

10.00

0.75

0.33

30.00

0.30

0.50

0.80

27.71

4.76

20.00

2.00 sodium lauryl sulphate (94%) flavor triclosan

1.60 0.95 0.30 100.0 ^x copolymer of polyvinyl methyl ether and maleic anhydride (BASE

Corp.).

”Silica-based polishing agent (J.M.Huber Corp.) 'θ' Silica-based thickening agent (Degussa Co.)

A detergent composition of the above composition is manufactured in a conventional manner and used as a test environment for the stability of triclosan when exposed to a variety of plastics commonly used as container materials or parts thereof, in particular dispensers under conditions in which the product is stored. The plastics used were Pibiflex 46, (Inmont) and Amittel 460 EM (AKZO); these plastics are typically used as membranes or bottoms of the dispensing means of FIG. 3. Six plastic samples, three samples from each of the above plastic materials, were tested, each of which was molded using a different means to facilitate the release of the product from the mold to demonstrate whether the nature of the mold release agent affects stability of triclosan in contact with plastic during storage. Silicone Master (5% silicone oil and 95% polypropylene), Silicone Master with silicone oil (more silicone oil in addition) and Armid 0 Master (5% oleic acid amide and 95% polypropylene) were used as mold release agent. . After two weeks of storage, together with a dentifrice at various temperatures (room temperature, 38 and 49 ° C), the composition is removed from the plastic container and the plastic is washed with water and immersed in methanol to dissolve any amount of triclosan that could be trapped in the plastic during storage. The methanol used for washing and immersion is decanted and analyzed by HPLC. It was found that approximately the same amount of triclosan bob captured by the different membrane materials, and although some small differences between the plastics and the mold release agents used were shown, the final results were essentially the same in all cases. Elastomeric copolymers of polyester and polyether absorb large amounts of triclosan from the composition, as can be confirmed by using these materials as part of the dispensing composition and the aforementioned or other composition of the invention. Accordingly, the use of the elastomeric copolymers of the polyesters and polyethers for contact with the dentifrices and mouthwashes of the present invention should be considered inappropriate, even if the compositions contain at least 0.1% by weight of terpene-containing flavorants as stabilizers.

When experiments were repeated using Guala-type dispensers as reservoirs and using an Arnittel membrane of an elastomeric copolymer of polyester and polyether, the loss of triclosan was also unacceptable, but when the elastomer was replaced with an acceptable plastic such as polyfluoroethylene substantial improvement and the amount of triclosan was within an acceptable range. Also, other parts made of plastics, such as polypropylene, do not absorb too much triclosan and do not significantly reduce the effectiveness of the dentifrice against the formation of dental plaques, possibly due to the presence of terpenes in the flavorings of the composition.

Panel tests were performed using at least ten volunteers who used the dentifrice of this example either from a polyethylene terephthalate or polyethylene lined tube 2 times a day for 1 month to perform a dental plaque evaluation. The results showed that the composition appears to have an anti-dental plaque performance similar to that shown in the mouthwashes of Examples 1 and 2, so that it is clear that sufficient triclosan is available as an anti-dental plaque.

Example 4 Component Option in% Glycerol7.00 Propylene Glycol3.00 Iota Carragenan0.75 Sorbitol (70%) 30.00 Sodium Saccharin0.30 Sodium Fluoride0.33 Titanium Dioxide0.50

Gantres S-97 (13% solution) 15.00 deionized water16.07 sodium hydroxide (50% aqueous solution) 0.80 Zeodenite 113 (J.M.Huber Corp.) 20.00

Sylodent 15 (Thickener based on

SiO ₂ (WRGrace Corp.) 3.00 Flavor0.95 Sodium Lyuryl Sulfate2.00 Triclosan0.30

100.00

The toothpaste of the above composition was stored in a Guala-type container with Arnitel-type membranes. Then, the composition was also filled into laminate tubes with polyethylene terephthalate on the inside of the laminate in contact with the composition. The compositions were stored at 5, 25 and 39 ° C for 2.4 and 6 weeks. After this time, 1.5 g of the composition per day were examined at weekly intervals for triclosan content. In the case of the Guala-type container, there was a loss of approximately 27% of triclosan, which is unacceptable. This loss is approximately constant regardless of storage time and storage temperature, which is probably due to the absorption of triclosan by the membrane prior to testing. These membranes are made of an elastomeric polymer of polyester and polyether, which is unsuitable for this use as a material for the manufacture of a storage or dispensing means. However, if this material is replaced

An acceptable plastic, such as polyethylene terephthalate, which can serve as a membrane in dispensers modified due to the different properties of the material, the stability of the triclosan is increased and the composition has sufficient coating performance.

Gel toothpastes in the same containers have the same efficiency under similar storage conditions.

In similar tests, small losses (less than 5%) of triclosan were observed when using polyethylene terephthalate to leach tubing, so it is clear that the presence of terpenes in an amount of 0.1% or more, including limonene, in the flavoring agent prevents triclosan loss or inactivation. When tubes with polyfluoroethylene lining are used, there will be little loss of triclosan even if the flavor is omitted in the formulation, as can be seen when polyvinyl chloride is used as the lining material or parts of the package made of polysulfone or polycarbonate in contact with the composition. However, as mentioned above, these materials are generally not used.

If, in the above tests using a Guala-type container, the Gantrez S-97 Luviform (35%) was replaced with 4.76 parts and the difference was equalized with deionized water, there would be no significant differences in the stability of the triclosan.

In the above compositions, a silica-based system and not an alumina-based system was used as the polishing agent. When alumina is used as the polishing agent, problems with the use of some plastics are lessened, but still persist. Again, the presence of terpenes increases the stability of the triclosan, as in silicon dioxide formulations.

Example 5

Mouthwashes and dentifrices of the preceding examples may be varied such that the content of the individual components varies between ± 10% and ± 25%, provided that the amounts do not exceed the range indicated in the description of the application as binding. In this way, it is possible to obtain other compositions having antibacterial and anti-coating activity which can also be deposited in the aforementioned containers. These may be gels, pastes, liquids, capsules, tablets, lozenges, sublingual pads and pads of the above type. In all of these compositions, triclosan or other halogenated diphenyl ether or other anti-coating agent will be sufficiently stable in the presence of polyfluoroethylene, polyvinyl chloride, polycarbonate and polysulfone as the reservoir material or components thereof, even if no composition is present in the composition. flavor and no terpene. In addition, oral compositions are still present in the presence of polyethylenes, polypropylenes, polyethylene terephthalates, polyalomers, nylons and polymertylpentenes, provided that the composition comprises terpene, for example limonene or a flavoring agent as a stabilizer. As with mouthwashes and dentifrices, the presence of elastomers based on polyester-polyether copolymers together with triclosan is inappropriate.

Example 6

The dentifrice compositions of Examples 3 and 4 were prepared and then, after monthly storage at 30 ° C, in compressible tubes lined with polyethylene or polyethylene terephthalate, they were applied to toothpastes as shown in FIG. The amount of toothpaste on the toothbrush was in the range of 0.8 to 2.0, preferably 1 to 1.5 g.

When 1.5 g is applied, the amount of active triclosan in the toothbrush composition is about 4 mg, with only 10% triclosan inactivated.

If the storage lasts for a long time or at a higher temperature or when using less suitable plastic, the amount of toothpaste on the brush

Μ contain 3 mg triclosan, if applied, 5 g toothpaste. If only 1 g of toothpaste was applied, the amount of triclosan with a smaller inactivation would be 2.7 and with a larger 2 g. For pastes containing 0.25 to 0.7% triclosan, the brush paste may contain 2.2 to 8 mg triclosan if the inactivation is 10 to 25% or 8 mg if the inactivation does not occur.

The described packaged dentifrices are used in an amount of 0.2 to 2 g per tooth brush. Teeth were cleaned 2 times a day, morning and evening for 1 minute 4 weeks, after which time a marked improvement in coating performance was observed compared to the triclosan-free control composition. This improvement is also visible. Marked improvement was also achieved by using compositions containing terpene compared to a composition without its content for storage in containers, unloaded ^r olyetylénom or polyethylene terephthalate.

The invention has been described in connection with some embodiments, but it will be apparent that many other embodiments may be envisaged, also within the scope of the invention. Thus, the invention is not limited to the embodiments described.

Claims (18)

An assembly comprising a metering cartridge (s). 4 drawbar, of a solid, synthetic, organic, non-elastomeric plastic polymeric material in contact with a toothpaste, oral gel or liquid dentifrice, a liquid mouthwash composition or a paste, gel or liquid dentifrice " % to 1% of an antibacterial and anti-dental plaque effective proportion of a non-cationic antibacterial and anti-dental plaque substantially water insoluble, having a water solubility of less than 10 grams / liter at 25 ° C, that a) _f the solid polymeric material is selected from materials which are compatible and nonreactive with said coating agent and does not cause the loss of more than 25% of the initial antibacterial activity and activity against the formation of a coating of the oral composition on storage. ' In a storage tank at 20 to 40 ° C for several weeks or b) _; the oral composition contains a stabilizing fraction of 0.1% to 2% terpene when the solid polymeric material is incompatible and reactive with the anti-coating agent. Assembly according to claim 1, characterized in that the antibacterial agent comprises a halogenated diphenyl ether. Assembly according to either of Claims 1 and 2, characterized in that the antibacterial agent comprises a halogenated diphenyl ether substituted with 1 to 3 hydroxyl groups and 1 to 4 halogen atoms selected from the group consisting of chlorine and bromine. 'vj7a0ti1-re.oj.1gaa' The assembly of any one of claims 1 to 3, wherein said antibacterial agent is 2 ', 4, 4'-trichloro-2-hydroxy-diphenyl ether in an amount ranging from about 0.02% to 0.8% weight. Assembly according to any one of claims 1 to 4, characterized in that the oral composition comprises a fluoride ion compound which provides 0.001% to 1% fluoride ions in the composition. Assembly according to any one of claims 1 to 5, characterized in that the oral composition comprises a synthetic, linear, molecularly dehydrated polyphosphate compound against dental caries. Assembly according to any one of claims 1 to 6, characterized in that the polyphosphate compound against dental caries comprises sodium or potassium pyrophosphate or a mixture thereof. An assembly according to any one of claims 1 to 7, characterized in that. the composition comprises about 0.5% to 4% by weight of a vinyl ether / maleic acid copolymer or maleic anhydride in a ratio of 1: 4 to 4: 1, preferably 1: 1, with a molecular weight ranging from 30,000 to 1,000,000 , preferably 70,000. An assembly according to any one of claims 1 to 8, wherein the solid polymeric material comprises one or more substances selected independently from the group consisting of polyethylene, polypropylene, polymethylpentene, polyacrylate, polyalomer, nylon, polyfluoroethylene, polyvinyl chloride, polycarbonate and polysulfone. The assembly of claim 9, wherein the solid polymeric material comprises polyethylene. Assembly according to claim 9, characterized in that the solid polymeric material comprises polyethylene terephthalate. An assembly according to any one of claims 1 to 11, characterized in that The composition contains stabilizing amounts of terpene. 1998- Assembly according to claim 12, characterized in that the terpene comprises limonene. An assembly according to any one of claims 1 to 13, characterized in that iperene is a component of the fragrance agent. Assembly according to any one of claims 1 to 14, characterized in that the composition contains 0.25% to 0.8% by weight of 2 ', 4, 4'-trichloro-2-hydroxy-diphenyl ether. Assembly according to any one of claims 1 to 15, characterized in that the oral composition is a liquid mouthwash containing 0.02% to 0.2% by weight of 2 ', 4, 4'-trichloro-2-hydroxy-diphenyl ether. Assembly according to one of claims 1 to 15, characterized in that the oral composition is a toothpaste or gel dentifrice containing 0.02 to 0.2% by weight of 2 ', 4, 4'-trichloro-2-hydroxy- diphenyl ether. Assembly according to one of claims 1 to 17, characterized in that the container is opaque. VJ-MH-15U5 1098