FI98121C - A permanent, anti-plaque oral composition during storage - Google Patents

Description

- 98121

This invention relates to a storage stable oral composition having anti-plaque properties and included in a dispensing container. This container composition contains an anti-plaque antibacterial agent such as 2 ', 4,4'-trichloro-2-hydroxydiphenyl ether (THDE) as an effective anti-plaque component.

10

Plaque on the tooth surface is considered to be a causal factor in negative periodontal conditions and dental plaque is a precursor of tartar. Plaque can form on any tooth surface, including the gum line. It makes a tooth look bad and in addition to promoting tartar development, it is associated with the occurrence of gingivitis. Therefore, oral compositions with anti-plaque components that prevent or inhibit dental plaque on teeth are valuable aids in dental care.

Although it is known that antimicrobial agents in oral compositions may reduce plaque, sometimes being very effective in combination with other materials, numerous such antibacterial compounds have disadvantageous properties that reduce their use in such oral compositions. For example, cationic antibacterial compounds, such as quaternary ammonium halides, tend to darken teeth and may be inactivated by anionic materials in oral preparations (and it is often desirable to use anionic surfactants or detergents in oral compositions).

Substantially water-insoluble halogenated (and often hydroxylated ethers), such as THDE (triclosan) and 2,2'-dihydroxy-5,5'-dibromodiphenyl ether (DDDE), are effective antibacterial agents for dental plaque, but nonionic surfactants and many plastics can inactivate them, as users have observed. Thus, it has been an object of the present invention to incorporate antibacterial anti-plaque agents such as halogenated diphenyl ethers, especially THDE and DDDE, and similar anti-plaque agents into oral compositions and to store and dispense such compositions from packages or containers in which they do not lose unreasonable antibacterial properties. before the intended use. In the prior art triclosan dentifrice, dispensed from a dispenser, triclosan dispensing has not occurred in an effective amount to significantly reduce plaque when used once or twice daily at 1.5 g / use by brushing for 1 min, which is considered approximately normal brushing practice. . For it to be effective, such uses should result in at least a 25% reduction in plaque after three weeks of use, compared to three weeks of use of control ham-5 mastah in a similar manner.

The most preferred antibacterial dental plaque inhibitor component of the oral composition of the invention is THDE, also known as triclosan. Such is disclosed in U.S. Patent 4,022,880 as an antibacterial agent, together with an anticalculus agent (which releases zinc ions) and in DE Patent Publication (OLS) 3,532,860 together with a copper compound. It is also disclosed in EP patent applications 0 161 898 and 0 161 899 and in EP patent application 0 220 890 it is disclosed in dentifrices with polyethylene glycol and an oil-based spice.

Various oral compositions or dental preparations are known, such as paste, gel, powder, liquid, lozenge, bag and packaged dentifrices, liquid and tableted mouthwashes; and professionally used dental treatment agents (such as tooth curing compositions, e.g., fluoride solutions). Such products are packaged in compressible tubes, pump dispensers, pressurized dispensers, 20 packages, bottles, containers and other containers. Although compressible or collapsible tubes were originally made of metals such as aluminum and bottles were made of glass, in recent years such containers have often been made of synthetic, organic polymeric plastics or made of laminates containing such plastics. The interactions between the oral compositions and the materials of the containers in which they are packaged are known, such as reactions between toothpastes and aluminum containers, and in order to prevent such reactions, the containers have been specially treated or various container materials have been used. However, the present inventors do not believe that prior to their invention it was known that any plastic packaging material could adversely affect the dental plaque of antibacterial halogenated diphenyl ether compounds incorporated in oral compositions and packaged in containers in which they did not come into contact with such plastics. that it has been found that certain plastics could be used in such parts of the container without causing loss of dental plaque inhibitory activity of the halogenated diphenyl ethers or that oral compositions packaged in contact with "reactive" plastics (which react, absorb or otherwise reduce oral composition), the loss of activity could be prevented or prevented - 98121 3 by the inclusion of terpenes limonene, and other spice components of oral preparations.

Accordingly, this invention relates to a stable oral composition having anti-plaque properties when stored in a dispensing container having a solid polymeric material in contact with said composition, wherein the composition in the container comprises an orally acceptable medium, about 0.02-1% by weight. a substantially water-insoluble non-cationic anti-plaque agent and other conventional excipients, and wherein it has been found that at least about 25% of the anti-plaque activity of the anti-plaque agent is lost upon storage at elevated temperature for at least 3 weeks in said container. with. The invention is characterized in that said container uses a compatible polymeric material in contact with the composition which does not cause such a loss, such as polyfluoroethylene, polyvinyl chloride, polycarbonate or polysulfone, or II. when such a polymeric material 20 in contact with the composition is incompatible, normally causing such loss as polyethylene, polypropylene, polyethylene terephthalate, polymethylpentene, polyallomer and / or Nation, said composition contains about 0.01-2% of a stabilizer such as terpene or which prevents such loss, and said composition optionally includes about 0.5-4% vinyl methyl ether / maleic anhydride copolymer and / or about 25-5000 ppm fluoride ions.

Although various plastics can reduce the anti-plaque effect of antibacterial agents, certain plastics, such as polyfluoroethylene and polyvinyl chloride, have been found to be compatible with THDE and have not been found to cause unreasonable loss of antibacterial and anti-plaque activity in oral compositions. at room temperature or elevated temperatures (such as at temperatures in the range of 20-40 ° C for several weeks to 35 and, preferably up to a year or longer). Even when the plastic portion (s) in contact with the container is / are plastic, which in itself is not completely compatible with the antibacterial compound, the compatibility can be improved by including in the oral composition a stabilizing portion of an antibacterial compound stabilizer such as terpenic, e.g. limonene, or essential oil (natural or synthetic) which may be present in the flavors of oral compositions. Such a stabilizing material is present in a sufficient proportion so that the oral composition, when packaged and dispensed, is an effective anti-plaque composition.

5

The packaged oral composition is generally a toothpaste, gel-like dentifrice, or mouthwash in a compressible dispensing tube, pump dispenser, or bottle, respectively, free of plastic parts adversely affecting an antibacterial agent (preferably a halogenated diphenyl ether) such as trichloroethane ether. the effect or oral composition contains a component that prevents or inhibits any adverse "reaction" between the antibacterial agent and the plastic portion of any container that would otherwise adversely affect the anti-plaque effect of the composition.

The invention will be readily understood from its description in this detailed description, taken in conjunction with the drawings, in which:

Figure 1 is a perspective view of the toothpaste tube and its removed cap when 20 toothpastes have been pressed from the tube into the brush;

Fig. 2 is an enlarged partial cross-sectional view of the lamella wall of the extrudable tube, as in Fig. 1;

Figure 3 is a vertical section of a pump dispenser in which toothpaste or dentifrice gel is held and dispensed as desired; Figure 4 is a side elevational view of a heat sealed pouch or pocket with toothpaste for one-time use; and Figure 5 is an elevational view of a capped mouthwash bottle.

In Figure 1, a packaged anti-plaque toothpaste product 11 includes a collapsible 30-toothpaste tube 13 having anti-plaque toothpaste 15 shown to be dispensed in a uniform amount, such as about 0.8-2 g by squeezing into a brush 17. The tube 13 is opaque and made of synthetic organic polymer. a plastic material such as polyfluoroethylene or coated with a material such as a laminate which does not adversely affect the anti-plaque activity of the toothpaste during storage. Alternatively, the tube may be made or coated with a plastic that has been found to adversely affect the anti-plaque activity of toothpaste (by reducing the antibacterial and anti-plaque halogenated diphenyl ether , which may be terpene, e.g. limonene, or other effective flavoring components. Preferably, neither the toothpaste tube nor its cap 19 or any other part of the tube that may come into contact with the toothpaste (such as the inner wall of the cap) should be made of a copolyester / polyether elastomer or other plastic that substantially reduces the anti-plaque activity of the oral preparation, even in the presence of a stabilizer of the anti-plaque component. It is also considered desirable to avoid other elastomers, such as isobutadienes, polychloroprenes, butadiene rubbers and nitrile rubbers, which may react with or absorb THDE. Hopefully, such parts are made of plastics which do not adversely affect the anti-plaque activity, not even in the absence of terpenes or other stabilizers in the dentifrice, but such other destabilizing plastics may be used when such a stabilizing agent is acting on the toothpaste against the plastic. (preferably, however, elastomeric copolyester / polyethers and other disadvantageous elastomers are avoided).

Figure 2 shows a polyfluoroethylene film laminate 21, an aluminum sheet 23 and a poly-20 ethylene film 25 with the polyfluoroethylene inside the wall of the tube where it is in contact with the toothpaste. The inner wall of the cap 19, shown in Figure 1, may also be polyfluoroethylene so that all surfaces in contact with the toothpaste during storage are compatible with the anti-bacterial halogenated diphenyl ether component of the toothpaste and do not unduly lose its anti-plaque activity. Instead of having an inner wall 21 of polyfluoroethylene laminate, it may be polyethylene and wall 21 may be polyethylene or other suitable polymer.

The toothpaste pump dispenser shown in Figure 3 is of the type marketed by Guala S.p.A., Italy, mark-30, which is U.S. Pat. as the subject of patent 4776496. The pump dispenser 27, when ready for use, contains toothpaste in a compartment 29 bounded by a bottom wall 31 and a diaphragm 33. Depression of the control plane 35 causes a downward movement of the diaphragm 33 by pushing the toothpaste through the tube 37 and out of the nozzle 39. is elastic, returns to its original configuration 35 and moves the tube 37 and the plane 35 back to their original positions. At the same time, the base 31 protrudes upwards due to atmospheric pressure. The various interiors of the pump dispenser in contact with the toothpaste are preferably plastic (s) that do not inactivate the anti-981216 bacterial and anti-plaque halogenated diphenyl ether. However, in the case where it is not possible to use plastics that have the necessary physical properties for different contact parts and are still compatible with the anti-plaque agent, other plastics may be used provided the dental paste composition (or gel dentifrice) contains a stabilizing agent such as Limoene or other active terpene or spice components. However, it is preferred to avoid the use of any copolyester / polyether elastomers, especially for the pumpable membrane 33, which plastic appears to be particularly active against THDE in oral compositions of the type described.

10

In Figure 4, the bag, pocket, or package is shown as a hot-soldered unit with heat-sealing on its three sides, represented by the numbers 43 and 45.

The fourth page 47 is merely folded twice and does not need to be heat sealed. Inside the sealed package, an oral composition, such as toothpaste, is not visible, and the inner surface of such a bag is made of a plastic material that does not contribute to the unreasonable loss of anti-plaque activity of the antibacterial compound in the oral composition. As other containers for oral anti-plaque compositions, laminates may be used with a plastic layer inside it which does not adversely affect the antibacterial agent or, when the plastic does not have such a negative effect, it may be rendered ineffective by a suitable stabilizer in the oral composition.

Figure 5 shows a cloudy bottle 49 with a sealed cap 51. Both the bottle and the sealing insert (not shown) in the cap are made of plastic materials compatible with THDE, which is the anti-plaque component of the mouthwash 53 in the bottle. As given in other examples, when using "reactive" plastic as the bottle liner material or cap seal, the mouthwash has a suitable stabilizer to prevent the unreasonable loss of anti-plaque activity of THDE or another halogenated diphenyl ether.

30

In addition to the compositions described, which are present in exemplary packages that include gel dentifrices and thick liquids instead of toothpastes, such packages may also include dental compositions suitable for professional use, such as tooth cured, which may contain fluoride and phosphates, mixed antibacterials. substances, plaque-indicating dye solutions and other suitable oral compositions. Pressurized containers (usually pressurized with nitrogen gas) may also be packaged with pressurized or "aerosol" compositions containing said anti-plaque compounds, provided that the contacting plastic parts of such containers are made of materials which do not cause toothpaste or other toothpaste compositions or other unreasonable loss of anti-plaque properties of the substance.

5 In addition to the various containers exemplified in the drawing and mentioned above, compression bottles, capsules, cans, sponge-like trays, and various types of mechanical dispenser containers can also be used. Because some antibacterial halogenated diphenyl ether compounds are photosensitive, it is sometimes desirable for such containers to be composed of, covered, or laminated with a chemical or physical light screening material, many of which are known to prevent the transfer of all inactivating radiation, e.g., ultraviolet light, to inhibitory compound. Such containers are often preferably opaque to prevent photochemical radiation from inactivating the anti-plaque component of the oral preparation, such as toothpaste.

The cause (s) of plastic-induced inactivation of THDE and other substantially non-cationic antibacterial agents with anti-plaque properties in oral compositions has not yet been established. To date, research has not accurately demonstrated the mechanism responsible for the disappearance of 20 such desired activities, but to date, the results do not conclusively indicate either chemical reactions or physical absorption. Tests of base mouthwash or mouthwash formulations containing THDE show that when such mouthwash or mouthwash expires in a dispensing container at room temperature, 38 ° C, or 49 ° C for up to twelve weeks, it is "unreasonable" to 25 toams (more than 25% of the initial concentration of THDE) when the mouthwash has been in contact with the walls and parts of a container of low density polyethylenes, high density polyethylenes, polyethylene terephthalates, polypropylenes, nations, polyallomers . Similarly, when stored in containers with inner walls or portions of co-polyester / polyether elastomers, such as those previously used in Guala pump membranes, large losses occur. It was found that polyfluoroethylenes such as polytetrafluoroethylenes, polyvinyl chlorides, polycarbonates and polysulfones do not absorb or react with an excessive amount of THDE. However, polycarbonates and polysulfonates are brittle and therefore not suitable for use as parts of a dispenser container. Polyvinyl chlorides sometimes impart a foreign taste to oral compositions such as toothpastes and are therefore often avoided as a container material, except in certain cases where such a flavor is mixed with the flavoring agent used in the toothpaste. Thus, of all the available polymeric plastics. 98121 8 materials, polyfluoroethylene has been particularly found to be a suitable material for use in these containers or packages, which does not actually reduce the anti-plaque activity of anti-plaque agents. However, as previously shown, by incorporating anti-plaque stabilizing components into oral compounds, such as terpenes, of which limonene is representative, essential oils (often with terpenes), and other flavoring components with similar "stabilizing" properties, it is able to reduce the activity of anti-plaque agents. disappearance when in contact with containers or container parts made of the various polymeric plastics mentioned, with which there is an unreasonable loss of anti-plaque activity.

Therefore, it is not necessary to be dependent on polyfluoroethylene as a container delivery material, provided that the oral composition also contains stabilizing portions of terpene or other suitable "stabilizers". When such a stabilizer is in oral compositions, or when polyfluoroethylene (or polyvinyl chloride, polycarbonate, or polysulfone) is the only polymeric plastic in contact with the oral composition, storage losses of anti-plaque activity are less than 25% and preferably less than 10% at ambient temperature. after storage at a relatively high temperature, for example 20 ° -40 ° C, for periods of several weeks to a year or more. The most stable oral compositions are those that include a stabilizing portion of terpene or other suitable stabilizer, and also include polyfluoroethylene-only contact container parts (or any other unreacted plastic). Although terpenes and essential oils are the primary stabilizers of this invention, other spice components may also contribute to the stabilization of anti-plaque material, either by interfering with any destabilizing reaction or by inhibiting the absorption of halogenated diphenyl ether by plastic (or other unknown). Thus, it has been theorized that some components of oral compositions that tend to dissolve THDE may function to maintain it in the oral composition or prevent its regrouping into form. On the other hand, it has also been theorized that such a dissolving action could promote the regrouping of dissolved THDE in plastic. Since the issue has not been resolved, scholars are not committed to either theory. While it is also preferred that terpenes and other stabilizers be flavor components, it is not necessary, and stabilizers may be useful for stabilization purposes only.

Although it is preferred that the packages of this invention have inner walls (in contact with the compositions) either coated with or coated with a solid synthetic organic polymeric material, it is within the scope of the invention to use other solid (98/981219) (and / or film forming) polymeric materials, whether or not synthetic. organic or even plastic. Thus, polyethylene glycols and methoxy polyethylene glycols, such as those of the Carbowax type, e.g., Carbowax 4000 and Carbowax 6000, can often be used as liner material in dispenser containers for the compositions described. Inorganic silicone polymers such as siloxanes and non-synthetic organic film-forming materials such as gums, e.g., carrageenan, tragacanth, karaya, are also useful liner materials for dispensers. In addition, solid polymeric materials such as cellulose and starch and their derivatives are also useful container materials in contact with the antibacterial and anti-plaque components of these packaged oral compositions.

The various oral compositions of this invention that are most commonly made are toothpastes, dentifrice gels, and mouthwashes (sometimes referred to as mouthwashes). The former two are referred to herein as dentifrices and the latter is commonly referred to as mouthwash. Dental cleaners contain three main groups of components, an excipient, a polishing material and a surfactant (or detergent). An antibacterial agent, e.g., halogenated diphenyl ether, is usually present in about 10-80% (all numbers are based on the final composition) of the dentifrice. The excipient comprises about 3-40% water, about 7-77% wetting agent such as glycerol, sorbitol, propylene glycol or mixtures thereof, and 0.5-10% gelling agent such as sodium carboxymethylcellulose, carrageenan, iota-carrageenan or hydrogen. -ethylcellulose or the like, including mixtures thereof. The polishing material of the dentifrice is normally about 10-75% in a gel or tooth-paste or about 50-99% in powder, and such a polishing material may be colloidal silicate, precipitated silicate, sodium aluminosilicate, insoluble sodium metaphosphate, aluminum hydroxide, aluminum hydroxide, phosphate dihydrate, anhydrous dicalcium phosphate or calcium carbonate, other known materials or mixtures thereof. Surfactants include anionic, nonionic, cationic and amphoteric ionic surfactants, but the use of a nonionic surfactant is often avoided due to its adverse effect on antibacterial compounds, e.g. THDE, and the use of cationic and amphoteric ionic surfactants is often avoided. because they tend to stain or darken teeth. Thus, synthetic organic anionic surfactants, which are also detergents, are preferred cleaning materials in dentifrices, and of these, sodium lauryl sulfate and other higher sodium alkyl sulfates having 10 to 18 carbon atoms in its alkyl groups are preferred, although they can be replaced with various other well-known and sulfonated detergents, at least in part.

10 93121

Other active ingredients, such as fluoride-donating compounds, e.g., sodium fluoride or sodium monofluorophosphate, may be curing teeth, usually in proportions that provide about 0.001-1% fluoride to the composition, and adjuvants, such as flavoring and sweetening, in proportions of 0.1-10%. may be used. In addition, it may be desirable to use a polycarboxylate such as polyvinyl methyl ether maleic anhydride (PVM / MA) copolymer (Gantrez®) in an amount corresponding to about 0.5-4% of the dentifrice. Such a polycarboxylate material has been found to substantially enhance the antibacterial activity of an antibacterial compound. The use of such polycarboxylates in oral compositions is described in U.S. Patent No. 4,627,977, the disclosure of which is incorporated herein by reference.

In mouthwashes, the oral excipient is preferably aqueous and alcoholic, the alcohol being ethanol or isopropanol. The excipient is normally 90-99.9% of the composition, of which the alcohol is 5-30% and propylene glycol is often 2-10% based on the final product. The remainder of the composition, 0.1-10%, may contain flavoring, surfactant, sweetener, colorant, anti-plaque agent and other adjuvants for specific purposes. In dentifrice and mouthwash compositions, the effective amount of the anti-bacterial anti-plaque compound (s) is normally in the range of 0.02-0.2%, more preferably 0.03-0.1% in mouthwashes and normally about 0.25- 1%, more preferably 0.25-0.5% or 0.6% in dentifrices, the ratio limits do not exceed 0.8% for THDE in toothpastes and 0.2% for THDE in mouthwashes (due to possible oral anesthetic effects) at higher concentrations-la) and is not less than indicated to avoid ineffectiveness against plaque at low concentrations. Preferably, the compositions to be distributed contain proportions of anti-plaque agent and THDE within the given limits, but when the initial concentration is within the given limits, a loss of up to 25% may be acceptable and such divided compositions are within the scope of this invention.

In order to stabilize oral compositions intended to be packaged in containers having plastic walls or other parts in which the plastics are those which are "reactive" with antibacterial compounds, 0.01-2% terpene (s) or stabilizer (s) is desirably in oral compositions, preferably 0.05-1% and more preferably 0.1-0.5%. Such stabilizers may be present in suitable dentifrice flavors if desired (and often desirable) and present in at least 35% flavor, preferably at least 10%, more preferably at least 25%, and most preferably at least 50%.

98121 π

Although the above description relates primarily to dentifrices and mouthwashes, other oral compositions of the invention (e.g., including chewing gums) have similar proportions of the compositions, depending on the form of the composition (less in liquids such as mouthwashes and thicker compositions such as toothpastes). are additions of specific substances to supplement the purposes of such compositions. Thus, tooth curing compositions may include fluorides and phosphates, such as sodium or potassium fluoride, either as a dentifrice or mouthwash base, often in percentages in the range of 1-5%. Plaque-indicating dye solutions may include a suitable color (red is apparently the most popular color for such products), often in a concentration range of 0.001-0.1%, based on mouthwash. The compositions of other products are adjusted according to what is known to those skilled in the art.

An antibacterial agent is a non-cationic material that is insoluble or substantially insoluble in water (having a solubility in water at 25 ° C of less than 10 g / L and sometimes less than 1 or 0.1 g / L). Such materials are soluble or dispersible in dentifrice excipients containing glycerol, sorbitol and / or propylene glycol, and in end products based on such media. They are also soluble or dispersible in aqueous alcohol media for mouthwashes.

Of the antibacterial agents, halogenated diphenyl ethers usually contain bromine and / or chlorine, with chlorine being the preferred halogen. They are preferably substituted with 1 to 3 hydroxyl and 1 to 4 halogen. More preferably, they are substituted with 1 or 2 hydroxyls and 2 or 3 halogens, preferably with four substituents, two in each ring. More preferred such compounds include 2,2'-dihydroxy-5,5'-dibromodiphenyl ether and 2 ', 4,4'-trichloro-2-hydroxydiphenyl ether, with the latter compound (THDE) being most preferred. Various displaceable halogenated phenolic, non-cationic, substantially water-insoluble anti-plaque compounds, such as those specified in S.N. 07/398566 on pages 2-8, filed August 25, 1989, which is incorporated herein by reference, is substituted in whole or in part by halogenated diphenol ethers, as appropriate.

35 Terpenes, a term for the purposes of this detailed disclosure, includes terpene hydrocarbons and their oxidized derivatives, including compounds such as cU-limonene, menthol, diterpenes, polyterpenes and its derivatives, many of which are found in various essential oils and other spices. In addition, in order to be useful as stabilizers for halogenated diphenyl ethers, they often impart desirable flavors to the oral compositions of this invention. Of the terpenes and their derivatives, limonene is considered to be the best balancer of these properties, although other terpenes, including those without spices, are also useful, as are other emulsifiable lipophilic essential oils and spices with stabilizing components.

The various plastics previously described as components of container and / or dispenser components have only been briefly described, as their chemical nature and degrees of polymer-10 foundation are considered well known, so a detailed explanation is unnecessary in this presentation. More detailed information can be found in the Modem Plastics Encyclopedia, published annually by McGraw-Hill Inc., New York, New York.

15 As S.N. 07/398566, the compositions (of the invention) may contain a source of fluoride ions capable of delivering 25-5000 ppm of fluoride ions to the oral cavity, preferably 300-2000 ppm and more preferably 800-1500 ppm. See U.S. Patent 4,627,977 for further details on suitable fluorides, ratios, and manufacturing details. Fluoride acts primarily as a tooth hardener, but also stabilizes anti-calculus polyphosphate compounds when present. Such a polyphosphate is preferably a mixture of sodium and potassium pyrophosphates and is also stabilized by Gantrez S-97. Relationship limits are given in U.S.S.N. 07/398605, filed August 25, 1989, which application is incorporated herein by reference and U.S. Patent 4,627,977 and U.S. Patent 4,806,340, which are incorporated herein by reference.

25

For further details on formulations, components, adjuvants, preparations and uses, see the patent, detailed explanations and applications previously mentioned in this disclosure, which are hereby incorporated by reference.

The described oral compositions are prepared by any of a variety of standard techniques for producing class compositions. With reference to specific examples, for simplicity, THDE is dispersed and / or soluble in the dentifrice excipient and terpene is present as a flavor. In the preparation of a dentifrice, an excipient comprising glycerol, sorbitol and propylene glycol, gelling agents and 3 3 suitable adjuvants (including Gantrez® S-97 and triclosan) and an excipient and an aqueous anionic detergent (preferably sodium lauryl sulfate or sodium lauryl sulfate or sodium lauryl) ryyl is prepared. then mixed with the polishing component with a premixer. Finally, a flavoring agent, including terpene, dissolved in ethanol is added and the pH is adjusted. When making mouthwash, its various components are mixed with alcohol alone or an aqueous alcohol medium and mixed until dissolved. Preferably, a mixture of sodium lauryl sulfate (SLS) and sodium methyl cocoyl taurate (in a ratio of 1: 4-4: 1) is used as the anionic mouthwash surfactant component, with the presence of taurate correspondingly allowing a reduction in the desired SLS content, which is desirable. Other oral compositions are prepared according to similar relevant methods.

When packaging an oral composition in dispenser containers, it is desirable to avoid contacting the compositions with the copolyester / polyether elastomer plastic parts, and it is also desirable to avoid contacting any compositions without a stabilizing agent (such as terpene or spice) made with plastic parts. were listed in this presentation as reactive with THDE and other such antibacterial and anti-plaque compounds. It is particularly important to avoid said plastic parts comprising tanks or any other containers, pipes, pumps or equipment in which the oral composition can be kept for any appreciable period of time or kept for shorter periods at elevated temperatures.

20

Although contact with reactive plastics is avoided when preparing the packaged compositions of this invention and oral compositions containing THDE or other halogenated diphenyl ether antibacterial composition, it is still desirable to minimize the exposure of packaged compositions to heat and light. loss of inhibitory activity. The compositions thus invented are preferably stored and packaged in opaque containers and dispensers at a temperature in the range of 10 ° C to 38 ° C and also stored at such a temperature. Otherwise, the packaged compositions can be stored and used in the normal manner and their desired anti-plaque effects are maintained. Such efficiencies have been confirmed by laboratory tests and evaluation of the teeth of volunteer subjects using various packaged compositions and controls, as instructed. Significant improvements in anti-plaque activity were observed with the packaged compositions of this invention compared to the packaged control compositions, which included 35 plastic parts that were "reactive" with the antibacterial halogenated diphenyl ether compound and lacked a stabilizing agent in the oral composition. Such improvements are also observed when packages made of "reactive" plastics (but not copolyester / polyether elastomer) are used with terpenes-containing oral compositions and compared to controls without terpenes and flavorings in the oral compositions.

The following examples illustrate but do not limit the invention. Unless otherwise stated, all percentages and ratios in these examples, detailed representations and appended claims are by weight and all temperatures are in ° C.

Example 1

Component Percent 10 Water, deionized 47.84

Sorbitol (70% aqueous solution) 20.00

Ethanol (95% aqueous solution) 12.50

Glycerol 10.00

Propylene glycol 7.00 15 * Gantrez S-97 (13% solution) 1.92

Sodium hydroxide (50% aqueous solution) 0.12

Sodium lauryl sulphate 0.25 ** Tauranol WSHP 0.20 ♦♦♦ Spice mixture 0.12 20 **** Triclosan (Irgasan® DP 300, manufactured by CibaGeigy) 0.05 100.00 * Polyvinyl methyl ether / maleic anhydride copolymer (GAF limited liability company) 25 ** Sodium methylate ** Contains at least 25% terpenes, including at least 25% limonene **** THDE (2 ', 4,4'-trichloro-2-hydroxydiphenyl ether) The mouth rinse (or mouthwash) of this example is done by mixing together the various 30 components of the list where in any suitable order, according to standard methods, but preferably triclosan is first dissolved in a mixture of propylene glycol and ethanol, followed by mixing with an aqueous solution of sorbitol, glycerol and anionic surfactants, the spice mixture being added last. Sodium hydroxide solution is used to neutralize the resulting acidic mixture, with neutralization to pH 6.84 (it is desirable for the product to be at or near neutral pH).

The resulting mouthwash has excellent cosmetic stability and has an acceptable taste and the flavor and triclosan are satisfactorily dissolved, such dissolution being due, at least in part, to the presence of Tauranol WSHP. When only 0.25% SLS is used as an anionic surfactant, the solubilities of the flavoring agent and triclosan are not satisfactory. Although such solubilities can be increased by using more SLS, the maximum acceptable limit for such a compound in oral washes is often about 0.25% and Tauranol® WSHP and SLS are safe and acceptable in the ratios used. The described mouthwash tests the in vitro bioavailability of triclosan against comparable mouthwash formulas lacking Tauranol WSHP in one case and replacing it with half the amount of non-ionic surfactant (Pluronic F-127) in the other case. In triclosan uptake assays, by measuring the absorption of triclosan on hydroxyapatite plates coated with saliva and protein absorption by "zonal inhibition" assays, it was found that the mixture of anionic surfactant with no non-ionic detergent other than the one with the formula of non-ionic detergent (Pluronic® F-127).

The mouthwash life of the formula of this example is determined at elevated temperatures (41 ° C) of three and five weeks, which is considered equivalent to an actual duration of at least about six months and one year at room temperature. Such lifetimes are performed in dispenser containers (bottles) made of glass, polyvinyl chloride and polyethylene terephthalate (or coated with plastic materials). Although chemical analyzes of mouthwashes after such durations showed no disappearance of triclosan when the container is glass, disappearances of triclosan from mouthwashes were observed when the containers are polyethylene terephthalate or 25% of the polyvinyl chloride of this sample, but are significantly less than tolerable. or 10%.

When di-limonene is used in amounts of 0.1, 0.2 and 0.4% instead of the spice mixture, even better stabilizations of triclosan are available in the described packaged dentifrices of this invention, and such stabilizations are also obtained with other terpenes from any of the various essential oils and spices. in similar relationships. Such good results are also obtained when the container material or its coating is polymethylpentene, polyallomer, polypropylene, high or low density polyethylenes and nylon, although such materials in the absence (and containing) of the spice mixture especially at elevated temperatures.

16 98121

Example 2

Component Percent

Water, deionized 84.42

Ethanol (95%) 10.0 5 Propylene glycol 5.0

Sodium lauryl sulphate 0.50 Triclosan 0.06

Sodium saccharin 0.02 100.00 10

The mouthwash of the above formula is tested for the availability of triclosan after three weeks of storage in dispenser containers made or coated with various plastics. The tests are performed at room temperature, 38 ° C and 49 ° C, with elevated temperature storage simulating longer storage times, up to 15 years or more at room temperature. More than 25% of triclosan disappears from stored mouthwash when the containers are made of polymethylpentene, polyallomer, polypropylene, high or low density polyethylenes and nylon, unacceptable results (unreasonable disappearances) are observed when the containers are made of polypropylene and polyethylene, polyethylene ). When the container material or coating is polyvinyl chloride, polycarbonate, polysulfone or polyfluoroethylene, e.g. polytetrafluoroethylene or Teflon®, there is no substantial loss of triclosan. Disappearances of triclosan from mouthwashes stored in containers coated with or coated with said polymers (polymethylpentene, etc.) can be reduced in the same manner as described in Example 1 by adding limonene, other terpenes or essential oils to the mouthwash formula, which may contain with a terpene ratio of preferably at least 0.1% and more preferably greater, e.g. 0.2% or 0.4% based on the final composition. In some cases, even the use of spice materials that do not have a significant proportion of terpenes may have a positive effect, although such an effect is not expected to be as good as that of the terpenes of the formula.

98121 17

Example 3

Component Percent

Propylene glycol 10.00

Iota-carrageenan 0.75 - 5 Sodium fluoride 0.33

Sorbitol (70%) 30.00

Sodium saccharin 0.30

Titanium oxide 0.50

Sodium hydroxide (50% aqueous solution) 0.80 10 Water, deionized 27.71 + LuviformTM (35% solution) 4.76 ++ Zeodent ™ 113 20.00 +++ Sident ™ 22S 2.00

Sodium lauryl sulphate (94% active) 1.60 15 Taste 0.95

Triclosan 0.30 100.0 + Polyvinylmethyl ether / maleic anhydride copolymer (BASF Corp.) 20 ++ Quartz-containing polish (J.M. Huber Corp.) +++ Quartz-containing thickener (Degussa Co)

The dentifrice of the above formula is made in a normal manner and is used as a substrate to test the stability of triclosan when the dentifrice containing it is exposed to various plastics used as container materials or as parts of dispensers in which the dentifrices are stored and dispensed. The plastics used for the tests are Pibiflex® 46, manufactured by Inmont, and AmitelTM 460 EM, mf’d from AKZO, which are plastics used as membranes or bellows for a pump dispenser, as illustrated in Figure 3. Six plastic samples are tested, three of each of said plastics, each of which is treated with a different release agent (to determine whether the nature of the release agent has to do with the stability problem of triclosan when in contact with the plastics during storage). The release agents are Silicone Master® M (5% silicone oil and 95% propylene), Silicone Master plus Silicone Oil (with excess silicone oil) and 35 Armid O Master® M (5% oleoamide and 95% polypropylene), respectively. After the test samples have been stored for two weeks in contact with the dentifrice at various temperatures (room temperature, 38 ° C and 49 ° C), the dentifrice is removed from the plastic container materials and the plastics are washed with water and immersed in methanol to dissolve all triclosan. could have taken over during storage. Methanol washes are collected and analyzed using high performance liquid chromatography. It is found that substantially similar absorbances of triclosan occur with different membrane materials, and although there are variations between them and some depend to some extent on the release materials used, the results are essentially the same in all cases. The copolyester / polyether elastomers are found to absorb significant percentages of triclosan from the dentifrice, results that can be confirmed when using copolyester / polyether elastomers in bellows pump dispensers having the described dentifrice and other dentifrices within the scope of the invention. Accordingly, it is undesirable to use copolyester / polyether elastomers in contact with these dentifrices or mouthwashes, even though the dentifrices and mouthwashes contain flavors including terpenes (as a spice in the dentifrice formula) in an amount of at least 0.1% of the dentifrice.

When tests are repeated using Guala pump dispensers as dental cleaning containers with Amitel® M copolyester / polyether elastomer membranes, triclosan losses are also unacceptable, but when the copolyester / polyether-20 elastomer is replaced with other acceptable plastics, e.g. Also, plastic parts of other pump dispensers, such as its polypropylene inner walls, have not been found to absorb excessive amounts of triclosan and do not severely reduce the anti-plaque activity of the dentifrice, apparently due to the terpenes in the dentifrice flavor contained.

A participant test of at least 10 human subjects using the dentifrice of this example dispensed from polyethylene terephthalate and polyethylene lined tubes is performed twice daily for one month, during which time a plaque subject is evaluated by a trained observer. The test results showed that the dentifrice composition has a clear anti-plaque activity, similar to that observed in the tests with the mouth rinses of Examples 1 and 2, and at the same time proves that triclosan is not unacceptably inactivated and is still effective as an antibacterial and anti-dental anti-plaque agent. .

i · su.i- get i.i j -sm 98121 19

Example 4

Component Percent

Glycerol 7.00

Propylene glycol 3.00 to 5 Iota-carrageenan 0.75

Sorbitol (70%) 30.00

Sodium saccharin 0.30

Sodium fluoride 0.33

Titanium dioxide 0.50 Gantrez® S-97 (13% solution) 15.00

Deionized water 16.07

Sodium hydroxide (50% aqueous solution)

Zeodent® (J.M. Huber Corp.) 20.00

Sylodent® 15 (silica thickener; 15 W.R. Grace Corp.) 3.00

Flavor 0.95

Sodium lauryl sulphate 2.00

Triclosan 0.30 100.00 20

Toothpaste of the above formula is prepared and stored in Guala® M pump dispensers with Amitel-type bellows membranes. The dentifrice is also filled into laminated tubes with polyethylene terephthalate in inner laminates in contact with the dentifrice. Dental-25 cleaners are allowed to age at 5 ° C, 25 ° C and 39 ° C for two, four and six weeks. After such aging periods, the dentifrices are dispensed at a rate of about 1.5 g per day, and the triclosan contents of the dentifrices dispensed weekly are determined by analysis. In the case of the Guala pump dispenser, the split toothbrush loses about 27% of the triclosan, which is unreasonable and questionable.

The disappearance is almost constant regardless of the storage temperature or storage time, which can be explained by the absorption of the pump membrane with which it is contacted before partitioning with triclosan. Such a membrane is often a copolyester / polyether elastomer, a class of plastics of which should be avoided as reservoir materials for triclosan-containing dentifrices or as part of a reservoir or dispenser 35. However, when the elastomeric copolyester / polyether membrane is replaced with any of the aforementioned approved plastics, such as polyethylene terephthalate, which can act as a membrane material in modified pump dispensers (modified to compensate for various properties of such plastics)

Gel toothpaste formulations in such packages behave similarly with respect to the stability of triclosan after storage and distribution. '

In similar tests using polyethylene terephthalate lined tubes, a slight disappearance of triclosan (less than 5%) is observed, indicating that the presence of terpenes (0.1% or more of the composition), including limonene, in the flavor (or the flavor itself) prevents triclosan loss or inactivation. .

When polyfluoroethylene lined tubes are used, there is some loss of triclosan, even when the flavor is omitted from the dentifrice composition, and this is also the case when polyvinyl chloride is used as a liner in contact with the dentifrice or when the polysulfone or polycarbonate package is in contact with the dentifrice. However, as previously shown, such three latter plastics are not generally used.

In a reported test in which toothpaste is dispensed from a Guala dispenser,

Gantrez S-97 is replaced by 4.76 parts of Luviform (35%), the difference is filled with deionized water, no significant differences in the stability of triclosan are observed between the formulations.

In the above formulations, the polishing system is a quartz-like system rather than an aluminum-based one. When the polish is changed to aluminum, the aforementioned problems observed with some plastics are reduced but still exist. The presence of terpenes in dentifrices also contributes to the stability of triclosan, as do the presence of terpenes in similar dentifrice compositions based on quartz-containing polishes.

30 Example 5

In the mouthwashes and dentifrices of the above examples, the composition of the various components may vary from + 10% to + 25%, provided such percentages are not outside the directions given elsewhere in this presentation and operative and effective antibacterial and anti-plaque products are available that can be distributed as effective dental plaque. dispenser containers made of miscible plastics. The products can also be modified by converting toothpaste gels, oral gels, pastes, liquids, lozenges, capsules, tablets and bags of the type 98121 21 previously mentioned in the presentation. Such products also behave similarly in the presence of triclosan or other halogenated diphenyl ether or antibacterial anti-plaque agent in the presence of polyfluoroethylene, polyvinyl chloride, polycarbonate and polyethylene polyethylene and polyethylene packaging, , in the presence of polyallomers, nylons and polymethylpentenes as packaging or component materials, provided that the oral composition contains a terpene such as limonene or a stabilizing flavor component. As with other previously discussed toothpaste and mouthwashes, copolyester / polyether and other elastomers due to excessive absorption or other unfavorable performance over triclosan, the use of such materials is advantageously avoided.

Example 6 The dentifrices of the formulations in Examples 3 and 4 are made and dispensed after one month of storage at 30 ° C in torsional toothpaste tubes lined with polyethylene, in one case, and polyethylene terephthalate in another, on toothbrush bristles, as illustrated in Figure 1. The amounts of toothpaste for the toothbrush are in the range of 0.8-2.0 g, with 1-1.5 g being preferred-20 Sleep. When 1.5 g is dispensed, the active triclosan in the toothbrush on the brush is about 4 mg (only 10% of the triclosan is inactivated). When stored for a longer period of time or at a higher temperature, or that more destabilizing plastic is in contact with the dentifrice during storage, the packaged compositions may contain about 3 mg of triclosan per 1.5 g with a brush. Thus, 1 g of dentifrice with a brush 25 amounts of triclosan to about 2.7 mg and 2 mg, respectively. For dentifrices containing 0.25-06% triclosan, the toothbrush may contain 2.2-8 mg triclosan if the inactivation of triclosan is in the range of 10-25% or up to about 9 mg when triclosan is not inactivated.

The packaged dentifrices described are used to brush teeth, typically dispensing about 0.8-2 g into toothbrushes for each brushing. Brushing is twice a day, morning and evening, one minute at a time, for four weeks, after which there is a clear improvement in anti-plaque activity compared to a control dentifrice without triclosan. The improvement in anti-plaque 35 activity is also visible compared to the unflavoured control (terpenes free) with triclosan in a dentifrice kit in polyethylene and polyethylene terephthalate lined tubes.

98121 22 The present invention has been described in terms of illustrative examples and embodiments thereof, but is not intended to be limited thereto, as it will be apparent to those skilled in the art that the present invention will be able to use substitutes and substitutes without departing from the invention.

Claims (14)

In storage, stable oral composition having anti-tooth stick properties, which composition is enclosed in a dosing container having a solid polymeric material in contact with said composition, wherein the composition in the container comprises an orally acceptable medium, about 0.02-1. weight percent of a substantially water-insoluble non-cationic antitanding agent and other conventional aids, and thinning that at least about 25% of the antitanding activity of the antitanding agent disappears upon storage at elevated temperature for at least 3 weeks in said container as a result of said composition comes into contact with the polymeric material, characterized in that, in said container, a compatible polymeric material which comes into contact with the composition and which does not cause such a loss, such as polyfluoroethylene, polyvinyl chloride, polycarbonate or polysulfonate, or II, is used. where such polymeric material which comes into contact with the composition is incompatible and normally causes such loss, such as polyethylene, polypropylene, polyethylene terephthalate, polymethyl pentene, polyallomer and / or nylon, about 0.01-2% has been included in said composition of a stabilizing agent such as a terpene or flavoring agent which prevents such loss, and in said composition may have included about 0.5-4% vinyl methyl ether / maleic anhydride copolymer and / or 25-5000 ppm fluoride ions. Composition according to Claim 1, characterized in that it further contains an effective amount of an anti-dental surfactant which is a synthetic, linear molecular dehydrated polyphosphate. Composition according to claim 1 or 2, characterized in that point I is used and that the composition possibly contains about 0.01-2% of a stabilizing agent defined in point II. A composition according to claim 1 or 2, characterized in that point II is used. Composition according to claim 4, characterized in that the polymeric material comprises polyethylene. 35 98121 26 Composition according to claim 4, characterized in that the polymer material comprises polyethylene terephthalate. Composition according to any of the preceding claims, characterized in that the antifouling or flavoring comprises the limonene. Composition according to any one of the preceding claims, characterized in that the anti-tooth plaque agent comprises a halogenated diphenyl ether. Composition according to claim 8, characterized in that the halogenated diphenyl ether contains 1-3 hydroxyl substituents and 1-4 chlorine or bromine substituents. Composition according to claim 8, characterized in that the halogenated diphenyl ether comprises the triclosan. 15 11. Composition according to any of the preceding claims, characterized in that, as a container, a deformable metering tube, pump dispenser, pressurized dosed, bag, bottle or any other container is used. Composition according to any of the preceding claims, characterized in that the composition is in the form of a toothpaste, a gelatinous dentifrice, a liquid dentifrice, a liquid mouthwash or a cream-shaped, gelatinous or liquid dentifrice. Composition according to claim 12, characterized in that the composition is in the form of a liquid mouthwash containing 0.03-0.1% triclosan as anti-tooth plaque. Composition according to claim 12, characterized in that the composition is in the form of a toothpaste or a gelatinous dentifrice containing about 0.25-1% triclosan as an anti-tooth plaque agent.