UA55363C2 - Item comprising dosing container - Google Patents

Abstract

The item comprising the dosing container is designed for the storage of the peroral composition used for teeth brushing and washing the oral cavity with the aim of inhibiting the dental deposit. The walls of the container are coated inside with polyethylene or polyethylene terephtalate to prevent the excessive loss of the substance. The stabilizing ingredient provides for the compatibility of the internal polymeric coating of the container with the composition inhibiting the dental deposit.

Description

The present invention relates to packaging of oral (non-oral) plaque-preventing compositions containing a plaque-preventing antibacterial agent such as 27 4 4"-trichloro-2-dihydroxydiphenylene sulfur (THCG) as an effective plaque-preventing agent, and such compositions enclosed in a container made of a polymeric plastic material in contact with the oral composition, such plastic being compatible with the composition's antibacterial agent. Although various plastics can reduce the plaque-preventing effect of said antibacterial agents, certain plastics such as polyfluoroethylene and polyvinyl chloride , as it was found, are compatible with ТХГЗ and it was found that the plastics do not suffer excessive wear preventing the formation of dental plaque and the antibacterial activity of the oral compositions contained in them during storage and at room and elevated temperatures. Even if the plastic parts of the container are made of plastic, which is not completely compatible with the antibacterial compound, the compatibility can be improved by introducing into the composition stabilizing amounts of the stabilizer of the antibacterial compound, such as, for example, terpone limonene or safflower oil (natural or synthetic), which can be present in the flavoring zlemente oral composition. Such a stabilizer is present in sufficient quantity, so that the oral composition in a packaged and ready-to-use form is an effective plaque-preventing composition, the purpose of which is the present invention. The scope of the invention includes a method of contacting internal surfaces with oral compositions containing an effective amount of a plaque-preventing agent. The scope of the invention also includes a toothbrush containing on its bristles an effective amount of plaque-preventing means for cleaning teeth.

It is believed that plaque is the cause of negative periodontal factors and that plaque is a precursor to tartar. Plaque can form on any part of the teeth, including the edges of the gums. Plaque makes the teeth dull, and in addition to promoting the formation of tartar, it is considered the cause of gingivitis. Thus, oral compositions containing a plaque-preventing component that prevents or inhibits the development of plaque on the teeth are valuable dental care products.

Although it was known that antimicrobial agents in oral compositions can reduce dental plaque, sometimes especially effectively in combination with other substances, nevertheless, the various such antibacterial compounds have disadvantages that prevent their use in oral compositions. For example, cationic antibacterial compounds such as quaternary self-halides have a tendency to discolor teeth, and can be deactivated by the presence of anionic substances in oral preparations (which may often be desirable in oral compositions of anionic surfactants or detergents).

Essentially, water-insoluble halogenated (and often hydroxylated) diphenyl sulfates, such as: THCG (triclosan) and 2,2'-dihydroxy-5,5-dibromodiphenyl sulfate (DDDoZ) are effective antibacterial agents that prevent the formation of dental plaque, but they can beat the activations! non-ionic surface-active substances and many plastics, which were discovered by the applicants.

Thus, the purpose of the present invention is to introduce antibacterial plaque-preventing agents, such as halogenated diphenyl ether, in particular, ТХГЗ and DDDO, and similar agents, into oral compositions, storing such compositions and extracting them from packages or containers in which the compositions, when stored, do not lose a noticeable degree of activity as plaque-preventing agents before intended use. In known toothpastes containing triclosan extracted from the corresponding dosing devices, triclosan was delivered in quantities insufficient for a noticeable reduction in dental plaque in the case of using the product once or twice a day in the amount of 1.5 g/time during one-minute brushing. What is considered to be the usual exemplary practice of brushing teeth. In order to be effective, such a practice should lead to at least a 2595th decrease in plaque as a result of its three-week use compared to the use of a similar control toothpaste for three weeks.

The most recommended antibacterial and plaque-preventing component present in packaged compositions is THCG, also known as triclosan. Triclosan is described in US patent 4,022,880 as an antibacterial agent in combination with an anticalcification agent that neutralizes copper ions! zinc), as well as described in the patent of the Federal Republic of Germany (OJ 5) Mo 35 22 860 in combination with a copper compound. In addition, triclosan is described in European patent applications! Me0161898 and Me0161899 and in the application for the European patent 0220890 in the composition of means for cleaning teeth in a mixture with polyethylene glycol and fragrance based on oil.

Many oral compositions or preparations are known, including: pastes, gels, powders, liquids, tablets, lozenges, teeth cleaning agents in pouches and sachets, liquid and tablet mouth rinses, as well as dental treatment agents (such as compositions for hardening teeth, for example, fluoride solutions). Such a product! detachable tubes, inflating dosing devices, pressurized dosing devices, sachets, bottles, vessels and other containers are packed in removable containers. Although deformable or collapsible tubes were originally made of metals such as lead or aluminum, and bottles were made of glass, in the latter case! such a container! were often made from synthetic organic polymer plastics or from laminates including such plastics.

It is known that there is an interaction between oral compositions and the materials in which they are packaged, for example, the reaction of toothpastes with aluminum containers, and to prevent such reactions, the containers were subjected to special processing or other materials were used for their manufacture!. However, the applicants believe that prior to the creation of the present invention, the prior art did not know about the adverse effect of certain plastic packaging materials on the plaque-preventing activity of halogenated diphenyl ethers used as antibacterial agents, introduced into oral compositions and packaged in containers in which they come into contact with such plates, and do not assume what was known about the possibility of using such plastics for the manufacture of parts of containers without losing the plaque-preventing activity of halogenated diphenyl ethers or losing the same activity with oral compositions, packaging and contact with "reactive" plastics (which react, absorb or otherwise reduce the plaque-preventing activity of an oral composition) due to the inhibition or elimination of the action of plastics by the introduction of terpe nov, such as lemon or other flavoring components for the oral preparation.

In accordance with some of its aspects, the present invention relates to an oral composition containing an effective plaque-preventing amount of a substantially water-insoluble non-cationic antibacterial agent, the composition is packaged in a dispensing container made of a material that includes a solid polymer material, such as a synthetic organic polymer plastic , in contact with the oral composition, and such a polymer material is compatible with the antibacterial agent in the oral composition and does not cause excessive loss of antibacterial and plaque-preventing activity of the oral composition when stored in a container (for example, at 20 - 402C for several weeks, preferably up to a year or more). The packaged oral composition, as a rule, is a toothpaste, gel toothpaste or mouthwash, contained in a deformable dosing tube, an inflating dosing device or a bottle, respectively, without plastic parts that adversely affect the prevention of dental caries an antibacterial agent (which is preferably represented by a halogenated diphenyl ether such as triclosan), or the oral composition includes a component that inhibits or prevents any such undesirable reactions between the antibacterial agent and any plastic part of the container that might otherwise have an undesirable effect on preventing the formation of dental plaque activity of the oral composition.

The invention can be easily understood from its description combined with the accompanying drawings, where:

Fig. 1 is a perspective view of a tube with toothpaste and a removable cover to it, it shows squeezing toothpaste from the tube onto a toothbrush;

Fig. 2 represents an enlarged section of a part of the layered wall of a collapsible tube, similar to that shown in Fig. 1; fig.3 represents a vertical section of an inflating dosing device for distributing toothpaste at will! or means for cleaning teeth in the form of a gel; Fig. 4 shows a vertical section of a side view of a heat-sealed sachet or pouch for a single amount of toothpaste!; Fig. 5 represents a vertical section of a bottle with a lid for mouthwash.

In Fig. 1, the product I for the packaging of the anti-plaque toothpaste consists of a tube 13 for the toothpaste, which contains the anti-plaque toothpaste 15, shown extracted in a unit amount, for example, 0.8 - 2 grams by squeezing on brush 17. The tube 13 is opaque and made of synthetic organic polymer plastic, such as polyfluorinated or lined with such a material, for example, in the form of a laminate, which does not have an adverse effect on preventing the formation of dental plaque. during storage. Or the tube 13 is made or lined with plastic, which has been found to have an adverse effect on the plaque-preventing activity of the toothpaste (by reducing the plaque-preventing and antibacterial activity of the halogenated diphenyl ether included in the toothpaste), but nevertheless has an adverse effect on the plaque-preventing activity the formation of plaque activity is eliminated or inhibited by the introduction of a stabilizer into the toothpaste, which can include a terpene, for example, limonene, or another effective fragrance component. It is recommended that neither the toothpaste tube itself, nor the cap 19 to it, nor any other part of the tube that can come into contact with the toothpaste (for example, the lining of the cap) should not be made of zlastomer nozzle (complex) zfir/poly (simple ) zephyr or a second plastic that significantly reduces the anti-plaque effect of the oral composition even in the presence of a stabilizer for the anti-plaque component of the composition. It is also considered desirable to avoid the presence of other harmful substances, such as: isobutadione, polychloropropene, butadione rubbers and nitrile rubbers, which can react with THGZ or adsorb it. It is desirable to make such parts from plastics that do not have an adverse effect on the plaque-preventing activity even in the absence of terpenes or other stabilizers in the toothpaste, but other such destabilizing plastics can still be used if there is a stabilizer in the toothpaste that counteracts the deactivating effect of the plate (with the exception of zlastomer sopola (complex zfir/poly(simple) zfir and other undesirable zlastomers, which are recommended to be avoided).

Fig. 2 shows a laminate made of polyfluoroethylene film 21, aluminum sheet 23 and polyfluoroethylene film 25, where polyfluoroethylene is located on the inner part of the tube wall, in contact with toothpaste. The lining (not shown) of the cap 19 in Fig. 1 can also be polyfluoroethylene, in as a result, all surfaces in contact with toothpaste during storage are compatible! with halogenated diphenyl zephyr is an antibacterial component of toothpaste and does not promote excessive loss of plaque-preventing activity of toothpaste when stored. The inner side of the wall 21 of the laminate can be not only polyfluoroethylene but also polyethylene, and the wall 21 can be made of polyethylene or another acceptable polymer.

Figure 3 shows an inflating dosing device for toothpaste! of the type manufactured by the company Sshaia 5.r.A, Italy and which is the subject of US patent 4776496.

The pumpable dosing device 27, ready for use, contains a toothed flipper in a separate 29, limited by the lower wall 31 and the membrane 33. The weakening of the movable lever 35 causes the downward movement of the membranes! 33 with vyiidavlivaniem mouth! through tube 37 and neck 39.

With the cessation of pressure on the movable lever 35, the elastic membrane 33 returns to its original state and returns the tube 37 and the lever 35 to its original position.

At the same time, the bottom layer 31 is pushed up under the action of atmospheric pressure. The various internal parts of the inflating dispensing device in contact with the toothpaste are recommended to be made of plastic - (ov), which does not affect the deactivation of the applied and anti-bacterial and plaque-preventing means of halogenated diphenyl ether. However, if it is not possible to use plastics with the necessary physical properties , required for contacting parts, and at the same time compatible with plaque prevention means can be used! other plastics, provided that the composite toothpaste (or gel toothpaste) includes a stabilizer such as lemon or another applicable terpene or fragrance component.

However, it is considered better to avoid maliciously sized (complex) resins/poly(simple) resins, especially for the manufacture of inflatable membranes (33), the plastic material of which is apparently especially active in relation to THCG in oral compositions of the described type.

Figure 4 shows a bag or packet in the form of heat-sealed units, soldered on three sides, designated by the numbers 43 and 45. The fourth side 47 is formed by simple bending of the material and does not require soldering. Inside the sealed bag is an oral composition, for example, a toothpaste (not shown), and the inner surface of such a bag is made of plastic that does not promote excessive losses, preventing the formation of dental plaque, the antibacterial compound contained in the oral composition enclosed in the bag.

As for other containers for oral compositions that prevent the formation of dental plaque, in this case they can be used! laminate! with an inner plastic layer that does not have an adverse effect on the antibacterial agent, or if the plastic still has such a negative effect, then the effect can be counteracted by the presence of an acceptable stabilizer in the oral composition, which is also recommended to be used as a flavoring additive.

Fig. 5 shows an opaque bottle 49, which has a sealing cap 51. Both the bottle and the seal (not shown) in the cap are made of plastic materials compatible with THGOZ, i.e., the plaque-preventing component of the mouthwash contained in the bottle mouth 53, As in the case of the second given examples, when "reactive" plastic is used as the material of the inner part of the bottle or the sealing of the lid to prevent excessive losses of plaque-preventing activity of THGZ or the second halogenated diphenyl ether, an acceptable stabilizer must be present in the mouthwash.

In addition to the compositions given as examples of the filling of the described packages and including means for cleaning teeth in the form of a gel and a thick liquid instead of toothpaste!, such packages may also contain compositions for the treatment of teeth, suitable for professional purposes, such as tooth hardeners, which may include fluoride and phosphate, mixtures of antibacterial agents, dye solutions for plaque indication, and other acceptable oral compositions.

In addition, pressurized or "azosol" compositions containing the mentioned plaque-preventing compounds can be enclosed in pressure-retaining containers (the pressure in which is usually created by gaseous nitrogen) under the conditions that the contacting plastic parts of the container are made of non-corrosive material excessive loss of plaque-preventing activity of the corresponding agent,

contained in toothpaste or other oral composition.

In addition to the various containers shown in the drawings and mentioned above, collapsible bottles, capsules, cans, sponge-like media and various types of mechanical dosing containers can also be used. Because some halogenated diphenyl ethers are used as antibacterial agents! sensitivity to the action of the world, sometimes it is desirable, so that! such a container! they were standing, they were covered! or they were layered with a material that shields them from chemical or physical radiation, many of which are lime, to protect the oral composition and prevent the formation of dental plaque from the effects of deactivating radiation, for example, UV radiation. In addition, it is often desirable that such containers be opaque to photochemically active radiation, which deactivates the plaque-preventing component contained in an oral preparation, for example, toothpaste.

The reason(s) for the deactivation by plastic of THGZ and other non-cationic antibacterial agents, which give oral compositions properties to prevent the formation of dental plaque, has not yet been elucidated. At the present time, the research did not clearly reveal the mechanism responsible for the loss of such desired activity, however the result is obtained! point, but not definitively, to chemical reactions or physical absorption. Tests of base compositions for rinsing or rinsing the mouth, subjected to aging in dosing containers at room temperature, 382C and 49"C for twelve weeks, lead to "excessive" losses (more than 2595 of the initial concentration of THGZ) when the composition for mouthrinse comes into contact with the walls and container parts made of low-density polyethylene, high-density polyethylene, polyethylene terephthalate, polypropylene, nylon, polyallomers, and polymethylpentenes.

Similar high losses are observed when stored in containers with inner walls or parts made of coarse-grained (complex) zephyr/poly(simple) zephyr of the type previously used by the company

Sai for the production of inflatable membranes. It was found that polyfluoroethylene), such as polytetrafluoroethylene, polyvinyl chloride), polycarbonate and polysulfonium do not absorb and do not react with excess amounts of THGZ. However, polycarbonate and polysulfone! fragile and, therefore, often unusable! for the manufacture of parts of dosing containers, Polyvinyl chloride! sometimes they add an aftertaste to oral compositions, except in some cases when such an aftertaste is compatible with the taste of the fragrance used in the toothpaste.

Thus, of all the available polymer materials, only polyfluorostyrene is recognized as a quality material for the manufacture of containers and packages that do not significantly reduce the plaque-preventing activity of the corresponding agents.

However, as mentioned earlier, the introduction of stabilizers for plaque-preventing agents, such as terpenes, for example, limonene, essential oils (often containing terpenes) and other components of perfumes with similar stabilizing properties into the oral composition of plaque-preventing agents, can reduce the loss of activity of the plaque-preventing agent upon contact with the container or parts of the container made of various mentioned polymer plastics, which show large losses of tartar-preventing activity. Thus, if the oral composition contains a stabilizing amount of terpene or a second acceptable "stabilizer", it is possible not to depend on polyfluoroethylene as a material for the manufacture of dosing containers. In the case of the presence of a stabilizer in the oral composition or if polyfluoroethylene (and also polyvinyl chloride, polycarbonate or polysulfone) is the only polymer material in contact with the oral composition, the loss of plaque-preventing activity during storage is less than 2595 and preferably less! be less than 1095 at room temperature and even at higher temperatures, for example, at 20 - 402C for several weeks and up to a year or more. It is believed that the most stable oral compositions are those compositions that include a stabilizing amount of terpene or another acceptable stabilizer and that come into contact only with parts of the container made of polyfluorostyrene (or any other non-reactive plastic).

Although terpene and zfirnse oils are the first among the stabilizers of the present invention, other components are too! fragrances can contribute to the stabilization of plaque-preventing substances either by interfering with destabilizing reactions or by inhibiting halogenated diphenyl ether with plastic (or by another unknown mechanism). Thus, a theory is proposed, according to which the oral composition contains a component that tends to solubilize THCG, with its retention in the oral composition and prevention or inhibition of its migration into plastic. On the other hand, the theory put forward is that such a solubilizing action can promote the migration of solubilized THGZ into plastic. Since this issue has not been resolved, the applicants do not want to be bound by either theory. In addition, although it is desirable that terpenes and other stabilizers were components of the fragrance, this condition is not mandatory, and the stabilizer can only be used for stabilization purposes.

Although it is recommended that the packages of the present invention have inner walls (in contact with the compositions) made or lined with a hard synthetic organic plastic, the scope of the invention also covers the use of other hard (and/or film-forming) polymer materials, whether or not they are synthetic,

organic and even plastic materials.

Thus, polyethylene glycol and methoxypolyethylene glycol of the KarbovaxF type, such as Karbovax 400 or Karbovax 600, can often be used as a lining material for dosing containers for the described compositions.

Inorganic silicone polymer), such as siloxane, as well as natural organic film-forming materials, such as gums, for example: carrageenan, tragacanth, carrageenan are also applicable! for lining distribution containers.

In addition, a solid polymer product, such as cellulose, starch and their derivatives, can also be used as a material for containers in contact with antibacterial and plaque-preventing components of the packaged oral compositions of the invention.

Different oral packaging of the compositions of the present invention, which are produced most often, that is, toothpastes, gel toothpastes and mouthwashes (often called mouthwashes), the first two compositions will be called toothpastes, and The latter is a mouthwash.

Means for cleaning teeth include three main groups of components: a carrier, a polishing agent and a surface-active substance (or detergent). An antibacterial agent, for example, halogenated diphenyl ether, is usually present in the carrier, which makes up approximately 10 - 8095 (all numbers! tax! in terms of the final composition) of the toothpaste. The composition of the carrier includes 3 - 4095 of a driver, 7 - 77905 of a humectant, such as: glycerin, sorbitol, propylene glycol and their mixtures, as well as 0.5 - 1095 of a gelling agent, such as sodium carboxymethylcellulose, Irish moss, iotacarrageenan, hydroxyethylcellulose, etc. ., including their mixtures. The polishing material of the teeth cleaning agent is generally 10 - 7595 in gel or toothpaste and 50 - 9995 in powder, and such a polishing agent can be colloidal silicon oxide, precipitated silicon oxide, sodium aluminum silicate, insoluble sodium metaphosphate, hydrated aluminum oxide, calcined aluminum oxide , dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, calcium carbonate and other calcareous substances or their mixtures. Surfactants include anionic, nonionic, cationic, and zwitterionic surfactants, but the use of nonionic surfactants is often avoided due to their undesirable effect on antibacterial compounds, such as THC, just as cationic and zwitterionic surfactants are often avoided. substances due to their propensity to stain and blacken teeth.

Thus, synthetic organic anionic surface-active substances, which are also detergents, are among the recommended cleaning agents in toothpaste, of which sodium lauryl sulfate and other sodium (higher) alkyl sulfate are preferred! with 10 - 18 carbon atoms in alkyl, although they can be replaced by other well-known sulfated and sulfonated detergents, at least partially. Other, active components!, such as fluoride-ion supplying compounds, for example, sodium fluoride and sodium monofluorophosphate, may be present for the purpose of hardening the teeth, usually in quantities that provide 0.001 - 195 fluoride ions into the composition, and other auxiliary agents may also be used substances, such as flavoring and sweetening agents in the amount of 0.1 - 1095. In addition, it may be desirable to use polynarboxylate in the amount of 0.5 - 495, such as a copolymer of polyvinyl methyl sulfur with maleic anhydride (PVM/MA, Gantrez). Such a polycarboxylate, as it was found, significantly improves the anti-plaque effect of the antibacterial agent.

The use of such a polycarboxylate in oral compositions is described in US Patent 4,627,977, which is incorporated herein by reference.

In mouthwashes, a water or alcohol oral carrier is recommended, where ethanol or isopropanol is the alcohol. The carrier is generally present in the composition in the amount of 90 - 99,995, of which the share of alcohol is 5 - 3095, and the share of propylene glycol is 2 - 1095 in terms of the final product. The remaining amount of the composition, i.e. 0.1 - 1095, may include fragrance, surface-active substance, sweetener, plaque-preventing agent, and other auxiliary substances of special purpose. In compositions for brushing teeth and mouthwash, the effective amount of antibacterial and plaque-preventing agent is generally in the range of 0.02 - 0.295, more preferably 0.03 - 0.196, in a mouthwash, generally 0.25 - 195, more preferably 0.25 - 0.595 or 0.695, where the amount of THCG does not exceed 0.895 in toothpastes and 0.295 in mouthwashes (at higher concentrations, numbness of the mouth is possible), but not below the indicated limits, in order to avoid ineffectiveness in preventing the formation of dental plaque at low concentrations concentrations

It is recommended that these dosage compositions contain plaque-preventing compounds and THCG within the specified limits, and with the initial concentration of the agent within the specified limits, the loss of activity in 2595 can be considered acceptable, and such dosage compositions are covered by the scope of the present invention.

For stabilization of oral compositions packed in a container! with plastic walls or parts, where such plastic is "reactive" plastic with respect to antibacterial compounds, in oral compositions it is desirable to have 0.01 - 295 terpene (ov) or stabilizer (ov), preferably 0.05 - 195 more preferably 0.1 - 0.595.

Such stabilizers! may be present in acceptable flavoring additives for on-demand dentifrices (and often their presence is desirable), and the stabilizer is present in the fragrance in an amount of at least 595 per fragrance, preferably at least 1095, more preferably at least 2595 and most preferably at least 5095.

Although all of the above primarily refers to teeth cleaning and mouth rinses, other oral compositions (for example, chewing gum) of the invention contain a similar number of components, depending on the form! compositions (liquid compositions, such as mouthwash, contain less, and thicker ones, such as toothpaste, contain more), often with the addition of specific substances corresponding to the purpose of such compositions. Thus, compositions for hardening teeth can include fluoride and phosphate), such as potassium or sodium fluoride, or sodium fluorophosphate in both tooth brushing and mouthwash bases, often in the range of 1 - 595. Staining solutions for the indication of dental plaque can include an acceptable dye (red color, apparently, is the best color of such products), often in a concentration of 0.001 - 0.195 bases! for rinsing the mouth.

The composition of other products can be established accordingly according to the principles known to the specialist.

An antibacterial agent is a non-cationic substance insoluble in water or practically insoluble in water (with a solubility in water at 2523 less than 10 g/l, sometimes less than 1 or

Oh, 1g/l)u. Such substances are soluble or dispersible in a toothpaste carrier containing glycerin, sorbitol and/or propylene glycol, as well as in the final product with such an environment as the basis. They are also soluble or dispersible in a water-alcohol environment mouthwash.

Antibacterial agents, such as halogenated diphenyl ether), usually contain bromine and/or chlorine, of which chlorine is the preferred halide. It is recommended that such agents be substituted with 1 - Z hydroxyls and 1 - 4 halogen atoms. Substitution with 1 or 2 hydroxyls and 2 or 3 halide atoms is more preferable, preferably with four substituents, two in each ring. Among the most recommended such compounds are: 2,2'-dihydroxy-5,5: dibromodiphenyl sulfur to 2", 44-trichloro-2--hydroxydiphenyl sulfur (TXgZ), of which the last is the most preferable. If necessary, halogenation of diphenyl they can be completely or partially replaced by various halogenated phenolic non-cationic, essentially water-insoluble compounds with antibacterial and plaque-preventing properties, a list of which is given on page 2 - 8

Izayavki 5.M. 07/398566, registered on August 25, 1989, which is included in the present description as a link.

Terpenes are described here, so the term includes terpene hydrocarbons and their oxygenated derivatives) include such compounds as 1-limonene, menthol, diterpene, polyterpene! and their production, many of which can be found in essential oils and other flavoring additives.

In addition to their utility as stabilizers of halogenated diphenyl ethers, they also impart a desirable flavor to the oral compositions of the present invention. Among terpenes and their derivatives, it is believed that limonene best combines both properties, although other terpenes, including those that do not have aromatizing properties, are also applicable, as they are! and other emulsifiable lipophilic ghee oils and flavoring additives containing a stabilizing component!

Various plastics, previously characterized as components of containers and/or dispenser parts, were described only briefly, since it is considered that their chemical nature and degree of polymerization are well known and do not require detailing in this description. If you need details, you can refer to the Modern Encyclopedia of Plastics, published annually, McGraw-Hill Inc., New York, New York.

As indicated in the link 5.M. 07/398566, compositions (inventions) may contain a source of fluoride ions capable of delivering 25 - 5 BOObch/million to the oral cavity. fluoride ions, preferably 300 - 2000 ppm and more preferably 800 - 1500 ppm. For additional details on acceptable fluorides, their amounts and details of their preparation, see the introduction as a reference to US patent 4627977. Fluoride is primarily necessary for hardening the teeth, but it can also serve to stabilize the polyphosphate compound, which can be present as a calculus-preventing agent. As such polyphosphate, a mixture of sodium and potassium pyrophosphates is recommended, which is also stabilized with Gantrez 5-97. Interval! applicable quantities of references in (0.55.M 07/398605, registered on August 25, 1989), which is incorporated into the present description as a reference, as well as in (US patent 4627977 and US patent 4806340) also incorporated by reference.

Regarding other details of compositions, components, auxiliary additives, production and application, see the above-mentioned patent, descriptions and applications, which are introduced in the form of links.

Preparation of the described oral compositions can be carried out by any standard method of preparation of that class of compositions. Here is an example of a simplified scheme! this way ТЧЗ are dispersed and/or dissolved in the carrier of the tooth cleaning agent, the terpene is present in the flavoring additive. To obtain a teeth cleaning agent, prepare a carrier containing glycerin, sorbitol, and propylene glycol, a gel-forming agent, and acceptable auxiliary substances (including GantrezF 5-97 and triclosan), mix the carrier, and an aqueous solution of an anionic detergent (sodium lauryl sulfate or a mixture of sodium lauryl sulfate and sodium methyloxyltaurate is recommended ) and the resulting mixture is mixed with a polishing agent. Finally, the flavoring additive containing the terpene is dissolved in ethanol, mixed and the pH is set. When a mouthwash is released, different ego components! simply mix with alcohol or water-alcohol medium and stir until complete dissolution. A mixture of sodium lauryl sulfate (Nle) with sodium methyl coxyltaurate (in ratios from 1 : 4 to 4 : 1) is recommended as a surface-active component of the toothpaste, and the presence of taurate makes it possible to reduce the amount of NLS accordingly, which is desirable. Other oral compositions are prepared by similar local methods.

When packing an oral composition in a dosing container, it is desirable to avoid contact of the composition with plastic parts made of malicious sopoli (complex) zephyr/poly(simple) zephyr, and it is also desirable to avoid contact with any such compositions that do not contain a stabilizer (for example, terpene or its fragrance). and plastic parts made of plastics previously listed in the description as reactive in relation to ТЧГЗ and other antibacterial and plaque-preventing compounds.

It is especially important to avoid the manufacture of the mentioned plastic parts in storage tanks or other containers, pipes, pumps or equipment in which the oral composition can be kept for significant periods of time or shorter periods of time at elevated temperatures.

But even if it is possible to avoid contact of packaging compositions containing THCG or other halogenated diphenyl ethers as antibacterial agents with reactive plastics during the production of the compositions, it is still desirable to minimize the effect of light and heat on such packaging compositions, since, as was found, both types of exposure accelerate the loss of plaque-preventing activity. Thus, the composition of the invention is recommended to be stored and packed in an opaque container and dispenser at a temperature of 10 - 3822 and stored at the same temperature. In this case, the packaged compositions can be stored and used in ordinary ways while retaining their targeted plaque-preventing action. This effect was verified by laboratory tests and observation of the teeth of volunteers who used different packaging of the composition and the control composition according to the instructions. At the same time, a significant improvement in the plaque-preventing activity of the packaging compositions of the present invention is observed in comparison with the control packaging compositions in which the packaging included plastic parts made of "reaction-free" in relation to the halogenated diphenyl ether of plastics used as an antibacterial agent, and also in the absence of oral stabilizer composition. Such improvements are also found if packages made from "reactive" plastics, rather than from malicious sol (complex) spheroids/poly(simple) spheroids, are used with oral compositions that do not contain terpenes and flavoring additives.

The following examples illustrate the invention without limiting it. If not specified, all percentages and ratios are described in the examples and accompanying claims, and the temperature is given in es.

Example 1

Fo component

Water (deionized) 47.84

Sorbitol (7095th aqueous solution) 20.00

Ztanol (9595th aqueous solution) 12.50

Glycerin 10.00

Propylene glycol 7.00

HgHantrez 5-97 (1395th solution) 1.92

Sodium hydroxide (5095-th hydrogen 012 solution) " xHTauranol M/5 HP 0.20

Sodium dilauryl sulfate 0.25 xxx Flavoring mixture 012 hoch Triclosan (IrgazanfF DR 300, 0.05 produced by SIBA-Geigy) " 100.00

Hydropolymer of polyvinyl methyl zephyr with maleic anhydride (HAf Corp.), xx Sodium methyloxyltaurate xx contains at least 2595 terpenes, including at least 2595 limonene oh tXha (g", 4, 4-trichloro-2-hydroxydiphenyl zephyr)

The mouthwash (mouthwash) of this example is obtained by mixing various components from the above list in any acceptable order in accordance with the standard method, but it is recommended to first dissolve triclosan in a mixture of propylene glycol and ethanol, then mix with an aqueous solution of sorbitol, glycerin and anionic surface - active agents, the last one is added to the flavoring mixture. A sodium hydroxide solution is used to neutralize the resulting acidic mixture to a pH value of 6b.84 (it is desirable to have a product with a neutral pH value or close to this value).

The resulting mouthwash has excellent cosmetic stability, has an acceptable taste and smell, triclosan and fragrance dissolve satisfactorily, which can be partially attributed to the presence of Tauranol M/HP.

When using only 0.2595 NLS as an anionic surface-active substance, the solubilization of flavoring additives and triclosan is not quite satisfactory. Although solubilization can be increased by using large amounts of VAT, its maximum limit in mouthwashes is often only 0.2595, but the mixture of TauranolF M/5NR and UFO is safe and acceptable in applied quantities. The described mouthwash was tested for the bioavailability of triclosan in comparison with a similar mouthwash, but without Tauranol M/ZNR in one case and with its replacement by half the amount of a nonionic surfactant (Pluronic E-127) in the other case. In triclosan absorption tests by measuring the absorption of triclosan by hydroxyapatite disks covered with mica, and in tests of protein absorption by the "inhibition zone", it was found that the presence of a mixture of anionic surfactants leads to a comparable bioavailability of triclosan in comparison with the bioavailability in the case of the presence in the composition only NLS, and such availability is significantly higher for compositions that do not contain a nonionic detergent compared to compositions that contain an original detergent (PluronicF E-127).

The mouthwash of this example is aged at an elevated temperature (412C) for three to five weeks, which is believed to be equivalent to real ageing, at least for six months and a year at room temperature. Such aging tests are carried out in dosing containers (bottles) made of glass, polyvinyl chloride and polyethylene terephthalate (or lined with plastic).

Although the chemical analysis of the mouthwash after the specified aging periods did not show the loss of triclosan from the mouthwash in the glass bottle, the loss of triclosan from the mouthwash was noted! for bottles made of polyethylene terephthalate and polyvinyl chloride, but they are significantly lower than the permissible 2595 (from the original concentration), and can be lower than 595 or 1095.

If, instead of the flavoring mixture, 41-limonene is used in the amount of 0.1, 0.2, and 0.495, an even better stabilization of triclosan is achieved in the described packaged toothpastes according to the invention, and similar stabilization is observed in the presence of other terpenes from various essential oils and flavoring additives in similar amounts.

Such good results are achieved if the material of the container or the facing material is polymethylpentene, polyallomer, polypropylene, polysilten! low and high density and nylon, although it is the same material! in the absence of the aromatizing mixture (and the terpenes contained in it), a significant and excessive loss of triclosan from the mouthwash, especially at elevated temperatures, is observed when stored.

Example 2

Fo component

Water (deionized) 84.42

Ztanol (9595) 10.00

Propylene glycol 5.0

Sodium lauryl sulfate 0.5

Triclosan 0.06

Sodium saccharin 0.02 100.00

The mouthwash of the above composition is tested for triclosan after storage for three weeks in dosing containers made or lined with various plastics, tests are carried out at room temperature, 382C and 492C, where storage at higher temperatures simulates longer storage periods (up to a year and more) at room temperature. Losses of triclosan from mouthwash during storage of more than 2595 were noted for containers made of polymethylpentene, polyallomer, polypropylene, high and low density polyethylene and nylon with unacceptable results (excessive losses) for containers made of polypropylene, polyethylene and nylon, and for nylon the worst result ).

If the material or lining of the container is a material made of polyvinyl chloride, polycarbonate, polysulfone or polyfluorostyrene, for example, polytetrafluorostyrene or Teflon, essentially no loss of triclosan occurs. Losses of triclosan from mouthwashes stored in containers made or lined with the mentioned polymers (polymethylpentene, etc.) can be reduced in the same way as in example 1, i.e. the introduction of limonene, other terpenes or essential oils containing them in the composition of the mouthwash in an amount, preferably at least 0.195 and more, preferably more, for example, 0.295 or 0.495 in terms of the final composition, in some cases even the use of a flavoring additive , which does not contain significant amounts of terpenes, may have a positive effect, although one cannot expect that such an effect will be as noticeable as in the case of the presence of terpenes in the composition.

Example C

Fo component

Propylene glycol 10.00

Iota-carrageenan 0.75

Sodium fluoride 0.33

Sorbitol (7095) 30.00

Sodium saccharin 0.30

Titanium dioxide 0.50

Sodium hydroxide (5095-th hydrogen 080 solution) "

Water (deionized) 27.71 Luviform TM (3595 solution) 4.76 Zeoden TM 113 20.00 tnbilent TM 22 2.00

Sodium lauryl sulfate (activity 1.60 94905)

Fragrance 0.95

Triclovan 0.30 100.00 "Bopolymer of polyvinyl methyl sulfur with maleic anhydride (VASF Corp.) n Oxidized silicon polishing agent (Zh. M. Huber Corp.) nt Oxidized silicon thickener (Degussa Co.)

The toothpaste of the above composition is obtained in a general way and is used as a medium in tests on the stability of triclosan when acting on the triclosan-containing agent of various plastics used as the material of containers or parts of the dispenser, in which the toothpaste is stored or from which it is dosed. The investigated plastics include Pibiflex TM 46 by Mnmont and Arnitel TM modified by AKZO, which are used for the manufacture of membranes and bellows of the inflating dispenser shown in Fig. 3.

Six plastic samples were tested, each three of which were treated with different lubricants for molds (to determine the influence of the nature of lubricants for molds on the problem of the stability of triclosan, which is in contact with plastics during storage). Lubricants for molds are silicone master TM (595 silicone oil and 9595 polypropylene).

Silicone master plus silicone oil (predominantly silicone oil) and Armid 0 Master

TM (595 oleoamide and 9595 polypropylene), respectively. After two-week storage of the samples in contact with the toothpaste at different temperatures (room temperature, 387C and 4920), the toothpaste is removed from the plastic container, the plastic is washed with water and immersed in methanol to dissolve triclosan, which could be captured by the plastic during storage.

The methanol solution is collected and analyzed using high-performance liquid chromatography. It was found that the same type of triclosan absorption by different membrane materials actually takes place, and although there are possible variations, to some extent depending on the lubricant used for the molds, nevertheless, in fact, in all cases, results were obtained! the same result. It was found that zlastomernye soly (complex) zphyr/poly(simple) zphyr absorb a significant amount of triclosan from a toothpaste, and this conclusion is confirmed by using zlastomerny zypry (complex) zphyr/poly(simple) zphyr for the manufacture of bellows of pumping dispensers containing the described tooth brush and another tooth brush within the scope of the invention.

Correspondingly, it is considered undesirable to use malicious sopoli (complex) sapphires/poly(simple) sapphires in contact with the means for cleaning teeth or mouthwash of the invention, even if these means contain aromatizing additives, including terpenes (which are present in the fragrances of compositions for brushing teeth) in in quantities of at least 0.195% of toothpaste.

When tested repeatedly using real pumping dispensers of companies! Brushes for tooth cleaning products with membranes made of slatomer (complex) sapphire/poly(simple) sapphire (Arnitel TM) containing triclosan are also unacceptable, but if the slatomer (complex) sapphire/poly(simple) sapphire is replaced with other acceptable plastics, for example , the activity of triclason is maintained at an acceptable level by polyfluoroethylene. It was also found that other parts of such an inflating dispenser, for example, the inner walls of polypropylene, do not absorb excessive amounts of triclosan and do not seriously reduce the plaque-preventing activity of the dental plaque agent, apparently due to the presence of the fragrance of the packaged toothpaste terpenes.

Conducting a group test with the participation of at least ten people who used the toothpaste of this example, dosed from tubes lined with polyethylene terephthalate and polyethylene, with brushing twice a day for a month, during which the appearance of dental plaque on the teeth of the subjects was observed by experts . As a result, the examinee established that the composite teeth cleaning agents have a certain plaque-preventing activity, similar to that observed in the case of the mouthwashes of examples 1 and 2, which serves as additional evidence of the absence of unacceptable deactivation of triclosan, which continues to be present in the agent for toothbrushes in effective, plaque-preventing and antibacterial quantities.

Example 4

Fo component

Glycerin 7.00

Prolylene glycol 3.00

Iota-carrageenan 0.75

Sorbitol (7095) 30.00

Sodium saccharin 0.30

Titanium dioxide 0.50

Sodium fluoride 0.33

Gantref 5-57 (1395th solution) 15.00

Deionized water 16.07

Sodium hydroxide (5095% aqueous solution) "

Geodectfb 113 (J.M. Huber Corp,) 20.00

Silodentb 15 (silica thickener, VR Grace Corp.) 3.00

Flavoring additive 0.95

Sodium lauryl sulfate 2.00

Triclosan 0.30 100.00

Toothpaste of the above composition is stored in pumping dispensers of the Stshaia company with bellows membranes from Arnitel. Tubes made of laminate are also filled with toothpaste with a layer of polyethylene terephthalate, which is in contact with the toothpaste. Toothpastes are aged at 52C, 252C and 392C for two, four and six weeks. After the indicated aging periods, the toothpaste is dosed in the amount of 1.5 g/day at weekly intervals, and the content of triclosan in the dosed toothpaste is determined. In the case of pumping dispenser companies! A single-dose toothpaste loses about 2795 triclosan, which is excessive and should be discarded. Losses are approximately constant and do not depend on temperature and storage time, which can be explained by the absorption of triclosan by the membrane of the dispenser, with which triclosan contacts before dating. This membrane is made of zlastomeric sophire/poly(simple) zephyr, i.e. plastic that should be avoided as a container material or part of a container or dispenser for toothpastes containing triclosan. However, when replacing the zlastomer nozzle (complex) sapphire/poly(simple) sapphire with any of the above-mentioned acceptable plastics, such as polyethylene terephthalate for the manufacture of the membrane of a modified dispenser (modified to compensate for the various properties of such plastics), the stability of triclosan increases, and the dosage composition is satisfactory and effective as a toothpaste that prevents the formation of dental plaque.

Toothpastes in the form of a gel in such packages behave similarly from the point of view of the stability of triclosan during storage and dosing.

In similar tests using tubes lined with polyethylene terephthalate, small losses of triclosan (less than 595) were noted, indicating that the presence of terpenes (0.195 or more per composition), including limonene in the flavoring additive (or the flavoring additive itself) prevents losses triclosan or its deactivation.

Triclosan is lost in small amounts when using tubes made of polyfluoroethylene, even if there are no flavoring additives in the composition, which is also true in the case of using polyvinyl chloride as a lining material in contact with a toothpaste, or when packaging parts made of polysulfone or polycarbonate come into contact with the same agent. .

However, as mentioned earlier, it is not always possible to use the last three plastics.

If in the described tests, in which the toothpaste is dosed from the dispensers of the firm!

Sai, Gantrez 5-97 replaced 4.76 parts of Luviform (3595) and with a difference in relation to deionized water, no particular differences from the point of view of stability of triclosan for different compositions were noted.

In the above compositions, the polishing system is a silicon-containing system, and not an aluminum oxide-based system. When replacing the polishing agent with aluminum oxide, the difficulties mentioned above in connection with some plates are reduced, but still remain. And in this case, the presence of terpenes in toothpaste promotes the stability of triclosan, as in the case of the presence of terpenes in similar compositions for cleaning teeth based on silicon-containing polishing agents.

Example 5

Means for rinsing the mouth and brushing the teeth of the examples given above can vary in composition within 41095 or 1.2595 for each component, provided that the indicated deviations do not exceed the previously indicated intervals in the description and that at the same time they receive an applicable and effective antibacterial and preventive education plaque product, dosed in an effective plaque-preventing condition from the mentioned dosing containers made of compatible plastics, Such a product! they can also be modified by transformation into teeth cleaning agents in the form of gel, oral gels, pastes, liquids, lozenges, capsules, tablets and sachets of the types previously mentioned in the description.

Such products will behave in a similar manner to triclason or other halogenated diphenyl ether or antibacterial anti-plaque agent, remaining quite stable in the presence of polyfluorostyrene, polyvinyl chloride, polycarbonate and polysulfone as packaging materials or packaging details even in the absence of flavoring additives in the compositions and terpenes, as well as remaining stable in the presence of polysethylenes, polypropylenes, polystylene terephthalates, polyallomers, nylons and polymethylpentenes as packaging materials or their parts under the conditions of the presence of a terpene such as limonene or a stabilizing flavoring component in the oral composition. As in the case of previously discussed means for rinsing the mouth and cleaning the teeth, due to excessive absorption or the second undesirable effect on triclosan from the side of (complex) zephyr/poly(simple) zephyr and other zlastomers, the use of such materials is recommended to be avoided.

Example 6

Teeth cleaning agents of the compositions of examples C and 4 are obtained, which are dosed on bristle toothbrushes (see fig. 1) after a month of storage at 302 in collapsible toothpaste tubes lined with polystylene in one case and polystylene terephthalate in the other. Amount of toothpaste! on a toothbrush in the range of 0.8 - 2 g., but 1 - 1.5 g is preferable. At a dosage of 1.5 g, the amount of active triclosan in the toothpaste per brush is about four milligrams (when deactivating triclosan, only 1095). When stored for a longer time or at a higher temperature, or if during storage the toothpaste comes into contact with destabilizing plastic in a larger volume, the packaging of the composition may contain about Zmg of triclosan in 1.5 g per brush. So, with 1 g of toothpaste per brush, the amount of triclosan in it is 2.7 mg and 2 mg, respectively. When the content of triclosan in a toothpaste is 0.25 - 0.695, there can be 2.2 - 8 mg of triclosan on a toothbrush, if the deactivation of triclosan reaches 10 - 2595, and up to Omg in the absence of deactivation of triclosan.

The described means for cleaning teeth are used in the amount of 0.8 - 2 g, dosed on a toothbrush with each cleaning.

They brush their teeth twice a day, in the morning and in the evening, within minutes! four weeks, after which a marked improvement in plaque prevention was observed compared to a control toothpaste that did not contain triclosan. The improvement from the point of view of preventing the formation of dental plaque is also noticeable in comparison with the unscented control (no terpene), containing triclosan in the toothpaste, tube packaging, lining with polystylene and polystylene terephthalate.

The present invention is characterized with the help of illustrative examples and embodied, but the invention is not limited only to them, since it is obvious that a specialist, having this description in front of his eyes, will be able to use its replacement and equivalent without departing from the invention. dis st i m nya

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Claims (12)

1. A device that includes a dosing container, in which the material in contact with the oral composition contained in the mentioned container is a solid polymeric material - polyethylene or polyethylene terephthalate, and the mentioned composition contains an amount of practically insoluble non-cationic antibacterial agent effective for preventing the formation of dental plaque - halogenated diphenyl ether, as well as a stabilizing substance to ensure the compatibility of the mentioned polymeric material with the mentioned agent contained in the mentioned oral composition. 2. Produced according to point I, characterized by the fact that the mentioned composition is a toothpaste, a gel-like or liquid agent for cleaning teeth, a liquid agent for rinsing the mouth or a paste-like, gel-like or liquid agent for the treatment of teeth, and the mentioned container is a deformable dosing device tube, pump dispenser, pressurized dispenser or sachet for toothpaste, gel toothpaste or paste or gel toothpaste, or a bottle or other container for liquid toothpaste, mouthwash or toothpaste. 3. The product according to point I, characterized by the fact that the mentioned composition contains an amount of fluoride ions effective for increasing the strength of teeth and an amount of polyphosphate or a mixture of polyphosphates effective for preventing tartar formation. 4. The product according to claim 3, characterized by the fact that the mentioned composition is a toothpaste, a gel toothpaste or a liquid mouthwash, and the mentioned antibacterial agent is a diphenyl ether substituted with 1-3 hydroxyls and 1-4 halogen atoms , selected from groups including chlorine and bromine. 5. Produced according to item I, characterized by the fact that the mentioned antibacterial agent is 2,4,4-trichloro-2-hydroxydiphenyl sulfur (THG Z). b. Produced according to claim 5, characterized by the fact that the said composition is a liquid mouthwash containing 0.03-0.196 THGO, and the said solid polymer material in contact with the said oral composition contained in the container is polyethylen. 7. Produces according to claim 5, characterized by the fact that the mentioned composition is a toothpaste or a gel-like agent for cleaning teeth, containing 0.25-0.590 ТХГЗ, in a deformable dosing tube, an injection dispenser or a sachet-sachet, and the mentioned solid polymer material, in contact with the oral composition contained in the container, is polyethylen. 8. Produced according to point I, characterized by the fact that the said composition as the said stabilizing substance contains a stabilizing amount of terpene or an aromatizing additive that stabilizes the said antibacterial agent in the presence of the said solid polymeric material. 9. Produced according to claim 7, characterized by the fact that the mentioned toothpaste or the mentioned gel toothpaste contains a terpene or a flavoring additive in the amount of /0.01-290 as the mentioned stabilizing substance, which stabilizes THGO in the presence of the mentioned solid polymer material, contacting with the mentioned toothpaste or the mentioned gel toothpaste. 10. The product according to claim 8, characterized by the fact that limonene is a terpene. 11. The product according to item I, characterized by the fact that the mentioned composition contains 0.5-490 of a copolymer of polyvinyl methyl simple sulfur with maleic anhydride. 12. The product according to claim 4, characterized by the fact that the mentioned composition contains fluorine ions and 0.5-496 copolymer of polyvinyl methyl simple sulfur with maleic anhydride, which, together, stabilize the mentioned polyphosphate(s), counteracting the loss of enzymatic activity by prevention of tartar formation.