Hydrogel compositions with erodible substrate

FIELD: medicine.

SUBSTANCE: invention is related to composition containing water-swellable, water-insoluble polymer, mixed hydrophilic polymer and complementary oligomer capable to form hydrogen bridges and electrostatic couplings with said hydrophilic polymer, and a substrate. The invention is also applied to the method for teeth wigthening.

EFFECT: tooth hypersensitisation minimal or not observed.

58 cl, 3 ex

 

The technical field to which the invention relates

The present invention relates in General to compositions of the hydrogel. More specifically, the invention relates to hydrogel compositions suitable for covering wounds and for the introduction of a wide range of active agents into the tissue of the mucous membranes, such as the mouth, including bleaches teeth.

The level of technology

In society there is a widespread change the color of teeth and it is estimated as occurring in two out of three adults. Change the color of teeth is considered as an aesthetic flaw or defect and may have negative consequences in the lives of affected people, causing a shift in consciousness and even suppressing a smile. Tooth discoloration can be particularly unpleasant or troubling situations and professions, when the essential is to demonstrate the clean and white teeth.

The tooth consists of an inner dentin layer and the outer layer of hard enamel, which is slightly porous. The outer layer is a protective layer of the tooth. The natural color of the tooth is white or slightly yellowish, from opaque to translucent. Staining of teeth occurs as a result of exposure to tannins and other polyphenolic compounds on the teeth. These compounds become captured or associated with the protein layer on the surface of UPOV and can penetrate the enamel and even in the dentin. Sometimes staining may occur from sources inside the tooth, such as tetracycline, which can start to Deposit in the teeth, if were administered to the individual in his youth.

Surface stains can usually be removed by mechanical brushing. However, changing the color of the enamel or dentin is not amenable to the action of mechanical methods of tooth cleaning and penetration into the tooth structure to remove staining requires chemical methods. The most effective treatment options change the color of the teeth are compositions containing an oxidizing agent such as hydrogen peroxide, which is able to interact with the Chromogen molecules responsible for the color change, providing or decolorizing action, or giving them a solubility in water or both effects.

Therefore, the composition for whitening teeth usually fall under two categories: (1) gels, pastes or liquids, including toothpastes, which are mechanically mixed on the painted surface of the tooth, in order to influence the removal of staining of the tooth by abrasive erosion dyes the surface; and (2) gels, pastes or liquids, which have the effect of teeth whitening using a chemical process during contact with the painted surface of the tooth within specific the th period of time, after which the composition is removed. In some cases, the mechanical process is added auxiliary chemical process, which may be oxidative or enzymatic.

Some songs for teeth, such as tooth powders, toothpastes, gels and powders that contain whitening agents, releasing active oxygen or hydrogen peroxide. Such bleaching agents include peroxides, percarbonates and perborates alkali and alkaline earth metals or complex compounds containing hydrogen peroxide. It is also known that teeth whitening is suitable peroxide salts of alkali and alkaline earth metals.

Among the many peroxides are available to obtain compositions for whitening teeth, used almost exclusively hydrogen peroxide (and its addition products or the associated complexes, such as carbamide peroxide and percarbonate sodium). Chemistry of hydrogen peroxide are well known, although the specific nature of its interactions with Chromogens tooth obscure. It is believed that the hydrogen peroxide destroys the Chromogens of the tooth by the oxidation of unsaturated carbon-carbon, carbon-oxygen and carbon-nitrogen linkages, found in the dye molecules, giving them thus transparency or solubility.

A related class of compounds, nakilat is, used in surface-active substances for Laundry for effective whitening service in the first place because of their stability in solution and their specific binding capacity for certain types of dye molecules. Used a number of stable, solid nagkalat, including diperoxide acid and a magnesium salt monoperoxyphthalic acid. Other nagkalat, such as peracetic acid, is available in the form of solutions containing the equilibrium distribution of acetic acid, hydrogen peroxide, peracetic acid and water. Alternatively, get the part of the donor peroxide, such as perborate sodium or percarbonate sodium, together with the predecessor, nagkalat. Upon contact with water donor peroxide releases hydrogen peroxide, which interacts with the precursor of nagkalat with the formation of the existing nagkalat. Examples of nagkalat created in situ, include peracetic acid (hydrogen peroxide and tetraacetylethylenediamine) and proxynodename acid from hydrogen peroxide and sulfonate of nonenvironmental).

Nagkalat was also used in compositions for the care of oral hygiene to whiten stained teeth. In U.S. patent No. 5279816 owned by Church et al., describes a method of whitening teeth comprising applying the composition containing peracetic is islote, having an acidic pH. In the patent EP 545594 A1, owned by Church et al., describes the use of peracetic acid to obtain a composition for whitening teeth. Peracetic acid may be present in the composition or, alternatively, may bein situin the process of applying the combination of a source of peroxide with peracetic acid precursor. For example, in U.S. patent No. 5302375 owned Viscio, describes a composition in which peracetic acid is generated in the mediain situusing a combination of water, acetylsalicylic acid and percarbonate water-soluble alkali metal.

The most common agent used for teeth whitening is carbamide peroxide (CO(NH2)H2O2), also known as hydrogen peroxide urea hydrogen peroxide urea and perhydroanthracene. Carbamide peroxide has been used by dentists for several decades as an antiseptic oral cavity, and teeth whitening was detected side effect of prolonged contact time. Nonprescription composition 10% carbamide peroxide feature Marion Laboratories as GLY-OXIDE®and Reed and Carnrick as PROXIGEL®they are the compositions of low viscosity, which should be placed in a tray or similar container in order to provide the th contact with the teeth. The whitening gel, which is able to stay in comfortably fit dental tray in place for a long period of time, available under the trademark OPALESCENCE®from Ultradent Products, Inc., in South Jordan, Utah.

To such compositions remained in place, the composition must be a viscous liquid or gel. The use of dental trays also requires that the bath was adapted for convenience and are adjusted so that the bath did not exert any pressure on the teeth or gums of the patient or did not cause them irritation. It is necessary that such bleaching compositions were prepared to be quite sticky and viscous for stability against dilution by saliva.

In one method of teeth whitening of the individual dentist will need to construct a custom-made dental whitening tray for the patient to cast made in accordance with the location of the patient's teeth, and to prescribe the use of oxidizing gel distributed in the bleaching bath, and wear periodically over a period of from about 2 weeks to about 6 months, depending on the degree of staining of the teeth. These oxidizing composition, usually Packed in small plastic syringes or tubes, are prepared directly PAC is entom in custom-designed dental bleaching tray, held in the mouth with a contact time of more than about 60 minutes, and sometimes with such duration as from 8 to 12 hours. Slow speed whitening is mostly a consequence of the very nature of the compositions, which are designed to maintain the stability of the oxidizing composition.

For example, in U.S. patent No. 6368576 owned Jensen, describes the teeth whitening composition that is preferably used with a tray, so that the composition is held in position adjacent to the surfaces of the teeth of the individual being treated. These compositions are described as adhesive matrix material formed by combining a sufficient amount of an agent that increases the stickiness, such as carboxypolymethylene with a solvent, such as glycerine, glycol or water.

In another example, in U.S. patent No. 5718886 owned Pellico, describes a teeth whitening composition in the form of a gel composition containing carbamide peroxide, dispergirovannoyj in anhydrous gelatinous medium, which includes a polyol, a thickener, and xanthan gum.

Another example is described in U.S. patent No. 6419905 belonging to Hernandez, which describes the use of compositions containing carbamide peroxide (0.3 to 60%), xylitol (from 0.5 to 50%), potassium salt (0.001 to 10%) and salt fluoride (0.15 to 3%), compiled in the gel, which will gain from 0.5 to 6% by weight of a suitable gelling agent.

Whitening teeth composition, which adheres to the teeth, is described in U.S. patent No. 5989569 and 6045811 belonging Dirksing. According to these patents gel containing 30-85% glycerol or polyethylene glycol, 10-22% complex urea/hydrogen peroxide, 0-12% carboxypolymethylene, 0-1% sodium hydroxide, 0-100% triethanolamine (TEA), 0-40% water, 0-1% odorants, 0-15% sodium citrate and 0-5% ethylenediaminetetraacetic acid. The preferred gel on Dirksing has a viscosity of from 200 to 1,000,000 cycle/sec at low shear rates (less than one sec-1) and is sufficiently adhesive so as to avoid application of the dish.

Currently available compositions for whitening teeth have a significant disadvantage in that they cause increased tooth sensitivity by over 50% of patients. The sensitivity of the teeth may be the result of flow of fluid through the dentinal tubules, which is perceived nerve endings of the tooth, due to the presence in these compositions of glycerol, propylene glycol and polyethylene glycol. This can lead to varying degrees to increase tooth sensitivity after exposure to the teeth to heat, cold, overly sweet substances and other causal factors.

Long-term effects on teeth bleaching compositions, as is currently practiced, has a number of side effect is mswb in addition to increased tooth sensitivity. These side effects include the leaching of calcium from the enamel layer at pH less than 5.5; penetration of the intact enamel and dentin, bleaching agents and the risk of damage to the pulp tissue; and breeding bleaching compositions saliva, leading to leaching from dental trays and subsequent ingestion by the consumer.

Some oxidizing composition (usually with a relatively high concentration of oxidants) applied directly on the tooth surface of a patient in the dental office under the supervision of a dentist or specialist in dental hygiene. Theoretically, such a strategy of teeth whitening give faster results and better meet patients. However, due to the high concentration of oxidizing agents contained in the so-called "Cabinet" compositions, they can be dangerous for the patient as well as for the practitioner, if it is not handled with care. The soft tissue of the patient (gums, lips and other mucous surfaces) must first be isolated from the potential impact of active oxidizing agent through the use of a perforated rubber sheet (known as a rubber gasket), so that only had teeth. Alternatively, a soft cloth can be used to isolate from oxidizers, intended for use in the chill the tion, by covering the soft tissue capable of polymerization composition, which shape the contours of the gums and then allowed to harden with exposure light source of high intensity. After soft tissue was isolated and protected, the practitioner can apply the oxidizing agent directly on the painted surfaces of the tooth during a specific period of time or until the occurrence of significant changes the color of the tooth. Typical results obtained using office teeth whitening, are in the range of from about 2 to 3 shades (when measuring VITA Shade Guide, VITA Zahnfarbik).

The range of shades of teeth in the VITA Shade Guide varies from very light (B1) to very dark (C4). A total of 16 shades of teeth is the full range of colors between these two endpoints on the brightness scale. Patient satisfaction with the procedure of teeth whitening increases with the number of changes shades with the usual acceptable minimum desirable changes from approximately 4 to 5 shades VITA.

For products for caring for teeth in teeth whitening, it is desirable to provide products for the care of teeth using adhesive hydrogel that includes a bleaching agent to remove staining of teeth of the individual. In addition, there is constantly the traveler is a need to develop products to provide a protective coating of mucous surfaces, or to ensure the delivery of active agents for example, transmucosal delivery of agents to the mucous tissues of the teeth, gums, mucous membranes and other tissues of the oral cavity. Desirable are compositions that do not require the use of dental trays to ensure contact between the active agent and the teeth or other surfaces of the oral cavity. Such products should ideally not cause or cause a minimal increase in the sensitivity of the tooth, should minimize or eliminate leakage of the active agent, leading to the ingestion by the consumer or leading to damage to or irritation of the gums or mucous membranes of the oral cavity, should provide more long-wearing, permanent dissolution of the active agent, improved efficiency and better tolerated by patients. It should be also desirable that the software product for the care of teeth, which is a solid composition and is self-adhesive, but which does not stick to the fingers of the user or which is not solid (e.g., liquid or gel) and which forms a film upon drying. Finally, modern products for caring for teeth require that the system wore during a specific period of time, for example, 30 minutes before removal by the consumer. It is desirable to develop products that can smorodinovaia after visual the statement of the active phase or achieve the desired therapeutic or cosmetic effect, as such systems should improve the satisfaction of the patient. The present invention pursues these objectives.

Disclosure of invention

One aspect of the invention relates to a hydrogel composition that includes swelling in water, the water-insoluble polymer, a mixture of hydrophilic polymer and a complementary oligomer capable of forming hydrogen bonds or electrostatic communication with the hydrophilic polymer. Can also be the active agent, such as teeth whitening agent. The composition additionally includes a substrate, which erodium (destroyed) in a humid environment with a slower speed than the hydrogel. The hydrogel may be solid and containing a substrate connected to the substrate before applying. The hydrogel may also be solid, and adhere to the substrate in the process of application.

In the preferred implementation of swelling in water, the water-insoluble polymer is an ester of cellulose or acrylate polymer; hydrophilic polymer is a poly(N-vinylacetal), poly(N-vinylamide), poly(N-alkylacrylate) or a copolymer or their mixture; and a complementary oligomer capable of forming hydrogen bonds or electrostatic communication with hydrophilic polymer is a polyhydric alcohol, polyalkyleneglycol or polyaki anglical with limit carboxyla. The preferred active agent is a bleaching agent, such as peroxide.

The composition optionally includes a plasticizer of low molecular weight and may also include at least one additive selected from the group consisting of fillers, preservatives, pH regulators, softeners, thickeners, coloring agents (e.g., pigments, dyes, refractive particles, etc.), flavorants (for example, sweeteners, flavors, stabilizers, surfactants, agents that increase the rigidity, and agents that reduce the stickiness.

In a preferred method of applying the composition, the composition is a composition for whitening teeth and is used for teeth that need whitening, and then removed when it reaches this degree of bleaching. In certain implementations, the composition for whitening teeth is translucent and composition are removed when a consumer is satisfied with the achieved degree of bleaching.

In another aspect the invention relates to compositions, including swelling in water, the water-insoluble polymer, a mixture of hydrophilic polymer and a complementary oligomer capable of forming hydrogen bonds or electrostatic communication with the hydrophilic polymer and an active agent. In one aspectuality agent selected from the group consisting of peroxides, metal chlorite, perborates, percarbonates, nakilat and their combinations. The composition additionally includes a substrate, which erodium with a slower speed than the hydrogel.

In another aspect the invention relates to a method for producing the film of the hydrogel, which is suitable for inclusion in the means to care for the oral cavity or in the proposed transmucosal composition. This method includes obtaining a solution or gel, swelling in water, the water-insoluble polymer, a hydrophilic polymer and a complementary oligomer capable of forming hydrogen bonds or electrostatic communication with the hydrophilic polymer in a solvent; placing a layer of the solution on the substrate to provide a coating; and heating the coated substrate to a temperature in the range from approximately 80°to approximately 100°C for a period of time ranging from about 1 to about 4 hours, thereby providing a hydrogel film on the substrate.

In another method of forming the composition of the invention, the method includes the process of melting through the extruder a mixture of swelling in water, the water-insoluble polymer, a hydrophilic polymer and a complementary oligomer capable of forming hydrogen bonds or electrostatic communication with the hydrophilic polymer with the formation of compositions for extrusion, where the composition is extruded in the form of a film of the desired thickness on a suitable substrate. The substrate may be ertirea substrate, or the composition may later be pressed on or laminated to erodium substrate. The method further includes overlaying film hydrogel with an active agent such as whitening agent, offering thus a composition for whitening teeth.

The adhesive compositions of the invention provide several significant advantages compared to prior art. In particular, the present compositions provide one or more of the following advantages over known in the art:

(1) provide ease of circulation;

(2) is easily modified upon receipt, so that their properties such as adhesion, absorption, transparency and swelling can be controlled and optimized;

(3) can be made so that the adhesiveness is increased or decreased in the presence of the humidifier, so that the composition is not adhesive to moisture;

(4) minimize the leakage of the active agent, when activated, from the composition to the surface of the mucous membranes (for example, in the oral cavity of the consumer);

(5) can be obtained in a translucent form, providing the user with the opportunity to observe the degree of whitening without removing the composition hydroge the I teeth or mucosal surface;

(6) minimize damage to the gums or mucous membranes in the oral cavity;

(7) can be worn with comfort and unobtrusive;

(8) can be easily removed from the teeth or mucosal (mucosal) surface and leave no residue;

(9) are characterized by high duration of wearing or action;

(10) can provide supported and controlled release of various active agents;

(11) can be prepared as susceptible to erosion after a predefined period of time; and

(12) can be prepared for delivery of active agents in one direction, for example, only in the direction of the mucosal tissue, or in two directions, such as towards the mucosa (mucosal) surface and in the direction of the oral cavity, and the relative speed of delivery towards the mucosal surface and in the direction of the oral cavity are controlled by selecting the substrate having a predetermined permeability.

WAYS of carrying out the INVENTION

I. Definitions and nomenclature

Before a detailed description of the present invention should be understood that unless otherwise indicated this invention is not limited to the specific hydrogel materials or methods of preparation, they, as such may vary. It should be clear also that used here the terminology aims to describe only specific implementations and should not be considered as limiting. It should be noted that, used in this description and the attached claims forms in the singular include references to the plural, unless the context clearly indicates otherwise. Thus, for example, reference to "hydrophilic polymer" includes not only the hydrophilic polymer, but also a combination or mixture of two or more different hydrophilic polymers, reference to "plasticizer" includes a combination or mixture of two or more different plasticizers, as well as the only plasticizer, and the like.

In the description and the formula of the present invention will be applied following terminology in accordance with the definitions set forth below.

The definition of "hydrophobic" and "hydrophilic polymers are based on the amount of water vapour absorbed by the polymer at 100% relative humidity. In accordance with this classification hydrophobic polymers absorb only up to 1 wt.% water at 100% relative humidity (“rh”), while moderately hydrophilic polymers absorb 1-10 wt.%, hydrophilic polymers are able to absorb more than 10 wt.% water and hygroscopic polymers absorb more than 20 wt.% water. "Swelling in water of the polymer is such that absorbs an amount of water, higher than, at least 25 wt.% his own who assy, and preferably at least 50 wt.% its own weight when immersed in the aquatic environment.

The term "cross-linked" refers here to the composition containing intramolecular and intermolecular cross-linking occurring either by covalent bonds or by non-covalent binding. "Non-covalent linkage includes both hydrogen bonds and electrostatic (ionic) bond.

The term "polymer" includes linear and branched polymer structure and also covers cross-linked polymers and copolymers (which may not be cross-linked), thus including block copolymers, alternate copolymers, statistical copolymers, and the like. These compounds, referred to here as "oligomers", are polymers having a molecular weight below about 1000 Da, preferably below about 800 Da.

The term "hydrogel" is used here in the usual sense to denote a swelling in water of polymer matrices that can absorb significant amounts of water with the formation of elastic gels, where the matrices represent a three-dimensional network of macromolecules held together by covalent or non-covalent cross-links. When placed in an aqueous environment dry hydrogels swell to the limit, be aemula degree of cross-links. Hydrogels are also urodinamiku.

The term "erodium", as in the case of hydrogel erodium", or "entireity", as in "erodium substrate"is intended to include processes of erosion, dissolution, disintegration and degradation, and to incorporate such materials, which often are referred to as affected bioerosion or biodegradation. Regardless of the mechanism by which the hydrogel and uroderma the substrate is dispersed in a humid environment, components erodium substrate is preferably chosen so that the substrate had "eroded" with a lower speed than the components of the hydrogel.

The terms "active agent", "pharmacologically active agent" and "drug" are used here interchangeably to refer to a chemical product or compound that induces a desired pharmacological, physiological effect, and these include agents that are effective therapeutically, prophylactically effective or cosmetically effective. The terms also encompass pharmaceutically acceptable, pharmacologically active derivatives and analogs of those active agents specifically mentioned herein, including, but not limited to, salts, esters, amides, prodrugs, active metabolites, the compounds include, analogs and the like. When using the terms "active agent", "f is macological active agent" and "drug", it should be understood that included as an active agentper seand pharmaceutically acceptable, pharmacologically active salts, esters, amides, prodrugs, active metabolites, the compounds include, analogs and the like.

The term "teeth whitening composition" refers to compositions which contain a hydrogel, as described above, and a whitening agent.

The term "whitening agent" generally refers to oxidizing agent such as peroxide or chlorite, as will be discussed in more detail below. In some cases, the bleaching agent can be an enzyme or other catalytic agent to remove the staining of teeth. The whitening agent may include one or more incremental bleaching agents, surfactants, agents against dental plaque agents against Tartar and abrasive agents. The whitening agent may have additional therapeutic benefits.

The term "effective amount" or "cosmetically effective amount" cosmetically active agent refers to a nontoxic but sufficient amount of cosmetically active agent to provide the desired cosmetic effect. The term "effective amount" or "therapeutically effective amount" of a drug or pharmacologically active agent p is adnanced to refer to non-toxic, but sufficient amount of the drug or agent to provide the desired therapeutic effect. The amount that is "effective"will vary from subject to subject, depending on age and General condition of the individual, the particular active agent or agents and the like. Thus, it is not always possible to describe the exact "effective amount". However, an appropriate "effective" amount in any individual case may be determined by the specialist in the art using conventional practices. Moreover, the effective amount of active agent included in the composition or dosage form of the invention, is not critical as long as the concentration is within the range, sufficient for the potential application of the finished composition to deliver the quantity of active agent, which is within therapeutically effective range.

The term "surface", as in the case of surfaces of the oral cavity or the surface of the organism"is intended to include mucous surfaces of the body (for example, sublingual, cheek, vaginal, rectal, urethral), as well as surfaces in or around the oral cavity (e.g., teeth, lips, gums, mucous membranes). These surfaces are usually that on ivalsa here as "wet" environment.

"Transmucosal" shipping medication means medication on the surface of the mucosal tissue of the individual so that the drug is passed through the mucosal tissue (e.g., sublingual, cheek, vaginal, rectal, urethral) and into the bloodstream of the individual, thereby providing a systemic effect. The term "transmucosal is intended for embracing both local and systemic effects and, therefore, includes local introduction, i.e. the local delivery agent to mucosa, as, for example, in the case of treatment of various abnormalities of the mucosal tissue to provide a local effect.

The term "stickiness" and "adhesive" are qualitative. However, used here, the term "essentially non-tacky", "slightly sticky" and "sticky" can be quantified using the values obtained by the method for determining the stickiness PKI or TRBT, as follows. By "essentially no adhesive" refers to the composition of the hydrogel, which has a value of stickiness, less than about 25 g·cm/sec, under "slightly sticky" refers to the composition of the hydrogel, which has a value of stickiness in the range of from about 25 g·cm/sec to about 100 g·cm/sec, and under the "adhesive" refers to the composition of the hydrogel, which has the value of the adhesiveness of at least 100 g·cm/sec.

The terminology is "water-insoluble" refers to a compound or composition, whose solubility in water is less than 5 wt.%, preferably less than 3 wt.%, more preferably less than 1 wt.% (when measured in water at 20°C).

The term "translucent" is used here to denote a material capable of transmitting light so that objects or images can be seen through the material. Translucent materials here can be or not to be "translucent"means that the material is optically pure. The term "transparent" indicates that the material is not "impenetrable"in which the target objects and images may not be visible through the material.

II. The composition of the hydrogel

The composition of the invention is a single-phase hydrogel, including swelling in water, the water-insoluble polymer and a mixture of hydrophilic polymer and a complementary oligomer, and optionally an active agent, such as a whitening agent. As swelling in water, the water-insoluble polymer or oligomer may have the ability to form hydrogen bonds or electrostatic ties with the hydrophilic polymer.

The composition also includes a substrate that includes a polymer composition which erodium in a humid environment with a slower speed than the hydrogel.

Swelling in water, not water-soluble polymer, i.e. a polymer which is capable of is to abuat when immersed in the aquatic environment, but that is not water-soluble in a selected range of pH (typically pH less than 5.5), is an ester of cellulose, alginic acid or acrylate polymer. The term "acrylate polymer" is intended to include acrylate polymers and copolymers, polymers and copolymers based on acrylate is a polymer of acrylic acid or esters of acrylic acid. The polymer typically swells to at least 25 wt.% and preferably at least 50 wt.% from its own weight when placed in water or an aqueous solution. In some implementations, using certain hydrophilic polymers, the composition may swell up to 1400 wt.% from its dry mass.

In one implementation, the composition is a teeth whitening composition, where the bleaching agent is working for whitening a tooth surface to which the composition is applied. However, the whitening agent may have other uses, for example, as a therapeutic agent or cosmetic agent of another type, for example, for skin lightening. Consequently, the compositions described herein can be used as pharmaceutical compositions for application to the body surface (e.g., teeth, nails, skin, mucous etc) for the treatment of pathological conditions. For example, the hydrogen peroxide and heat properties of the antibiotic and protivougrevoe agent, as well as a bleaching agent. Therefore, the invention also covers the treatment of infection or acne with coating compositions of the invention containing hydrogen peroxide on the surface of the body. Other pathological conditions include, as an example, but not limitation, fungal infections, acne, wounds, skin whitening and so on. In addition, a number of active agents may be included in the composition of the invention for the treatment of various diseases that affect the oral cavity.

A. Swelling in water, not soluble polymers

For solid compositions swelling in water, not water-soluble polymer is about 1-20 wt.%, preferably about 6-12 wt.% composition; hydrophilic polymer is about 20-80 wt.%, preferably about 40-60 wt.% composition; the complementary oligomer is about 10-50 wt.%, preferably about 15-35 wt.% composition; and an active agent, when present, is about 0.1-60 wt.%, preferably about 1-30 wt.% of the composition. It is not necessary that the complementary oligomer was approximately 10-80 wt.%, preferably about 20-50 wt.% a mixture of the hydrophilic polymer/complementary oligomer.

For compositions that are not solid, swelling in the de, the water-insoluble polymer is about 0.1-20 wt.%, preferably about 2-6 wt.% composition; hydrophilic polymer is about 1-40 wt.%, preferably about 4-10 wt.% composition; the complementary oligomer is about 0.1-20 wt.%, preferably about 0.5-10 wt.% composition; and an active agent, when present, is about 0.1-60 wt.%, preferably about 1-40 wt.% of the composition. It is not necessary that the complementary oligomer was approximately 1-85 wt.%, preferably about 5-50 wt.% a mixture of the hydrophilic polymer/complementary oligomer.

The profile of adhesion can be specified based on the type of polymer, relationships, composition and quantity of water in the mixture. Swelling in water, not soluble in water, the polymer is chosen so as to provide the desired profile of adhesion with respect to hydration. This means that when swelling in water, the water-insoluble polymer is an ester of cellulose, the composition is typically an adhesive prior to contact with water (e.g. with a wet surface), but gradually loses its stickiness as the composition absorbs moisture. When swelling in water, the water-insoluble polymer is an acrylate polymer or copolymer, the composition of the submission is as such, she is usually essentially no adhesive before contact with water, but becomes adhesive upon contact with a wet surface.

Swelling in water, the water-insoluble polymer capable of, at least to some extent to swell when immersed in liquid water, but not dissolved in water. The hydrophilic polymer can act, helping to solubilize the water-insoluble polymer. The polymer may be composed of a complex of cellulose ether, for example, cellulose acetate, dual ether acetate and cellulose propionate (CAP), dual ether acetate and cellulose butyrate (CAB), cellulose propionate (CP), cellulose butyrate (CB), dual ether propionate and butyrate cellulose (CPB), cellulose diacetate (CDA), cellulose triacetate (CTA) or the like. Data esters of cellulose are disclosed in U.S. patent No. 1698049, 1683347, 1880808, 1880560, 1984147, 2129052 and 3617201 and can be obtained using methods known in the art or purchased commercially. Commercially available esters of cellulose, which are suitable here include CA 320, CA 398, CAB 381, CAB 551, CAB 553, CAP 482, CAP 504, all available from Eastman Chemical Company, Kingsport, Tenn. Such esters of cellulose are usually average molecular weight between about 10,000 and about 75000.

Usually an ester of cellulose include cellulose mixture and monomer e is the INIC complex cellulose ether; for example, a commercially available dual ether acetate and cellulose butyrate contains Monomeric units of cellulose acetate, as well as Monomeric units of the cellulose butyrate and Monomeric units deesterification cellulose, while the dual ether acetate and cellulose propionate contains Monomeric units, such as cellulose propionate. Shown here is the preferred esters of cellulose are the compositions of dual ether acetate and cellulose propionate and compositions dual ether acetate and butyrate cellulose content Butrimova, proponiamo, acetylator esters and reesterification (OH) cellulose specified below:

Acetyl (%)OH (%)Mm
(g/mol)
Tg(°C)Tm(°C)
Dual ether acetate and cellulose butyrate17-52% butyratea 2.0 to 29.51,1-4,812000-7000096-141130-240
Dual ether acetate and cellulose propionate 42,5-47.7% of the propionate0,6-1,51,7-5,015000-75000142-159188-210

Indicated are also the preferred molecular weight, the glass transition temperature (Tg) and melting temperature (Tm). Suitable polymers cellulose usually have their own viscosity (I.V.) of from about 0.2 to about 3.0 deciliter/gram, preferably from about 1 to about 1.6 deciliter/gram when measured at a temperature of 25°C for the sample of 0.5 g in 100 ml of a phenol/tetrachlorethane 60/40 by weight. When obtaining with the method of the casting solvent of swelling in water, not soluble in water, the polymer should be selected to ensure greater cohesion and thus to accelerate the education of the film (typically, for example, dual ether acetate and propionate cellulose tends to improve the adhesion forces to a higher degree than double ether acetate and cellulose butyrate).

Other preferred swelling in water, the polymers are acrylate polymers, typically formed from acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, and/or other vinyl monomers. Suitable acrylate polymer is mi are their copolymers, available under the trade name "Eudragit" from Rohm Pharma (Germany). The copolymers of series Eudragit® E, L, S, RL, RS and NE available as solubilization in an organic solvent, dispersed in water or in the form of a dry powder. Preferred acrylic polymers are copolymers of methacrylic acid and methyl methacrylate, such as polymers series Eudragit L and Eudragit s Such especially preferred polymers are Eudragit L 30D-55 and Eudragit L 100-55 (the latter copolymer is a dried spray form Eudragit L 30D-55, which can be restored with the help of water). Molecular weights of copolymers Eudragit L 30D-55 and Eudragit L 100-55 is approximately 135000 Yes with the ratio of free carboxyl groups to the groups of ester is about 1:1. The copolymer Eudragit L 100-55 is not normally soluble in aqueous liquids having a pH below 5.5. Other particularly suitable copolymer of methacrylic acid-methyl methacrylate is Eudragit S-100, which differs from Eudragit L 30D-55 the fact that it is the ratio of free carboxyl groups to the groups of ester is 1:2. Eudragit S-100 insoluble at pH below 5.5, but unlike Eudragit L 30D-55 poorly soluble in aqueous fluids having a pH in the range from 5.5 to 7.0. This copolymer is soluble at pH 7.0 and above. Can also be applied Eudragit L 100, which has a pH-dependent solubility profile, temporarily is passed between Eudragit L 30D-55 and Eudragit S-100, until it becomes insoluble at pH below 6.0. Specialists in the art it should be clear that Eudragit L 30D-55, L 100-55, L 100 and S 100 may be replaced with other suitable polymers having similar characteristics pH-dependent solubility. Other suitable acrylate polymers are the copolymers of methacrylic acid/ethyl acrylate available under the trade mark "Kollicoat" from BASF AG (Germany). For example, Kollicoat MAE has the same molecular structure as the Eudragit L 100-55.

When swelling in water, the polymer is a polymer of acrylic acid or acrylate, offers a hydrogel, which may be reversible to be dried, i.e. after removal of water and any other solvents dried hydrogel can be restored to its original state by adding water. In addition, hydrophilic hydrogels obtained from swelling in water of the polymer of acrylic acid/acrylate, are usually essentially non-adhesive prior to contact with water, but become adhesive upon contact with a moist surface, such as a detectable inside the mouth, such as on the surface of the teeth. This property to be non-tacky prior to contact with water allows you to position or re-position the hydrogel on the selected surface before or during the process, as it becomes gluing is. Once the hydrogel is hydrated, it becomes sticky and adheres to the tooth surface or mucosal surface.

Besides containing acrylate composition can usually provide a swelling in the range of from about 400% to 1500% when immersed composition of the hydrogel in water or other aqueous liquid at a pH of less than 5.5, although the ratio of acrylic polymer to the mixture of the hydrophilic polymer/complementary oligomer can be selected so that the rate and extent of swelling in an aqueous environment has a predefined dependence on pH. This feature also provides retroactive inclusion of bleaching agents or other active agents, such as load composition peroxide, nagkakamali, chlorite, stabilizers, perfumes, etc.

On the contrary, the inclusion complex of cellulose ether as a swelling in water of the polymer attached to the hydrogel adhesion before application to a damp surface, but the lack of stickiness when it is soaked with water. It should be clear that this arrangement may be desirable when it is desirable reduction of stickiness for the final removal of the product from the teeth.

Other suitable swelling in water, the water-insoluble polymer is alginic acid, which is insoluble at pH below 5.5, but is able to absorb water and swell.

B. G is ProfiLine polymers

The second component of the hydrogel composition is a mixture of hydrophilic polymer and a complementary oligomer capable of forming hydrogen bonds or electrostatic communication with the hydrophilic polymer. Link to this as a "mixture" is intended to indicate that the interaction of the hydrophilic polymer and the oligomer is dominant for the properties of the hydrogel. However, the addition of swelling in water, the water-insoluble polymer is used to adjust the properties of the mixture so as to obtain single-phase hydrogel with the desired characteristics. This adjustment can be made by selecting a specific swelling in water, the water-insoluble polymer or enable a specific quantity of polymer or even through the regulation of time adding polymer and other ingredients (hydrophilic polymer, complementary oligomer, an active agent, etc. in the production process.

The hydrophilic polymer is typically a polymer with a relatively high molecular weight and a complementary oligomer is typically a polymer with a lower molecular weight. For solid compositions swelling in water, not water-soluble polymer is about 1-20 wt.%, preferably about 6-12 wt.% composition; hydrophilic polymer pillar is t approximately 20-80 wt.%, preferably about 40-60 wt.% composition; the complementary oligomer is about 10-50 wt.%, preferably about 15-35 wt.% composition; and the whitening agent is approximately 0.1-60 wt.%, preferably about 1-30 wt.% of the composition. Optimally, to the complementary oligomer was approximately 10-80 wt.%, preferably about 20-50 wt.% a mixture of the hydrophilic polymer/complementary oligomer.

Suitable hydrophilic polymers include repeating units derived from the monomer N-vinylacetate, monomer carboxyvinyl, monomer vinyl ester, complex ester carboxyvinyl monomer, monomer vinylamide and/or monomer hydroxyphenyl. Such polymers include, as an example, poly(N-vinylacetate), poly(N-vinylacetate), poly(N - alkylacrylate), polymers of substituted and unsubstituted acrylic and methacrylic acids (e.g., polyacrylic acid and polymethacrylic acid), polyvinyl alcohol (PVA), polyvinyliden, their copolymers and copolymers with other types of hydrophilic polymers (e.g. vinyl acetate).

Apply here poly(N-vinylacetate) are preferably not cross-linked, the homopolymers or copolymers of monomer units of N-vinylacetate with Monomeric units of N-vinylacetate, representing the e greater part of the total Monomeric units of the copolymer poly(N-vinylacetate). Preferred poly(N-vinylacetate) for use in connection with the invention are obtained by polymerization of one or more of the following monomers N-vinylacetate: N-vinyl-2-pyrrolidone; N-vinyl-2-valerolactam and N-vinyl-2-caprolactam. Limitiruyuschie examples of non-N-vanillacaroleb of comonomers used with N-vinilacetatom Monomeric units include N,N-dimethylacrylamide, acrylic acid, methacrylic acid, hydroxyethylmethacrylate, acrylamide, 2-acrylamide-2-methyl-1-propanesulfonic acid or its salt and vinyl acetate.

Poly(N-alkylacrylate) include as an example, poly(methacrylamide) and poly(N-izopropilakrilamid) (PNIPAM).

Polymers carboxyvinyl monomers usually formed from acrylic acid, methacrylic acid, crotonic acid, isocrotonic acid, basis of itaconic acid and anhydride, 1,2-dicarboxylic acid such as maleic acid or fumaric acid, maleic anhydride or mixtures thereof with the preferred hydrophilic polymers within this class, including polyacrylic acid and polymethacrylic acid and polyacrylic acid are most preferred.

Preferred hydrophilic polymers are the following: poly(N-vinylacetate), especially polyvinylpyrrolidone (PVP) and polyvinylcaprolactam (PVCap); poly(N-vinylacetate), the person is but polyacetate per se; polymers of monomers of carboxyvinyl, especially polyacrylic acid and polymethacrylic acid; and copolymers and mixtures thereof. Especially preferred are PVP and PVCap.

The molecular mass of the hydrophilic polymer is not decisive; however, the average molecular weight hydrophilic polymer is usually in the range of about 100000 to 2000000, more typically in the range of around 500,000 to 1,500,000. The oligomer is "complementary" hydrophilic polymers in that it is capable of forming with them a hydrogen or electrostatic connection. Preferably, the complementary oligomer terminated with hydroxyl groups, amino or carboxyl groups. The oligomer typically has a glass transition temperature Tgin the range from about -100°C. to approximately -30°C and the melting temperature Tmbelow approximately 20°C. the Oligomer may be amorphous. The difference between the values of Tghydrophilic polymer and oligomer is more preferably approximately 50°C, more preferably more than about 100°C. and most preferably in the range of from about 150°to about 300°C. Hydrophilic polymer and a complementary oligomer must be compatible, i.e. capable of forming a homogeneous mixture.

C. Complementary oligom the p

As described above, the complementary oligomer capable of forming hydrogen bonds or electrostatic communication with the hydrophilic polymer. Complementary oligomer can have also the ability to form covalent bonds with the hydrophilic polymer. In addition, complementary oligomer may have the ability to form hydrogen bonds or electrostatic ties with swelling in water water-insoluble polymer.

Usually complementary oligomer should have a molecular weight in the range from about 45 to about 800, preferably in the range of from about 45 to about 600. The complementary oligomer is a preferred polyalkyleneglycol low molecular weight (molecular weight 200-600), such as polyethylene glycol 400, which may also serve as a plasticizer of low molecular weight. Alternatively, as an additional low molecular weight plasticizer may be included another connection in this case can be used any of the low molecular weight plasticizers described below. In one implementation of the invention the complementary oligomer is a complementary low molecular weight or oligomeric plasticizer, which contains at least two functional groups is olukolu, which are capable of forming hydrogen bonds or electrostatic communication with the hydrophilic polymer.

In some examples, the complementary oligomer may also serve as a low molecular weight plasticizer. Alternatively, as an additional low molecular weight plasticizer may be included in another connection, if it is enabled, it must be present as approximately 30-35 wt.% song.

Examples of suitable complementary oligomers include, but are not limited to, polyhydric alcohols, low molecular weight (for example, glycerol or sorbitol), Monomeric and oligomeric alkalophile, such as ethylene glycol and propylene glycol, ethers, alcohols (for example, ethers, glycols), dicarboxylic acid, arcangioli from butanediol to octandiol, including ending carboxyla and ending with the amino derivatives of polyalkylene glycols. The polyalkylene glycols, optionally ending with carboxyla, here preferred, and polyethylene glycol having a molecular weight in the range from about 200 to 600, is optimal complementary oligomer.

From the above it should be clear that one connection, for example, low-molecular polyalkyleneglycol, such as polyethylene glycol having a molecular weight in the range of the E. from about 200 to 600, can serve as a complementary oligomer, or low molecular weight plasticizer.

As discussed in the patent publication U.S. No. 2002/0037977, in the name of Feldstein et al., the ratio of hydrophilic polymer to the complementary oligomer in the above mixtures : effect of adhesion force and traction force. As explained in the above patent application, the complementary oligomer reduces the glass transition temperature of the mixture of the hydrophilic polymer/complementary oligomer in a higher degree than predicted using equation Fox, which is represented by equation (1)

(1)=+

where Tg predictedrepresents the glass transition temperature of the mixture of the hydrophilic polymer/complementary oligomer, Wpolrepresents the weight fraction of the hydrophilic polymer in the mixture, Wplrepresents the weight fraction of complementary oligomer in the mixture, Tg polrepresents the glass transition temperature of the hydrophilic polymer and Tg plrepresents the glass transition temperature of complementary oligomer. As also explained in this patent application, the adhesive composition having an optimized adhesion force and adhesion, can be half the Jena from a hydrophilic polymer and a complementary oligomer by selecting components and their relative amounts with the receipt of a predetermined deviation from the T g predicted. Usually to maximize the adhesion of the pre-defined deviation from Tg predictedshould have the maximum negative deviations, while for minimizing the adhesion of any negative deviation from Tg predictedis minimized.

As a complementary oligomer itself can act as a plasticizer, is usually not necessary to include an additional plasticizer. However, the inclusion of additional low molecular weight plasticizer in the composition is optimally and may in some cases be beneficial. Suitable low molecular weight plasticizers include diallylphthalate, dicyclohexylamine, Directorate and mixed alkylacrylate, as represented by dimethylphthalate, diethylphthalate, dipropylamino, di(2-ethylhexyl)phthalate, diisopropylamino, tamilfilm and dicaprylate; alkyl and arylphosphate, such as tributyl phosphate, trioctylphosphine, tricresylphosphate and triphenyl; alkiliruth and esters of citric acid such as triethylcitrate, triethylcitrate, tributyltin, acetyltributyl and tryexecute; dialkyldimethyl, such as dioctyladipate (DOA); also referred to as bis(2-ethylhexyl)adipate), diethylacetal, di(2-methylethyl)adipat and disaccredit; dialkylated, such as diethyltartrate and dibutylated; dialkyl abacinate, such as diethylbenzene, dipropylamine and dinnerseating; dialkylamines, such as diethylamine and dibutylamine; alkylphenolate, alkylglycerols, esters of glycol and esters of glycerol, such as the diacetate of glycerol and glycerol triacetate (triacetin), malolactic and the diacetate of glycerol, methylpteroylglutamate, butylphenylmethyl, glycol diacetate, dibutyrate glycol, triethylene glycol diacetate, dibutyrate triethylene glycol and triethylene glycol dipropionate and their mixtures. Preferred low molecular weight plasticizers for continuous hydrophilic phase are triethylcitrate, tributyltin, diethylphthalate and dioctyladipate, with the most preferred dioctyladipate.

The properties of the composition of the invention is easily controlled by regulating one or more parameters upon receipt. For example, if you receive can be controlled by the strength of adhesion of the composition to increase, reduce or eliminate adhesion. This can be achieved by varying the type and/or quantity of the various components or by using a modification of the method of obtaining. The method of obtaining a composition obtained using the traditional method of extrusion from the melt, are usually, though not necessarily, slightly less sticky than the compo is icii, obtained with the method of the casting solution. Moreover, the degree to which the composition of the hydrogel will swell upon contact with water, can be varied by selecting different swelling in water of the polymers and compositions which contain a continuous hydrophilic phase, by bringing the relations of swelling in water of the water-insoluble polymer to the mixture of the hydrophilic polymer/complementary plasticizer. These compositions can vary from transparent, translucent to translucent to opaque. In addition, certain compositions can impart translucency by changing the relative amounts of components in the hydrophilic phase (for example, by reducing the number of complex cellulose ether) or by changing the method of obtaining a (semi-transparent hydrogels easier to obtain with the method of the casting solution in comparison with the extrusion from the melt). In this case, the translucent composition allows the user to observe therapeutic or cosmetic process (e.g., bleaching) in the process of its implementation and to determine, when is it achieved the desired effect, for example, when the teeth become quite white.

D. Active agents

The composition may also include any pharmaceutically active agent, suitable for L. the treatment of physiological conditions in respect of the teeth, the surrounding tissue, as well as other mucosal tissues. The active agent can be any substance that can be released from the composition for the treatment of undesirable physiological condition. Undesirable physiological state in relation to the teeth or surrounding tissue, can be treated using the present device include bad breath, periodontal infections and infections of the oral cavity; periodontal damage; caries or tooth decay, gingivitis and other periodontal diseases. The active agent may be in the hydrogel and/or a component of the coating. Moreover, in the composition of the invention may include several agents. For example, the hydrogel may contain a whitening teeth agent, which is released on the tooth surface, while the floor can be put another active agent, such as a breath freshener, which is released in the oral cavity.

Such agents will be in cosmetically or therapeutically effective amount. These include as an example, but without limitation, adrenergic agents, steroids of the adrenal cortex, the suppressor of the adrenal cortex, tools, limiting alcohol intake, aldosterone antagonists, amino acids, detoxifying ammonia tools, anabolic agents, analepticheskih agents, analgesias the e agents, androgenic agents, anesthetic agents, anorectic compounds anorexicskin agents, antagonists, activators of the anterior pituitary and the suppressor of the anterior pituitary gland, antihelminthic agents, protivougrevoe agents, antiadrenergicheskoe agents, antiallergic agents, protivooterne agents, antiandrogenna agents, Antianemic agents, antistenocardin agents, sedative agents, antiarthritic agents, Antiasthmatic agents, antiatherosclerotic agents, antibacterial agents, agents against gallstones, agents against the formation of gallstones, anticholinergic agents, anticoagulants, protivoraketnyi agents, anticonvulsant agents, antidepressants, antidiabetic agents, antidiarrheal agents, antidiuretic, antidotes, antidyskinetics agents, antiemetic agents, antiepileptic agents, anti-estrogenic agents, antifibrinolytic agents, antifungal agents, antiglaucoma agents, agents against hemophilia, antihemophilic factor, Antihemorrhagics agents, antihistamine agents, antihyperlipidemic agents, antihyperlipidemic agents, antihypertensive agents, antihypotensive agents, antiseptics, anti-inflammatory agents, agents against keratinization, antimalarial agents, proteomic is one of the agents, agents against migraine, antimitoticescoe agents, antifungal agents, antiemetic agents, antineoplastic agents, anti-cancer supplementary potentiating agents, antineuraminidase agents, agents against obsessions, antiparasitic agents, antiparkinsonian drugs, antipneumocystis agents, antiproliferative agents, medicines against prostatic hypertrophy, antibacterial agents, agents against itching, antipsoriasis agents, antipsychotic agents, Antirheumatic agents, antihistamine agents, antiseborrheic agents, antispasmodic agents, antithrombosis agents, anti-cough, anti-ulcer agents, anti-urolithiasis, antiviral agents, means for reducing appetite, agents for the treatment of benign prostatic hyperplasia, regulators of blood glucose level, inhibitors of bone resorption, bronchodilatory, carbonic anhydrase inhibitors, cardiac depressants, cardiotoxin tools, cardiotonic agents, cardiovascular agents, diuretic agents, cholinergic agents, cholinergic agonists, inactivator cholinesterase, coccidiostatic agents, adjuvants and amplifiers cognitive function, sedatives, diagnostician is ical means, diuretics, dopaminergic agents, means of destruction ectoparasites, material resources, enzyme inhibitors, estrogens, fibrinolytic agents, traps for free radicals of oxygen, agents motility of the gastrointestinal tract, glucocorticoids, gonadoliberin agents, hair growth stimulants, hemostatic agents, H2 receptor antagonists histamine, hormones, hypocholesterolemic agents, hypoglycemic agents, hypolipidemic agents, anti-hypertensive agents, inhibitors of HMGCoA-reductase, immunizing agents, immunomodulators, immunoregulatory, Immunostimulants, immunosuppressants, AIDS the treatment of impotence, inhibitors, keratolytic agents, LHRH agonists, treatment of disorders of the liver, luteolytic agents that AIDS improve memory, boosts mental activity, mood regulators, mucolytic agents, agents protect mucous, midriatichesky agents, nasal decongestants, neuroleptics, blockers, neuromuscular transmission, neuroprotective agents, NMDA antagonists, non-hormonal Sterol derivatives, enabling clan activities agents, plasminogen activators, antagonists of platelet-activating factor, platelet aggregation inhibitors, treatment after a stroke, and t is Amy head, potentiating tools, progestins, prostaglandins, growth inhibitors of the prostate gland that stimulates the thyroid-stimulating hormone agents, psychotropic agents, radioactive agents, regulators, ward, repartitioning agents, anti-itch, sclerosing agents, sedatives, sedative-hypnotic agents, selective antagonists of the adenosine A1 antagonists serotonin inhibitors, serotonin antagonists serotonin receptor, steroids, stimulants, suppressive means synergistic tools, thyroid hormones, inhibitors thyroid cancer, agents that mimic thyroid hormones, tranquilizers, agents against unstable angina, agents that promote the excretion of uric acid, vasoconstrictor tools, vasodilator, helping to heal, tools for wound healing, inhibitors of xanthine oxidase and the like.

In one implementation described above, the composition of the hydrogel contains a bleaching agent and thereby serves as a delivery system when applied on the teeth. Releasing bleaching agents, "loaded" in the present composition of the hydrogel typically includes both water absorption and desorption agent through the mechanism controlled by the swelling of diffusion. Containing the bleaching agent component is icii hydrogel can be used similar to the use, for example, local pharmaceutical compositions.

Suitable agents for teeth whitening include peroxides, metal chlorites, perborates, percarbonates, nagkalat and combinations thereof. Suitable peroxide compounds include hydrogen peroxide, calcium peroxide, peroxide of magnesium, urea peroxide, and mixtures thereof. The preferred peroxides are hydrogen peroxide and urea peroxide. Other suitable peroxides include organic peroxides, including, but not limited to, dialkylamide, such as peroxide, tert-butyl and 2,2 bis(tert-BUTYLPEROXY)propane, diazepamonline, such as benzoyl peroxide and acetylmuramic, complex madefire, such as tert-butylperbenzoate and tert-Builder-2-ethylhexanoate, permitability, such as dicetylperoxydicarbonate and dicyclohexylperoxydicarbonate, ketone peroxides such as cyclohexanone peroxide and methyl ethyl ketone peroxide, hydroperoxides, such as the hydroperoxide cumene and tert-butyl hydroperoxide. The whitening agent is preferably a peroxide such as hydrogen peroxide or urea peroxide, and most preferably hydrogen peroxide.

Suitable metal chlorites include chlorite calcium, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite and potassium chlorite; hypochlorite and chlorine dioxide. The preferred chlorite are the two which is sodium chlorite.

In another implementation, the active agent can represent, for example, non-steroidal anti-inflammatory/analgesic agent; steroid anti-inflammatory agents; local anesthetics; bactericidal/disinfectant; antibiotics; antifungal agents; antisense teeth agents; fluoride agents against dental caries/tooth decay; agents against dental plaque/anticellulite agents; enzymes that inhibit the formation of plaque, stone or dental caries; abrasive agents, such as pyrophosphates; metal chelators, such as ethylenediaminetetraacetic acid, chetyrehmatchevaya salt; antioxidants, such as bottled hydroxyanisol; bottled hydroxytoluene; food supplements for local delivery to the teeth and surrounding tissue, and so forth.

Suitable non-steroidal anti-inflammatory/analgesic tools include acetaminophen; methyl salicylate; nonagricultural; aspirin; mefenamico acid; flufenamic acid; indomethacin; diclofenac; alclofenac; diclofenac sodium; ibuprofen; flurbiprofen; Frantisek; bufexamac; piroxicam; phenylbutazone; oxyphenbutazone; Clifton; pentazocine; Marisol and tiaramide hydrochloride.

Suitable steroid anti-inflammatory agents include hydrocortisone; prednisolone; dexamethas is n; triamcinolone acetonide; fluoqinolona acetonide, hydrocortisone acetate, prednisolone acetate; methylprednisolone; dexamethasone acetate; betamethasone; betamethasone valerate; flumetazon; formation; budesonide and beclomethasone dipropionate.

Suitable local anesthetics include dibucaine hydrochloride; dibucaine; lidocaine hydrochloride; lidocaine; benzocaine; hydrochloride of the ethyl ester of para-butylaminoethyl acid 2-(diethylamino); procaine hydrochloride; tetracaine hydrochloride; chloroprocaine hydrochloride; oxyproline hydrochloride; mepivacain; cocaine hydrochloride and piperocaine hydrochloride.

Suitable bactericidal/disinfectant include thimerosal; phenol; thymol; benzalkonium chloride; benzene chloride; chlorhexidine; povidone iodide; cetylpyridinium chloride; eugenol and trimethylammonium bromide.

Suitable antibiotics include penicillin; methicillin; oxacillin; cefalotin; tsefaloridin; erythromycin; lincomycin; tetracycline; chlortetracycline; oxytetracycline; metatsiklina; chloramphenicol; kanamycin; streptomycin; gentamicin; bacitracin and cycloserine. Suitable antifungal drugs include amphotericin; clotrimazole; econazole nitrate; fluconazole; griseofulvin; Itraconazole; ketoconazole; miconazole; nystatin; terbinafine hydrochloride; undecanoyl acid and undecenoic zinc.

Suitable antisense agents for teeth include potassium nitrate and strontium chloride. Suitable fluoride agents against tooth decay/destruction include sodium fluoride, potassium fluoride and ammonium fluoride.

Additional bleaching agents include agents against dental plaque/anticellulite agents, including phosphates such as pyrophosphates, polyphosphates, polyphosphonates (for example, ethane-1-hydroxy-1,1-diphosphonate, 1-azacycloheptane-1,1-diphosphonate and diphosphonates linear Akilov) and their salts; linear carboxylic acids; sodium citrate zinc and mixtures thereof. Preferred pyrophosphate salts are dibasic pyrophosphate alkali metal salts, chetyrehskatnye pyrophosphate alkali metal salts; and hydrated and UN-hydrated form acidic dinitropyridine (Na2H2P2O7), tetrahydrofolate (Na4P2O7and tetrakaidecahedral (K4P2O7). Pyrophosphate salt is described in more detail in Kirk &Othmer, Encyclopedia of Clinical Technology, Third Edition, Volume 17, Woley-Interscience Publishers (1982). Optional bleaching agents may also include dissolving plaque agents, such as betaines, aminoxide and Quaternary amines as described in U.S. patent No. 6315991 owned Zofchak.

In the compositions could also be useful enzymatic agents that act by inhibiting the formation of plaque, stone or dental caries. Enzymatic agents can be stored together with a bleaching agent or they can be placed in a separate layer inside the multilayer system as described here. Suitable enzymes include proteases that destroy proteins of saliva, which are absorbed by the surface of the teeth and form a film or the first layer plaques; lipase, destructive bacteria by lysis of proteins and lipids, which form a structural component of the walls and membranes of bacterial cells; dextranase, glucanohydrolase, endoglycosidase and mucinase destroying the skeletal structure of bacteria, which forms a matrix for adhesion of bacteria to the teeth; and amylase, which prevent the development of stone by breaking down the complex carbohydrate-protein that binds calcium. Preferred enzymes include any of the commercially available proteases; dextrans, glucanohydrolase; endoglycosidase; amylases; Atanas; lipases; Mucins; and compatible mixtures. In some implementations can be used enzymatic bleaching agent.

Optional enzymatic bleaching agent is a peroxidase, the hydrogen peroxide formedin situ. When the enzyme whitening agent or agent against dental plaque include in the composition, the composition should be such that the enzyme remained in its active form, for example, the pH should b the th approximately neutral, and peroxide may not be included or placed in a separate layer.

Appropriate nutritional supplements for local delivery to the teeth and surrounding tissue include vitamins (such as vitamins C and D, thiamine, Riboflavin, calcium Pantothenate, Niacin, folic acid, nicotinamide, pyridoxine, ciankobalamin, para-aminobenzoic acid and bioflavonoids) and mineral compounds (e.g., calcium, phosphorus, fluoride, zinc, manganese and potassium and mixtures thereof. Vitamins and mineral compounds suitable in the present invention, are disclosed in Drug Facts and Comparisons (service information about drugs in the attached sheet), Wolters Kluer Company, St. Louis, Mo., 1997, pp 3-7.

The composition may also comprise any cosmetically active agent. Used here "cosmetically active agent" includes any substance that may be released from the composition for inducing desired changes to the appearance of the teeth or surrounding tissue, or which gives the consumer a socially desirable property, such as fresh breath. For example, the cosmetically active agent can be a refreshing breath remedy or agent that whitens or attached white teeth. Recognizing that the staining of teeth in some cultures or certain segments of Western society may have a value or be desirable, cosmetically active agent may be an agent that gives CEE is or shade of the teeth.

The composition may include additional whitening agents. For example, may also be present surfactants, such as detergents, and they should work together with bleaching agents described above, to give the teeth a more shiny appearance.

In any of these implementations teeth whitening composition of the invention preferably includes peroxide for teeth whitening and may also include conventional additives such as fillers, preservatives, pH regulators, plasticizers, thickeners, dyes, pigments, paints, refractive particles, stabilizers, hardening agents, pharmaceutical agents, odorants or breath freshening agents and penetration enhancers. In those implementations in which the adhesion is subject to reduction or elimination, can be used as a traditional reduce tackiness agents. The composition can be incorporated data of the additive and the number selected so that they do not influence significantly on the desired chemical and physical properties of the teeth whitening composition or had no effect on the delivery of a whitening teeth agent. Such additional ingredients include coloring compounds, food additives, flavors, sweeteners and preservatives.

E. Other ingredients

The composition of izobreteny which may be included any natural or synthetic flavorant or dietary Supplement such as described in Chemicals Used in Food Processing, Pub. No. 1274, National Academy of Sciences, pages 63-258. Suitable flavorant include simalube, pepper mint, curled mint, menthol, fruit flavors, vanilla, cinnamon, spices, aromatic oils and resins (balms), known in the art, and combinations thereof. Commonly used number flavorant is a matter of preference and depends on such factors as the type of scent, individual taste and desired power. Preferably the composition includes from about 0.1 to 5 wt.% flavorant.

Sweeteners suitable in the present invention include sucrose, fructose, aspartame, xylitol and saccharin. Preferably the composition includes sweeteners in an amount of from about 0.001 to 5.0 wt.%.

A suitable substrate may be semi-transparent substance, such that the composition is not clearly visible after application. However, the substrate or the composition optionally can be dyed, so that the composition is well visible after application. If you want the tinting, it is preferable that the dye was in the substrate. For example, the substrate can be painted in a bright or vibrant color that the consumer may find enjoyable. The substrate, thus, may include a coloring compound, such as, for example, a dye, pigment or substance to the e imparts color when added to a material forming the substrate.

For example, for dyeing of the substrate can be used dye compounds of the type commonly used in food, drugs or cosmetics for humans, especially coloring additives permitted for use in food, which are classified as "likely to be recognized" or "exempt from certification". Coloring compounds used for coating the substrate, can originate from natural sources such as vegetables, minerals or animals, or can be artificially obtained by the counterparts of natural derivatives.

Coloring connections, certified to date Food Drug &Cosmetic Act for use in food and swallow medicines include dyes such as FD&C Red No. 3 (sodium salt of tetraiodofluorescein); Food Red 17 (disodium salt of 6-hydroxy-5-{(2-methoxy-5-methyl-4-sulfophenyl)azo}-2-naphthalenesulfonate); Food Yellow 13 (sodium salt of a mixture of mono - and disulfonic of chieftan or 2-(2-chinolin)indandion); FD&C Yellow No. 5 (sodium salt of 4-para-sulfophenylazo-1-pair-sulfophenyl-5-hydroxypyrazol-3-carboxylic acid; FD&C Yellow No. 6 (sodium salt of para-sulfophenylazo-B-naphthol-6-monosulphate); FD&C Green No. 3 (disodium salt of 4-{[4-(N-ethyl-para-sulfanilamide)phenyl]-(4-hydroxy-2-sulfanilyl)-meth is-ethylene}-[1-(N-ethyl-N-para-sulfobutyl)for 3,5-cyclohexadiene]); FD&C Blue No. 1 (disodium salt of anhydrite dibenzylidene-diaminodiphenylamine trisulphonate); FD&C Blue No. 2 (sodium salt of dissolvability of indigotine); FD&C Red No. 40; Orange B; and Citrus Red No. 2 and their combinations in different proportions.

Coloring compounds, exempt from certification FDA, include annatto extract; beta-APO-8'-carotenal; beta-carotene; powder beet; canthaxanthin; burnt sugar; carrot oil; extract cochinilla (Carmine); toasted partially defatted, heat treated flour from the seeds of the cotton plant; iron gluconate; fruit juice; extract dye grapes; the extract of grape skins (enocyanin); paprika; resin paprika; Riboflavin; saffron; turmeric, resin turmeric, vegetable juice, and combinations thereof in various proportions.

Form a dye compound for use in the composition preferably includes painted forms of supplements, but can also include forms of varnish that are compatible with the material comprising the substrate. In accordance with the present method can be used water-soluble dyes, coming in the form of powders, granules, lipid or other forms of special purpose. For staining of the substrate used preferably varnish or water-insoluble form of the dye. For example, if the application is subject to suspension coloring connections, the can is to be used in form of supplements varnish. Suitable water-insoluble coloring varnishes obtained by adding calcium salts or aluminium to the dye, FD&C aluminum salts include FD&C Green #1 varnish, FD&C Blue #2 lacquer, FD&C R&D #30 Lac and FD&C Yellow # 15 Lac.

Other suitable coloring compounds include non-toxic, water-insoluble inorganic pigments such as titanium dioxide; green dyes on the basis of chromium oxide; ultramarine blue and pink dyes; and iron oxides. Such pigments preferably have a particle size in the range from about 5 to about 1000 microns, more preferably from about 250 to about 500 microns.

The concentration of the coloring compounds in the substrate is preferably from about 0.05 to 10 wt.% and more preferably from about 0.1 to 5 wt.%.

The substrate can be more than one coloring connections, so he is given a lot of flowers. These multiple colors can be distributed in the form of stripes, dots, spirals, or in any other form that the consumer may find enjoyable. Coloring the connection can also be used with other improving views of substances such as glittering particles.

To control the degree of hydration, when the adhesion on the surface of the teeth, can also be successfully included absorbe the respective fillers. Such fillers may include microcrystalline cellulose, talc, lactose, kaolin, lures, colloidal silicon dioxide, aluminum oxide, zinc oxide, titanium oxide, magnesium silicate, a double salt of magnesium and aluminum silica, hydrophobic starch, calcium sulfate, calcium stearate, calcium phosphate, dihydrate calcium phosphate, alumina, such as laponite, woven and non-woven paper and cotton materials. Other suitable fillers are inert, i.e. essentially neabsorbiruemye, and include, for example, polyethylene, polypropylene, copolymers of polyurethane and polyetherimide, polyesters and copolymers of polyesters, nylon and viscose. The preferred filler is colloidal silicon dioxide, for example, Cab-O-Sil® (Cabot Corporation, Boston MA).

Preservative agents include, as an example, para-chloro-meta-cresol, phenethyl alcohol, phenoxyethylamine alcohol, chlorobutanol, methyl ester of 4-hydroxybenzoic acid, the polyester 4-hydroxybenzoic acid, benzalkonium chloride, cetylpyridinium chloride, chlorhexidine diacetate or gluconate, ethanol or propylene glycol.

Compounds suitable as pH regulators include, but without limitation, glycerol buffers, citrate buffers, borate buffers, phosphate buffers, or may also include a citrate-phosphate acid buffers such about what atom, to ensure the compatibility of the pH of the composition of the hydrogel with a pH environment of the oral cavity and not to videocialis mineral compounds from the surface of the teeth. To optimize the bleaching without demineralization of the teeth in the composition can be included calcium salts and/or fluoride.

Suitable plasticizers include esters of citric acid such as triethylcitrate or acetyltributyl, esters of tartaric acid, such as dibutylated, esters of glycerol, such as glyceraldehyde and glyceroltrinitrate; esters of phthalic acid such as dibutyl phthalate and diethylphthalate; and/or hydrophilic surfactants, preferably hydrophilic non-ionic surfactants, such as, for example, partial esters of fatty acids and sugars, esters of polyethylene glycol and of fatty acids, ethers of polyethylene glycol and of fatty alcohols and esters of polietilenglikolya fatty acids.

Preferred thickeners are natural compounds or their derivatives, which include as an example, collagen; galactomannan; starches; derivatives and hydrolysates of starch; cellulose derivatives such as methylcellulose, hydroxypropylcellulose, hydroxyethyl cellulose and hypromellose; colloidal silicon sour the s & sugar such as lactose, sucrose, fructose and glucose. You can also use synthetic thickeners such as polyvinyl alcohol, copolymers of vinyl pyrrolidone-vinyl acetate, polyethylene glycols and polypropylenglycol.

The substrate may also be surrounded or decorative items, such as balls, beads or the like, if these products do not violate the viscosity-elastic properties of the substrate necessary for the proper deformation of the composition on the teeth, as described above. The substrate also may exhibit letters, words or images, designed for pleasure or attractiveness to the consumer.

F. Uroderma substrate

Uroderma substrate consists of a polymeric composition, which erodium in a humid environment at a slower rate compared with hydrogel and is essentially non-adhesive. There are many materials that can be applied to a substrate, comprising as an example, without limitation, acrylate polymers, polymers, cellulose derivatives, esters of cellulose, starches, alginic acid, alginates, polyaminoamide. As the substrate material can also serve as a combination, i.e. a mixture of any of the data from different polymers.

In one implementation of the hydrogel erodium within from about 1 second to 24 hours after the SIP is recorded in the moist environment, and in another implementation the hydrogel erodium for from about 10 seconds to 8 hours after placing. Uroderma the substrate in one implementation erodium within approximately 12 to 24 hours after the erosion of the hydrogel, when in another implementation, the substrate erodium within approximately 12 hours after the erosion of the hydrogel. Material erodium substrate may be selected so that erosion was a bit slower or about the same speed (for example, when both components erogenous within approximately 24 hours), but preferably it is chosen so that the application he erodium at a slower rate than the composition of the hydrogel. In one implementation uroderma substrate erodium, at least about 200% slower than the hydrogel, in another implementation, the substrate erodium, at least about 100% slower, in another implementation, the substrate erodium, at least about 50% slower, and in yet another implementation, the substrate erodium, at least about 25% slower than the hydrogel.

Suitable acrylate polymers described above as swelling in water, water-insoluble polymers and include, as examples, without limiting the above, the polymers formed from acrylic acid, methacrylic acid, metelak elata, ethyl acrylate, methyl methacrylate, ethyl methacrylate, and/or other vinyl monomers. Preferred acrylic polymers are copolymers Eudragit® (copolymers of methacrylic acid and methyl methacrylate), such as copolymers Eudragit® series E, L, S, RL, RS and NE. As noted above, these polymers Eudragit also used as swelling in water, water-insoluble polymer component of the hydrogel. As the Eudragit polymers are available in different forms with different indicators dependent on pH solubility and permeability, the form used for erodium substrate may be selected so that it had a lower solubility compared to the form used in the hydrogel. For example, if for use in the hydrogel selected L 100-55, the substrate can be used Eudragit L 100; if Eudragit L 100 is used in the hydrogel, the substrate could be used Eudragit S 100; and so forth. In addition, for adjusting the rate of erosion of the substrate to that of the hydrogel can be used a mixture of Eudragit polymers or mixtures of Eudragit polymers with other polymers or fillers (for example, buferiruemoi agents, pH modulators).

Suitable polymers are cellulose derivatives include as an example, without limitation, hydrocellulose (cellophane), methylcellulose, ethylcellulose, hydroxyethyl cellulose (EC), hydroxypropylcellulose (HPC), hypromellose (HPMC), carboxymethylcellulose (CMC), and carboxymethylcellulose sodium (Na-CMC). The preferred cellulose are hydrocellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose, carboxymethylcellulose, carboxymethylcellulose sodium, and mixtures thereof.

Suitable esters of cellulose as described above swelling in water, water-insoluble polymers, and include as an example, without limitation, cellulose acetate, dual ether acetate/propionate cellulose, dual ether acetate/butyrate cellulose, cellulose propionate, cellulose butyrate, dual ether propionate/butyrate cellulose, cellulose diacetate, cellulose triacetate and mixtures, polymers and copolymers. Typical copolymers of esters of cellulose are dual ether acetate/butyrate cellulose and dual ether acetate/propionate cellulose. Preferred esters of cellulose are cellulose acetate, dual ether acetate/propionate cellulose, dual ether acetate/butyrate cellulose, cellulose propionate, cellulose butyrate, dual ether propionate/butyrate cellulose, cellulose diacetate, cellulose triacetate, dual ether acetate/butyrate cellulose and dual ether acetate/propionate, cellulose and mixtures thereof.

Suitable cu is hmily include as an example, without limitation, acetate potato starch, corn starch, etc. (for example, starches Clearam®from Roquette), and mixtures thereof.

Suitable alginates include, as an example, but not limitation, propylene glycol alginate, sodium alginate, calcium alginate, and so forth, and mixtures thereof.

Suitable polyaminoamide include as examples, but not limitations, polylysin, polyglycine, polyalanine, Protamine, and so forth, and mixtures thereof.

It should be understood that any of the active agents and other ingredients described in connection with the composition of the hydrogel may also be present in the substrate. For example, the hydrogel may contain an active agent that is released on the surface of the teeth or the mucous membrane of the oral cavity, whereas in the substrate can be entered flavorant, which is released in the oral cavity.

IV. Ways to get

The hydrogel composition of the invention generally are processed from the melt and can be obtained using a simple method of mixing and extrusion. The components of the composition is weighed and then mixed, for example, by using a Brabender mixer or Baker Perkins, usually, though not necessarily, at an elevated temperature, for example, from about 90 to 140°C. If desired, can be added solvents or water. The resulting composition may be extruded with the help of the simple or dual extruder or granular. Alternative components of the composition of the hydrogel can be melted at the same time and then mixed before extrusion. The hydrogel composition may be extruded directly on ertirea substrate. The hydrogel composition may be first extruded and then laminated to a substrate or laminated on a substrate. Can also be included gasket release. The thickness of the obtained containing hydrogel films for most purposes, should be in the range of approximately 0.050 to 0.80 mm, more in the range of approximately from 0.37 to 0.47 mm

Alternatively, compositions can be obtained by casting a solution by mixing components of the composition in a suitable solvent, for example, volatile solvent such as ethyl acetate, or particularly preferred lower alcohols (e.g. ethanol, isopropyl alcohol and so on), at a concentration typically in the range of from about 35 to 60% wt./about. The solution is poured on ertirea substrate or pad release, as described above. And mixing, and casting is preferably carried out at ambient temperature. Film-coated substrate is then subjected to heat treatment at a temperature in the range from about 80 to 100°C., optimally about 90°C., for a time ranging from approximately one to four hours, opt is normal for approximately two hours. Accordingly, one implementation of the invention is a method of obtaining a hydrogel film, suitable for inclusion in the composition of the invention, which includes the following stages: obtaining a solution of swelling in water, water-insoluble polymer, a hydrophilic polymer and a complementary oligomer capable of formation of hydrogen or electrostatic ties with hydrophilic polymer in the solvent; the location of a layer on ertirea substrate to ensure its coating; and heating the coated substrate to a temperature in the range from about 80 to 100°C for a time ranging from approximately 1 to 4 hours, thereby creating a hydrogel film on a substrate.

When the desired adhesive composition of the hydrogel, the preferred method is the casting solution. To obtain a translucent compositions can be used in the methods or extrusion melting or casting of the solution, although implementation is generally preferable casting solution. Accordingly, another implementation of the invention is a method of forming a composition that includes a continuous hydrophilic phase, which includes the following stages: transmission to melt through the extruder a mixture of swelling in water, water-insoluble polymer, a hydrophilic polymer and to elementarnogo oligomer, capable of forming hydrogen bonds or electrostatic ties with hydrophilic polymer to form a composition for extrusion; extrusion of the composition in the form of a film of the desired thickness on a suitable ertirea substrate; and after cooling, the coating film of an aqueous solution of an active agent, such as peroxide, to obtain the concentration of the whitening agent is from about 1 to 20 wt.%.

The invention also provides a multilayer system that includes one or more hydrogel or dehydrogenase layers. For example, it may be desirable to include additional active agents that may not be compatible with the primary active agent during storage. In this way, one layer may be a hydrogel layer that contains the primary active agent and the other layer (s) may contain additional active agents. These other layers may be made of compositions described herein hydrogel or any other biocompatible composition known in the art (for example, polyisobutylene, dimethylsiloxane, ethylene vinyl acetate, polyvinyl acetate, acetate, butyrate, cellulose propionate, ethyl cellulose and water-insoluble acrylate). In addition, depending on the location of the layers may be desirable, the presence of CL is icogo layer, for example, a layer for the location directly on the teeth, and the non-adhesive layer, for example the outer layer, which is located near the mouth. Another advantage of having a multi-layer system is that the ratio of the polymers used in the outer layer, can be changed to achieve the non-adhesive layer, in order to avoid the necessity of inclusion in the product of a separate layer of the substrate.

In one implementation, the composition includes an outer ertirea substrate, which serves as the outer surface of the composition after application to the teeth, the tissue of the oral cavity or mucosal surface; attached to it an adhesive layer in contact with the surface, which should usually be the adhesive composition of the invention, optionally containing additional active agents; and removing the layer of release. After removal of the release layer, for example, the composition applied to the surface, for example, the teeth to be processed, and placed on the surface so that the layer in contact with the surface of the oral cavity, were in contact with the teeth or other surfaces of the oral cavity. In another implementation, the composition is packaged without laying release. Accordingly, after removal from the packaging composition ready for application to the surface of the oral cavity.

the song hydrogel erodium substrate may include an additional layer of the substrate, which can serve as the primary structural element and to provide the composition of the substrate or at the time of receipt or at the time of application. Used for the substrate material should be inert and incapable of absorbing hydrogel composition erodium substrate. In addition, applied to the substrate material should allow the device to follow the contours of the teeth or other surfaces of the body and comfortable to disintegrate in the mouth without rubbing or other irritation of lips or tongue. Examples suitable for substrate materials include polyesters, polyethylene, polypropylene, polyester amides, polyurethanes and polyesters. The substrate is preferably in the range from about 15 microns to about 250 microns in thickness and may be, if desired, pigmented, metallized or provided with a matte finish suitable for writing.

In one implementation, the substrate is preferably, though not necessarily, occlusive (i.e. "not breathing") and does not allow any active agent in the composition to pass through the layer and in contact with the mucous membranes of the mouth and chewing gum. Ready-to-use composition is pre-moistened, so that the adhesiveness is increased, and the composition should stick to the teeth. One of the advantages of this accomplished what I is the active agent may not substantially penetrate through the substrate and cause irritation of those subjects who are sensitive to the active agent or any odor or feeling.

Other suitable substrate materials can be polimernye materials such as waxes (e.g., microcrystalline or paraffin waxes) or layered material wax/foam. Paraffin waxes are low molecular weight hydrocarbons with a linear circuit with melting points of approximately 48-75°C and a molecular mass of approximately 300-1400 g/mol and are usually produced through synthesis by the Fischer-Tropsch. Microcrystalline waxes are flexible and morphophonemic and tend to possess great tensile strength and smaller size of the crystals compared to paraffin waxes. Microcrystalline waxes typically have a melting point of approximately 60-95°C and a molecular weight of approximately 580-700 g/mol and preferably contain hydrocarbons with branched chain and some ring-type connection, although there may be a hydrocarbon with a linear chain. The substrate material can also be a cellular plastic open-cell foam, such as polyurethane, polystyrene or polyethylene foam.

Alternatively, in another implementation, the substrate is what I reocclusion and therefore, to fully hydrogenate itselfin situwhen placed on the teeth or other body surface.

Interlayer for release is a disposable element, which serves to protect the system to the application. Interlayer for release should be formed from a material impermeable to the active agent and the composition of the hydrogel, and it easily separates from the contact adhesive. Layer to release usually treated with silicones or fluorocarbons and usually made of polyester and polyethylene terephthalate.

The preferred composition is usually obtained with the use of acrylic polymer as a water-insoluble, swellable polymer in water; and mixing polyvinylpyrrolidone and polyethylene glycol as a mixture of hydrophilic polymer and a complementary oligomer capable of formation of hydrogen or electrostatic ties with the hydrophilic polymer.

The adhesive film composition can be obtained by thermal melting and co-mixing the above components at temperatures ranging from about 100 to 170°C. the Film ekstragiruyut to a desired thickness on a suitable substrate. Alternatively, the components may be dissolved in a single solvent or mixture of solvents, and the solution can be poured on visualaid the General or epigastric film. The solvent then is evaporated to obtain a hydrogel film.

One way to load the composition of the active agent includes layering the desired active agent, i.e. the agent for whitening teeth, in aqueous solution on the surface of the hydrogel, located on a corresponding substrate, or the location of the active agent directly to the substrate. Release film-coating is then applied on top of the composition, forming a structure of type "sandwich", and the solution containing the bleaching agent is absorbed into the songs through his swollen properties. Alternatively, the composition nalivaika on the substrate may be pre-connected to the solution containing the desired concentration of the whitening agent, and the solution is absorbed into the composition. Measurement of the rate of weight gain by absorption in a liquid the percentage loading of the composition of the active agent can be determined and controlled.

Another approach to loading the active agent in the composition is the addition of active agent in the form of solids or in the form of a solution of the composition dissolved in the solvent. The mixture was then poured as usual on a suitable substrate and allowed to dry, although the application of this method to download the desired lower temperature drying. Composition, n is obtained in this way, can be dried at ambient temperature for a time varying from about 1 hour to several days.

Normal film thickness is from about 0.050 to 0.80 mm, preferably from 0.25 to 0.50 mm film Thickness is not crucial and may vary in accordance with the concentration of bleaching agent included in the film, the length of time during which the film is exhibited with teeth, comfort level requested by the consumer, and the degree of staining, which is desirable to correct.

V. applications

In practice, the composition can be used by simply removing the product from its packaging, remove the strip to release (when enabled) and applying an adhesive layer on the teeth you want to whiten (or put in any moist environment of the body or a wet surface, if the composition is intended for another use, or if you will use another active agent). These systems can be offered in many sizes, so that the composition may be applied to all or part of the teeth, any number of teeth at the same time or on any part of the oral cavity or other wet areas.

The substrate may be composed so as to be occlusive or impermeable to the active agent, so h is usually used to reduce or prevent leakage of the active agent from the composition, until the consumer has a composition within the desired time, i.e. the composition should then deliver the drug unidirectional, for example, only on the mucous tissue. Alternatively, the substrate may be designed so that it has a predetermined permeability in order to ensure the delivery of a medicinal product in two directions, for example, to the surface of the mucous membrane, as well as to the oral cavity. To control the relative speeds of delivery to the mucosal surface and oral cavity can also be used level of permeability, i.e. the nature of its selectivity.

The composition can be left in the desired place within such a short period of time, several minutes, several hours, all day or night and then delete after reaching the desired degree of bleaching or desired therapeutic or cosmetic effect. Alternatively, the composition can be left in place and give it to completely erode. Accordingly, in one implementation of the invention a method of whitening teeth can simply include applying the composition to needy in whitening the teeth, and in another implementation, the method may further include removing composition after reaching the desired degree of bleaching.

If this is desirable, you may be prompted to poluprozrachnaya, which is worn invisible or unnoticeable. Can also be developed without the active ingredient, which may find application as a protective coating for the surface of the oral cavity, for example, as coating the wound.

The composition can be worn for an extended period of time, but usually it should be worn within a predetermined period of time from about 10 minutes to about 24 hours, after which the composition can be removed, or it should erode. To apply for teeth whitening preferred period of time is from about 10 minutes to about 8 hours (e.g., night), and the preferred implementation is also a period of from 30 minutes to approximately 1 hour. For other active agents therapeutically or cosmetically effective time can be easily set on the basis of subject to application of the active agent, and subject to treatment status.

In one implementation, the hydrogel is a solid and is attached to the substrate during production. Accordingly, the composition is applied in one step. Alternatively, the hydrogel may be unsteady and can be produced and packaged separately from the substrate. In this case, the consumer initially applied hydro is spruce and then the outer surface of the hydrogel to the consumer applied to the substrate. In any implementation, the consumer may form a song around the upper or lower teeth or other tissue of the oral cavity using a conventional pressure on the substrate with the tips of the fingers and thumb, not necessarily by lightly wetting composition or body surface before application. Taking the surface area of the finger or thumb of an adult is equal to one square centimeter, the normal pressure created by the tip of the finger and thumb, is from about 100,000 to about 150,000 PA (i.e. approximately 3 pounds or 1.36 kg) per square centimeter. The pressure is normally supplied to the composition of the tip of each finger and thumb, lasts approximately one to two seconds. After removing the pressure on the substrate with fingertips and thumb composition remains in shape and glued to the surface of the teeth and adjacent soft tissue, on which it was generated.

When the user is ready to remove the composition, the composition may be removed by a simple peeling from the surface of the teeth or other surfaces of the oral cavity or body. If desired, the composition can be easily re-glued for extra processing time. Any residue is minimal and can be removed through the traditional way is cleaning the teeth or mouth.

In one implementation of the invention, the composition is solid, with a pressure-sensitive adhesiveness, and absorbs water.

The composition can also be applied in the form of a non-solid composition, for example, to apply a liquid or gel. For example, the user can squeeze the composition from a tube on your finger for application to the teeth or other body surface, squeeze the composition from the tube directly onto the teeth, apply the composition with a brush or other applicator, and so forth. Uroderma the substrate can then be applied as a separate stage after the application of liquid or gel. After evaporation of the solvent liquid or gel composition is dried for education is similar to the matrix of the polymer film or gel on the surface of the body. In one implementation of this liquid or gel-forming film of the hydrogel composition contains a sufficient amount of water or other solvent to give the properties of fluidity. In another implementation of the polymeric components of the liquid or gel compositions are soluble in a mixture of water with ethanol at ambient temperature, and the temperature of the refrigerator at approximately 4°C, and able to mix after evaporation of the solvent. In yet another implementation of this liquid or gel forming a film of a composition of the polymer of the first composition has a lower critical solution temperature of approximately 36°C in an ethanol water mixture. The obtained film (after evaporation of solvent) is preferably insoluble or slowly soluble in saliva at body temperature, which thereby provides continuous contact between the hydrogen peroxide and tooth enamel. Finally, the hydrogen peroxide must be stable in liquid or gel composition, and the polymeric film after drying.

In the practical implementation of the present invention should be used, if not stated otherwise, the traditional methods of polymer chemistry, manufacturing, adhesive agents, and obtain a hydrogel, which are known in the art. Such methods are fully explained in the literature.

It should be understood that although the invention has been described in connection with preferred specific implementation, the above description and the following examples are intended to illustrate but not to limit the scope of the invention. Other aspects, advantages and modifications should be obvious to experts in the art to which the invention relates.

The following examples are offered in order to provide the specialists in the art a complete disclosure and description of how to obtain and apply the compounds of the invention, but they are not intended to limit the scope of what the inventors consider the indicate as his invention. Efforts have been made to ensure accuracy in respect to numbers (e.g., amounts, temperatures, etc), but should take into account some errors and deviations. If not indicated otherwise, parts are parts by weight, temperature is expressed in degrees Celsius (°C), and the pressure is close to atmospheric.

In the examples the following abbreviations and trade names:

Eudragit L 100-55Methacrylic acid copolymer (Rohm America Inc.)
Eudragit L 100Methacrylic acid copolymer (Rohm America Inc.)
PEGThe polyethylene glycol 400
PVPKollidon® 90 polyvinylpyrrolidone (BASF)

EXAMPLES

Example 1

Preparation of solid compositions

One composition for whitening teeth can be obtained from the following ingredients using the method of extrusion melting:

Eudragit L 100-559 wt.%
PVP44 wt.%
PEG 22 wt.%
The peroxide6 wt.%
Water, stabilizers, pH modulators19 wt.%

The ingredients are melted in a simple worm extruder Brabender as follows: first, in the extruder add Eudragit L 100-55, then PVP and PEG at a temperature of from 100 to 150°C. the Composition ekstragiruyut to a thickness of 0.35 mm between the polyethylene terephthalate gasket for release and erodium substrate obtained from Eudragit S 100 with a suitable plasticizer, if necessary. To the extruded film was added a solution of hydrogen peroxide.

Example 2

Getting unsteadily composition

The composition for whitening of the teeth is obtained from the following ingredients:

Deionized waterto 35.0 wt.%
Ethanolto 35.0 wt.%
Eudragit L 100-554,00 wt.%
PEG1.00 wt.%
PVP7.00 wt.%
Carbamide peroxide180 wt.%
Sodium citrate0.13 wt.%

The composition is mixed in a laboratory mixer with high torque and low speed Cole-Parmer supplied coated with Teflon impeller (diameter 2 inches), as follows. Deionized water is mixed with ethanol and then add PEG. Then under intensive stirring sodium citrate. Slowly (over 2-5 minutes) add Eudragit L 100-55 under vigorous stirring (500-600 rpm). After approximately 5-10 minutes (not necessary to wait for the dissolution of all Eudragit) slowly (over 5 minutes), add the powder PVP. High speed mixing keep for 5-10 minutes Add the powder carbamide peroxide (within 1-2 min) and the mixture is stirred to obtain a homogeneous solution (approximately 30 minutes at 800-900 rpm). The solution is then left for 2-5 hours in order disappeared bubbles.

This teeth whitening composition can be packaged for use with erodium substrate Eudragit RL 100.

Example 3

Getting unsteadily composition

The composition for whitening of the teeth is obtained from the following ingredients:

Ethanol
Deionized waterto 35.0 wt.%
to 35.0 wt.%
Eudragit L 100-552.50 wt.%
PEG1,92 wt.%
PVP6.00 wt.%
Carbamide peroxide18.0 wt.%
Sodium citrate0.08 wt.%
Methocel A4C1.50 wt.%

The composition is mixed in a laboratory mixer with high torque and low speed Cole-Parmer supplied coated with Teflon impeller (diameter 2 inches). Deionized water is mixed with ethanol, then add PEG. Then under intensive stirring sodium citrate. Slowly (over 5 minutes), add Eudragit L 100-55 under vigorous stirring (500-600 rpm), and then slowly (over 5 minutes), add the powder Metorele A4C under vigorous stirring (500-600 rpm). After approximately 10 min slowly (over 5 minutes), add the powder PVP. High speed mixing keep for 5-10 minutes Add the powder carbamide peroxide (within 1-2 min) and the mixture is stirred to obtain a homogeneous solution (approximately 30-60 minutes at 500-Ob/min). The solution is then left for 2-5 hours in order disappeared bubbles.

This teeth whitening composition can be packaged for use with erodium substrate Eudragit RL 100.

1. Composition, including
(a) a hydrogel that includes
(i) swelling in water, water-insoluble polymer;
(ii) a mixture of hydrophilic polymer and a complementary oligomer capable of formation of hydrogen or electrostatic ties with hydrophilic polymer; and
(iii) an optional active agent; and
(b) a substrate, where the substrate includes a polymer composition which erodium in a humid environment at a slower rate than the hydrogel, where swelling in water, water-insoluble polymer and the substrate include acrylic polymers, and acrylate polymer substrate has a lower solubility than swelling in water, a water-insoluble acrylate polymer.

2. The composition according to claim 1, where the swelling in water, water-insoluble polymer is an ester of cellulose, alginic acid or acrylate polymer.

3. The composition according to claim 2, where the complex cellulose ether comprises at least one polymer of cellulose containing free monomer units of the cellulose monomer units of cellulose acetate and either monomer units of the cellulose butyrate, or monomer units of the cellulose propionate.

4. Composers who ia according to claim 2, where the acrylate polymer is selected from polymers and copolymers of acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate or ethyl methacrylate.

5. The composition according to claim 1, where the hydrophilic polymer is selected from poly(N-vinylacetate), poly(N-vinylamide), poly(N-alkylacrylate), polyacrylic acid, polymethacrylic acid, polyvinyl alcohol, polyvinylidene and their copolymers and mixtures.

6. The composition according to claim 1, where the complementary oligomer selected from polyhydric alcohols, Monomeric and oligomeric alkalophile, polyalkylene glycols terminated carboxyla polyalkyleneglycol, ending with the amino group of the polyalkylene glycols, ethers of alcohols, alkanediols and dicarboxylic acids.

7. The composition according to claim 1, where the complementary oligomer capable of forming hydrogen bonds or electrostatic ties with swelling in water, water-insoluble polymer.

8. The composition according to claim 1, where the substrate includes a material selected from acrylate polymers, polymers derived from cellulose, cellulose ethers, starches, alginic acid, alginates, polyaminoacid and their combinations.

9. The composition of claim 8, where the acrylate polymer is selected from polymers formed from acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate and ethyl methacrylate.

10. The composition of claim 8, where the polymer is a derivative of cellulose selected from the hydrate-cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethyl cellulose, sodium salt of carboxymethyl cellulose and mixtures thereof.

11. The composition of claim 8, where the complex cellulose ether selected from cellulose acetate, dual ether acetate/propionate cellulose, dual ether acetate/butyrate cellulose, cellulose propionate, cellulose butyrate, dual ether propionate/butyrate cellulose, cellulose diacetate, cellulose triacetate, and mixtures thereof, polymers and copolymers.

12. The composition of claim 8, where the starch is selected from acetate potato starch, maize starch and mixtures thereof.

13. The composition of claim 8, where the alginate is selected from propylene glycol alginate, sodium alginate, calcium alginate and mixtures thereof.

14. The composition of claim 8, where polyaminoamide selected from polylysine, polylysine, polyalanine, Protamine, and mixtures thereof.

15. The composition according to claim 1, where the relative amount of swelling in water, water-insoluble polymer, a hydrophilic polymer and a complementary oligomer is selected so as to make the hydrogel translucent.

16. The composition according to claim 1, where the hydrogel is solid.

17. The composition according to item 16, which includes about 0.1-60 wt.% the active agent.

1. The composition according to item 16, which comprises about 1-20 wt.% swelling in water, water-insoluble polymer.

19. The composition according to item 16, which includes approximately 20-80 wt.% hydrophilic polymer.

20. The composition according to item 16, which includes about 10-50 wt.% complementary oligomer.

21. The composition according to claim 1, where the hydrogel is a liquid or gel.

22. The composition according to item 21, which includes about 0.1-60 wt.% the active agent.

23. The composition according to item 21, which includes about 0.1-20 wt.% swelling in water, water-insoluble polymer.

24. The composition according to item 21, which includes approximately 1-40 wt.% hydrophilic polymer.

25. The composition according to item 21, which includes about 0.1-20 wt.% complementary oligomer.

26. The composition according to claim 1, which further includes an absorbent filler.

27. The composition according to claim 1, where the composition has a pressure-sensitive adhesion and absorbs water.

28. The composition according to claim 1, where the hydrogel erodium after approximately 1 second to 24 hours after placing in the wet environment.

29. The composition according to p, where the hydrogel erodium through approximately from 10 seconds to 8 hours after placing in the wet environment.

30. The composition according to claim 1, where the substrate erodium in a humid environment after approximately 12 to 24 hours after the AROS and hydrogel.

31. The composition according to item 30, where the substrate erodium in a humid environment after approximately 12 hours after the erosion of the hydrogel.

32. The composition according to claim 1, where the substrate erodium, at least about 25% slower than the hydrogel.

33. The composition according to p, where the substrate erodium, at least about 50% slower than the hydrogel.

34. The composition according to p, where the substrate erodium, at least about 100% slower than the hydrogel.

35. The composition according to clause 34, where the substrate erodium, at least about 200% slower than the hydrogel.

36. The composition according to claim 1, where the hydrogel is solid and attached to the substrate before applying.

37. The composition according to claim 1, where the hydrogel is a liquid or gel and is attached to the substrate during application.

38. The composition according to claim 1 where the active agent.

39. The composition according to § 38, where the substrate is impermeable to the active agent.

40. The composition according to § 38, where the substrate is selectively permeable to the active agent.

41. The composition according to § 38, where the active agent is a bleaching agent selected from the group consisting of peroxides, metal chlorite, perborates, percarbonates, nakilat and their combinations.

42. The composition according to paragraph 41, where the peroxide is selected from the group consisting of hydrogen peroxide, calcium peroxide is, peroxide, magnesium peroxide, urea and mixtures thereof.

43. The composition according to paragraph 41, where the peroxide is selected from the group consisting of dialkylamides, diarilpirimido, Nadyrov, perichromatin, ketone peroxides and hydroperoxides.

44. The composition according to paragraph 41, where the metal chlorite selected from the group consisting of chlorite calcium, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite, potassium chlorite, hypochlorite and chlorine dioxide.

45. The composition according to claim 1, further comprising flavorant.

46. The composition according to item 45, where flavorant selected from the group consisting of simalube, pepper mint, curled mint, menthol, fruit flavors, vanilla, cinnamon, spices, aromatic oils and balms and their combinations.

47. The composition according to claim 1, further comprising a sweetener selected from the group consisting of sucrose, fructose, aspartame, xylitol and saccharin.

48. The composition according to claim 1, additionally comprising at least one additive selected from the group consisting of fillers, preservatives, pH regulators, plasticizers, thickeners, dyes, pigments, paints, refractive particles, flavorants, sweeteners, stabilizers, hardening agents, reducing tackiness agents and penetration enhancers.

49. The method of teeth whitening, including
the coating composition according to claim 1 on needing whitening C the least.

50. The method according to § 49, further comprising removing composition after reaching the desired degree of bleaching.

51. The method according to § 49, where the hydrogel is solid and attached to the substrate, and where the stage of applying includes applying the composition in a single phase.

52. The method according to § 49, where the hydrogel is unsteady, and where the stage of applying includes applying a hydrogel to the teeth and the subsequent application of the substrate to the hydrogel.

53. The method according to § 49, where the composition includes a gasket for release, and the gasket to release removed before applying the composition to the teeth.

54. The method according to § 49, where the desired degree of whitening is achieved through a pre-defined period of time.

55. The method according to item 54, where the predefined period of time is from about 10 minutes to about 24 hours.

56. The method according to § 55, where a predefined period of time is from about 10 minutes to about 8 hours.

57. The method according to p, where a predefined period of time is from about 30 minutes to 1 hour.

58. The method according to § 49, where the composition can be worn for an extended period of time.



 

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1 tbl

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10 cl, 4 dwg, 3 ex

FIELD: medicine.

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17 cl, 1 tbl, 1 ex

FIELD: microbiology.

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20 cl

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19 cl, 4 ex

FIELD: medicine.

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10 cl, 6 ex, 6 tbl

FIELD: medicine.

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3 ex, 2 tbl

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22 cl, 2 ex, 1 tbl

Hand cream // 2382635

FIELD: medicine.

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1 ex

FIELD: medicine.

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31 cl

FIELD: medicine.

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3 cl, 3 dwg, 3 tbl, 11 ex

FIELD: medicine.

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57 cl, 2 tbl

FIELD: medicine.

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14 cl, 18 dwg, 26 tbl, 10 ex

FIELD: medicine.

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23 cl, 1 ex

FIELD: medicine.

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10 cl, 8 tbl, 3 ex

FIELD: medicine.

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EFFECT: local plasters containing odourless physiological coolant, and methods of application thereof.

25 cl, 3 tbl, 3 dwg

FIELD: medicine.

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15 cl, 6 tbl, 3 ex

FIELD: medicine.

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18 cl, 7 tbl, 5 ex

FIELD: medicine.

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24 cl, 11 tbl, 15 ex

FIELD: medicine.

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EFFECT: novel pharmaceutical composition and methods of its production.

39 cl, 2 tbl, 11 ex

FIELD: medicine.

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EFFECT: invention also concerns the methods of therapeutic purification and skin treatment with said compositions.

35 cl, 5 tbl, 4 ex

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