Hydrogel compositions showing separation of phases at contact with water medium

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared invention concerns hydrogel compositions useful as a dressing material or protective agent, and for application of a wide range of active substances in relation to the skin and tissues of mucosas, such as mouth, including tooth bleaches. The faza-parted, film-forming composition containing an admixture is offered: (a) the first polymer bulking up in water, and the specified polymer is not dissolved in water at pH less than approximately 5.5, or water-soluble polymer; (b) an admixture of hydrophylic polymer and additional low-molecular polymer, capable to formation of hydrogen communications with hydrophylic polymer; (c) the second polymer bulking up in water, and the specified polymer we will not dissolve in water at all value pH; and (d) unessential active substance, in a dissolvent or in an admixture of dissolvents where the composition is exposed to separation of phases at hydration.

EFFECT: treatment of a disease state of various surfaces of a body (teeth, fingernails, skin, mucosas etc).

44 cl, 7 ex

 

The technical field

This invention in General relates to hydrogel compositions. More specifically, this invention relates to hydrogel compositions, useful as bandages or protective means and for applying a wide range of active substances to the skin and tissues of the mucous membranes such as the mouth, including dental bleach.

The prior art inventions.

Change the color of teeth are common in society, and estimates inherent in two of the three adults. Change the color of teeth is considered as an aesthetic flaw or defect, and it can have negative consequences in the lives of the affected individuals, causing feelings of embarrassment and even suppress a smile. Tooth discoloration can especially cause distress and anxiety in situations and occupations where it is important to demonstrate clean white teeth.

The tooth is composed of dentin layer and the outer hard enamel layer, which is slightly porous. The outer layer is a protective layer of the tooth. Natural tooth color from opaque to translucent white or slightly yellowish. Staining of teeth occurs as a result of exposure to the teeth of compounds such as tannins and other polyphenolic compounds. These compounds are captured or bound protein layer on the surface of UPOV and can penetrate the enamel and even dentin. Sometimes staining may occur from sources in the teeth, such as tetracycline, which may be deposited in the teeth, if administered to children.

Surface stains can usually be removed mechanically when brushing your teeth. However, broken color enamel or dentin is not amenable to mechanical methods of cleaning the teeth and remove staining necessary chemical methods, which can penetrate into the structure of the teeth. The most effective treatment for discoloration of teeth is a composition containing an oxidizing agent such as hydrogen peroxide, which is capable of reacting with a chromogenic molecules responsible for the violation of the painting, and translating them or colorless or water-soluble state, or both.

Therefore, the composition for whitening teeth fall mainly into two categories: (1) gels, pastes or liquids, including toothpaste, which are mechanically mixed on the surface of the stained tooth, in order to affect the removal of dental stains (staining) using abrasive erosion of the surface of the paint; and (2) gels, pastes or liquids, which achieve the effect of tooth bleaching using a chemical process during contact with the stained tooth surface for a certain period of time, after which the composition is removed. In some cases, the additional the first chemical process, which may be oxidative or enzymatic complements the mechanical process.

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

Many peroxides are available to the developer formulations teeth whitening compositions, uses only hydrogen peroxide and its adducts or associated complexes, such as carbamide peroxide and percarbonate sodium). Chemistry of hydrogen peroxide are well known, although the specific nature of its interactions with dental Chromogens are poorly understood. It is believed that hydrogen peroxide destroys dental Chromogens oxidation of unsaturated carbon-carbon, carbon-oxygen and carbon-nitrogen linkages, are painted in molecules and, thus turning them into a discolored or soluble state.

A related class of compounds, peroxyacids, used in washing detergents for effective whitening service, the chief of the time because of their stability in solution and their specific ability to bind with specific types of colored molecules. Used a number of stable solid peroxyketal, including depreciationof acid and a magnesium salt monoperoxyphthalic acid. Other peroxyacids, such as peracetic acid, is available in the form of solutions containing the equilibrium quantity of acetic acid, hydrogen peroxide, peracetic acid and water. Alternatively, the peroxide donor, such as perborate sodium or percarbonate sodium, add in the recipe along with the predecessor peroxyacids. In contact with water, peroxide donor releases hydrogen peroxide, which then reacts with the precursor peroxyacids with the formation of the actual peroxyacids. Examples of peroxyketal formedin situinclude peracetic acid from hydrogen peroxide and tetraacetylethylenediamine) and proxynodename acid from hydrogen peroxide and nanoelectromechanical).

Peroxyacids also used in compositions for the care of oral hygiene to whiten stained teeth. In US patent No. 5279816 Church et al. describes a method of whitening teeth comprising applying the composition containing peracetic acid, having an acid pH. EP 545594 A1 Church, and the other describes the use of peracetic acid in the manufacture of a composition for whitening teeth. Peroxyacids may be present in the composition or alternatives is about, may formin situby combining peroxide with the predecessor peroxyacids during use. For example, US No. 5302375 Viscio describes the composition, which forms peracetic acid in the mediain situby combining water, acetylsalicylic acid and water-soluble percarbonates alkali metals.

The most widely used substance for whitening teeth is carbamide peroxide (CO(NH2)2·H2O2), also called urea hydroperoxide, hydroperoxidation and perhydrol-urea. Carbamide peroxide was used dentists few decades as an antiseptic for the mouth and teeth whitening was found as a side effect of prolonged contact time. Nonprescription composition of 10% carbamide peroxide is available as GLY-OXIDE®from Marion Laboratories and PROXIGEL®from Reed and Carnick, which is a composition with a low viscosity, which should be stored in a tray or similar capacity, to ensure contact with the teeth. The whitening gel, which can be stored in a convenient dental tray in position for long periods of time, available under the trademark OPALESCENCE®from Ultradent Products, Inc. from South Jordan, Utah.

To such compositions were willing to work, this is the song must be a viscous liquid or gel. The use of dental trays also requires that the tray was adapted for the convenience and adjusted so that the tray had no pressure or did not cause irritation of the teeth or gums of the patient. Such bleaching compositions must be made so that they were quite sticky and viscous to resist dilution by saliva.

In one method of teeth whitening of the individual, the dentist will design custom-made dental tray for whitening patient imprint location of the teeth of the patient and prescribes the use of oxidizing gel, which should be distributed in the tray for whitening and run periodically in a period of 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 distributed directly by the patient in a custom-made dental tray for teeth whitening that is maintained in place in the mouth during the time of contact is less than about 60 minutes, and sometimes 8-12 hours. Slow speed whitening in large measure it is a consequence of precisely the nature of the formulations, which are designed to ensure the stability of the oxidizing compositions.

For example, US No. 6368576 Jensen teeth whitening composition which preferably is used with the tray so that the composition contains at the position adjacent to the treated surfaces of the teeth of the patient. These compositions are described as adhesive matrix material formed by combining a sufficient number of enhancing the adhesion of a substance, such as carboxypolymethylene with a solvent, such as glycerine, glycol, or water.

In another example, US No. 5718886 Pellico describes a teeth whitening composition in the form of a gel composition containing carbamide peroxide dispersed in anhydrous gelatin carrier, which contains a polyol, xanthan thickener and resin.

Another example is described in US no 6419905 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 fluoride salt (0.15 to 3%), compiled in the form of a gel, which contains from 0.5 to 6 weight. % suitable gelling.

Composition for whitening teeth that stick to the teeth described in US no 5989569 and No. 6045811 Dirsking. According to these patents gel containing 30-85% glycerol or polyethylene glycol, 10-22% of the complex of urea and hydrogen peroxide, 0-12% carboxypolymethylene, 0-1% sodium hydroxide, 0-100% triethanolamine (tea), 0-40% water, 0-1% flavorant, 0-15% sodium citrate and 0-5% ethylenediaminetetraacetic acid. The preferred gel is according to Dirksing, has a viscosity between 200 and 1,000,000 CP at low shear rates (less than 1 s-1), and adhesion sufficient to eliminate the need of the tray.

Currently available compositions for whitening teeth have an important drawback, namely that they cause sensitisation teeth in more than 50% of patients. Tooth sensitivity can be caused by the movement of fluid through dentinal tubules that you can feel the nerve endings in the teeth due to the presence of glycerol, propylene glycol and polyethylene glycol in these compositions. This can lead to changes in sensitivity of the teeth exposed to heat, cold, overly sweet and other substances causing substances.

Prolonged exposure to bleaching compositions to the teeth, as practice shows, has a number of adverse consequences, in addition to tooth sensitivity. These adverse effects include the leaching of calcium from the enamel layer at pH below 5.5, the penetration of bleaching agents in intact enamel and dentin with the risk of damage to the pulp and dilution of the bleaching compositions of saliva, leading to leaching from dental tray with subsequent swallowing by the patient.

Some oxidizing composition (mainly with relatively high con is entrale oxidants) are applied directly to the surface of the patient's teeth in the dental office under the supervision of a dentist or dental hygienist. Theoretically, this strategy of teeth whitening gives you faster results and more satisfied patient. However, due to the high concentration of oxidants contained in the so-called “outpatient” compositions, they can be dangerous for the patient and also for the practicing Clinician, if applied carelessly. The soft tissue of the patient (gums, lips and other mucosal surface) must first be isolated from the potential impact of active oxidants with perforated rubber place (known as a rubber gasket), so that was out (it was) only the teeth. Alternatively, the soft tissue can be isolated from oxidizing agents which are used in the bleaching process by coating the soft tissues of the polymerized composition that takes the contours of the gums, and then hardens under the influence of a light source of high intensity. Once the soft tissue is isolated and protected, a practicing Clinician may cause oxidant directly on the surface of the teeth with broken color for a certain period of time or until will not occur until a sufficient staining teeth. Typical results obtained using outpatient bleach teeth correspond to the hue in the range of about 2-3 (smerenney on a scale of shades VITA, VITA Zahnfarbik).

The range of shades of teeth on the scale of VITA shades ranging from very light (B1) to very dark (C4). A total of 16 shades of teeth comprise the full range of colors between these two endpoints on the brightness scale. Patient satisfaction with the procedure of teeth whitening increases with the achieved change rooms shade of teeth, and an acceptable minimum change preferably is about 4 to 5 shades VITA.

With regard to care for your teeth intended for teeth whitening, it is desirable to provide dental care products, using adhesive (adhesive) hydrogels that contain bleach to remove stains with individual teeth. In addition, there is a continuing need to develop means of providing protective dressing materials (coatings) or a protective agent for the skin and the surface of mucous membranes or delivering active substances, for example the delivery of substances through the skin and mucous membrane to the skin, mucous membrane, teeth, gums, mucous membranes and other tissues of the oral cavity. Desirable compositions that do not require the use of dental trays to ensure contact between the current (active) substance and teeth or other surfaces of the oral cavity. Such cf is DSTV ideally would cause minimal or does not cause tooth sensitivity, to minimize or eliminate leakage of the active substance, which leads to its ingestion by the user or damage to or irritation of the gums or mucous membranes membranes in the mouth, to provide a longer wearing time, long-term (slow) dissolution of the active substance, superior efficacy and better tolerability by patients. It would also be desirable to provide a means of caring for the 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 when dry. The present invention is directed to solving these needs.

Disclosure of invention

One aspect of the invention relates to compositions, including: swelling in water, water-insoluble polymer or a water-soluble polymer; and a mixture of hydrophilic polymer and complementary oligomer capable of forming hydrogen bonds or electrostatic ties with the hydrophilic polymer. Can also be enabled active substance such as bleach for teeth. In one embodiment, the composition also includes a second swelling in water, water-insoluble polymer that is different from the first nabukelevu in water, insoluble in the e polymer or water-soluble polymer characteristics pH solubility.

Another aspect of the invention relates to phase-separate, film-forming composition, comprising: first of swelling in water of the polymer that is not soluble in water at pH less than about 5.5, or water-soluble polymer; a mixture of hydrophilic polymer and optionally oligomer capable of hydrogen bonding with the hydrophilic polymer, the second swellable in water polymer which is not soluble in water under all pH values; and optional active substance. The composition undergoes a phase separation immediately after use, leaving behind a number of film layers.

In a preferred embodiment, the first swelling in water, the water-insoluble polymer is a polymer or copolymer based on acrylate; hydrophilic polymer is a poly(N-vinylacetal), poly(N-vinylamide), poly(N-alkylacrylate), or a copolymer and a mixture thereof; an additional oligomer capable of hydrogen bonding to the hydrophilic polymer is polyalkyleneglycol or polyalkyleneglycol with terminal carboxyl group; a second swelling in water, water-insoluble polymer is a cellulose ether, or a polymer or copolymer based on acrylate. The preferred active agent is a bleach, such as hydrogen peroxide.

The composition is optional VK is uchet low molecular weight plasticizer and may also include at least one additional substance, selected from the group consisting of flavorants, sweeteners, fillers, preservatives, pH regulators, softeners, thickeners, coloring agents (for example, pigments, dyes, refractive particles, flavorants (for example, sweeteners, flavorants), stabilizers, surfactants, additives, providing durability and substances to reduce the stickiness.

In a preferred method of use of the composition, the composition is a composition for whitening teeth, and it is applied to the teeth that need whitening, and then removed when the degree of whitening is achieved. In a specific embodiment, the tooth whitening composition is translucent, and the composition is removed when the user is satisfied with the degree of progress of bleaching.

Another aspect of the invention relates to compositions, including the first swellable in water, not water-soluble polymer or water-soluble polymer; the second swelling in water, not water-soluble polymer; a mixture of hydrophilic polymer and complementary oligomer capable of hydrogen bonding to the hydrophilic polymer; and a substance selected from the group consisting of peroxides, metal chlorite, perborates, percarbonates, peroxyketal, and combinations thereof.

Another aspect of the invention regarding the seeking to the way to obtain hydrogenio film, suitable for inclusion (introduction) in the product for the care of the oral cavity, which provides transmucosal or transdermal composition or system. This method includes obtaining a solution or gel of the first, swelling in water, not the water-soluble polymer or the water-soluble polymer; the second, swelling in water, the water-insoluble polymer; a hydrophilic polymer; and complementary oligomer capable of hydrogen bonding or electrostatic bonding to the hydrophilic polymer in the solvent; the deposition of a layer on the substrate to provide thereon the coating, heating the coated substrate to a temperature in the range of from about 80°to about 100°C for a period from about 1 hour to about 4 hours, thus providing hidrogeno film on the substrate.

In another method of forming the composition of the invention, the method includes processing the melt through the extruder the mixture of the first, swelling in water, not the water-soluble polymer or the water-soluble polymer; the second, swelling in water, the water-insoluble polymer; a hydrophilic polymer; and complementary oligomer capable of hydrogen bonding or electrostatic bonding to the hydrophilic polymer with the formation in extruded polystyrene (extruded) composition; which is nosily ekstragiruyut in the form of a film of the desired thickness on a suitable substrate.

The method further includes loading hydrogenio film active substance such as bleach, the resulting composition for bleaching (tooth whitening composition).

The adhesive compositions of the invention provide several significant advantages relative to prior art. In particular, the present composition:

1) provide easy handling;

2) is easily modified in the production process, so that properties such as adhesion, absorption, x-raying and swelling can be controlled and optimized;

3) can be made so that the adhesiveness is increased or decreased in the presence of moisture, so that the composition does not stick to hydrate;

4) minimize the leakage of the active substance, when it is introduced, from the composition to the surface of the skin or mucous membranes (e.g. mouth of the user);

5) can be performed in a translucent form, allowing the user to see the degree of whitening without removal of the hydrogel compositions with teeth or skin/mucosal surface;

6) minimize damage to the gums or mucous membranes in the mouth;

7) can be worn comfortably and unobtrusively;

8) is easily removed from the teeth or skin/mucosal surface and leave no residue

9) are pliable for longer wear or actions; the

10) can provide long-term (slow and controlled release of different active substances.

A detailed description of the invention.

I. definition and nomenclature the names.

Before describing the present invention in detail it is necessary to understand that unless otherwise stated, the invention is not limited to specific Hydrogenium materials or manufacturing processes. It must also be understood that the terminology used here is only the description of particular embodiments and is not intended to be limitations. It should be noted that as used in the description and the claims, the singular number include plural references, until the context clearly does not prescribe otherwise. Thus, for example, reference to “hydrophilic polymer” includes not only one hydrophilic polymer, but also a combination or mixture of two or more different hydrophilic polymers, reference to “plasticizer” includes not only one plasticizer, but also a combination or mixture of two or more different plasticizers, etc.

In the description and claims of the present invention is used terminology in accordance with the definitions below.

The definition of “hydrophobic” and “hydrophilic polymers based on kolichestvennogo pair, absorbed by the polymer at 100% relative humidity. According to this classification, hydrophobic polymers absorb only up to 1 weight. % of water at 100% relative humidity (“RH”), whereas moderately hydrophilic polymers absorb 1-10 weight. % of water, hydrophilic polymers capable of absorbing more than 10 weight. % water and hygroscopic polymers absorb more than 20 weight. % of water. “Nabuhay in the water” polymer is a polymer which absorbs water in an amount above at least 25 weight. % of its own weight, preferably at least 50 weight. % of its own weight when immersed in the aquatic environment.

The term “cross-linked” here refers to compositions containing intramolecular and/or intermolecular cross-links arising from covalent or non-covalent binding. “Non-covalent linkage comprises hydrogen binding and electrostatic (ion) binding.

The term “polymer” includes linear and branched polymeric structure, and also covers cross-linked polymers and copolymers (which can be stitched or unstitched), including thus the copolymers, alternating copolymers, random copolymers and the like. Those compounds, which are referred to here as “oligomers”, are polymers having a molecular the popular weight below about 1000 daltons, preferably below about 800 daltons.

The term “hydrogel” is used in the conventional sense of swelling in water of the polymer matrix, which can absorb significant amounts of water with the formation of an elastic gel, where the matrix is a three-dimensional grid of macromolecules held together by covalent or non-covalent cross-links. When placed in an aqueous environment dry hydrogels swell to the extent permitted by the degree of crosslinking.

“Phase” is traditionally defined as a homogeneous part of a heterogeneous system. “Phase separation” is a transformation of the homogeneous system in a heterogeneous. Usually the process of phase separation is accompanied by the formation of interfacial boundaries between phases of different composition. Typical examples of phase separation include transitions Sol-gel, precipitation from solution or spontaneous formation of multi-layer (laminar) structure.

The terms “active agent”, “pharmacologically active agent” and “drug” are used here interchangeably to refer to a chemical material or compound that induces (causes) the desired pharmacological, physiological effect, and includes agents that are therapeutically effective, prophylactically effective and or cosmetically effective. The term also includes pharmaceutically acceptable, pharmacologically active derivatives and analogs of such active substances, separately mentioned herein, including, but not limited to, salts, esters, amides, prodrugs, active metabolite, inclusion complexes, analogs and the like. When the terms “active agent”, “pharmacologically active agent” and “drug”, it should be clear that are included as active agents per se (in itself), as well as pharmaceutically acceptable, pharmacologically active salts, esters, amides, prodrugs, active metabolite, inclusion complexes, analogs, etc.

The term “composition for tooth whitening” refers to a composition that contains a hydrogel as defined here, and bleach.

The term “bleach” generally refers to the oxidizer such as peroxide or chlorite that detail will be discussed below. In some cases, bleach can be an enzyme or other catalytic agent to remove stains on teeth. Bleach may include one or more additional bleaching agents, surfactants, anti-plaque, anti-Tartar and abrasive materials. Bleach, may have an additional terap ticheskie useful actions.

The term “effective amount” or “cosmetically effective amount” cosmetically active substance is meant a nontoxic but sufficient to provide the desired cosmetic effect, the number of cosmetically active substances. The term “effective amount” or “therapeutically effective amount” of a drug or pharmacologically active substance is intended to refer to a nontoxic but sufficient to provide the desired therapeutic effect of the amount of the drug or substance. The amount that is “effective”will vary from subject to subject, depending on age, General condition of the patient, the specific active substance or substances and the like. Thus, it is not always possible to accurately determine the “effective amount”. However, an appropriate “effective” amount in any individual case may be determined by the person skilled in the art by conventional experimentation. Moreover, the exact “effective” amount of active substance incorporated in the composition or dosage form of the present invention has no critical values as long as the concentration is within sufficient to deliver the quantity of the active substance, which is within therapeutic effect of the main range, to allow the use of the recipe.

The term “surface” as the combined surface of the mouth”, or “body surface” includes a body surface such as skin, nails and mucous membranes (e.g., sublingual, buccal, vaginal, rectal, urethral), as well as the surface in and around the oral cavity (e.g., teeth, lips, gums, mucous membranes), as well as surface wounds on the skin.

Drug delivery through the skin and through mucous membranes” means the application of medication to the surface of the skin or mucous membranes of a person, so that the drug passes through the skin and tissue of the mucosa and into the bloodstream, thereby promoting the overall effect. The term “through the mucous membranes” means the application of drugs to the surface of the mucous membrane (e.g., sublingual, buccal, vaginal, rectal, urethral) person, so that the drug passes through the mucosa and into the bloodstream. The terms “through the skin and through mucous membranes comprise both local and General effects, and therefore include topical application, i.e. the local delivery agent to the skin or mucous as, for example, when processing the various disorders of the skin and mucous membranes to obtain a local effect.

The term “stickiness” and “sticky” are qualitative. However, the terms “the society is not sticky”, “a bit sticky” and “sticky”as used herein may be characterized quantitatively using values obtained by the method of determining the stickiness according to PKI or TRBT, as set forth below. By “essentially no adhesive” refers to a hydrogel composition that has a value of stickiness less than about 25 g-cm/c, under “a bit sticky” refers to a hydrogel composition that has a value of stickiness in the range of from about 25 g-cm/sec to about 100 g-cm/sec, and under the “sticky” refers to a hydrogel composition that has a value of stickiness at least 100 g-cm/c.

The term “water-insoluble” refers to a compound or composition whose solubility in water (measured in water at 20oC) is less than 5 weight. %, preferably less than 3 weight. %, more preferably less than 1 weight. %. Similarly, the term “water-soluble” refers to a compound or composition whose solubility in water (measured in water at 20oC) exceeds 5 weight. %, preferably greater than 3 weight. %, more preferably greater than 1 weight. %.

The term “translucent” is used here to denote a material that can transmit light so that through him visible objects or images. Translucent material here may or may not be transparent is, meaning that the material is optically transparent. The term “transparent” indicates that the material is not “opaque”, in this case, objects and images may not be visible through the material.

II. Composition

The composition according to this invention consists of Vodonaeva, water-insoluble polymer or a water-soluble polymer, a mixture of hydrophilic polymer and complementary oligomer capable of hydrogen bonding with the hydrophilic polymer, and an optional active agents, such as bleach. The composition also includes a second vodosnabzhenie, water-insoluble polymer. In certain embodiments implement one or both vodonapornyh, water-insoluble polymers can also form hydrogen bonds with the hydrophilic polymer. Similarly, in certain embodiments implement one or both of the water-soluble polymer and Vodonaeva, water-insoluble polymer can also form hydrogen bonds with the hydrophilic polymer.

In one embodiment, not solid compositions of the present invention, the first vodosnabzhenie, water-insoluble polymers or water-soluble polymers) and the second vodosnabzhenie, water-insoluble polymer is about 0.1-20 weight. %, preferably about 4-15 weight. % of the composition; hydrophily polymer is about 1-30 weight. %, preferably about 5-25 weight. % of the composition. In another embodiment, not solid composition of the invention, the first vodosnabzhenie, water-insoluble polymers or water-soluble polymers) and the second vodosnabzhenie, water-insoluble polymer is about 1-30 weight. %, preferably about 5-25 weight. % of the composition; and the hydrophilic polymer is about 0.1-20 weight. %, preferably about 4-15 weight. % of the composition. The active substance when it is present, may be approximately 0.1-60 weight. %, preferably about 1-40 weight. % of the solid composition. Additional oligomer may be about 0.1-20 weight. %, preferably about 0.5-10 weight. % of the solid composition. Optimally, additional oligomer is about 1-85 weight. %, preferably about 5-50 weight. % of a mixture of the hydrophilic polymer/complementary oligomer in non-solid composition.

In one embodiment, the solid composition of the present invention, the first vodosnabzhenie polymer or water-soluble polymer) and the second vodosnabzhenie water-insoluble polymer is about 1-20 weight. %, preferably about 6 to 12 weight. % of the composition; and the hydrophilic polymer is about 20-80 weight. %, preferably approx the positive 40-60 weight. % of the composition. In another embodiment, the solid composition of the invention, the first vodosnabzhenie polymer or water-soluble polymer) and the second vodosnabzhenie, water-insoluble polymer is about 20-80 weight. %, preferably about 40-60 weight. % of the composition; and the hydrophilic polymer is about 1-20 weight. %, preferably about 6 to 12 weight. % of the composition. The active substance when it is present, may be approximately 0.1-60 weight. %, preferably about 1-30 weight. % of the solid composition. Additional oligomer may be about 10-50 weight. %, preferably about 15-35 weight. % of the solid composition. Optimally, additional oligomer is about 10-80 weight. %, preferably about 20-50 weight. % of a mixture of the hydrophilic polymer/complementary oligomer in the solid composition.

In one embodiment, the composition is a tooth whitening composition, where the function of bleach consist of whitening a tooth surface to which is applied a composition. However, bleach can have other applications, for example, as a therapeutic agent or cosmetic agent of another type, for example for skin lightening. Consequently, the compositions described herein can find use what begins as pharmaceutical compositions which can be applied to the surface of the body (e.g., teeth, nails, skin, mucous membranes, etc.) for the treatment of painful conditions. For example, hydrogen peroxide also has an antiseptic property and property against acne, as well as a whitening agent. Therefore, the invention also involves the treatment of infection or acne by applying the composition containing hydrogen peroxide of the present invention on the surface of the body. Other painful conditions include, for illustration and not for limitation, a fungal infection (mycosis), acne, wounds, skin whitening and so on. In addition, a number of active substances may be included in the composition of the present invention to treat a variety of diseases affecting the oral cavity.

A. Swelling in water, water-insoluble polymers and water-soluble polymers.

First of swelling in water, water-insoluble polymer is part of the composition in contact with the superficiality of the body and is used, for example, to ensure adhesion properties or regulation swelling and dissolving properties. The second swelling in water, water-insoluble polymer serves to provide a protective film layer over a layer in contact with the body surface.

The first and second swelling in water, water-insoluble polymers can be of the underwater and the same basic class of polymers, but each will be selected so that they had different characteristics solubility in water environment. The first polymer is selected so that it was insoluble in water, i.e. water, in a selected range of pH, typically at pH less than about 5.5, i.e., the first polymer has a pH-dependent solubility. The first polymer will generally be dissolved in water at pH greater than 5.5. The second polymer is selected so that it was insoluble in water at all pH values, i.e. the second polymer has a pH-independent insolubility. Thus, when the composition is added in an aqueous environment, such as at pH 6-8, which is characteristic of the oral cavity, phase separation occurs between the first polymer which is soluble at high pH) and the second polymer. This leads to the formation of the film of the second swelling in water, water-insoluble polymer over the film of the first polymer/hydrophilic polymer/complementary oligomer.

External film formed by the second polymer, insoluble in water, but remains permeable. Over time, the underlying film layer is dissolved, and the outer film may be either removed, or if left for a long period of time, it breaks down into tiny particles, which are gradually washed away, for example, saliva. Removal as the underlying p is Enki, and external film can contribute to soft wipe with a toothbrush or fingers of the user.

The weight ratio of the first and second swelling in water, water-insoluble polymer may be in the range of about 1:3-3:1. In a preferred embodiment, the ratio is in the range of about 1.5:1-2:1.

The first and second swelling in water, water-insoluble polymers are polymers that can swell when immersed in water liquid. Polymers mainly swell by at least 25 wt.% and preferably at least 50 wt.% from their own weight when immersed in water or an aqueous solution. In some embodiments, the implementation of which use certain hydrophilic polymers, the composition may swell more than 1400 wt.% from its dry weight.

1. First of swelling in water of water-insoluble polymer.

The adhesion profile can be modeled based on the type of polymer, the first polymer, the composition ratio and the amount of water in the mixture. First of swelling in water, water-insoluble polymer is selected to provide the desired adhesion profile in relation to hydration. Ie provided a composition, which, as a rule, does not inherently tacky prior to contact with water, but becomes sticky upon contact with the wet surface.

First of swelling in water of water-insoluble polymer capable at least to some extent to swell when immersed in liquid water, but not dissolved in water at pH less than about 5.5, at the same time dissolves at higher pH values observed in the mouth.

First of swelling in water of water-insoluble polymer may be a polymer or copolymer based on acrylate, i.e. a polymer or copolymer of acrylic acid or acrylic ester (“acrylate” polymer).

Acrylate polymers are particularly suitable for use as the first swelling in water of the polymers and in General, they are formed from acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, and/or other vinyl monomers. Suitable acrylate polymers are copolymers available under the trade name “Eudragit” from Rohm Pharma (Germany). Eudragit® E-series, L, S, RL, RS and NE copolymers available as solubilization in an organic solvent, aqueous dispersion or as a dry powder. Preferred acrylic polymers are copolymers of methacrylic acid and methyl methacrylate, such as a series of polymers Eudragit L and Eudragit S. Particularly preferred copolymers Eudragit L 30D-55 and Eudragit L 100-55 (the latter copolymer is dried by spraying Eudragit L 30D-55, the cat is who can be restored water). Molecular weights of copolymers Eudragit L 30D-55 and Eudragit L 100-55 is approximately 135000 daltons and a ratio of free carboxyl groups to ester groups is approximately 1:1. The copolymer Eudragit L 100-55 practically insoluble in liquids, water-based, having a pH below 5.5, and, therefore, particularly well suited for use as the first Vodonaeva polymer. Another particularly suitable copolymer of methacrylic acid and methyl methacrylate is Eudragit S-100, which differs from Eudragit L 30D-55 the fact that the ratio of free carboxyl groups to ester groups it is approximately equal to 1:1. Eudragit S-100 insoluble at pH below 5.5, but unlike Eudragit L 30D-55 poorly soluble in liquids, water-based, having a pH in the range from 5.5 to 7. This copolymer is soluble at pH 7 and above. You can also use Eudragit L 100, which has a pH-dependent solubility profile between the profiles of Eudragit L 30D-55 and Eudragit S-100, to such an extent that it is not soluble at pH below 6. The specialist in this area will be clear that Eudragit L 30D-55, L 100-55, L 100 and S 100 can be replaced by suitable other polymers having similar dependence of solubility on pH.

Other suitable polyacrylates are copolymers of methacrylic acid and ethyl acrylate available under the name “Kollicoat” from BASF AG (Germany). For example, Kollicoat MAE has come akuu same molecular structure, as Eudragit L 100-55.

When the first vodosnabzhenie polymer is a polyacrylic acid or polyacrylate, provides a hydrogel, which may be reversible dried, for example, after removal of water and any other solvent, the dried hydrogel can restore its original state by adding water. In addition, hydrophilic hydrogel made with Vodonaeva polymer based on polyacrylic acid/polyacrylate, as a rule, does not inherently tacky prior to contact with water, but becomes sticky in contact with a moist surface, such as inside the mouth, such as the surface of the teeth. This property not be sticky to contact with water allows you to place or re-placed on the selected surface before or when the hydrogel becomes sticky. Being gidratirovannym, the hydrogel becomes sticky and adheres to the tooth surface or skin/mucosal surface.

In addition, galatsaray composition, as a rule, can provide a swelling in the range of about 400%-1500% when immersed hydrogel composition in water or other water-based 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 chosen so that the rate and extent nabahani is in an aqueous environment has a predefined pH-dependence. This feature also provides retroactive inclusion of bleaching agents or other active substances, for example, loading a song peroxide, peroxynitrate, chlorite, stabilizers, flavorants etc.

The inclusion of the cellulose ether as one of vodonapornyh polymers, on the contrary, leads the hydrogel in a tacky condition to be applied on a wet surface, and not sticky upon absorption of water. It is clear that this composition would be desirable, when reducing the stickiness, it is desirable to completely remove the tool from the teeth.

2. Water-soluble polymers

Suitable water soluble polymers include, as an illustration, but are not limited to, water-soluble polymers based on cellulose, polyvinyl alcohol, collagen, a naturally occurring polysaccharides.

Examples of water-soluble polymers based on cellulose include hydroxypropylcellulose, hydroxyethyl cellulose, methylcellulose, hypromellose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydrocellulose (cellophane) and hypromellose.

Examples of naturally occurring polysaccharides include agars of different origin, such as dekstrinovym agar, alginates such as alginic acid, alginic acid salts (for example, alginate calcium, al is inat potassium, sodium alginate and derivatives of alginic acid (propilenglikolstearat, Kelcoloid®, Monsanto), carragenan, including Kappa-, iota - and lambda-carrageenan, chitin, chitosan, glucomannan, Gellan gum (Kelcogel®, Monsanto), gelatin, guar gum (TIC Gums), gum Arabic, homegate, gommitalia, tragacanth gum, resin plodotvornogo tree, pectins, such as pectin and amylopectin, pullulan, starch and derivatives of starch such as potato starch acetate, Clearam®CH10, Roquette, tamarind gum, xanthane, such as xanthan gum and combinations thereof.

3. Second vodosnabzhenie water-insoluble polymer

Second vodosnabzhenie water-insoluble polymer capable at least to some extent to swell when immersed in the water-based liquid but insoluble in water at all pH values.

Second vodosnabzhenie water-insoluble polymer may be a polymer of cellulose, a cellulose ether, a polymer or copolymer based on acrylate, that is, a polymer or copolymer of acrylic acid or esters of acrylic acid (“acrylate polymer). The second polymer may also to some extent to provide the desired adhesion to phase separation. For example, when the second polymer is a cellulose ether, the song in General has a stickiness to contact with water (the EU is ü wet surface), but gradually loses its stickiness, when the composition absorbs moisture. When the second polymer is an acrylate polymer or copolymer, is obtained a composition which, as a rule, essentially has no stickiness to contact with water, but becomes adhesive in contact with the wet surface.

Typical cellulose ethers include, for example, acetate cellulose, acetate-propionate, cellulose (CAP), acetate-butyrate cellulose (CAB), acetate-cellulose phthalate, cellulose propionate (CP), cellulose butyrate (CB), propionate-butyrate cellulose (CPB), cellulose diacetate (CDA), cellulose triacetate (CTA) or similar. These cellulose ethers are described in US№ 1698049, 1683347, 1880808, 1880560, 1984147, 2129052 and 3617201, and can be obtained by methods known in this field, or obtained commercially. Commercially available esters suitable here include CA 320, CA 398, CAB 381, CAB 551, CAB 553, CAP482, CAP 504, all from Eastman Chemical Company, Kingsport, Tenn. Such cellulose ethers are usually srednecenovogo molecular weight of from about 10,000 to about 75000.

Typically, the cellulose ether comprises a mixture of cellulose and celluloseand of monomer units, for example, commercially available acetate-butyrate cellulose contains monomer units of the cellulose acetate, and monomer units of the cellulose butyrate and monomer units neeterificirovannah cellulose, whereas acetate-prop is ONAT pulp contains monomer units, as cellulose propionate. Preferred cellulose ethers are compositions based on acetate-propionate cellulose acetate-butyrate cellulose, containing butyryl-, propionyl, acetyl - and neeterificirovannah (OH) cellulose in amounts shown below:

Acetyl
(%)
OH
(%)
mm
g/mol)
Tstack
(C)
Tthe Plava
(C)
Acetate-butyrate cellulose17-52% butyratea 2.0 to 29.511,1-4,812000 - 7000096-141130-240
Acetate-propionate, cellulose42,5-47.7% of the propionate0,6-1,51,7-5,015000-75000142-159188-210

Also shows the preferred molecular weight, the glass transition temperature (Tglass) and melting temperature (Tthe Plava). Suitable cellulosic polymers typically have characteristics the Yu viscosity (I.V.) of approximately 0.2 to approximately 3.0 DL/g, preferably from approximately 1 to approximately to 1.6 DL/g as measured at 25°C on a sample of 0.5 g in 100 ml of a phenol/tetrachlorethane 60/40 by weight. In the case of manufacturing a molding method by dipping in the solution, vodosnabzhenie water-insoluble polymer should be selected so as to provide greater traction force and, thus, to ensure the formation of film in General, for example, acetate-propionate, cellulose tends to improve the bond strength to a greater extent than the acetate-butyrate cellulose).

Typical cellulosic polymers include, for example, methylcellulose and ethylcellulose.

Acrylate polymers are also particularly suitable for use as a second vodonapornyh polymers, and these include the above-described polymers Eudragit®and Kollicoat. However, for use as a second vodonapornyh polymers choose acrylate polymers whose solubility depends on pH. There are numerous pH-independent polymers in the series of Eudragit®RL and Eudragit®RS, including RL 30D, RL PO, RL 100, RS 30D, RS PO and RS 100. Eudragit®RL 100 and RS 100 copolymers are particularly suitable for use as the second Vodonaeva polymer.

B. Hydrophilic polymers

The second component of the hydrogel composition is a mixture of hydrophilic polymer and additional olig the measure, capable of hydrogen bonding with the hydrophilic polymer and, optionally, also capable of ionic or covalent bonding with the hydrophilic polymer. Hydrophilic polymer, as a rule, is a polymer with a relatively high molecular weight, and the complementary oligomer, as a rule, is a polymer with a lower molecular mass.

Suitable hydrophilic polymers contain repeating units derived from the monomer N-vinylacetate, carboxyvinyl monomer, a vinyl ester monomer, ester carboxyvinyl monomer, vinylamide monomer and/or hydroxyquinolines monomer. As an example, we note that such polymers include poly(N-vinylacetate), poly(N-vinylacetate), poly(N-alkylacrylate), substituted and unsubstituted polymers of acrylic and methacrylic acids (e.g., polyacrylic and polymethacrylic acid), polyvinyl alcohol (PVA), polyvinyliden, their copolymers, copolymers with other types of hydrophilic monomers (e.g. vinyl acetate).

Poly(N-vinylacetate)used here, preferably are not cross-linked homopolymers or copolymers of units of the monomer N-vinylacetate, and monomer units of N-vinylacetate constitute a large part of the links of copolymers of poly(N-vinylacetate). Preferred for use in esteem the invention poly(N-vinylacetate) is produced by polymerization of one or more of the following monomers based on N-vinylacetate: N-vinyl-2-pyrrolidone, N-vinyl-2-valerolactam, N-vinyl-2-caprolactam. Non-limiting examples of N-vigilantly of comonomers used with monomer units of N-vinylacetate 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, polymethacrylamide and poly(N-izopropilakrilamid) (PNIPAM).

Polymers based on carboxyvinyl monomers usually formed from acrylic acid, methacrylic acid, crotonic acid, isocrotonic acid, basis of itaconic acid and anhydride, 1,2-dicarboxylic acids such as maleic and fumaric acid, maleic anhydride or mixtures thereof, preferably hydrophilic polymers of this class include 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), especially polyacetate, polymers of carboxyvinyl monomers, especially polyacrylic acid and polymethacrylic acid, copolymers and mixtures thereof. PVP and PVCap especially preferred.

Molecular the ACCA hydrophilic polymer is not critical, however, Brednikova molecular weight hydrophilic polymer, typically is in the range of about 100000-2000000, more typically in the range of about 500000-1500000. The oligomer is “additional” to the hydrophilic polymer in that it is capable of forming hydrogen bond with him. Preferably, additional oligomer contains at the end of hydroxyl group, amino group and carboxyl group. The oligomer typically has a glass transition temperature Tgin the range from about -100°C to about -30°C and the melting temperature Tmlower than approximately 20°C. the Oligomer may also be amorphous. The difference between the values of Tghydrophilic polymer and oligomer preferably greater than approximately 50°C, more preferably greater than approximately 100oC and most preferably is in the range from approximately 150°C to about 300°C. the Hydrophilic polymer and additional oligomer must be compatible, that is capable of forming a homogeneous mixture, which shows one Tgintermediate between the values of the unmixed components.

C. Additional oligomer

As a rule, additional oligomer will have a molecular weight in the range of about 45-800, preferably in the range of approximately what about 45-600. Additional oligomer preferably is polyalkyleneglycol with low molecular weight (molecular weight of 300-600), such as polyethylene glycol 400, which can also serve as a low molecular weight plasticizer. Alternatively, another connection may be included as an additional low molecular weight plasticizer, in this case, you can use any of the low molecular weight plasticizers described below. In one embodiment of the invention additional oligomer is an additional oligomer of low molecular weight or oligomeric plasticizer, which contains at least two functional groups per molecule that can form hydrogen bonds with the hydrophilic polymer.

In some cases, additional oligomer may also serve as a plasticizer of low molecular weight. Alternatively, another connection may be included as an additional low molecular weight plasticizer and, if included, may be present in an amount of about 30-35% of the composition.

Examples of suitable additional oligomers include, but are not limited to, low molecular weight polyalcohol (for example, glycerin), Monomeric and oligoantigenic, such as ethylene glycol and propylene glycol partial esters of a polyhydric alcohol (i.e. ethers of glycols), dicarboxylic acid, arcangioli from butanediol to octandiol, including derivatives of polyalkylene glycols with integral carboxyglutamic and amino groups. Preferred are polyalkylene glycols, optionally, with terminal carboxyl groups and polyethylene glycol having a molecular weight in the range of about 300-600 is optimal additional oligomer.

From the foregoing it is clear that one connection, for example low-molecular polyalkyleneglycol, such as polyethylene glycol having a molecular weight in the range of about 300-600 may serve additional oligomer and a low molecular weight plasticizer.

As discussed in patent publication US No. 2002/0037977 Feldstein and others, the ratio of the hydrophilic polymer and additional oligomer in the above-mentioned mixture affects both the strength (force) of adhesion and bond strength. As explained in the aforementioned patent application, additional oligomer reduces the glass transition temperature of a mixture of hydrophilic polymer and additional oligomer to a greater extent than predicted by the Fox equation, which is given by the following equation:

whereTg predictedis the predicted glass transition temperature of a mixture of hydrophilic polymer and further the part of the oligomer, wpolis the weight fraction of the hydrophilic polymer in the mixture,wplis the weight fraction of additional oligomer in the mixture,Tg polis the glass transition temperature of the hydrophilic polymer andTg plis the glass transition temperature of the additional oligomer. As was also explained in this patent application, the adhesive composition having an optimized adhesion force and traction force can be obtained from a hydrophilic polymer and additional oligomer by selecting the components and their relative amounts to provide a predetermined deviation from theTg predicted. As a rule, to maximize adhesion, a predetermined deviation from theTg predictedis the maximum negative deviation, whereas to minimize adhesion, any negative deviation from theTg predictedis minimized.

Because the additional oligomer can itself act as a plasticizer, as a rule, there is no need to include additional plasticizer. However, the inclusion of additional low molecular weight plasticizer in the composition is optional and may, in some cases, be beneficial. Suitable low molecular weight plasticizers include diallylphthalate, dicyclohexylamine, Directorate, mixed alkyl is ritalahti, presented by dimethylphthalate, diethylphthalate, dipropylamino, di(2-ethylhexyl)phthalate, diisopropylamino, tamilfilm and dicaprylate; alkyl and arylphosphate, such as tributyl phosphate, trioctylphosphine, tricresylphosphate and triphenyl; alkilinity and esters of citric acid such as triethylcitrate, triethylcitrate, tributyltin, acetyltributyl and trihexoside, dialkyldiphenyl, such as dioctyladipate (DOA), also referred to as bis(2-ethylhexyl)adipate, diethylamine, di(2-methylethyl)adipate and vexillationes; dialkylated, such as diethyltartrate and dibutylated; diallylmalonate, such as diethylbenzene, dipropylamine and dinnerseating; dialkylamines, such as diethylamine and dibutylamine; alkylphenolate, alkylglycerol, ethers and esters of glycols, such as glycerinated, glyceryltrinitrate (triacetin), glycerylmonostearate, methylpteroylglutamate, butylphthalocyanine, etilenglikolevye, etilenglikolevye, dietilenglikoluretan, triethyleneglycoldinitrate, triethylenemelamine and mixtures thereof. Preferred low molecular weight plasticizers for hydrophilic dispersing medium is triethylcitrate, diethylphthalate, dioctyladipate, and dioctyladipate especially preferred.

The properties of the composition of the present invention can be easily adjusted by adjusting one or more parameters at the time of manufacture. For example, the adhesion strength of the composition can be adjusted during manufacture to increase, reduce or eliminate adhesion. This may involve a change in type and/or quantity of the various components, or by changing the method of manufacture. Also, regarding the manufacturing process, composition, obtained using conventional melt extrusion, typically, though not necessarily, slightly less sticky than compositions made by casting from solution. Moreover, the extent to which the hydrogel composition will swell upon contact with water, can be varied by selecting different vodosnabzhenie polymers, and compositions containing hydrophilic dispersing medium, by adjusting the ratio of vodonapornyh water-insoluble polymer to the mixture of the hydrophilic polymer/plasticizer. These compositions may differ in appearance from clear, transparent to translucent to opaque. In addition, certain compositions can be made semi-transparent by changing the relative amounts of the components of the hydrophilic phase (for example, decreasing the amount of cellulose ether), or by izmenenyaya manufacturing (semi-transparent hydrogels easier obtained by using a molding method from a solution, than melt extrusion). Thus, the translucent composition allows the user to observe therapeutic or cosmetic (e.g., bleaching) process as it proceeds, and to determine when the desired effect has been achieved, for example, when the teeth are bleached to a sufficient degree.

III. The active substance

The composition can also contain any pharmaceutically active substance suitable in the treatment of physiological conditions, including the teeth and surrounding tissue, as well as the skin and mucous tissue. The active substance may be any substance that can be released from the composition for the treatment of undesirable physiological conditions. Undesirable physiological condition, including the teeth or surrounding tissue, which are amenable to therapy these tools include: bad breath, periodontal and oral infections, periodontal lesions, dental caries and tooth decay, gingivitis and other periodontal diseases.

Such substances could be present in a therapeutically or cosmetically effective amount. They include, for example, but not limited to, adrenergic substances, adrenocortical steroids, adrenocortical suppressants, anti-alcohol deterrent, aldosterone antagonists, is minamikata, the ammonium detoxicant, anabolics, analeptics, analgesics, androgenic drugs, anesthetic substance, anorectics connection, anorectics substances, antagonists, activators of the anterior lobe of the pituitary gland and the suppressor of the anterior lobe of the pituitary gland, antihelminthic agents, agents against acne, antiadrainergicakimi substances, anti-allergic drugs, antiamebic substances antiandrogenna substances, Antianemic substances protivougonnye substances, medicines from fear, the anti-arthritis agents, anti-asthma agents, anti-sclerotic substances, antibacterial substances, anticelulitic, anticholinergenic substances, anticholinergic agents, anticoagulants, antioksidantnye substances, anticonvulsants, antidepressants, antidiabetic agents, antidiarrheal substances, antidiuretic, antidotes, antidyskinetics matter, anti-matter, anti-epileptic substances, anti-estrogenic substances, antifibrinolytic substances, antifungal substances, protivoglaucomny substances antihemophilia substances protivogerpeticheskiy factor protivogemorragicheskim substances, anti-histamine substances, antihyperlipidemic substances antihyperlipidemics substances, antihypertensive substances, antihypotensive substances, protivin actionee substances, anti-inflammatory agents, agents against the keratinization, antimalarial agents, antimicrobial agents, agents for migraine antimitoticescoy substances, antifungal substances, anti-vomiting, antineoplastics funds, additional reinforcing agents against cancer, antineuraminidase substances, substances which obsessions, funds from parasites, antiparkinsonian medications, antipneumocystis substances, antiproliferative substances, medicines from hypertrophy of the prostate, Antiprotozoal substance, antipruritic, protivopolozhnye substances, antipsychotic drugs, Antirheumatic agents, antihistaminics substances antisabotage substances, antispasmodic agents, antithrombotic agents, antitussives, anti-ulcer agents, urological drugs, antiviral substances the appetite suppressors, means the treatment of benign prostate hyperplasia, regulators of glucose in the blood, inhibitors of bone resorption, bronchodilators, carbonic anhydrase inhibitors, cardiac depressant, heart protective agents, cardiovascular agents, cholagogue, cholinergic tools, cholinergic agonists, decontamination officers cholinesterase, coccidiostatic substances, umsta the major stimulants and enhancers perception, sedatives, auxiliary diagnostic agents, diuretics, dopaminergic agents, ectoparasiticide, gag substances, enzyme inhibitors, estrogens, fibrinolytic agents, traps free radicals, regulators of gastrointestinal activity, glucocorticoids, components stimulants sexual glands, hair growth stimulants, hemostatic, antagonists, H2 receptor histamine, hormones, hypocholesterolemia substances, hypoglycemic agents, hypolipidemic agents, antihypertensives, inhibitors of HMGCoA reductase, immunizing agents, immunomodulators, immunoregulatory, Immunostimulants, immunosuppressants, AIDS against impotence, inhibitors, keratolytic substances, substances with affinity to the LHRH receptor, cures diseases of liver, luciolinae treatments improve memory, amplifiers mental activity, mood regulators, mucolytics, protection of the mucous membranes, mydriatic, nasal decongestants tools, neuroleptic agents, neuromuscular blocking agents, neuroprotective agents, NMDA antagonists, non-hormonal Sterol derivatives, funds, enabling clan activity, plasminogen activators, antagonists of platelet activating factor, inhibit the s platelet aggregation, care after a stroke and boil, potentiating tools, progestins, prostaglandins, growth inhibition of prostate protrotrombinovoe substances, psychotropic substances, radioactive substances, regulators, relaxants, redistributive substances, scabicide, sclerosing agents, sedatives, sedative-hypnotics, selective A1 antagonists of adenosine, serotonin antagonists, inhibitors of serotonin antagonists serotonin receptor, steroids, stimulants, suppressive means, synergistically acting drugs, thyroid hormones, inhibitors of the thyroid gland, analogs of thyroid hormones, tranquilizers, drugs for unstable angina, tools, promote the excretion of uric acid, vasoconstrictors, vasodilators, tools, tools that promote wound healing, medicine for the healing of minor wounds, inhibitors of xanthine oxidase and the like.

In one embodiment, the above-described hydrogel composition comprises a bleach, and therefore, when applied to the teeth acts as a delivery system. Releasing bleaching agents, “loaded” in the present hydrogel composition typically includes both water absorption and desorption of substances controlled by the swelling of the diffusion mechanism is the ZMA. Hydrogel compositions containing bleach may be used, for example, in a manner similar to the method of using the pharmaceutical compositions for local application.

Suitable substances for teeth whitening include peroxides, metal chlorites, perborates, percarbonates, peroxyacids, and combinations thereof. Suitable peroxide compounds include hydrogen peroxide, calcium peroxide, carbamide peroxide, and mixtures thereof. The preferred peroxides are peroxidation and carbamide peroxide. Other suitable peroxides include organic peroxides, including, but not limited to, dialkylamide, such as tertBUTYLPEROXY and 2,bis(tertBUTYLPEROXY)propane, diazepamonline, such as benzoyl peroxide and acetylmuramic, esters of nakilat, such as tertbutylphenol and tertbutyl per-2-ethylhexanoate, pentaborate, such as dicetylperoxydicarbonate and dicyclohexylperoxydicarbonate, ketone peroxides such as cyclohexanone peroxide and methyl ethyl ketone peroxide, and hydroperoxides, such as cumene hydroperoxide and tertBUTYLPEROXY. Bleach is preferably a peroxide such as hydrogen peroxide or carbamide peroxide, and most preferably hydrogen peroxide.

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

In another embodiment, the pharmaceutically active substance may be, for example, non-steroidal anti-inflammatory/analgesic; steroid anti-inflammatory agents; drugs local anesthesia; bactericidal/disinfectant; antibiotics; antifungal agents; antisense funds for teeth; fluoride remedies against the formation of cavities/anti-fracture; anti-Tartar/anti-calculus; the enzymes that inhibit the formation of plaque, calculus or dental caries; abrasive substances such as phosphates, chelating metals, such as sodium salt of ethylenediaminetetraacetic acid; antioxidants, such as butylhydroxyanisole that is equivalent; nutritional additives for local delivery to the teeth and surrounding tissues; and so on.

Suitable not steroid anti-inflammatory/analgesic substances include acetaminophen, methyl salicylate, nonagricultural, aspirin, methenamine acid, flufenamic acid; indomethacin, diclofenac, alkoven, diclofenac sodium, ibuprofen, flurbiprofen, Frantisek, bufexamac, piroxicam, phenylbutazone, oxygen Utzon, clopton, pentazocine, Marisol, tiaramide hydrochloride.

Suitable steroid anti-inflammatory agents include hydrocortisone; prednisolone; dexamethasone; triamcinolone acetonide; fluotsinolon acetonide; hydrocortisone acetate; prednisolone acetate; methylprednisolone; dexamethasone acetate, betamethasone; betamethasone valerate; flumetazon; fluorometholone; budesonide; beclomethasone dipropionate.

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

Suitable bactericidal/disinfectant include thimerosal; phenol; thymol; benzalconi chloride; benzethonium chloride; chlorhexidine; provide iodide; cetylpyridinium chloride; eugenol; trimethylammonium bromide.

Suitable antibiotics include penicillin; methicillin; oxacillin; cefalotin; tsefaloridin; erythromycin; lincomycin; tetracycline; chlortetracycline; oxytetracycline; metatsiklina; chloramphenicol; kanamycin; streptomycin; gentamicin; bacitracin; and cycloserine. Similar antifungal agents include amphotericin; clotrimazole; IVF is Azola nitrate; fluconazole; griseofulvin; Itraconazole; ketoconazole; miconazole; nystatin; terbinafine hydrochloride; undeceive acid; and undecent zinc.

Suitable antisense funds for teeth include potassium nitrate, strontium chloride. Suitable fluorine-containing means against the formation of cavities/anti-fracture include sodium fluoride, potassium fluoride and ammonium fluoride.

Additional bleaching agents include agents against dental stone/against calculus, including phosphates such as pyrophosphates, polyphosphates, polyphosphonates (for example, ethane-1-hydroxy-1,1-diphosphonate, 1-azacycloheptane-1,1-diphosphonate, and linear alkyldithiophosphate) and their salts; linear carboxylic acid; and zinc citrate sodium; and mixtures thereof. Preferred pyrophosphate salt is disubstituted pyrophosphate alkali metal salts, Tetra-substituted pyrophosphate alkali metal salts; and acidic or medium salt - dihidrogenofosfat sodium (Na2H2P2O7and chetyrehkolenny sodium pyrophosphate (Na4P2O7and chetyrehkolenny pyrophosphate potassium (K4P2O7). Salts of pyrophosphates are described in more detail in Kirk &Othmer, Encyclopedia of Clinical Technology, third edition, volume 17, Wiley-Interscience (1982), the complete disclosure of which is included by reference as a whole. Optional, bleaching, washes the VA may also include substances dissolving Tartar, such as betaines, aminoxide and Quaternary compounds, as described in US no 6315991 (Zofchak).

Enzymes, which will inhibit the formation of plaque, calculus or dental caries can also be used in the composition. The enzymes can be introduced together with household bleach or they can be located in a separate layer in a multilayer system, as described here. Suitable enzymes include proteases, which break down the proteins of saliva absorbed on the surface of the teeth and form plaque, or the first layer of plaque; lipase, which destroy bacteria by lysis of proteins and lipids, which form a structural component of the walls of the bacterial cells and membranes; dextranase, glucanohydrolase, endoglycosidase; and mucinase that destroy bacterial skeletal structure, which forms a matrix for bacterial adhesion to teeth; and amylase, which prevent the development of calculus by the destruction complex carbohydrate protein that binds calcium. Preferred enzymes include any of the commercially available proteases; dextrans, glucanohydrolase, endoglycosidase; amylases, mutans, lipases, Mucins, and compatible mixtures. In some embodiments, the implementation can be used enzymatic bleach.

Long is Ino, enzymatic bleaching substance is peroxidase, so that peroxide is generated onin situ. When the enzymatic bleaching or against plaque substance is introduced into the composition, the composition should be such that the enzyme is maintained in its active form, i.e. pH should be approximately neutral, and peroxide may not be included or contained in a separate layer.

Appropriate nutritional supplements for local delivery to the teeth and surrounding tissues include vitamins (such as vitamin C and D, thiamine, Riboflavin, calcium Pantothenate, Niacin, folic acid, nicotinamide, pyridoxine, cyanocobalamin, para-aminobenzoic acid and bioflavonoids); minerals (e.g. calcium, phosphorus, fluoride, zinc, manganese, potassium); or their mixture. Information about vitamins and minerals used in the present invention, presented in the publication Drug Facts and Comparisons (loose leaf drug information service), Wolters Kluer Company, St. Louis, Missouri 1997, p.3-17.

The composition may also comprise any cosmetically active substances for the implementation of desired changes in the appearance of the teeth or surrounding tissue, or which give socially desirable characteristics to the consumer, such as fresh breath. For example, cosmetically active substance can be a breath freshener or a substance which performs discoloration or Orbelian the e teeth. It is known that in some cultures or certain segments of Western society staining of the teeth may be important or desirable, cosmetically active substance may be any substance that imparts color or shade of the teeth.

The composition may include additional bleaching agents. For example, surface-active substances, such as detergents, may also be present, and which will work together with household bleach, described above, to ensure a brighter looking teeth.

In any of these embodiments tooth whitening composition of the invention preferably includes peroxide for teeth whitening and may also include conventional additives such as fillers, preservatives, pH regulators, softeners, thickeners, colorants, pigments, dyes, refractive particles, stabilizers, additives, providing strength, pharmaceutical agents, flavorant or breath fresheners, and amplifiers permeability. In these variants of implementation, where it is necessary to reduce or eliminate adhesion, can be used substances to reduce stickiness. These additives and their amounts are selected so that they are slightly interfere with the desired chemical and physical properties of the tooth whitening composition, or interfere with shortcuts is VCE whitening tooth substance, when they are included in the composition. Such additional ingredients include colorants, food additives, flavorant, sweeteners and preservatives.

Any natural or synthetic flavorant or food additive can be used, for example, such as those described in Chemicals Used in Food Prossesing, publication No. 1274, National Academy of Sciences, p.63-258 full disclosure of which is included here by reference. Suitable flavorant include integrin, pepper mint, spikelet mint, menthol, fruit flavors, vanilla, cinnamon, pepper, fragrant oils and balms, known in the technology, and their combinations. The number flavorant is usually a matter of preference, depending on such factors as the type flavorite, individuality flavorite and desired power. Preferably, the composition includes about 0.1-5 wt.% flavorant.

The sweeteners used in the present invention include sucrose, fructose, aspartame, xylitol and saccharin. Preferably, the composition includes from about 0.001 to 5.0 wt.% sweetener.

A suitable substrate may be translucent, so that the composition is unobtrusive when applied. However, the substrate or the composition can be optionally colored, so that the composition is well visible when applied. Preferably, if it is desirable colouring, the colouring is to risedronate in the substrate. For example, the substrate can be painted in a bright color or “exciting” color, which consumers may find enjoyable. The substrate may, therefore, include a coloring compound, such as, for example, a dye, pigment or substance that can impart color when added to the material forming the substrate.

For example, for coloring substrate you can use the dye compounds of the type commonly used in foods, medicines or cosmetics in connection with the human body, especially the coloring additives permitted for use in food products, which are classified as “certified” or “exempt from certification”. Coloring compounds used for coating the substrate, can be obtained from natural sources such as vegetables, minerals or animals, or may be made by a person of analogues of natural products.

Coloring connections, certified today by the Food Drug and Cosmetic Act for use in food and ingested drugs include dyes like 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-naphtalenesulfonic acid); Food Yellow 13 (sodium salt of a Mixture of mono - and disulfonic acid chieftan or 2-(2-chinolin)indandion); FD&C Yellow No.5 (soda is ewww salt of 4-p-sulfophenylazo-1-p-sulfophenyl-5-hydroxypyrazol-3-carboxylic acid); FD&C Yellow No.6 (sodium salt of p-sulfophenylazo-B-naphthol-6-monosulphate); FD&C Green No.3 (disodium salt of 4-{[4-(N-ethyl-p-sulfanilamide)phenyl]-(4-hydroxy-2-sulfonatophenyl)-m-ethylene}-[1-(N-ethyl-N-p-sulfobutyl)for 3,5-cyclohexadiene]); FD&C Blue No.1 (anhydrous disodium salt dibenzyldithiocarbamate acid); FD&C Blue No.2 (sodium salt indigotindisulfonate acid); FD&C Red No.40; Orange B, Citrus Red No.2 and combinations thereof in various proportions.

Coloring compounds, exempt from certification FDA, include annatto extract, beta-APO-8'-carotenal, beta-carotene, beet powder, canthaxanthin, burnt sugar, carrot oil, extract of cochineal (Carmine), toasted partially defatted cooked flour from the seeds of the cotton plant, iron gluconate, fruit juice, coloring grape extract, extract from the skin of grapes (animania), pepper, turpentine paprika, Riboflavin, saffron, turmeric, turpentine turmeric, vegetable juice, and combinations thereof in various proportions.

Form a dye compound for use in the composition preferably includes an additive in the form of dye, but may also include lacquer form that is compatible with the material containing the substrate. Water-soluble dyes are provided in the form of powders, granules, liquids or other forms of special purpose, you can use the with in accordance with the present method. Preferably, for the dyeing of the substrate used “lucky” or water-insoluble form of the dye. For example, if there should be used the suspension colorants, you can use lacquer additive form. Suitable water-insoluble coloring varnishes obtained by exposure to calcium or aluminum salts of FD&C dyes on alumina include lacquer, FD&C Green #1, lacquer, FD&C Blue #2, Lac FD&C R&D #30 and Lac FD&C # Yellow 15.

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

The concentration of the dye compounds in the substrate is preferably about 0.05-10 weight. %, more preferably about 0.1-5 wt.%.

The substrate may contain more than one coloring substance, so to give it a color composite. These component colors can be made in the patterns in the form of stripes, dots, swirls or any other picture that the consumer will find enjoyable. Coloring the connection can also be used with other which improves the appearance of substances such as blestiastei.

When the adhesive is on the surface of the teeth, to control the degree of hydration may be appropriate introduction of absorbing fillers. Such fillers may include microcrystalline cellulose, talc, lactose, kaolin, mannitol, colloidal silica, aluminum oxide, zinc oxide, titanium oxide, magnesium silicate, magnesium aluminosilicate, hydrophobic starch, calcium sulfate, calcium stearate, calcium phosphate, dihydrate calcium phosphate, clays, such as laponite, woven and non-woven papers and materials of the cotton. Other suitable fillers are inert, i.e. essentially non-adsorbents, and include for example, polyethylene, polypropylene, polyurethanes, polyetherimide copolymers, polyesters and polyester copolymers, nylon and rayon. The preferred filler is, for example, Cab-O-Sil®(Cabot Corporation, Boston, Mass.).

The preservatives include, for example, p-chloro-m-cresol, phenethyl alcohol, phenoxyethylamine alcohol, chlorobutanol, methyl ester of 4-hydroxybenzoic acid, propyl ester of 4-hydroxybenzoic acid, benzalkonium chloride, chloride of cetylpyridinium, chlorhexidine diacetate or gluconate, ethanol and propylene glycol.

Compounds suitable as pH regulators include, but are not limited to, glycerol buffers, citrate buffers, borate buffers, ostatnie buffers or buffers, citric acid phosphate can also be included so as to ensure that the pH of the hydrogel composition was compatible with the pH of the mouth and did not lead to the leaching of minerals from the tooth surface. To optimize the whitening without demineralization teeth, the composition can include calcium salts and/or fluorides.

Suitable softening tools include esters of citric acid such as triethylcitrate or acetyltributyl, esters of tartaric acid, such as dibutylated, esters of glycerol, such as glycerinated or glyceroltrinitrate, esters of phthalic acid such as dibutyl phthalate or diethylphthalate; and/or hydrophilic surfactants, preferably non-ionic hydrophilic surface-active substances such as, for example, partially-esterified fatty acids sugar, polietilenglikolya esters of fatty acids, ethers of glycols with fatty alcohols, esters polietilenglikolsuktsinata with fatty acids.

Preferred thickeners are naturally occurring compounds or their derivatives, and include, as an example, collagen, galactomannan, starches, derivatives and starch hydrolysates, derivatives of cellulose, such as methylcellulose, hydroxypropylcellulose, hydroxyethyl cellulose and hypromellose, colloidal who renevue acid, sugars such as lactose, sucrose, fructose and glucose. Synthetic thickeners such as polyvinyl alcohol, vinyl pyrrolidone-vinyl acetate copolymers, polyethylene glycols and polypropylenglycol can also be used.

The substrate can also be inserted or the substrate may be adorned with decorative items such as beads (balls), artificial diamonds or similar, as these items do not violate the viscoelastic properties of the substrate required for proper deformation of the composition on the teeth, as described above. The substrate can also display letters, words, or images taken for pleasure or attractiveness of the consumer.

IV. The manufacturing methods

Compositions of the present invention, generally are processed from the melt and, thus, can be manufactured by simple methods of mixing and extrusion. The components of the composition are weighed and mixed, for example, by using a Brabender mixers or Baker Perkins Blender, usually, though not necessarily, at an elevated temperature, for example approximately 90-140oC. If desired, can be added solvents or water. The resulting composition may be subjected to extrusion using a single or dual extruder, or granular. Alternatively, the components of the composition can be melt on PTS is ready and then mix before extrusion. Preferably, the composition ekstragiruyut directly on a suitable substrate, such as a protective layer or a removable strip, and then the composition is pressed. The thickness of the obtained film containing hydrogel, for most purposes, will be in the range of about 0.05-0.80 mm, more in the range of about from 0.37 to 0.47 mm

Alternatively, the composition can be manufactured by casting from a solution, by mixing components of the composition in a suitable solvent, for example, volatile solvent, such as ethyl acetate, or lower alcohols (for example ethanol, isopropyl alcohol and so on)that are particularly preferred, at a concentration, which is typically in the range of about 35-60 weight./about. %. The solution was poured on a suitable substrate, such as a protective layer or a removable strip, as described above. As a mixture, and molding is preferably carried out at ambient temperature. The substrate coated film is subjected to firing at a temperature in the range of about 80-100oC, optimally about 90oC for a time period of approximately 1-4 hours, optimally about two hours. Accordingly, one implementation of the invention is a method of obtaining a hydrogel films suitable for inclusion in the composition of the present invention, which includes the following stages: a solution Vodonaeva, water-insoluble polymer or a water-soluble polymer, a hydrophilic polymer, additional oligomer capable of forming hydrogen bonds with the hydrophilic polymer, and the second Vodonaeva, water-insoluble polymer in a solvent; applying a layer of the solution on the substrate (the substrate) to provide the coating and heating the coated substrate to a temperature in the range of about 80-100oC for a time period in the range of about 1-4 hours, providing this hydrogel film on a substrate.

When it is desirable to get sticky hydrogel composition, the melt extrusion is the preferred method, although casting from a solution can still be used. To obtain essentially non-sticky compositions preferably by casting from solution. Also the extrusion of the melt can be applied to any of the compositions of the present invention. In addition or melt extrusion, or casting from solution can be applied to obtain a translucent compositions, although usually casting from solution is preferred for this type of implementation. Accordingly, another embodiment of the invention is a method of obtaining a composition which comprises the following stages: processing the melt through the extruder the mixture Vodonaeva, nerastvorim the polymer in water or a water-soluble polymer, hydrophilic polymer, additional oligomer capable of forming hydrogen bonds with the hydrophilic polymer, and the second Vodonaeva, water-insoluble polymer to form an extruded composition; the extrusion of the composition in the form of a film of the desired thickness on a suitable substrate; and, after cooling, the film loading an aqueous solution of the active substance, such as a peroxide, to obtain the concentration of bleach is about 1-20%.

The invention also proposed a multilayer system that includes one or more additional hydrogel or dehydrogenase layers. For example, you may want to include additional active substances which may be incompatible with the primary active substance during storage. In this case, one layer may contain primary active ingredient hydrogel layer and the other layer (s) may contain additional active substances. These other substances may be made of a hydrogel composition described herein, or any other biocompatible compositions known in the art (for example, polyisobutylene, dimethylsiloxane, ethylene vinyl acetate, polyvinyl acetate, cellulose acetate, cellulose butyrate, cellulose propionate, ethylcellulose and water-insoluble acrylate). In addition to the, depending on the location of the layers, it may be desirable to have an adhesive layer, for example, the layer located directly to the teeth, and not sticky layer, for example, an outer layer that is located near the mouth. Another advantage of the multilayer system is that the ratio of the polymers used in the middle of the outer layer can be varied so as to obtain a non-sticky layers, in order to dispense with the inclusion of a separate protective layer in the product.

In one embodiment, the composition includes: an external substrate, which serves as the outer surface of the composition after application to the teeth and tissues of the mouth, skin or mucous membrane; surface contact adhesive layer adhering to it, which typically will constitute the adhesive composition of this invention optionally contain additional active substances; and removing the removable strip. After removal of the removable strip, for example, the composition is applied on the treated surface, for example, teeth, and placed on the surface so that the surface of the oral cavity - contacting layer were in contact. In another embodiment, the composition is packaged without a protective layer or a removable strip. Accordingly, immediately after removal from the packaging composition ready for application to the surface is rnost body.

The substrate is the primary structural element and carries the song or at the time of manufacture or during use. The material used for the substrate, should be inert and incapable of absorbing hydrogel composition. In addition, the material used for poloski should allow the device to follow the shape of the teeth or other body surface and to be comfortable when worn in the mouth without rubbing or other irritation of lips or tongue. Examples of suitable substrate materials include polyesters, polyethylene, polypropylene, polyurethanes and polyetherimide. The substrate is preferably approximately 15 to 250 microns in thickness and may, if desired, be colored, metallized or provided with a matte finish suitable for writing.

In one embodiment, the substrate is preferably, though not necessarily, sealed (i.e. not “breathe”) and does not allow any active substance in the composition to flow through the layer, and in contact with mucous membranes of the mouth or gums. By the time of application of the composition is pre-moistened so that the viscosity increases and the composition sticks to the teeth. One advantage of this implementation is that the active substance may not essentially to penetrate through the substrate and to cause irritation in those who senses the tion to the current substance or any unpleasant taste or feeling.

Other suitable substrate materials can be polimernye materials such as waxes (e.g., microcrystalline or paraffin waxes or wax/layered foam. Paraffin waxes are low molecular weight unbranched hydrocarbons with a melting temperature of approximately 48-75oC and a molecular mass of approximately 300-1400 g/mol, typically obtained by the reaction of the Fischer-Tropsch process. Microcrystalline waxes are elastic (soft) and externally morphophonemic and tend to have higher tensile strength and a smaller crystal size than paraffin waxes. Microcrystalline waxes typically have a melting temperature of approximately 60-95oC and a molecular weight of approximately 580-700 g/mol, and preferably contain branched hydrocarbons and some cyclic compounds, although prosvetlennye hydrocarbons may also be present. The substrate can also serve foams with open cells, such as porous polyurethane, polystyrene or polyethylene.

Alternatively, in another implementation, the substrate is leaking and, therefore, can be fully hydrogenate itselfin situon the teeth or other body surface.

The removable lining is a removable (single) element, which is used to protect the system before use. Removable gasket should be made of a material impermeable to the active substance and the hydrogel composition, which is also easily removed with contact adhesive. Removable pads are usually treated with a silicone or ftoruglevodorodnyh and usually made of polyester and polyethylene terephthalate.

The preferred composition is usually made with the use of acrylate polymers as the first and second water-insoluble, vodonapornyh polymers; and mixtures of polyvinylpyrrolidone and polyethylene glycol as a mixture of hydrophilic polymer and complementary oligomer capable of forming hydrogen bonds with the hydrophilic polymer.

The adhesive film composition may be produced by thermal melting and mixing the above components together at temperatures in the range of about 100-170oC. Film ekstragiruyut to a desired thickness on a suitable substrate. Alternatively, the components can be dissolved in simple or mixed solvents, and the solution can be poured on or removable protective film. The solvents are then evaporated with obtaining hydrogel film.

One way to load composition active substance includes layering essential active substances, such as whitening teeth substances, the aqueous solution on the surface of the hydrogel, located on a suitable substrate, or the placement of the active substance directly on the substrate. Removable gasket is attached on top of the composition, forming a sandwich structure, and the solution containing the bleaching substance is absorbed by the composition due to its properties to swell in water. Alternatively, the composition of the layers deposited on the substrate can be immersed in a solution containing the bleaching agent in the desired concentration, and the composition absorbs the solution. Measuring the rate of increase of the weight of absorbed fluid to define and control the percentage of load composition active substance.

Another approach to load composition the active ingredient is the addition of the active substance in solid form or in the form of a solution of the composition dissolved in the solvent. The mixture is then poured, as usual, on a suitable substrate and allow to dry, although using this method of loading the desired low temperature drying. Compositions produced thereby, can be dried at ambient temperature for a time from about 1 hour to several days.

Typical film thickness is about 0.05-0.80 mm, preferably from 0.25 to 0.50 mm film Thickness is not critical and can vary in accordance with the concentration of the chill the living substance, included in the film, the length of time during which the film must be placed on the teeth, level of comfort for the user and the degree of violation of painting that needs to be corrected.

V. applications

In practice, the composition may be applied simply by removing the product from its packaging, remove the removable spacers (if any) and applying an adhesive layer on the teeth that should be replaced (or on any surface of the skin or mucous membranes of the body, if you want another application of bleach, or should be used more active substance). The system described herein may provide a variety of sizes, so that the composition can be applied to all or a particular part of the teeth, any number of teeth at the same time or on any part of the oral cavity. The substrate, when it is tight, reduces or prevents the leakage of the active substance from the composition, while the user wears the composition of the required amount of time. The composition can be maintained in a desired location within a few minutes, several hours, a whole day or during the night, and then removed when the desired degree of bleaching or desired therapeutic or cosmetic effect will be achieved. If necessary, may be provided with a translucent composition, which is you can wear unobtrusive or invisible to others. The system can also be created without the active ingredient and find application as a protective agent to the surface of the mouth, for example, aphthous stomatitis, herpes, etc. or as a dressing on the wound.

The composition can be worn for a long time, but is usually worn over a predetermined period of time from about 10 minutes to about 24 hours. For use in whitening your preferred period of time is from about 10 minutes to about 8 hours (e.g. at night), and the preferred embodiment is from 30 minutes to about 1 hour. For other active substances, therapeutically or cosmetically effective time can be easily determined based on the active substances and treatment conditions.

The user can put the composition around the upper or lower teeth or other oral tissues, using normal hand pressure on the substrate with the tips of the fingers (or thumb), optional wetting composition before use. Based on the fact that the surface area of the tip of the finger of an adult is about one square centimeter, the normal pressure exerted by the finger tips, is about 100000-150000 PA (i.e. about 3 pounds or 1.36 kg) per square centimeter. Usually to comp the positions applied pressure of each fingertip (or the tip of the thumb) within one or two seconds. After the pressure of fingertips on the substrate is removed, the composition retains its shape and adheres to the surface of the teeth and adjacent soft tissues on which it was formed.

When the user is ready to remove the composition, the composition may be removed simply by peeling it from the surface of the teeth or other surfaces of the mouth or body. If necessary, the composition may be re-applied for additional processing time. Any residue is minimal and can be removed using conventional methods for cleaning the teeth or mouth.

In one embodiment of the invention the composition is a solid and is a pressure-sensitive adhesive and absorbs water. This can be achieved by the production of fathersdelaware film-forming composition prior to application on the surface of the body. Solid compositions obtained in this way can then be Packed and removed from the packaging before use.

The composition is preferably used as a non-solid composition, for example, be applied as a liquid or gel. For example, the user may 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, to apply the composition by means of a brush or other applicator, etc. and After the evaporation of the solvent, liquid or gel composition is dried with the formation of the polymer film matrix type or gel on the surface of the body. In one embodiment, the implementation of this liquid or gel film-forming composition, the hydrogel contains a significant amount of water or other solvent to provide fluid properties. In another embodiment of this composition, the polymer components of the liquid or gel compositions are soluble in water-ethanol mixtures as at ambient temperature and at low temperatures around 4°C, and able to be mixed with the solvent evaporates. In another embodiment, this liquid or gel film-forming composition, the polymer composition has a lower critical temperature of dissolution of about 36°C in ethanol-water solution. The obtained film (after evaporation of the solvent) is preferably insoluble or slowly soluble in saliva at body temperature in order to ensure a permanent contact between the hydrogen peroxide and tooth enamel. Finally, hydrogen peroxide must be stable in liquid or gel composition in the polymer film during drying.

In the practice of the present invention will be applied, unless otherwise indicated, conventional methods of polymer chemistry, production of adhesives, manufacturing hydrogel the th, which are well known to specialists in this field of technology. Such techniques are fully explained in the literature.

It is clear that although the invention is described with specific preferred implementation, the preceding description, as well as the examples that follow are intended to illustrate but not to limit the scope of the invention. Other aspects, advantages and modifications will be obvious to experts in the given field of technology.

The following examples are offered in order to provide professionals in the art a complete disclosure and description of how to obtain and use the compounds of this invention and are not intended to limit the scope of the invention. Efforts have been made to ensure the accuracy of numbers (e.g., amounts, temperature, etc.), but keep in mind some errors and inaccuracies. Until stated otherwise, part of the mean mass part, temperatures are given in degrees Celsius (°C)and pressure is equal to or close to atmospheric pressure.

The following abbreviations and trade names used in the examples:

Eudragit L 100-55methacrylic acid copolymer (Rohm America Inc.)
PEGthe polyethylene glycol 400
PVP30Plasdone® K30, polyvinylpyrrolidone (ISP)
PVP90Kollidon® 90F polyvinylpyrrolidone (BASF)

Examples

Example 1

Preparation of solid compositions.

One variant of implementation of the composition for whitening of the teeth was made from the following ingredients using the method of melt extrusion:

Eudragit L 100-559 wt.%
PVP9044 wt.%
PEG22 wt.%
Hydrogen peroxide6 wt.%
Water, stabilizers, pH modulators19 wt.%

The ingredients were melted in a single screw Brabender extruder as follows: Eudragit L 100-55 was added to the extruder first, then PVP90 and PEG at a temperature of from 100 to 150°C. the Composition was extruded to a thickness of 0.35 mm between two polyethylene terephthalate removable pads. The hydrogen peroxide solution was added to the extruded film.

Example 2

In VITROthe release of hydrogen peroxide from the solid the second composition

The release of hydrogen peroxide from the composition for tooth whitening of the present inventionin vitroin buffer at pH 7.0, was investigated and compared with peroxide released from a commercial product, Crest WhitestripsTM(a product of Proctor&Gamble Co., Cincinnati, Ohio, referred to as “product Crest”). Product Crest contains 5.3% hydrogen peroxide in the gel Carbopol 956 thin polyethylene film.

The release ofin vitrothe hydrogen peroxide from compositions containing 3%, 6% or 9% hydrogen peroxide (prepared as described in Example 1) was compared with the release of hydrogen peroxide from the product Crest. Studied composition or product Crest was allowed to release hydrogen peroxide in the solution through filter paper, and hydrogen peroxide was determined using standard analytical methods. For product Crest observed peroxide levels decreased to baseline in approximately 30 minutes. These data are similar to published data (Pagel P.A. et al. (2000) Vital Tooth Whitening with a Novel Hydrogen Peroxide Strip System: Design, Kinetics, and Clinical Response. Compendium, Suppl. 29, Vol. 21:S10-S15).

Composition for tooth whitening of the present invention release the peroxide at a speed proportional to the initial concentration. Also found that the compositions of the present invention release the peroxide with greater speed than the Crest product at all times var is rhenium: 5, 30 and 60 minutes. The selection of the peroxide to the composition containing 6% peroxide, which is close to the product Crest was approximately 7.5, 24, and 10 times more than the product of the Crest at the same time points, respectively. The selection of the peroxide to the composition containing 3% peroxide, was approximately 3, 7, and 5 times more than the product of the Crest at the same time points, respectively.

Example 3

The efficiency of the solid composition

The efficacy of compositions for whitening teeth was tested using the following methodology. People have tested the efficacy of a composition for whitening teeth, obtained according to the procedure described in Example 1, by applying the composition on the bottom row of teeth once a day 1 hour 6 days in a row. Shade of human teeth was measured using Professional Tooth Shade Guide (Professional scale shades of teeth) before and after dental treatment composition for whitening teeth. In day 1 of human teeth was assessed shade 12, within one hour of processing composition for tooth whitening the teeth match the shade 10. After one hour of processing composition for whitening teeth in day 2 teeth consistent shade 8. After one hour of processing composition for whitening teeth in day 3 teeth match the shade 5. Similarly, after one hour of processing composition for whitening teeth in day 4 teeth respectively who were shade 4/5. On day 5 after one hour of processing composition for whitening teeth teeth consistent shade 2/3. The lightest shade was achieved after a further half-hour treatment on day 6, match assessment 2. Thus, the effectiveness of the composition for whitening teeth was evident at the time of processing.

Example 4

Getting no solid composition

A composition for whitening teeth were prepared from the following ingredients (Formula A):

Deionized waterto 35.0 wt.%
Ethanolto 35.0 wt.%
Eudragit L 100-554.00 wt.%
PEG1.00 wt.%
PVP907,00 wt.%
Carbamide peroxide18.0 wt.%
Sodium citrate0.13 wt.%

The composition was mixed at low speed with high torque laboratory mixer (Cole-Parmer covered with Teflon impeller (diameter 2 inches) in the following way. Deionized water was mixed with ethanol, then added EG. Then, with vigorous stirring, was added sodium citrate. Powder Eudragit L 100-55 was added slowly (over 2-5 min) with vigorous stirring (500-600 rpm). After about 5-10 minutes (you must wait until dissolve Eudragit L 100-55) slowly (within 5 min) was added to the powder PVP90. High speed stirring was maintained for 5-10 minutes was Added a powder of carbamide peroxide (1-2 min) and the mixture was stirred to obtain a homogeneous solution (approximately 30 minutes at a speed of 800-900 rpm). The solution was kept for 2-5 hours to prevent the vanishing of the air bubbles.

Example 5

Getting unsteadily composition

A composition for whitening teeth were prepared from the following ingredients (Formula B):

Deionized waterto 35.0 wt.%
Ethanolto 35.0 wt.%
Eudragit L 100-552,50 wt.%
PEG1.92 wt.%
PVP90to 6.00 wt.%
Carbamide peroxide18.0 wt.%
Sodium citrate 0.08 wt.%
Methocel A4C1.50 wt.%

The composition was mixed at low speed with high torque laboratory mixer (Cole-Parmer, supplied coated with Teflon impeller (diameter 2 inches). Deionized water was mixed with ethanol, then added to the PEG. Then, with vigorous stirring, was added sodium citrate. Powder Eudragit L 100-55 was added slowly (over 5 min) with vigorous stirring (500-600 rpm), followed by slow (over 5 minutes) add powder (Methocel A4C) with vigorous stirring (500-600 rpm). After about 10 minutes slowly (within 5 min) was added to the powder PVP90. High speed stirring was maintained for 5-10 minutes was Added a powder of carbamide peroxide (1-2 min) and the mixture was stirred to obtain a homogeneous solution (approximately 30-60 minutes at a speed of 800-900 rpm). The solution was kept for 2-5 hours to prevent the vanishing of the air bubbles.

Example 6

In Vitroa comparative study of solubility for non-solid composition

Dissolution is not solid compositions for whitening teeth, made according to the methods described in Example 4 (Formula A) and Example 5 (Formula B), compared with the dissolution of a commercial product, a transparent OTB is iwaisako gel Simply White ®(a product of Colgate-Palmolive Company, new York, new York, referred to as “product Colgate”), which contains 18,0% carbamide peroxide. The dissolution process was studied using microinterferometric wedge.

Discovered that the Formula forms A sharp interfacial boundary between the swollen polymer composition and polymer solution. At the phase boundary was observed a sharp rise in the concentration of the polymer (and hence viscosity of the polymer). It is established that in the area of mutual diffusion of the product Colgate/water such boundaries do not exist, the interference pattern of this area is typical for a fully mixed systems with a gradual decline in the concentration of the polymer (and hence, the viscosity of the polymer) in the direction from the matrix of the composition to water. Discovered that the Formula B is heterogeneous (colloidal) structure. Formed a sharp interfacial boundary between the opaque gel and translucent aqueous solution. It was also established that the Formula B contains “faster dissolving” and “slower dissolving” part. Slower dissolving parts form a relatively thin layer surrounding opaque heterogeneous swollen gel. Unlike Colgate product, Formulas A and B in contact with an aqueous medium capable of forming a single continuous viscous swollen gel coating, separated from the liquid solution of a sharp phase is ranica. The formation of the phase boundaries for Formulas A and B were observed in water with different pH ranging from 4.6 to 7.5.

When using Formulas A and B formed a sharp interfacial boundary separating the swollen polymer from the polymer solution. In the area of mutual diffusion of the product Colgate/water such boundaries do not exist, the interference pattern of this area is typical for a fully mixed systems with a gradual decline in the concentration of the polymer (and hence viscosity of the polymer) in the direction from the matrix of the composition of formula a and matrix formulas In to the water.

Effective constants of mass transfer of water in the Formula A or B of Formula A or B in water is comparable to the product Colgate and Formulas A and B. However, unlike Colgate product, in the case of Formulas A and B observed the formation of a sharp interface separating a single swollen gel from the liquid aqueous solution. The effective diffusion coefficient for the interfacial boundary 1-2 orders of magnitude lower than that of water in the Formula A or B of Formula A or B in water. The layer of the swollen gel, formed by the Formulas A and B in the aquatic environment may play the role of a protective coating with a slow rate of dissolution. The swollen gel also provides mechanical support to increase the residence time of the Formulas A and B on the surface of teeth.

The kinetics of penetration of the compositions in water almost identical for Formulas A and B, whereas kinetic is and move the interface to Formula B was slower. Effective constants for mass transfer of the product Colgate and Formulas A and B were comparable. However, in the case of Formulas A and B observed the formation of a sharp interface separating a single swollen gel from the liquid solution.

In the real world wearing erosion of Formulas A and B (and hence, the wearing time), depends mainly on two factors: 1) free mutual diffusion of the composition and water (saliva) and 2) accidental mechanical shear stresses applied to the floor while wearing (that is, the friction due to the movement of the lips). The first factor can be considered as the ultimate ideal (undisturbed) process, while the latter can act on the duration of wearing abruptly and randomly, because every case of destruction of the coating dramatically changes the initial conditions of mutual diffusion (i.e. the thickness of the coating and the ingredients of the composition). Preliminary studies of wearing showed that the Formulas A and B are able to remain on the teeth for 10-15 minutes, then as a product of Colgate, as has been shown, remains on the teeth for 2-3 minutes.

Example 7

ComparativeIn Vitroefficiency is not solid songs

In Vitroefficiency is not solid compositions for whitening teeth, made according to the method described in Example 4 (Formula A), was compared with the dissolution about the ukta Colgate.

The composition of Formula A and the product Colgate inflicted on the wall of the Cup with the tea bloom to demonstrate the “primary” treatment. After 30 seconds in a Cup of injected water to close the covered surface. After 30 minutes, water was removed and the Cup was rinsed with water to remove any remnants of the gel coating from the walls. The experiment was repeated, causing each composition on the same spot, to demonstrate the “secondary” processing.

Image of the treated areas was shot with a digital camera and the resulting image was converted into a 256-pixel image in grayscale using the program Scion Image. Image calibrated so that the pixel value equal to 1 corresponds to a pure white color, and the pixel value equal to 256 corresponds to the black color. The intermediate pixel values (from 2 to 255) correspond to intermediate colors, and darkness increases from 1 to 256. The program Scion Image was used to measure the density of staining (pixel/pixel2) treated areas. The results, shown below, demonstrate that the composition of A Formula whitens better than commercially available product Colgate. A higher value of the standard deviation observed for a Formula A, is due less homogeneous coloring of the original tea stains.

Among the moderate density (pixel/pixel 2) (standard deviation)

Before processingAfter the 1st treatmentAfter the 2nd treatment
Product Colgatefor 194.3 (3,8)185,7 (6,2)178,0 (6,6)
The formula A198,3 (5,2)178,6 (8,2)167,6 (9,0)

This experiment was repeated using a non-solid composition for whitening teeth, made according to the procedure described in example 5 (Formula B), except that it was made only “first” processing.

Average density (pixel/pixel2) (standard deviation)

Before processingAfter the 1st treatment
Product Colgate116,9 (6,6)89,4 (6,79)
Formula B117,3 (5,1)79,6 (7,3)

As you can see from theseIn Vitroabove, the effectiveness of bleach is the composition of Formula A markedly superior product Colgate, the properties of the composition Formula B are intermediate between the properties of the product Colgate and Formulas A.

Example 8

In Vitrothe selection of hydrogen peroxide from solid composition

The selection of hydrogen peroxide from a non-solid composition for whitening teeth of Example 4 (Formula A) was compared with the dissolution of the Colgate product. Product Colgate poured on the detachable strip and were dried at ambient temperature for one day. The resulting film product Colgate, of a thickness of approximately 300-400 μm, were placed in glass chemical beaker and add 200 ml of water. A composition of the Formula A was poured on the bottom of the chemical glass. After 2-3 minutes, was added 200 ml of deionized water. After an appropriate period of time, the solution was carefully separated from the swollen balance and determined the concentration of hydrogen peroxide using titrimetricheskogo method of the U.S. Pharmacopoeia. The amount of hydrogen peroxide released from Colgate product and Formula A shown below.

The percentage (weight/weight.) spin-off of hydrogen peroxide

Time (min)123510 152030
Product Colgate-38,7-47,772,478,796,8-
The formula A35,035,959,567,571,9-79,290,0

Unlike Colgate product, the schedule allocation of hydrogen peroxide from a film formed by A Formula was stable and was characterized by a rapid release of active substances for the first five minutes. Within 10 minutes of contact with water of the Formula A was allocated less hydrogen peroxide than from Colgate product. After 20 minutes of contact with water the product Colgate did not contain hydrogen peroxide, whereas the Formula A contained 20% of the initial injected hydrogen peroxide. It was evidence of stronger binding of hydrogen peroxide with polymers in the Formula A, than in the Colgate product. From a comparison of the data selection and data on dissolution also concluded that hydrogen peroxide, soderjaschiesya film Formula A, can be divided into weakly bound hydrogen peroxide and firmly bound hydrogen peroxide. This is opposed to product Colgate, where all the hydrogen is bound weakly.

Example 9

ComparativeIn Vivothe effectiveness of non-solid compositions

In Vivothe effectiveness of non-solid compositions for whitening teeth, made according to the method described in Example 4 (Formula A), was compared with the dissolution of the Colgate product. The effectiveness of the whitening Formula a and Formula B was compared with the efficiency of a product Colgate, using the scale on the Vita Shade. The study was conducted by the method of randomized parallel groups double random experimental search. Eleven people who have at least four of the six upper front teeth had a rating of A3 or darker according to the evaluation scale on the Vita Shade, were recruited to participate in the study.

All 11 patients were randomly assigned to one of three groups based on the evaluations of the front teeth on the Vita Shade. Patients received the drug in a quantity sufficient to apply within 14 days, and were instructed to use the product twice a day for two weeks. On the basis of estimates for Vita and results of a survey of patients, it is obvious that the Formula A, Formula B and Colgate product all provide statistically significant bleaching the step from the seventh day of treatment. Best bleaching effect was observed for the Formula A. Formula B showed bleaching action, intermediate between A Formula and a product of Colgate. Formula A was demonstrated earlier bleaching action in comparison with Colgate product.

Example 10

Getting unsteadily compositions with multiple phases

A composition for whitening teeth were prepared from the following ingredients:

Eudragit L 100-55
PVP30
PVP90
Water
Ethanol (95%)
PEG
Eudragit RL 100
Sodium citrate
Hydrogen peroxide
of 6.99 g
14,97 g
of 4.49 g
25,95 g
28,94 g
3,99 g
of 4.49 g
0.20 g
9,98 g

The composition was mixed at low speed with high torque laboratory mixer (Cole-Parmer, supplied coated with Teflon impeller (diameter 2 inches). PEG was mixed with ethanol. Eudragit RL 100 was dissolved in a mixture of PEG with ethanol, then added to Eudragit L 100-55. Then under stirring was added sodium citrate. Then to the mixture was added water, then hydrogen peroxide and then PVP90 and PVP30, and left the mixture was mixed for two hours. The solution was kept for 2-5 hours to prevent the vanishing of the air bubbles.

Example 11

Getting unsteadily compositions with multiple phases

A composition for whitening teeth were prepared with EBUSY ingredients and mixed, as described in Example 9:

Eudragit L 100-55
PVP30
PVP90
Water
4,99 g
12,97 g
2.50 g
23,95 g
Ethanol (95%)
PEG
Eudragit RL 100
Sodium citrate
Carbamide peroxide
26,95 g
7.98 g
2.50 g
0.20 g
17,96 g

Example 12

In Vitrothe selection of hydrogen peroxide non-solid composition capable of separation of the phases.

The experiments were conducted in a manner similar to described in Example 2 to evaluate the secretion of hydrogen peroxidein vitroof compositions for whitening teeth of Examples 10 and 11. Found that the formulations of Examples 10 and 11 provide a relatively more sustainable allocation of hydrogen peroxide in comparison with the same formulations that did not contain Eudragit RL 100. The formulations of Examples 10 and 11 also provide a more sustainable allocation of hydrogen peroxide in comparison with the product of Colgate Simply White®.

1. Fathersdelaware, film-forming composition comprising a mixture of:
(a) first of swelling in water of the polymer, with specified polymer is not soluble in water at pH less than about 5.5, or water-soluble polymer;
(b) a mixture of hydrophilic polymer and complementary oligomer capable of forming hydrogen bonds is a hydrophilic polymer;
(c) a second swelling in water of the polymer, with specified polymer is not soluble in water under all pH values; and
(d) optional active substances,
in the solvent or solvent mixture, where the composition is subjected to separation of the phases when hydrating.

2. The composition according to claim 1, in which the first swelling in water, the water-insoluble polymer is a polymer or copolymer of acrylate-based.

3. The composition according to claim 2, in which the polymer or copolymer based on acrylate selected from polymers and copolymers of acrylic acid,
methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate or ethyl methacrylate.

4. The composition according to claim 3 in which the copolymer based on acrylate is a copolymer of methacrylic acid and methyl methacrylate.

5. The composition according to claim 1, in which the water-soluble polymer chosen from water-soluble polymers based on cellulose derivatives, polyvinyl alcohol, collagen, naturally occurring polysaccharides.

6. The composition according to claim 1, in which the second swelling in water, not water-soluble polymer is a cellulose ether, or a polymer or copolymer of acrylate-based.

7. The composition according to claim 6, in which the cellulose ether comprises at least one cellulosic polymer containing monomer units neeterificirovannah cellulose monomer units of cellulose acetate and either monomer units of the cellulose butyrate, or monomer units of the cellulose propionate.

8. The composition according to claim 6, in which the polymer or copolymer based on acrylate selected from polymers and copolymers of acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate or ethyl methacrylate.

9. The composition of claim 8 in which the copolymer based on acrylate is a copolymer of methacrylic acid and methyl methacrylate.

10. The composition according to claim 1, in which the weight ratio between the first swelling in water, the water-insoluble polymer and the second swelling in water, the water-insoluble polymer is in the range of about 1:3-3:1.

11. The composition of claim 10 in which the ratio is in the range of approximately 1.5:1-2:1.

12. The composition according to claim 1, in which the hydrophilic polymer is chosen from the group comprising poly(N-vinylacetate), poly(N-vinylamide), poly(N-alkylacrylate), polyacrylic acid, polymethacrylic acid, polyvinyl alcohol, polyvinyliden and their copolymers and mixtures.

13. The composition according to item 12, in which the hydrophilic polymer is chosen from the group comprising poly(N-vinylacetate), poly(N-vinylamide), poly(N-alkylacrylate) and their copolymers and mixtures.

14. The composition according to item 13, in which the hydrophilic polymer is a poly(N-vinylacetal) homopolymer or poly(N-vinylacetate).

15. The composition according to item 12, to the second poly(N-vinylacetal) is selected from the group consisting of polyvinylpyrrolidone, polyvinylcaprolactam and mixtures thereof.

16. The composition according to item 15, in which poly(N-vinylacetal) is a polyvinylpyrrolidone.

17. The composition according to item 12, in which the hydrophilic polymer has srednecenovogo molecular weight in the range of about 10000-2000000.

18. The composition according to claim 1, in which additional oligomer has a molecular weight in the range of about 45-800.

19. The composition according to p in which additional oligomer has a molecular weight in the range of about 45-600.

20. The composition according to p in which additional oligomer selected from the group consisting of a polyalcohol, Monomeric and oligomeric alkalophile, alkylene glycols, polyalkylene glycols with integral carboxyglutamic, polyalkylene glycols with terminal amino groups, partial esters of polyhydric alcohols, alkanediols and dicarboxylic acids.

21. The composition according to claim 20, in which an additional oligomer selected from the group consisting of alkylene glycols and polyalkylene glycols with integral carboxyglutamic.

22. The composition according to item 21, in which an additional oligomer selected from the group consisting of polyethylene glycols and polyethylene glycols with integral carboxyglutamic.

23. The composition according to item 21, in which an additional oligomer is a polyethylene glycol.

24. The composition according to claim 1, in which the active substance is present and represents a bleach selected from the group consisting of peroxides, metal chlorite, perborates, percarbonates, peroxyketal and their combinations.

25. The composition according to paragraph 24, in which the peroxide is chosen from the group consisting of hydrogen peroxide, calcium peroxide, carbamide peroxide, and mixtures thereof.

26. The composition according A.25, in which the peroxide is chosen from the group consisting of dialkylamides, diarilpirimido, esters of nakilat, pentaborate, ketone peroxides and hydroperoxides.

27. The composition according to paragraph 24, in which 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.

28. The composition according to claim 1, additionally containing at least one additive selected from the group consisting of flavorants, sweeteners, fillers, preservatives, pH regulators, softeners, thickeners, coloring agents, pigments, dyes, refractive particles, flavorants, sweeteners, stabilizers, additives, providing durability, substances to reduce the stickiness and amplifiers permeability.

29. The composition according to claim 1, in which the relative amounts of the first and second swelling in water of the polymers, hydro is strong polymer and additional oligomer selected to make the composition is translucent.

30. The composition according to claim 1 which contains about 0.1-60 wt.% the active substance.

31. The composition according to claim 1 which contains about 0.1-20 wt.% first of swelling in water of the polymer or water-soluble polymer and the second swelling in water, the water-insoluble polymer and about 1-30 wt.% hydrophilic polymer.

32. The composition according to p in which additional oligomer is about 1-85 wt.% from the mixture of the hydrophilic polymer/complementary oligomer.

33. The composition according to claim 1, which contains about 1-30 wt.% first of swelling in water of the polymer or water-soluble polymer and the second swelling in water, the water-insoluble polymer and about 0.1-20 wt.% hydrophilic polymer.

34. The composition according to p in which additional oligomer is about 1-85 wt.% from the mixture of the hydrophilic polymer/complementary oligomer.

35. The composition according to claim 1, which contains about 1-20 wt.% first of swelling in water of the polymer or water-soluble polymer and the second swelling in water, the water-insoluble polymer and about 20-80 wt.% hydrophilic polymer.

36. The composition according to p in which additional oligomer is about 10-80 wt.% from the mixture of the hydrophilic polymer/additional olig the measures.

37. The composition according to claim 1, which contains about 20-80 wt.% first of swelling in water of the polymer or water-soluble polymer and the second swelling in water, the water-insoluble polymer and about 1-20 wt.% hydrophilic polymer.

38. The composition according to clause 37, in which an additional oligomer is about 10-80 wt.% from the mixture of the hydrophilic polymer/complementary oligomer.

39. The method of teeth whitening, including
the coating composition according to claim 1 on the teeth that need whitening, and removing the composition, when the desired level of whitening has been achieved.

40. The method according to § 39, in which the desired level of whitening is achieved after a predetermined period of time.

41. The method according to p in which a specified period of time is from about 10 minutes to about 24 hours

42. The method according to paragraph 41, in which a specified period of time is from about 10 minutes to about 8 hours

43. The method according to § 42, in which a specified period of time is from about 30 minutes to about 1 o'clock

44. The method according to § 39, in which the composition can be worn for an extended period of time.



 

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FIELD: medicine.

SUBSTANCE: composition contains water-swelling, water-insoluble polymer, mixed hydrophilic polymer and complementary oligomer able to form hydrogen bond with hydrophilic polymer, and a bleaching agent, preferentially peroxide. The composition is applied a dental bleaching composition and applied on teeth to be bleached, and then removed as the required bleaching is reached. In best versions the composition is unstable and translucent. There are also methods of preparation and application of the compositions.

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54 cl, 10 ex

FIELD: chemistry.

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7 cl, 3 dwg, 2 tbl, 4 ex

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3 cl, 4 tbl

FIELD: chemistry.

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17 cl, 8 tbl

FIELD: composite polymer biomedicine materials containing polymer binder, biocompatible filler and carbon reinforcing filler.

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EFFECT: polymer material having natural bone-like properties.

3 cl, 10 ex, 1 tbl

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2 tbl, 4 ex

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EFFECT: improved and valuable properties of composition.

2 tbl, 9 ex

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14 cl, 7 ex

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SUBSTANCE: composition contains water-swelling, water-insoluble polymer, mixed hydrophilic polymer and complementary oligomer able to form hydrogen bond with hydrophilic polymer, and a bleaching agent, preferentially peroxide. The composition is applied a dental bleaching composition and applied on teeth to be bleached, and then removed as the required bleaching is reached. In best versions the composition is unstable and translucent. There are also methods of preparation and application of the compositions.

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54 cl, 10 ex

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5 cl, 22 ex, 5 tbl

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EFFECT: production of impact strength modifiers minimum content of which provides sufficient improvement of impact strength when tested on cut moulding composition samples, not degrading at the same time other important properties of moulding composition.

17 cl, 8 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to impregnation and hermetisation of porous products with thermally hardened compositions based on (meth)acrylic monomers. Claimed is thermally hardened composition for impregnation and hermetisation of porous products, containing (in mass fraction): 100 (meth)acrylic monomer, 0.1-0.5 nitronitrile, 0.01-0.04 hydrohynone, 0.004-0.03 disodium salt of ethylendiaminetetraacetic acid, 0.001-0.03 2,2,6,6-tetramethyl-4-oxopiperidin-1-oxyl and 0.5-5.0 non-ionogenic emulsifying agent. Method of impregnation and hermetisation of porous products includes their vacuum processing with further impregnation under vacuum and atmospheric pressure with abovementioned composition and hardening at temperature ≥90°C. Thermally-hardened composition has higher serviceability and allows to increase productivity of impregnation and hermetisation method essentially.

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2 cl, 1 tbl, 15 ex

FIELD: technological processes.

SUBSTANCE: present invention relates to the technology of modifiers production on the basis of nuclear-shell type particles used for production of molding such as films, pipes, mirror housings etc. from poly(meth)acrylates. The nuclear-shell type particle consists of a nucleus, the first shell and, if required, the second shell that on every single case consist of alkylmetacrylate and styrene recurring units with minimum glass-transition temperature of 30°C. The said particles are produced by multistage emulsion polymerisation.

EFFECT: invention ensures implementation of the process with minimum labour costs and small investments for commercial deployment.

15 cl, 2 tbl

FIELD: physics.

SUBSTANCE: invention concerns manufacturing of integrated microcircuits and other electronic devices using planar technology based on photolithographic processes. The technical task was to develop a photoactivated composition for silicon dioxide film etching for photolithographic purposes, which would allow reduce technological process of photolithographical drawing in silicon layer. The offered composition contains (mass%): polymethylmethacrylate (3.2-3.9) as polymeric substrate, ammonium fluoride (3.0-3.7) as photosensitive component, and pyridine (75.0-80.3) and trifluoroacetic acid (12.1-18.8) as solvents.

EFFECT: application of the offered composition simplifies the technological process and decreases the number of flaws of production drastically.

1 cl, 2 ex

FIELD: heat-curable sealing compositions.

SUBSTANCE: composition is proposed, containing the following mass components: 100 (meth)acrylic monomer or its mixture with an allyic monomer, 0.5-2.5 initiator, 0.01-0.32 hydroquinone, 0.01-0.13 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl, 0.004-0.05 disodium salt of ethylenediaminetetraacetic acid, 20-125 filler and 5-30 functional additives. The proposed composition has polymerising activity at 100-250°C for 3-8 minutes and breaking stress of 605-15.5 MPa. This adhesive strength is sufficient for withstanding steam pressure of up to 4 MPa. Use of the proposed composition allows for repairing steam pipes with constant supply of steam.

EFFECT: design of a heat-curable sealing composition for repairing steam pipes without interruption of steam supply.

1 cl, 1 tbl, 5 ex

FIELD: textile industry.

SUBSTANCE: invention relates to manufacture of nonwoven fabrics possessing sorption ability and can be used in making various-modification filters suitable for cleaning liquid media. Impregnating composition contains blend constituted by latexes based on rigid chain- and flexible chain-nature copolymers taken at ratio between 95:5 and 50:5, respectively, solid filler, and water, wherein ratio of all components is expressed as 1:(2.5-3.0):1. Composition is obtained by mixing and vibration action in resonance mode at frequency 50-150 Hz and action time 5-15 min.

EFFECT: increased aggregative stability of composition and physicomechanical properties of material with no additional components added.

2 cl, 2 tbl, 6 ex

FIELD: composite polymer biomedicine materials containing polymer binder, biocompatible filler and carbon reinforcing filler.

SUBSTANCE: claimed composition contains polymer binder, namely mixture of polymethylmethacrylate or methylmethacrylate copolymer with methylacrylate and monomer methylmethacrylate in ratio of polymer part to monomer from 1:0.3 to 1:0.5 mass pts (50-72 mass pts); peroxide initiator (0.05-0.5 mass pts): carbon continuous fibers of 200-1000 filaments made of hydratcellulose fiber of polyacrylonitrile fiber (2-10 mass pts); and hydroxyapatite as filler (25-40 mass pts). Method for production of material from claimed composition useful in manufacturing of jowl implants also is disclosed.

EFFECT: polymer material having natural bone-like properties.

3 cl, 10 ex, 1 tbl

The invention relates to the field of solid state ionic conductors, namely, polymer electrolytes

FIELD: medicine.

SUBSTANCE: composition contains water-swelling, water-insoluble polymer, mixed hydrophilic polymer and complementary oligomer able to form hydrogen bond with hydrophilic polymer, and a bleaching agent, preferentially peroxide. The composition is applied a dental bleaching composition and applied on teeth to be bleached, and then removed as the required bleaching is reached. In best versions the composition is unstable and translucent. There are also methods of preparation and application of the compositions.

EFFECT: reduced dental sensitivity and damage or irritation of gums and oral mucous membranes, improved clinical effectiveness.

54 cl, 10 ex

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