Hydrogel compositions with an erodible backing member

TECHNICAL FIELD [0001] The invention relates generally to hydrogel compositions. More specifically, the invention relates to hydrogel compositions useful as wound dressings and for administering a wide range of active agents to mucous membranes such as in the mouth, including tooth whiteners.

BACKGROUND ART [0002] Discoloration of teeth occurs widely in society, it is estimated to occur in two out of three adults. Teeth discoloration is considered a defect or aesthetic flaw and it can have a negative impact on the life of the affected person, causing shyness and even discouraging smiling. Tooth discoloration can be particularly disturbing or troublesome in situations and professions where showing clean and white teeth is essential.

[0003] A tooth consists of an inner dentin layer and an outer hard enamel layer that is slightly porous. The outer layer is the protective layer of the tooth. The natural color of the tooth is opaque to translucent white or slightly whitish. Stains on the teeth appear as a result of tooth contact with such compounds as tannins and other polyphenolic compounds. These compounds are retained or bound to the protein layer of the tooth surface and can penetrate the enamel or even the dentin. It happens that the appearance of spots is due to the presence of a source inside the tooth, for example, tetracycline, which can accumulate in the teeth when administered at a young age.

[0004] Surface stains can usually be removed by mechanical tooth cleaning. However, discolored enamel or dentine do not yield to mechanical methods of cleaning teeth and removing stains from them requires chemical methods that can penetrate the tooth structure. The most effective means for discoloring teeth are compositions containing an oxidant, such as hydrogen peroxide, which can react with the chromogen molecules responsible for discoloration and turn them into a colorless or water-soluble form, or both.

[0005] As a result, tooth whitening compositions generally fall into two categories: (1) gels, pastes or lotions, including toothpastes mixed mechanically on the surface of a discolored tooth to perform stain removal by abrasion of surface stains; and (2) gels, pastes or liquids that exert a whitening effect on the teeth through a chemical process in contact with the surface of the discolored tooth for a specified period of time after which the formulation is removed. In some cases, the mechanical process is supplemented with an ancillary chemical process that can be an oxidative or enzymatic process.

[0006] Some tooth compositions, such as mouthwashes, toothpastes, gels and powders contain bleaching agents that release active oxygen or

- 2 hydrogen peroxide. Such whitening agents include: peroxides, percarbonates and peroxoborates of alkali and beryllium or peroxide complexes containing hydrogen peroxide. In addition, it is known that peroxide salts of alkali or beryllium are useful in whitening teeth.

[0007] Of the many peroxides available for the teeth whitening composition formulator, hydrogen peroxide (and its addition or association complexes such as carbamide peroxide and sodium percarbonate) is almost exclusively used. Hydrogen peroxide chemistry is well known, although the special nature of its interactions with tooth chromogens is poorly understood. Hydrogen peroxide is thought to destroy tooth chromogens by oxidizing unsaturated carbon-carbon, carbon-oxygen, and carbon-nitrogen bonds found in staining molecules, making them colorless or soluble.

[0008] A related class of compounds, peracids, is used in laundry detergents to effectively bleach clothes, mainly because of the stability of these compounds in solution and the ability to specifically bind to certain types of molecules found in stains. A number of stable, solid peroxyacids are used, including diperoxododecanoic acid and the monoperoxophthalic acid magnesium salt. Other peroxyacids, such as peroxyacetic acid, are available in solutions containing the equilibrium system of acetic acid, hydrogen peroxide, peroxyacetic acid and water. Alternatively, a peroxide donor such as sodium perborate or sodium percarbonate is formulated together with the peracid precursor. In contact with water, the peroxide donor releases hydrogen peroxide, which then reacts with the peracid precursor to form the correct peracid. Examples of peroxyacids formed in situ include: peroxyacetic acid (from hydrogen peroxide and tetraacetylethylenediamine) and peroxononanoic acid (from hydrogen peroxide and nonanoyloxobenzenesulfonate).

[0009] Peroxy acids are also used in oral care compositions to bleach discolored teeth. United States Patent No. 5,279,816 to Church et al. describes a method for whitening teeth that includes the use of compositions with acidic pH containing peroxoacetic acid. EP 545,594 A1 granted to Church et al. describes the use of peroxoacetic acid to prepare a tooth whitening composition. Peroxyacetic acid may be present in the composition or alternatively may be generated in situ by combining the peroxide source with the peracetic acid precursor during use. For example, US Patent No. 5,302,375 to Viscio describes a composition generating peroxoacetic acid within a carrier in situ by combining water, acetylsalicylic acid, and water-soluble alkali percarbonate.

[0010] The most commonly used tooth whitening agent is carbamide peroxide (CO (NH₂)₂ H₂ABOUT₂), also called the urea-hydrogen peroxide complex, carbamide-hydrogen peroxide and perhydrol-urea. Carbamide peroxide has been used by dentists for several decades as a mouth disinfectant, and teeth whitening has been observed as a side effect of prolonged contact. Over-the-counter 10% carbamide peroxide compositions are available under the name GLY-OXIDE® from Marion Laboratories and under the name PROXIGEL® from Reed and Carnrick, which are

- 3 compositions with low viscosity, which in order to ensure contact with the tooth must be kept in an impression spoon or similar container. A whitening gel that is able to hold a comfortably fitted impression tray in place for a long time is available under the name OPALESCENCE® from Ultradent Products, Inc., South Jordan, Utah.

[0011] For such compositions to remain in place, they must be a viscous liquid or gel. The use of impression spoons also requires the selection of a spoon for comfort and fit, so that it does not exert pressure and cause irritation of the teeth or gums. Such bleaching compositions should necessarily be formulated to be sticky enough to resist salivation.

[0012] In one method of teeth whitening, the dentist will build a patient-adapted impression spoon for whitening teeth based on the patient's tooth impression and prescribe the use of an oxidizing gel, which should be applied to the whitening spoon and worn with breaks for a period of about 2 weeks to about 6 months, depending on how severe the tooth discoloration is. These oxidizing compositions, usually packaged in small plastic syringes or tubes, are dispensed directly by the patient into a patient-tailored whitening spoon that stays in the mouth for a contact time of more than about 60 minutes, and sometimes even 8 to 12 hours. The low whitening speed is largely a consequence of the very nature of the formulation, which is formulated to maintain the stability of the oxidizing composition.

[0013] For example, US Patent No. 6,368,576 to Jensen describes tooth whitening compositions, preferably used together with a tray so that the composition is held adjacent to the surface of the whitened teeth. These compositions have been described as a viscous matrix material formed by combining a sufficient amount of binder, such as carboxypolymethylene, with a solvent such as glycerin, polyethylene glycol or water.

[0014] In another example, US Patent No. 5,718,886 to Pellico describes a tooth whitening composition in the form of a gel composition comprising carbamide peroxide dispersed in an anhydrous gelatinous carrier that includes polyol, thickener and xanthan gum.

[0015] Still another example is described in US Patent No. 6,419,905 to Hernandez, which describes the use of compositions containing carbamide peroxide (0.3-60%), xylitol (0.5-50%), potassium salt (0.001-10%) and fluorine salt (0.15-3%), formulated in a gel containing from 0.5 to 6% by mass the right thickener.

[0016] A tooth whitening composition that adheres to teeth is described in US Patent Nos. 5,989,569 and 6,045,811 to Dirksing. According to these patents, the gel contains 30-85% glycerin or polyethylene glycol, 10-22% urea / hydrogen peroxide complex, 0-12% carboxypolymethylene, 0-1% sodium hydroxide, 0-100% triethanolamine (TEA), 0-40% water, 0-1% flavor, 0-15% sodium citrate and 05% ethylenediaminetetraacetic acid. The preferred Dirksing gel has a viscosity of 200 to 1,000,000 cps at low shear rates (less than one 1 / s) and is viscous enough to eliminate the need for a spoon.

[0017] US 2003/0152528 discloses a composition comprising a water-swollen water-insoluble polymer, a blend of a hydrophilic polymer and a complementary oligomer capable of forming a hydrogen bond with the hydrophilic polymer, and a bleaching agent, preferably a peroxide. This composition is used as a tooth whitening composition.

[0018] Currently available tooth whitening compositions have a significant disadvantage in that they cause tooth sensitivity in more than 50% of patients. Teeth hypersensitivity may result from fluid movement through the dentinal tubules, which is sensed by the nerve endings in the tooth due to the presence of glycerin, propylene glycol and polyethylene glycol in these compositions. this can lead to varying degrees of tooth sensitivity after exposure to heat, cold, excessively sweet substances, and other causal factors.

[0019] Prolonged contact of teeth with whitening compositions as is currently practiced has a number of adverse effects besides tooth sensitivity. These adverse effects include leaching of calcium from the enamel layer at a pH lower than 5.5; the penetration of bleaching agents into intact enamel and dentin, and the risk of damage to the tooth pulp; and diluting the whitening compositions with saliva, leading to the rinsing of the composition from the impression spoon and subsequent swallowing by the user.

[0020] Some oxidizing compositions (usually having a relatively high concentration of oxidants) are applied directly to the patient's tooth surface in a dental office, under the supervision of a dentist or dental technician. Theoretically, such tooth whitening strategies result in faster results and greater overall patient satisfaction. However, due to the high concentration of oxidants contained in these so-called "cabinet" compositions, they can be harmful to both the patient and the doctor if not used with caution. The patient's soft tissues (gums, lips and other mucous membranes) should first be protected against possible contact with the active oxidant by using a perforated rubber sheet (also known as salivary gland) in such a way that only teeth protrude from it. Alternatively, soft tissue can be protected against oxidants to be used in the whitening process by covering it with a polymerizable composition formed to match the contours of the gums and then curing it with a high intensity light source. After isolating and securing soft tissue, the doctor can apply the oxidant directly to discolored tooth surfaces for a specific period of time or until sufficient color change occurs. Typical results achieved thanks to the use of a dental teeth whitener reach from about 2 to 3 shades (as measured by the VITA Shade Guide, VITAZahnfarbik standard).

[0021] The tooth shade range on the VITA Shade Guide ranges from very light (B1) to very dark (C4). The entire range between the two ends of the brightness scale includes 16 shades of the tooth. Patient satisfaction with the teeth whitening procedure increases with the number of tooth shade changes obtained, with the commonly accepted minimum change being from about 4 to 5 VITA shades.

[0022] Regarding whitening tooth care products, it is desirable to provide tooth care products using an adhesive hydrogel that

- 5 contains a bleaching agent for removing tooth stains. In addition, there is a continuing need for product development to provide a protective dressing for mucous membranes or to provide delivery of active agents, e.g., mucosal delivery, mucosal, surface, gums, mucous membranes and other oral tissues. Compositions that do not require the use of impression trays to provide contact between the active agent and a tooth or other oral surface are desirable. Such products would ideally cause minimal or no tooth hypersensitivity, minimize or eliminate leakage of the active agent leading to swallowing by the user or to damage or irritation of the gums or mucous membranes of the oral cavity, ensure longer durability, long-lasting dissolution of the active agent, increased efficiency, and were well tolerated by patients. It would also be desirable to provide a dental care product that is a solid and self-adhesive composition but that does not stick to the user's fingers or a product that is not solid (e.g., a liquid or gel) and that forms a film when dry. Finally, current dental care products require the system to be worn for a certain period of time, e.g. 30 minutes, before the user takes it off. It is desirable to develop products that can break down by themselves when the active agent is released or after achieving the desired therapeutic or cosmetic effect, since such systems would improve patient compliance. The present invention meets these needs.

DISCLOSURE OF THE INVENTION [0023] One aspect of the invention relates to a product comprising:

(a) a hydrogel containing:

(i) a water-swollen water-insoluble polymer, (ii) a blend of a hydrophilic polymer with a complementary oligomer capable of forming a hydrogen or electrostatic bond with the hydrophilic polymer; and (iii) an optional active agent; and (b) a primer, wherein the primer comprises a polymer composition comprising a water-swellable water-insoluble polymer composition;

where the hydrogel disintegrates within 1 second to 24 hours in a humid environment, and the primer disintegrates in a humid environment more slowly than the hydrogel.

The product may contain an active agent such as a tooth whitening agent. The product contains a primer that breaks down more slowly than a hydrogel in a humid environment. The hydrogel may be solid and attached to the foundation before use. The hydrogel may also not be solid and may be attached to the foundation during use.

[0024] In a preferred embodiment, the water-swellable water-insoluble polymer is a cellulose ester or an acrylate polymer; the hydrophilic polymer is poly (N-vinyl lactam), poly (N-vinylamide), poly (N-alkylacrylamide) or a copolymer and blend thereof; the complement oligomer capable of forming a hydrogen or electrostatic bond with the hydrophilic polymer is a polyhydric alcohol,

- 6 poly (alkylene glycol) or carboxy terminal poly (alkylene glycol). The preferred active agent is a bleaching agent such as peroxide.

[0025] The product optionally contains a low molecular weight plasticizer and may also contain at least one additive selected from the group consisting of fillers, preservatives, acidity regulators, plasticizers, thickeners, dyes (e.g. pigments, dyes, refractive particles etc.) , flavoring agents (e.g. sweeteners, flavors), stabilizers, surfactants, roughing agents and viscosity reducing agents.

[0026] In a preferred method of using the product, the product is a tooth whitening composition and is applied to the teeth when bleaching is required, and then removed when the desired degree of whitening is achieved. In some embodiments, the tooth whitening composition is translucent and is removed when the user is satisfied with the degree of whitening obtained.

[0027] Yet another embodiment of the invention relates to a product comprising a water swollen water insoluble polymer, a blend of a hydrophilic polymer with a complementary oligomer capable of forming a hydrogen or electrostatic bond with the hydrophilic polymer and an active agent. In one embodiment, the active agent is selected from the group consisting of peroxides, metal chlorates, perborates, percarbonates, peracids, and combinations thereof. The product also contains a foundation that breaks down more slowly than the hydrogel.

[0028] Also described is a method of obtaining a hydrogel film suitable for inclusion in an oral care composition or a mucosal membrane. This method includes preparing a solution or gel of a swollen water insoluble polymer, hydrophilic polymer and complementary oligomer capable of forming a hydrogen or electrostatic bond with a hydrophilic polymer in a solvent; putting a layer of the solution on the substrate to obtain a coating on it; and heating the coated substrate to a temperature in the range of from about 80 ° C to about 100 ° C for a time in the range of from about 1 to about 4 hours, thereby obtaining a hydrogel film on the substrate.

[0029] In another method of making the product of the invention, the method comprises hot extruder processing of a mixture of a water-swollen, water-insoluble polymer, a hydrophilic polymer and a complementary oligomer capable of forming a hydrogen or electrostatic bond with the hydrophilic polymer to produce an extruded composition; wherein the composition is extruded as a film of the desired thickness on a suitable support. The substrate may be a disintegrating primer or the composition may later be applied to a disintegrating primer by pressing or gluing. The method further comprises filling the hydrogel film with an active agent such as a whitening agent, thereby providing a tooth whitening composition. According to another embodiment of the invention, the product is used as a combined preparation for use in teeth whitening; where the hydrogel is applied to the teeth, and then the substrate is applied to the hydrogel.

[0030] Adhesive compositions and products of the invention provide a number of significant

- 7 advantages over the state of the art. In particular, the compositions and products described provide one or more of the following advantages over the prior art:

(1) ensure ease of use;

(2) they are easily modified during production, so that properties such as viscosity, absorption, transparency and swelling can be controlled and optimized;

(3) they can be formulated in such a way that the stickiness increases or decreases in the presence of moisture, so that the composition is not sticky until it is wetted;

(4) minimize leakage of active agent (when incorporated) from the composition onto the mucosal surface (e.g. into the user's mouth);

(5) they can be made in a translucent form, which allows the user to view the degree of whitening without removing the hydrogel composition from the teeth or from the mucosal surface;

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

(7) they can be worn comfortably and discreetly;

(8) they are easily removed from the surface of the teeth or mucosa and leave no residue;

(9) can survive prolonged abrasion or operation;

(10) they can ensure uniform and controlled release of a variety of active agents;

(11) they can be formulated in such a way that they fall apart after a certain time; and (12) they can be formulated so that they deliver active agents unidirectional, e.g., only towards mucosal tissue, or bidirectionally, e.g., towards the mucosal surface and towards the oral cavity, and the relative delivery rates towards the mucosal surface and towards the oral cavity is controlled by selecting a foundation with a fixed permeability.

WAYS OF CARRYING OUT THE INVENTION

I. DEFINITIONS AND NAMING [0031] Before describing the invention in detail, it should be understood that, unless otherwise indicated, the invention is not limited to specific hydrogel materials or manufacturing processes, as they may vary. It should also be understood that the terminology used in this document is for the purpose of describing specific embodiments only and is not intended to be limiting. It should be noted that the singular "a", "an" and "the" used in the (English) specification and appended claims includes plurals unless the context clearly indicates otherwise. Therefore, for example, reference to "hydrophilic polymer" includes not only a single hydrophilic polymer, but also a combination or mixture of two or more different hydrophilic polymers, reference to "plasticizer" includes a combination or mixture of two or more different plasticizers, as well as a single plasticizer etc. .

[0032] In the description and claims of the invention, the following terminology will be used in accordance with the definitions given below.

[0033] The definitions of "hydrophobic" and "hydrophilic" polymers are based on the amount of water vapor absorbed by the polymers at a relative humidity of 100%. According to this classification, hydrophobic polymers absorb only 1% by mass. water at 100% relative humidity ("rh"), while moderately hydrophilic polymers absorb 1-10% by mass. water, hydrophilic polymers are able to absorb over 10% by mass. water, and hygroscopic polymers absorb over 20% by mass. water. A "water-swollen" polymer is a polymer that absorbs more than 25% or more by weight of water. by weight, preferably at least 50% by weight own mass after immersion in an aqueous medium.

[0034] The term "cross-linked / cross-linked" in this document refers to compositions comprising intramolecular and / or intermolecular crosslinks resulting from covalent or non-covalent interactions. The "non-covalent" interaction includes both hydrogen and electrostatic (ionic) bonds.

[0035] The term "polymer" includes linear and branched polymeric structures as well as crosslinked polymers as well as copolymers (which may or may not be crosslinked), thereby including block copolymers, alternating copolymers, random copolymers etc. The compounds referred to in this document as "Oligomers" are polymers with a molecular weight below about 1000 Da, preferably below about 800 Da.

[0036] The term "hydrogel" is used in the conventional sense to mean water-swollen polymeric matrices that can absorb a significant amount of water and form flexible gels, where the "matrices" are three-dimensional networks of macromolecules held together by covalent or non-covalent crosslinks. When placed in an aqueous environment, dry hydrogels swell to an extent acceptable by the degree of crosslinking. Hydrogels are also degradable.

[0037] The term "disintegrates" as in the expression "disintegrating hydrogel" or "disintegrating" as in the expression "disintegrating undercoat" is intended to include processes of erosion, dissolution, disintegration and degradation, and also includes those materials which biodegradable or biodegradable. Regardless of the mechanism by which the hydrogel and primer disintegrate in a humid environment, the primer components are preferably selected so that the primer "disintegrates" more slowly than the hydrogel components.

[0038] The terms "active agent," "pharmacologically active agent" and "drug" are used interchangeably herein to designate a material or chemical compound that has the desired pharmacological, physiological effect, and contains therapeutically effective, prophylactically effective or cosmeceutically effective agents. These terms also include pharmaceutically acceptable, pharmacologically active derivatives and analogs of those active agents that are specifically mentioned in this document, including (but not limited to) salts, esters, amides, prodrugs, active metabolites, inclusion compounds, analogues, etc. When the terms "active agent", "pharmacologically active agent" and "drug" are used, it should be understood that it includes both active agent per se and pharmaceutically acceptable pharmacologically active agent

- 9 salts, esters, amides, prodrugs, active metabolites, inclusion compounds, analogues, etc.

[0039] The term "tooth whitening composition" refers to a composition that comprises a hydrogel as defined herein and a whitening agent.

[0040] The term "bleaching agent" typically refers to an oxidant such as peroxide or chlorate (III) as will be discussed in more detail below. In some cases, the whitening agent may be an enzyme or other catalytic agent for removing tooth stains. The whitening agent may include one or more additional bleaching agents, surfactants, anti-plaque agents, anti-calculus agents and abrasives. The whitening agent may have additional therapeutic benefits.

[0041] The term "effective amount" or "cosmeceutically effective amount" of a cosmeceutical active agent is intended to mean an amount of cosmeceutical active agent non-toxic but sufficient to produce the desired cosmetic effect. The term "effective amount" or "therapeutically effective amount" of a drug or pharmacologically active agent is intended to mean an amount of drug or non-toxic agent that is sufficient to produce the desired therapeutic effect. The amount of "effective" amount will vary, depending on the age and general condition of the individual, the particular active agent or agents, etc. Therefore, it is not always possible to accurately determine the "effective amount". However, in each individual case, the appropriate "effective" amount can be determined using one of the ordinary skill in the art using routine experimentation. In addition, the exact "effective" amount of active agent included in the composition or dosage form of the invention is not critical as long as the concentration is in a range sufficient to permit easy application of the formulation in such a way as to provide an amount of active agent within the therapeutically effective range.

[0042] The term "surface" as in the case of the "oral surface" or "body surface" is intended to include surfaces of the body mucosa (e.g., sublingual, oral, vaginal, rectal, urethral) as well as surfaces in the mouth and around her (e.g. teeth, lips, gums, mucous membranes). These surfaces are usually found in the environment known as "moist".

[0043] Delivery of the drug "through the mucosa" means the administration of the drug to the surface of the user's mucosa so that the drug passes through the mucosa (e.g. sublingual, oral, vaginal, rectal, urethral) and reaches the bloodstream, thereby producing a systemic effect . The term "trans-mucosa" is intended to include both local and systemic effects, thus including topical administration, i.e. delivery of a topical agent to the mucosa, such as in the treatment of various mucosal disorders to provide a local effect.

[0044] The terms "adhesive" and "adhesive" are qualitative. However, the terms "substantially non-adhesive" "slightly adhesive" and "adhesive" as used herein may be quantified based on the values ​​obtained in determining viscosity by the PKI or TRBT method as follows. The phrase "substantially non-adhesive" means a hydrogel composition whose adhesive value is less than 25 g-cm / s, the expression "slightly adhesive" means a hydrogel composition whose adhesive value is within

- in the range of about 25 g-cm / s to about 100 g-cm / s, and the term "adhesive" means a hydrogel composition with an adhesive value of at least 100 g-55cm / s.

[0045] The term "insoluble in water" refers to a compound or composition with water solubility below 5 wt.%, Preferably below 3 wt.%, More preferably below 1 wt.% (measured in water at 20 ° C).

[0046] The term "translucent" is used herein to mean a material that can transmit light so that objects or images can be seen through it. These translucent materials may or may not be "transparent", wherein transparent means that the material is optically transparent. The term "translucent" indicates that the material is not "opaque", in which case objects and images could not be seen through the material.

II. HYDROGEL COMPOSITIONS [0047] The product of the invention is a single-phase hydrogel comprising a water-swollen water-insoluble polymer and a blend of a hydrophilic polymer with a complementary oligomer and an optional active agent such as a bleaching agent. Both the water-swollen water-insoluble polymer and the oligomer may be able to form a hydrogen or electrostatic bond with the hydrophilic polymer.

[0048] The product also contains a primer containing a polymer composition that breaks down more slowly than a hydrogel in a moist medium.

[0049] The water-swollen water-insoluble polymer, i.e. a polymer that is able to swell when immersed in an aqueous liquid, but is insoluble in water in a selected pH range (usually below pH = 5.5), is a cellulose, acid ester alginate or acrylate polymer. The term "acrylate polymer" is intended to include acrylate and acrylate based polymers and copolymers and is a polymer of acrylic acid or acrylic acid ester. The polymer usually swells by at least 25% by mass. and preferably at least 50 wt. own mass after immersion in water or an aqueous solution. In some embodiments using certain hydrophilic polymers, the composition can swell by up to 1400% by weight. dry matter.

[0050] In one embodiment, the product is a tooth whitening composition in which the whitening agent acts to whiten the surface of the tooth to which the composition is applied. However, the whitening agent may have other functions, for example as a medicament or other type of cosmeceutical agent, e.g. for skin whitening. Therefore, the products described in this document may find use as pharmaceutical compositions for application to the surface of the body (e.g. teeth, nails, skin, mucous membranes, etc.) to treat the condition. For example, hydrogen peroxide also has antibiotic and anti-acne properties, and is also a bleaching agent. Therefore, the invention also contemplates treating an infection or acne by applying to the body surface a composition of the invention containing hydrogen peroxide. Other medical conditions include, as an illustration and not a limitation, fungal infections, acne, cuts, skin lightening, etc. In addition, a number of active agents may be incorporated into the product of the invention to treat a variety of oral diseases.

A. WATER-FOLDED WATER-SOLUBLE POLYMERS [0051] For solid compositions, the water-swollen water-insoluble polymer is about 1-20% by weight, preferably about 6-12% by weight. of the composition; the hydrophilic polymer constitutes about 20-80% by mass, preferably about 40-60% by mass of the composition; the complementary oligomer constitutes about 10-50 wt.%, preferably about 15-35 wt. of the composition; and the active agent, when present, comprises about 0.1-60 wt.%, preferably about 1-30 wt. of the composition. Optimally, the complement oligomer is about 10-80% by mass, preferably about 20-50% by mass hydrophilic polymer / complement oligomer blends.

[0052] For compositions other than solid water-swollen, the water-insoluble polymer is about 0.1-20 wt.%, Preferably about 2-6 wt. of the composition; the hydrophilic polymer constitutes about 1-40% by mass, preferably about 4-10% by mass of the composition; the complementary oligomer constitutes about 0.1-20% by mass, preferably about 0.5-10% by mass of the composition; and the active agent, when present, comprises about 0.1-60 wt.%, preferably about 1-40 wt.% of the composition. Optimally, the complement oligomer constitutes about 1-85% by mass, preferably about

5-50% by mass hydrophilic polymer / complement oligomer blends.

[0053] The viscosity profile can be adjusted based on the polymer type, composition ratio and amount of water in the mix. The water-swollen water-insoluble polymer is selected so as to provide the desired viscosity profile with regard to hydration. That is, when the water-swollen water-insoluble polymer is a cellulose ester, the composition is usually adhesive prior to contact with water (e.g., a wet surface), but gradually loses adhesion as the composition absorbs moisture. When the water-swollen water-insoluble polymer is an acrylate polymer or copolymer, a composition is provided that is generally substantially non-adhesive prior to contact with water, but becomes adhesive when in contact with a wet surface.

[0054] The water-swollen water-insoluble polymer is capable of at least some degree of swelling when immersed in an aqueous liquid, but is insoluble in water. The hydrophilic polymer may assist in dissolving water-insoluble polymer. This polymer may contain cellulose ester, e.g. cellulose acetate (CA), cellulose acetate propionate (CAP), butyrate cellulose acetate (CAB), cellulose propionate (CP), cellulose butyrate (CB), cellulose butyrate (CPB), cellulose diacetate (CDA), cellulose triacetate (CTA) or the like. These cellulose esters are described in US Patent Nos. 1,698,049, 1,683,347, 1,880,808, 1,880,560, 1,984,147, 2,129,052 and 3,617,201, and can be obtained using methods known in the art or purchased. Commercially available suitable cellulose esters include CA 320, CA 398, CAB 381, CAB 551, CAB 553, CAP 482, CAP 504, all available from Eastman Chemical Company, Kingsport, Tennessee. Such cellulose esters typically have a number average molecular weight from about 10,000 to about 75,000.

[0055] Typically, the cellulose ester comprises a mixture of cellulose monomer units and cellulose ester; for example, commercially available cellulose acetate butyrate contains monomeric units of cellulose acetate, as well as monomeric units of cellulose butyrate and monomeric units of non-esterified cellulose, while cellulose acetate propionate contains monomeric units such as cellulose propionate. Preferred esters here

- 12 cellulose are cellulose acetate propionate compositions and cellulose acetate butyrate compositions having a content of butyryl, propionyl, acetyl and non-esterified (OH) cellulose as indicated below:

<td></td><td></td><td>acetyl (%)</td><td>OH (%)</td><td>MW (g / mol)</td><td>Tg (° C)</td><td>T_m (° C)</td>

<td>pthalate cellulose</td><td>17-52% butyrate</td><td> 2,0-29,5</td><td> 1,1-4,8</td><td> 12.000-70.000</td><td> 96-141</td><td> 130-240</td>

<td>acetate propionate cellulose</td><td>42,5-47,7% propionate</td><td> 0,6-1,5</td><td> 1,7-5,0</td><td> 15.000-75.000</td><td> 142-159</td><td> 188-210</td>

The preferred molecular weight, glass transition temperature (T_g) and melting point (T_m). In addition, suitable cellulosic polymers typically have a log viscosity number (IV) of from about 0.2 to about 3.0 deciliter / gram, preferably about 1 to about 1.6 deciliter / gram, measured at 25 ° C for 0.5 gram samples in 100 ml solution 60/40 mass phenol / tetrachloroethane. When manufactured by immersion molding, the water-swellable polymer insoluble in water should be chosen in such a way that it provides greater resolving strength and thereby allows film formation (typically, for example, cellulose acetate propionate increases the resolving strength more than ozone acetate butyrate).

[0056] Other preferred water-swollen polymers include acrylate polymers, usually made 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, L, S, RL, RS and NE copolymers are available as organic solvent solutions, aqueous dispersions or dry powder. Preferred acrylate polymers are copolymers of methacrylic acid and methyl methacrylate, such as the Eudragit L and Eudragit S polymers. Particularly preferred such copolymers are Eudragit L 30D-55 and Eudragit L 100-55 (the latter is the spray-dried form of Eudragit L 30D-55 , which can be reproduced by connecting to water). The molecular weight of Eudragit L 30D-55 and Eudragit L 100-55 copolymer is approximately 135,000 Da, with a ratio of free carboxyl groups to ester groups of approximately 1: 1. Eudragit L100-55 copolymer is generally insoluble in aqueous liquids with a pH below 5.5. Another particularly suitable copolymer of methacrylic acid and methyl methacrylate is Eudragit S-100, which differs from Eudragit L 30D-55 in that the ratio of free carboxyl groups to ester groups is approximately 1: 2. Eudragit S-100 is insoluble at a pH below 5.5, but unlike Eudragit L 30D-55, it is poorly soluble in aqueous liquids with a pH in the range of 5.5 to 7.0. This copolymer is soluble at pH 7.0 and higher. You can also use Eudragit L 100, which has a pH-solubility profile intermediate between Eudragit L 30D-55 and Eudragit S-100, insofar as it is insoluble at a pH below 6.0. Those skilled in the art will appreciate that Eudragit L30D-55, L 100-55, L 100 and S 100 can be replaced with other acceptable polymers with similar pH-solubility characteristics. Other suitable acrylate polymers are acid copolymers

- 13 methacrylic / ethyl acrylate available under the trade name "Kollicoat" from BASF AG (Germany). For example, Kollicoat MAE has the same molecular structure as Eudragit L 10055.

[0057] When the water-swollen polymer is a polymer of acrylic acid or acrylate, a hydrogel is provided that can be reversibly dried, i.e. after removal of water and any other solvents, the dried hydrogel can be restored to its original state by the addition of water. In addition, hydrophilic hydrogels obtained from a water-swollen acrylic acid / acrylate polymer are generally substantially non-adhesive prior to contact with water, but become adhesive when in contact with a moist surface, such as that found inside the mouth, such as the surface of a tooth. The non-sticking property prior to contact with water allows placement or displacement on a selected surface before or during the hydrogel. After hydration, the hydrogel becomes sticky and sticks to the surface of the teeth or mucosal surface.

[0058] In addition, compositions containing acrylates can usually provide swelling in the range of about 400% to 1500% after immersing the hydrogel composition in water or another aqueous liquid at a pH below 5.5, although the ratio of the acrylate polymer to the hydrophilic polymer / complement oligomer blend can be select in such a way that the swelling rate and extent of the aqueous medium will have a predetermined dependence on the pH. This feature also ensures retroactive incorporation of bleaching agents or other active agents, such as the incorporation of peroxide, peracids, chlorates (III), stabilizers, flavors, etc. into the composition.

[0059] On the other hand, the introduction of cellulose ester as a water-swollen polymer makes the hydrogel sticky before application to a wet surface, but non-sticky after water absorption. It will be appreciated that such a composition may be desirable when a decrease in adhesion is needed to finally remove the product from the teeth.

[0060] Another suitable water-swellable insoluble polymer is alginic acid, which is insoluble in water at a pH below 5.5, but is capable of absorbing water and swelling.

B. HYDROPHILIC POLYMERS [0061] The second component of the hydrogel composition is a blend of a hydrophilic polymer with a complementary oligomer capable of forming a hydrogen or electrostatic bond with the hydrophilic polymer. Its term "blend" is intended to mean that the interaction of the hydrophilic polymer and oligomer dominates the properties of the hydrogel. However, the addition of a water-swollen water-insoluble polymer serves to adjust the properties of this blend for a single-phase hydrogel with the desired characteristics. Such alignment can be achieved by choosing a particular water-swollen water-insoluble polymer or by incorporating a certain amount of polymer, or even for a suitable time to add the polymer to the remaining ingredients (hydrophilic polymer, complement oligomer, active agent, etc.) during production.

[0062] The hydrophilic polymer is usually a relatively high molecular weight polymer and the complement oligomer is usually a lower molecular weight polymer. In case of

- 14 solid compositions, the water-swollen water-insoluble polymer constitutes about 120% by mass, preferably about 6-12% by mass. of the composition; the hydrophilic polymer constitutes about 2080 mass%, preferably about 40-60 mass% of the composition; the complementary oligomer makes up approx

10-50 wt.%, Preferably about 15-35 wt. of the composition; and the bleaching agent constitutes about 0.1-6 wt.%, preferably about 1-30 wt. of the composition. Optimally, the complement oligomer is about 10-80% by mass, preferably about 20-50% by mass hydrophilic polymer / complement oligomer blends.

[0063] Suitable hydrophilic polymers include repeat units derived from N-vinyl lactam monomer, carboxyvinyl monomer, vinyl ester monomer, carboxyvinyl monomer ester, vinylamide monomer and / or hydroxyvinyl monomer. Such polymers include, for example, poly (N-vinyl lactams), poly (N-vinylacrylamides), poly (N-alkylacrylamides), substituted and unsubstituted acrylic and methacrylic acid polymers (e.g. poly (acrylic acids) and poly (methacrylic acids)), poly (vinyl alcohol) (PVA), polyvinylamine, their copolymers and copolymers with other types of hydrophilic monomers (e.g. vinyl acetate).

[0064] The poly (N-vinyl lactams) useful herein are preferably non-crosslinked homopolymers or copolymers of N-vinyl lactam monomer units, wherein the N-vinyl lactam monomer units constitute the majority of the total amount of poly (N-vinyl lactams) monomer units. Preferred poly (N-vinyl lactams) for use in combination with the invention are obtained by polymerizing one or more of the following N-vinyl lactam monomers: N-vinyl-2-pyrrolidone; N-winylo2-valerolactam; and N-vinyl-2-caprolactam. Non-limiting examples of non-N-vinyl lactam comonomers useful for N-vinyl lactam monomer units include N, N-dimethylacrylamide, acrylic acid, methacrylic acid, hydroxyethyl methacrylate, acrylamide, 2-acrylamido-2-methyl-1-propanesulfonic acid or its salt and acetate chloride.

[0065] Poly (N-alkylacrylamides) include, for example, poly (methacrylamide) and poly (Nisopropylacrylamide) (PNIPAM).

[0066] Polymers of carboxyvinyl monomers are usually formed from acrylic acid, methacrylic acid, crotonic acid, isoconic acid, itaconic acid and anhydride, 1,2-dicarboxylic acid such as maleic acid or fumaric acid, maleic anhydride or mixtures thereof, with preferred polymers hydrophilic in this class include poly (acrylic acid) and poly (methacrylic acid), with poly (acrylic acid) being most preferred.

[0067] Preferred hydrophilic polymers herein are: poly (N-vinyl lactams), especially polyvinylpyrrolidone (PVP) and polyvinylcaprolactam (PVCap); poly (N-vinylacetamides), especially polyacetamide per se; polymers of carboxyvinyl monomers, especially poly (acrylic acid) and poly (methacrylic acid); and their copolymers and blends. PVP and PVCap are particularly preferred.

[0068] The molecular weight of the hydrophilic polymer is not critical; however, the number average molecular weight of the hydrophilic polymer is usually in the range from about 100,000 to 2,000,000, more typically in the range from about 500,000 to 1,500,000.

The oligomer is "complementary" to hydrophilic polymers in that it is capable of forming hydrogen or electrostatic bonds with them. Preferably, the complement oligomer is terminated with hydroxyl, amino or carboxyl groups. The oligomer usually has a glass transition temperature T_g in the range of about -100 ° C to about 30 ° C and melting point T_m below about 20 ° C. The oligomer may also be amorphous. The difference between T values_g the hydrophilic polymer and oligomer is preferably greater than about 50 ° C, more preferably greater than about 100 ° C, and most preferably in the range of about 150 ° C to about 300 ° C. The hydrophilic polymer and complement oligomer should be compatible, i.e. capable of forming a homogeneous mixture.

C. COMPLEMENTARY OLIGOMER [0069] As noted above, the complementary oligomer is capable of forming a hydrogen or electrostatic bond with a hydrophilic polymer. The complement oligomer may also be able to form a covalent bond with a hydrophilic polymer. In addition, the complement oligomer may be capable of forming a hydrogen or electrostatic bond with the water-swollen water-insoluble polymer.

[0070] Typically, the complement oligomer will have a molecular weight in the range from about 45 to about 800, preferably in the range from about 45 to about 600. The complement oligomer is preferably a low molecular weight poly (alkylene glycol) (molecular weight 200-600), such as poly (ethylene glycol) 400, which can also serve as a low molecular weight plasticizer. Alternatively, another compound may be introduced as an additional low molecular weight plasticizer, in which case any of the low molecular weight plasticizers described below may be used. In one embodiment of the invention, the complement oligomer is a low molecular weight or oligomeric complement plasticizer that contains at least two functional groups per molecule capable of forming a hydrogen or electrostatic bond with a hydrophilic polymer.

[0071] In some cases, the complement oligomer can also serve as a low molecular weight plasticizer. Alternatively, another compound may be introduced as an additional low molecular weight plasticizer and would have been present in an amount of about 30-35% by weight if it had been introduced. of the composition.

Examples of suitable complementary oligomers include, but are not limited to, low molecular weight polyhydroxyl alcohols (e.g. glycerol or sorbitol), monomeric and oligoalkylene glycols such as ethylene glycol and propylene glycol, alcohol ethers (e.g. glycol ethers) , carbonic acids, alkanediols from butanediol to octanediol, including carboxy-terminal and amino-terminal derivatives of poly (alkylene glycols). Poly (alkylene glycols), optionally carboxy terminal, are preferred here and poly (ethylene glycol) with a molecular weight in the range from about 200 to 600 is an optimal complement oligomer.

[0073] It will be appreciated from the above that a single compound, e.g., a low molecular weight poly (alkylene glycol), such as poly (ethylene glycol) with a molecular weight in the range from about 200 to 600, can serve as both a complementary oligomer and and low molecular weight plasticizer.

[0074] As discussed in US Patent Document 2002/0037977 to Feldstein et al., The ratio of hydrophilic polymer to complementary oligomer in the aforementioned blend affects both adhesion strength and resolvability. As explained in the aforementioned patent application, the complement oligomer lowers the glass transition temperature of the hydrophilic polymer / complement oligomer to a greater extent than the Fox equation predicts, expressed by formula (1) (1) = ^INpol + 0 ^

T TT g predicted g pol g pl where T_{g predicted} is the predicted glass transition temperature of the hydrophilic polymer / complement oligomer, in_afterand is the mass fraction of hydrophilic polymer in the blend, w_pand is the mass fraction of complement oligomer in the mixture, T_{g poi}is the glass transition temperature of the hydrophilic polymer and T_{g pi} is the glass transition temperature of the complement oligomer. As also explained in this patent application, the adhesive composition with optimized adhesion and resolvability can be made of a hydrophilic polymer with complementary oligomer by selecting components and their relative contents to obtain a predetermined deviation from T_{g predicted}. Usually a pre-determined deviation from T to maximize viscosity_gedi_cted will be the maximum negative deviation, while to minimize the viscosity any negative deviation from T_gpredicted is minimized.

[0075] Since the complement oligomer can itself act as a plasticizer, the addition of a plasticizer to be added is usually not necessary. However, the inclusion of an additional low molecular weight plasticizer in the composition is optional and may be preferred in some cases. Suitable low molecular weight plasticizers include: dialkyl phthalates, dicycloalkyl phthalates, diaryl phthalates and mixed alkylaryl phthalates such as dimethyl phthalate, di ethyl phthalate, dipropyl phthalate, di (2-ethylhexyl) phthalate, diisopropyl phthalate, and diisopropyl phthalate ; (V) alkyl and aryl phosphates such as tributyl phosphate, trioctyl phosphate, tricresyl phosphate and triphenyl phosphate; alkyl citrates and citrate esters such as trimethyl citrate, triethyl citrate, tributyl citrate, acetyltriethyl citrate and trihexyl citrate; dialkyl adipates such as dioctyl adipate (DOA), also called bis (2-ethylhexyl) adipate, diethyl adipate, di (2-methylethyl) adipate and dihexyl adipate; dialkyl tartrates such as diethyl tartrate and dibutyl tartrate; dialkyl sebacates such as diethyl sebacate, dipropyl sebacate and dinonyl sebacate; dialkyl succinates such as diethyl succinate and dibutyl succinate; alkyl glycolates, alkyl glycerylates, glycol esters and glycerol esters such as glyceryl diacetate, glyceryl triacetate (triacetin), glyceryl diacetate monomethate, methyl phthalyl ethyl glycolate, butyl phthalyl butyl glycolate, ethylene glycol diacetate, ethylene glycol triacetate, ethylene glycol diacetate ethylene and triethylene glycol dipropionate; and mixtures thereof. Preferred low molecular weight plasticizers for the continuous hydrophilic phase are triethyl citrate, tributyl citrate, diethyl phthalate and dioctyl adipate, with dioctyl adipate being most preferred.

[0076] The properties of the composition of the invention are easily controlled by adjusting one or more parameters during manufacture. For example, the adhesive strength of the composition can be controlled during production to increase, decrease or eliminate viscosity. This can be achieved by varying the type and / or amount of different ingredients by changing the production method. In addition, with respect to the manufacturing process, the compositions obtained by conventional hot extrusion are usually, but not always, slightly less sticky than compositions obtained by solution-film casting. In addition, the degree of future swelling of the hydrogel composition in contact with water can be changed by selecting other water-swollen polymers, and - in compositions containing a continuous hydrophilic phase, by adjusting the ratio of the water-swollen water-insoluble polymer to the hydrophilic polymer / complement plasticizer blend. These compositions may have a different appearance from clear, translucent to translucent to opaque. In addition, some compositions can be made translucent by changing the relative amounts of the hydrophilic phase ingredients (e.g., by reducing the amount of cellulose ester) or by changing the production method (translucent hydrogels are easier to obtain by casting the films from the solution than by hot extrusion). Thanks to this, the translucent composition allows the user to observe the therapeutic or cosmetic process (e.g. whitening) as it occurs and determining when the desired effect is achieved, for example, when the teeth have been sufficiently bleached.

D. ACTIVE AGENTS [0077] The product may also include any pharmaceutically active agent useful in the treatment of physiological conditions affecting teeth and surrounding tissue as well as other mucous membranes. The active agent may be any substance that can be secreted from the product to treat an undesirable physiological condition. Adverse physiological conditions affecting the teeth and surrounding tissue that may be treated by the invention include: halitosis; periodontal and oral infections; periodontal pathological changes; tooth decay or decay; gingivitis; and other periodontal diseases. The active agent may be present in the hydrogel and / or foundation. In addition, several agents may be incorporated into the product of the invention. For example, the hydrogel may contain a tooth whitening agent that is secreted onto the tooth surface, while the primer may contain another active agent, such as a breath freshening agent, which is secreted into the mouth.

[0078] Such agents would be in a cosmeceutically or therapeutically effective amount. These include, for example and without limitation, adrenergics, corticosteroids, corticosteroid inhibitors, alcohol discouragement agents, aldosterone antagonists, amino acids, ammonia antidotes, anabolic agents, anti-inflammatory agents, analgesics, androgenic agents, anesthetics. disincentives, anorexia, antagonists, anterior pituitary hormone activators and anterior pituitary hormone inhibitors, anthelmintics, anti-acne agents, anti-adrenergic agents, antiallergic agents, anti-amoebic agents, antiandrogenics, anti-anemia agents, antianginal agents, anxiolytics, agents

- 18 antiarthritics, anti-asthma agents, anti-arteriosclerosis agents, anti-bacterial agents, anti-gallstones, anti-gallstones, anti-cholinergic agents, anti-coagulants, anti-granulomatics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea agents, anti-diuretic, anti-motor dysfunction agents, anti-emetics, anti-epileptics, anti-estrogen agents, fibrinolysis inhibitors, anti-fungal agents, anti-glaucoma agents, antihemophilic agents, antihemophilic factor, antihemorrhagic agents, antihistamines, lipid lowering agents, lipoprotein lowering agents, antihypertensive agents, antihypertensive agents, antiinfectives, antiinfectives anti-inflammatory, anti -keratinics, anti-malarial agents, anti-microbial agents, anti-migraine agents, cytostatic agents, anti-fungal agents, anti-nausea agents, anti-cancer agents, anti-cancer drug support agents, anti-neutropenia agents, anti-obsessive agents, anti-parasite agents, anti-Parkinson drugs, anti-pneumocystosis agents, anti-proliferative agents, anti-hyperplasia drugs antiprotozoal agents, antipruritic agents, anti-psoriasis agents, antipsychotics, anti-rheumatic agents, anti-schistosomotic agents, anti-seborrhoeic agents, antispasmodics, anti-coagulants, antitussives, anti-ulcer agents, urolithiasis, antiviral agents, appetite suppressants, drugs for benign prostatic hyperplasia, blood glucose regulators, bone resorption inhibitors , bronchodilators, carbonic anhydrase inhibitors, cardiac sedative drugs, cardiac protective agents, cardiotonic agents, cardiovascular agents, bile stimulants, cholinergic agents, cholinergic agonists, cholinesterase deactivators, coccidiostats, perception aids and perception enhancers, sedatives, auxiliary diagnostic agents, diuretics, dopaminergic agents, ectoparasitics, enzyme inhibitors, estrogens, fibrinolytic agents, oxygen scavengers, agents for gastrointestinal motility, glucocorticoids, gonadotropic agents, agents for hair growth, haemostatic agents, histamine H2 receptor antagonists, hormones, hypocholesterolemic agents, hypoglycemic agents, hypolipidemic agents, hypotensive agents, HMGCoA reductase inhibitors, immunizing agents, immunomodulators immunostimulators, immunoinhibitors, agents supporting impotence treatment, inhibitors, keratolytic agents, LHRH agonists, drugs for liver disorders, luteolytic agents, memory aids, mental aids, mood regulators, mucolytic agents, mucolytic agents, pupil dilators, nasal passages cleaners, neuroleptic agents, neuromuscular blocking agents, neuroprotective agents , NMDA antagonists, non-hormonal sterol derivatives, labor inducing agents, plasminogen activators, platelet activating factor antagonists, platelet sticking inhibitors, post-stroke and post-head trauma drugs, enhancers, progestins, prostaglandins, prostate growth inhibitors, prothyrotropic agents, psychotropic agents, radioactive agents, regulators, loosening agents, repartition agents, scabies, curing agents, agents

Sedatives, sedatives and hypnotics, selective adenosine A1 antagonists, serotonin antagonists, serotonin inhibitors, serotonin receptor antagonists, steroids, stimulants, inhibitors, synergists, thyroid hormones, thyroid inhibitors, thyromimetic agents, ataractics, agents for unstable angina, enhancers uric acid excretion, vasoconstrictors, vasodilators, agents for the treatment of external injuries, wound care agents, xanthine oxidase inhibitors, etc.

[0079] In one embodiment, the hydrogel composition described above comprises a whitening agent and thereby acts as a delivery system when applied to the teeth. The separation of bleaching agents "loaded" into these hydrogel compositions is usually associated with both water absorption and desorption of the agent in the swelling-controlled diffusion mechanism. Hydrogel compositions containing a whitening agent may be used in a manner similar to, for example, topical pharmaceutical formulations.

[0080] Suitable teeth whitening agents include metal peroxides, metal chlorates, perborates, percarbonates, peroxyacids and combinations thereof. Suitable peroxide compounds include hydrogen peroxide, calcium peroxide, magnesium peroxide, carbamide peroxide, and mixtures thereof. Preferred peroxides are hydrogen peroxide and carbamide peroxide. Other suitable peroxides include organic peroxides, including (but not limited to) dialkyl peroxides such as t-butyl peroxide and 2.2 bis (t-butylperoxo) propane, diacyl peroxides such as benzoyl peroxide and acetyl peroxide, peroxobenzoate -butyl and t-butyl peroxy-2-ethylhexanoate, peroxydicarbonates such as dicetyl peroxydicarbonate and dicyclohexyl peroxydicarbonate, ketone peroxides such as cyclohexanone peroxide and methyl ethyl ketone peroxide, and hydroperoxides such as cumene hydroperoxide and tert-butyl hydroperoxide. The whitening agent is preferably a peroxide such as hydrogen peroxide or carbamide peroxide, and most preferably hydrogen peroxide.

[0081] Suitable metal chlorates include calcium chlorate, barium chlorate, magnesium chlorate, lithium chlorate, sodium chlorate and potassium chlorate; chlorate (I) and chlorine dioxide. The preferred chlorate (III) is sodium chlorate.

[0082] In another embodiment, the pharmaceutically active agent may be, for example, a non-steroidal anti-inflammatory / analgesic; steroidal anti-inflammatory agents; local anesthetics; bactericides / disinfectants; antibiotics; antifungal agents; anti-hypersensitivity agents; fluoride anti-caries agents; agents against tartar and plaque; enzymes that inhibit plaque, tartar or caries; abrasives such as (V) pyrophosphates; metal chelating agents such as ethylenediaminetetraacetic acid, tetrasodium salt; antioxidants such as butylated hydroxyanisole; butylated hydroxytoluene; dietary supplements for topical application to the teeth and surrounding tissue; e.t.c.

[0083] Suitable non-steroidal anti-inflammatory / analgesics include acetaminophen; methyl salicylate; monoglycyl salicylate; aspirin; mefenamic acid;

- flufenamic acid; indomethacin; diclofenac; alclofenac; diclofenac sodium; ibuprofen; flurbiprofen; fentizak; bufexamac; piroxicam; phenylbutazone; oxyphenbutazone; clofezon; pentazocine; mepirizole; and tiaramide hydrochloride.

[0084] Suitable steroidal anti-inflammatory agents include hydrocortisone; prednisolone; dexamethasone; triamcinolone acetonide; fluocinolone acetonide; hydrocortisone acetate; prednisolone acetate; methylprednisolone; dexamethasone acetate; betamethasone; betamethasone valerate; flumethasone; fluorometholone; budesonide; and beclometasone dipropionate.

[0085] Suitable local anesthetics include dibukain hydrochloride; dibucaine; lidocaine hydrochloride; lidocaine; benzocaine; 2- (diethylamino) ethyl pbutylaminobenzoate hydrochloride; procaine hydrochloride; tetracaine hydrochloride; chloroprocaine hydrochloride; oxyprocaine hydrochloride; mepivacaine; cocaine hydrochloride; and piperocaine hydrochloride.

[0086] Suitable bactericidal / disinfecting agents include thimerosal; phenol; thymol; benzalkonium chloride; benzethonium chloride; chlorhexidine; providone iodide; cetylpyridinium chloride; eugenol and trimethylammonium bromide.

[0087] Suitable antibiotics include penicillin; methicillin; oxacillin; cephalothin; cephaloridine; erythromycin; lincomycin; tetracycline; chlortetracycline; oxytetracycline; methacycline; chloramphenicol; kanamycin; streptomycin; gentamicin; bacitracin; and cycloserine. Suitable antifungal drugs include amphotericin; clotrimazole; econazole nitrate; fluconazole; griseofulvin; itraconazole; ketoconazole; miconazole; nystatin; terbinafine hydrochloride; undecenoic acid; and zinc undecenoate.

[0088] Suitable anti-hypersensitive agents include potassium nitrate and strontium chloride. Suitable fluoride anti-caries agents include sodium fluoride, potassium fluoride and ammonium fluoride.

[0089] Additional bleaching agents include tartar and plaque agents, including phosphates (V) such as pyrophosphates (V), polyphosphates (V), polyphosphonates (e.g. ethane-1-hydroxy-1,1-diphosphonate, 1-azacycloheptane-1,1-diphosphonate and linear alkyl diphosphonates) and their salts; linear carboxylic acids; and sodium zinc citrate; and mixtures thereof. Preferred pyrophosphate (V) salts are dilithium pyrophosphate (V) salts, tetralitite pyrophosphate salts; and hydrated or anhydrous forms of sodium dihydrogen pyrophosphate (Na₂H₂P₂ABOUT₇), tetrasodium pyrophosphate (V)₄P₂ABOUT₇) and tetrapotassium pyrophosphate (V)₄P₂ABOUT₇). Pyrophosphate (V) salts are described in more detail in Kirk &amp; Othmer, Encyclopedia of Clinical Technology, III edition, volume 17, Wiley-Interscience Publishers (1982). Optionally, whitening agents may also include tartar dissolving agents such as betaines, amine oxides and quaternary compounds as described in US Patent No. 6,315,991 to Zofchak.

[0090] Enzyme agents that would counter plaque, tartar, or caries would also be useful in these compositions. Enzyme agents can be placed together with the whitening agent or can be placed

- 21 in a different layer of the multilayer system as described here. Suitable enzymes include: proteases, which break down saliva proteins adsorbed on the tooth surface and forming a film, i.e. the first layer of plaque; lipases that destroy bacteria by lysing proteins and lipids that are a structural component of the bacterial wall and cell membranes; dextranase, glucanohydrolase, endoglycosidase and mucinase, which break down the bacterial skeletal structure that underlies the bacteria to the tooth; and amylases, which prevent tartar build-up by breaking down the carbohydrate-protein complex that binds calcium. Preferred enzymes include any commercially available proteases; dextranses; glucanohydrolase; endoglycosidase; amylase; mutanases; lipase; mucynazy; and their compatible mixtures. In some embodiments, an enzymatic whitening agent may be used.

[0091] Optionally, the enzymatic whitening agent is peroxidase, whereby the peroxide is generated in situ. When the enzyme whitening or anti-plaque agent is included in the composition, the composition should be such that the enzyme is maintained in active form, e.g., the pH should be approximately neutral and the peroxide may be omitted or placed in a separate layer.

[0092] Suitable dietary supplements for topical application to the teeth and surrounding tissue include vitamins (e.g., vitamins C and D, thiamine, riboflavin, calcium pantothenate, niacin, folic acid, nicotinamide, pyridoxine, cyanocobalamin, paraaminobenzoic acid and bioflavonoids); and mineral salts (e.g. calcium, phosphorus, fluorine, zinc, manganese and potassium); and mixtures thereof. Vitamins and mineral salts useful in this invention are disclosed in Drug Facts and Comparisons (loose drug information leaflets), Wolters Kluer Company, St. Louis, Mo., 1997, pp. 3-17.

[0093] The product may also include any cosmetically active agent. As used herein, a "cosmetically active agent" includes any substance that can separate from the product to produce the desired change in the appearance of teeth or surrounding tissue, or which gives the user a socially desirable feature, such as fresh breath. For example, the cosmetically active agent may be a breath freshening agent or a whitening or whitening agent. Due to the fact that in some cultures or in some parts of Western civilization, tooth coloring may be relevant or desirable, any cosmetically active agent may be any color or shade agent.

[0094] The product may contain additional bleaching agents. For example, surfactants such as detergents may also be present and interact with the whitening agents described above to give the teeth a lighter appearance.

[0095] In each of these embodiments, the teeth whitening composition of the invention preferably includes peroxide for whitening teeth and may also include conventional additives such as fillers, preservatives, acidity regulators, plasticizers, thickeners, dyes, pigments, refractive particles, stabilizers, tonics, pharmaceuticals, flavors or breath fresheners, and penetration enhancers. In those embodiments where the viscosity is to be reduced or eliminated, conventional means can also be used

- 22 reducing viscosity. These additives and their amounts are selected in such a way that they do not significantly affect the desired chemical and physical properties of the tooth whitening composition or interfere with the delivery of a tooth whitening agent that may be included in the composition. Additional ingredients include coloring agents; food additives, flavors, sweeteners and preservatives.

E. OTHER INGREDIENTS [0096] Any natural or synthetic flavoring or food additive may be incorporated into the products of the invention, such as described in Chemicals Used in Food Processing, Pub. Well. 1274, National Academy of Sciences, pp. 63-258. Suitable flavoring agents include brach, peppermint, spearmint, menthol, fruit flavors, vanilla, cinnamon, spices, essential oils and oleoresins, as well as combinations thereof. The amount of flavoring agent used is usually a matter of taste, subject to factors such as the type of taste desired, individual taste and desired strength. Preferably the product contains from about 0.1 to 5 wt. flavoring agent. &lt;

&gt; [0097] Sweeteners useful in the invention include sucrose, fructose, aspartame, xylitol and saccharin. Preferably, the product contains sweeteners in an amount of from 0.001 to 5.0 wt.%

[0098] A suitable substrate may be translucent, so that the composition to be worn is not conspicuous. However, the substrate or composition may optionally be colored so that the worn composition will be easily discernible. Preferably, when dyeing is desired, the color will be present in the substrate. For example, the substrate may be dyed in bright or bright colors that the consumer may find pleasant. The substrate may therefore contain a coloring compound such as, for example, a dye, pigment or substance that can give color when added to the material forming the substrate.

[0099] For dyeing the substrate, for example, coloring compounds of the type commonly used in food, drugs or cosmetics may be used in connection with the human body, especially food-approved color additives that have been classified as "acceptable" or "excluded from approval" . Coloring compounds used to dye the substrate can be obtained from natural sources, such as vegetables, minerals or animals, or they can be equivalents of man-made natural derivatives.

[0100] Coloring compounds currently approved by the Food Drug &amp; Cosmetic Act for use in food and swallowing drugs include dyes such as FD&amp;C Red No. 3 (tetrajodofluorescein sodium); Food Red 17 (6-hydroxy-5 - {(2-methoxy-5-methyl-4-sulfophenyl) azo} -2-naphthalenesulfonic acid disodium salt); Food Yellow 13 (sodium salt of a mixture of mono- and disulfonic acids of quinophthalon or 2- (2-quinolyl) indanedione); FD&amp;C Yellow No. 5 (4-p-sulfafenylazo-1-p-sulfophenyl-5-hydroxypyrazole-3-carboxylic acid sodium salt); FD&amp;C Yellow No. 6 (sodium salt of p-sulfophenyla-Benaphthol-6-monosulfonate); FD&amp;C Green No. 3 (disodium salt 4 - {[4- (N-ethyl-p-sulfobenzylamino) phenyl] - (4-hydroxy-2-sulfonophenyl) methylene} - [1- (N-ethyl-Np-sulfobenzyl) 3, 5-cykloheksadieniminy]); FD&amp;C Blue No. 1 (acid anhydride disodium salt)

- 23 dibenzyldieldieldiamine triphenylcarbinoltrisulfone); FD&amp;C Blue No. 2 (indigo carmine disulfonic acid salt); FD&amp;C Red No. 40; Orange B; and Citrus Red No. 2; and their combinations in different proportions.

[0101] Coloring compounds exempt from FDA approval include: annato; beta-apo-8'-carotenal; beta-carotene; beet powder; canthaxanthin; caramel dye; carrot oil; extract of cochineal (carmine); toasted partially defatted boiled cotton seed meal; iron (II) gluconate; fruit juice; grape dye extract; grape skin extract (enocyanine); pepper; pepper oleoresin; riboflavin; saffron; turmeric; turmeric oleoresin; vegetable juice; and their combinations in different proportions.

[0102] The form of the colored compound for use in the product preferably includes the pigment form, but may also include precipitated organic pigment forms that are compatible with the base material. Water-soluble dyes, supplied in the form of powders, granules, liquids or forms for special applications, can be used in accordance with the present method. Preferably, "precipitated organic pigment" or dye form insoluble in water is used to dye the substrate. For example, if a suspension of a coloring compound is to be used, the addition of an organic pigment precipitated may be used. Suitable water-insoluble organic precipitated pigments obtained by filling calcium or aluminum salts of FD&amp;C dyes with aluminum oxide include FD&amp;C Green # 1 precipitated organic pigment, FD&amp;C Blue # 2 precipitated organic pigment, FD&amp;C R&amp;D # 30 precipitated organic pigment and FD&amp;C # 30 organic pigment 15.

[0103] Other suitable coloring compounds include non-toxic water insoluble inorganic pigments such as titanium dioxide; chrome greens; ultramarine blues and blushes; and iron oxides. Such pigments preferably have a particle size in the range of from about 5 to about 1000 Pm, more preferably about 250 to about 500 Pm.

[0104] The concentration of the colored compound in the substrate is preferably from about 0.05 to 10% by weight. and more preferably from about 0.1 to 5 wt.

[0105] More than one coloring compound may be present in the substrate, giving many colors. These many colors can be modeled into stripes, dots, swirls or any other pattern that the consumer can find pleasant. The coloring compound can also be used together with other appearance enhancing substances such as shimmering particles.

[0106] Absorbent fillers can preferably be introduced to control the degree of hydration when the adhesive is on the tooth surface. Such fillers may include microcrystalline cellulose, talc, lactose, kaolin, mannitol, colloidal silica, alumina, zinc oxide, titanium oxide, magnesium silicate, magnesium aluminum silicate, hydrophobic starch, calcium sulfate, calcium stearate, phosphate (V ) calcium, calcium phosphate dihydrate, clays such as laponite, vellum and non-woven paper, and cotton materials. Other suitable fillers are passive, i.e. substantially non-adsorbing and include, for example, polyethylenes, polypropylenes, polyurethane and polyether amide copolymers, polyesters and polyester copolymers, nylon and rayon. A preferred filler is colloidal silica, e.g. Cab-O-Sil® (Cabot Corporation, Boston MA).

[0107] Preservatives include, for example, p-chloro-m-cresol, 2-phenylethanol, phenoxyethanol, chlorobutanol, methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, benzalkonium chloride, cetylpyridinium chloride, diacetate or chlorohexidine gluconate, ethanol and glycol propylene.

[0108] Compounds useful as acidity regulators include (but are not limited to) glycerol buffers, citrate buffers, borate buffers, phosphate buffers, or citric acid phosphate buffers can also be included to ensure that the pH of the hydrogel composition is compatible with the pH of the environment mouth and will not wash the mineral salts from the teeth. To optimize whitening without demineralizing teeth, calcium salts and / or fluorides can be included in the composition.

[0109] Suitable plasticizers include citric acid esters such as triethyl citrate or triethyl acetyl citrate, tartaric acid esters such as dibutyl tartrate, glycerol esters such as glyceryl diacetate and glyceryl triacetate; phthalic acid esters such as dibutyl phthalate and diethyl phthalate; and / or hydrophilic surfactants, preferably hydrophilic nonionic surfactants, such as, for example, partial fatty acid and sugar esters, fatty acid and poly (ethylene glycol) esters, fatty alcohol and poly (ethylene glycol) ethers and sorbitan fatty acid esters and poly (ethylene glycol).

[0110] The thickeners preferred herein are compounds of natural origin or derivatives thereof and include, for example: collagen; galactomannans; starches; starch derivatives and hydrolysates; cellulose derivatives such as methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and hydroxypropyl methyl cellulose; colloidal silicas; and sugars such as lactose, sucrose, fructose and glucose. Synthetic thickeners such as poly (vinyl alcohol), copolymers of vinyl pyrrolidone and vinyl acetate, poly (ethylene glycols) and poly (propylene glycols) may also be used.

[0111] The substrate may also have embedded or decorated with decorative elements such as pearls, rock crystal or the like as long as these elements do not affect the viscoelastic properties of the substrate required for proper deformation of the composition on the teeth as described above. The substrate may also contain letters, words or images designed to be pleasant or attractive to the consumer.

F. DISPOSABLE FOUNDATION [0112] The decomposable foundation contains a polymer composition that disintegrates in a humid environment more slowly than the hydrogel and is substantially non-sticky. There are many materials that can be used as primer materials, including, for example (but not limited to) acrylate polymers, cellulose derived polymers, cellulose esters, starches, alginic acid, alginates, poly (amino acids). Combinations can also be used as the foundation material, i.e. blends of any of the above various polymers.

[0113] The hydrogel breaks down in time from over 1 second to 24 hours after being placed in a moist environment and in one embodiment the hydrogel breaks down from 10 seconds to 8 hours after being placed. In one embodiment, the disintegrating pad disintegrates about 12 to 24 hours after the hydrogel has broken down during

When in another embodiment, the primer disintegrates within about 12 hours after the hydrogel has disintegrated. The material of the disintegrating undercoat can be selected so that it disintegrates slightly more slowly or at approximately the same rate (e.g. when both disintegrate within about 24 hours), but it is preferably selected so that it disintegrates more slowly than the hydrogel composition. In one embodiment, the disintegrating undercoat disintegrates at least about 200% more slowly than the hydrogel, in another embodiment, the undercoat disintegrates at least about 100% more slowly, in another embodiment the undercoat disintegrates at least about 50% more slowly, and in yet another embodiment the foundation breaks down at least about 25% more slowly than the hydrogel.

[0114] Suitable acrylate polymers have been described above as water swollen water insoluble polymers and include, for example (without limitation) polymers made from acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate and / or other vinyl monomers. Preferred acrylate polymers are Eudragit® copolymers (copolymers of methacrylic acid and methyl methacrylate), such as the Eudragit15® E, L, S, RL, RS and NE copolymers. As noted above, these Eudragit polymers also find use as a water-swellable hydrogel-insoluble polymer. Eudragit polymers are available in different varieties with different pH-solubility and permeability relationships, so the variant used as a degradable undercoat can be selected to have lower solubility than the variant used in the hydrogel. For example, if L 100-55 is selected for use in the hydrogel, Eudragit L 100 can be used in the primer; if Eudragit L 100 is used in the hydrogel, Eudragit S 100 can be used in the primer; e.t.c. In addition, mixtures of Eudragit polymers or mixtures of Eudragit polymers with other polymers and excipients (e.g. buffering agents, pH modulators) can be used to adjust the decomposition rate of the substrate relative to the hydrogel.

[0115] Suitable cellulose derivative polymers include, for example (without limitation) hydratocellulose (cellophane), methyl cellulose, ethyl cellulose, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), carboxymethylcellulose cellulose and carboxymethylcellulose ). Preferred celluloses are hydratocellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose and mixtures thereof.

[0116] Suitable cellulose esters have been described above as water-swollen water-insoluble polymers and include, for example (without limitation) cellulose acetate, cellulose acetate propionate, cellulose butyrate acetate, cellulose propionate, cellulose butyrate, cellulose butyrate cellulose, cellulose diacetate and mixtures thereof, polymers and copolymers. Exemplary cellulose ester copolymers include cellulose butyrate and cellulose acetate propionate. Preferred cellulose esters are cellulose acetate, cellulose acetate propionate, cellulose butyrate, cellulose propionate, cellulose butyrate, cellulose butyrate, cellulose diacetate, cellulose triacetate, cellulose butyrate and cellulose acetate propionate and mixtures thereof.

[0117] Suitable starches include, for example (without limitation) potato starch acetate, corn starch etc. (e.g. Roquette's Clearam® starches) and mixtures thereof.

[0118] Suitable alginates include, for example (without limitation) propylene glycol alginate, sodium alginate, calcium alginate, etc., as well as mixtures thereof.

[0119] Suitable poly (amino acids) include, for example (without limitation) polylysine, polyglycine, polyalanine, protamine etc., as well as mixtures thereof.

[0120] It is understood that any active agents and other ingredients described in connection with the hydrogel composition may also be present in the primer. For example, the hydrogel may contain the active agent released on the tooth surface or oral mucosa, while the undercoat may be filled with a flavoring agent that is secreted into the mouth.

IV. MANUFACTURING PROCESSES [0121] The hydrogel compositions of the invention are usually suitable for hot extrusion, so that they can be obtained by a simple mixing and extrusion process. The components of the composition are weighed and then mixed, for example using a Brabender or Baker Perkins mixer, usually, though not necessarily, at elevated temperatures, e.g. from about 90 to 140 ° C. If necessary, solvents or water can be added. The resulting composition can be extruded using a single or double extruder, or granulated. Alternatively, the components of the hydrogel composition may be melted one after the other and then mixed prior to extrusion. The hydrogel composition can be extruded directly onto the disintegrating undercoat. You can also first extrude the hydrogel composition, and then press it onto the foundation or stick to the foundation. A protective layer may also be introduced. The thickness of the resulting film containing the hydrogel in most applications will be in the range of about 0.050 to 0.80 mm, more often in the range of about 0.37 to 0.47 mm.

[0122] Alternatively, the compositions can be prepared by casting the layers from the solution by mixing the components of the composition in a suitable solvent, e.g. a volatile solvent such as ethyl acetate or lower alkanols (e.g., ethanol, isopropyl alcohol, etc.) is particularly preferred, in a concentration usually in the range from about 35 to 60% conc. the masses. The solution is poured onto a disintegrating primer or protective layer as above. Both mixing and casting are preferably carried out at ambient temperature. The film-coated primer is then dried at a temperature of about 80 to 100 ° C, optimally about 90 ° C, for a time period of about one to four hours, optimally about two hours. As a result, one embodiment of the invention is a method of obtaining a hydrogel film suitable for incorporation into the product of the invention, which requires the following steps: preparation of a solution of a water-swollen water-insoluble polymer, a hydrophilic polymer and a complementary oligomer capable of forming a hydrogen or electrostatic bond with a hydrophilic polymer, in a solvent; putting a layer of the solution on a decaying base to obtain a coating on it; heating the coated primer to a temperature of about 80 to 100 ° C for a time period of about 1 to 4 hours, with

- 27 thus obtaining a hydrogel film on the primer.

[0123] When adhesive hydrogel compositions are desired, the preferred process is to cast the films from the solution. In the case of obtaining substantially non-stick compositions, hot extrusion is preferred. To obtain translucent compositions, either the hot extrusion technique or the solution casting technique can be used, although casting the layers from the solution is usually preferred for these embodiments. The result of this other embodiment of the invention is a method for producing compositions comprising a continuous hydrophilic phase that requires the following steps: hot processing by an extruder of a mixture of a water-swollen water insoluble polymer, a hydrophilic polymer and a complementary oligomer capable of forming a hydrogen or electrostatic bond with a hydrophilic polymer in to produce an extruded composition; extruding the composition as a film of desired thickness onto a suitable disintegrating primer; and after cooling, filling the membrane with an aqueous solution of the active agent such as peroxide to obtain a bleaching agent concentration of from about 1 to 20% by weight.

[0124] The invention also contemplates a multi-layer system that includes one or more additional hydrogel or non-hydrogel layers. For example, it may be desirable to include additional active agents that may be incompatible with the main active agent during storage. In this way, one layer may be a hydrogel layer containing the main active agent and the other layer (s) may / may contain additional active agents. These other layers may be made of the hydrogel composition described herein or any other biocompatible formulation known in the art (e.g., polyisobutylene, dimethylsiloxane, ethylene vinyl acetate, polyvinyl acetate, acetate, butyrate, cellulose propionate, ethyl cellulose and water insoluble acrylates). Furthermore, depending on the arrangement of the layers, an adhesive layer, e.g. a layer to be placed directly on the teeth, and a non-adhesive layer, e.g. the outer layer that is placed closest to the lips. Another advantage of the multi-layer system is that the ratio of polymers used in the outermost layer can be changed to obtain non-adhesive layers to avoid having to introduce a separate primer layer into the product.

[0125] In one embodiment, the composition comprises: an outer disintegrating undercoat that serves as the outer surface of the composition when applied to a tooth, oral or mucosal surface; a surface-contact adhesive layer adhered to the primer, which will usually be the adhesive composition of the invention, optionally containing additional active agents; and a protective layer. After removing the protective layer, the composition is applied, for example, to the surface, e.g., the teeth to be treated, and placed on the surface in such a way that the layer in contact with the surface of the mouth is in contact with the teeth or other surface of the mouth. In another embodiment, the composition is packaged without a protective layer. As a result, the composition is ready to be applied to the oral surface immediately after removal from the package.

[0126] The hydrogel-disintegrating primer composition may contain an additional

- a substrate layer that can serve as the main structural element and provide the composition with support either during production or use. The material used for the substrate should be passive and unable to absorb the hydrogel composition - a disintegrating primer. In addition, the material used for the substrate should allow the device to track the contours of the teeth or other body surface and comfortable to wear in the mouth without rubbing or otherwise irritating the lips or tongue. Examples of materials useful for the substrate are polyesters, polyethylene, polypropylene, polyurethanes and polyether amides. The substrate preferably has a thickness in the range of from about 15 μm to about 250 μm and can be pigmented if desired, metallized or provided with a matte finish suitable for writing.

[0127] In one embodiment, the substrate is preferably although not necessarily tight (ie not "breathable") and does not allow any active agent to leak through the layer and contact with the mucous membranes of the mouth and gums. The ready-to-use composition is pre-wetted to increase its viscosity and to make the composition stick to the teeth. One advantage of this embodiment is that the active agent cannot leak significantly through the substrate and cause irritation to persons sensitive to the active agent or to an unpleasant taste or impression.

[0128] Other suitable base materials may be non-polymeric materials such as waxes (e.g., micro waxes or paraffins) or a wax / foam laminate. Paraffins are unbranched low molecular weight hydrocarbons, melting points about 48-75 ° C and molecular weights about 300-1400 g / mol, and are usually Fischer-Tropsch synthesis products. Micro waxes are flexible and resemble amorphous in appearance, and tend to exhibit greater tensile strength and smaller crystal size than paraffins. Micro waxes usually have a melting point of about 60-95 ° C and a molecular weight of about 580-700 g / mol, and contain primarily branched hydrocarbons and some ring compounds, although unbranched hydrocarbons may be present. The substrate material can also be open cell foam, such as polyurethane, polystyrene or polyethylene foam.

[0129] Alternatively, in another embodiment, the substrate is not airtight and thus may be completely hydrated in situ, positioned on the teeth or other body surface.

[0130] The protective layer is a removable element that performs the function of protecting the system against use. The protective layer should be made of an impermeable material for the active agent and the hydrogel composition that is easily detached from the contact binder. The protective layers are usually treated with silicone or fluorocarbons and are commonly made of polyesters and polyethylene terephthalate.

[0131] A preferred composition is usually obtained using an acrylate polymer as a water insoluble swollen polymer and a blend of polyvinylpyrrolidone and polyethylene glycol as a blend of a hydrophilic polymer with a complementary oligomer capable of forming a hydrogen or electrostatic bond with the hydrophilic polymer.

[0132] An adhesive film of the composition can be made by melting and mixing together the above components at a temperature from about 100 to 170 ° C. Błonia is extruded from

- 29 the desired thickness on a suitable surface. Alternatively, the components may be dissolved in a single solvent or a mixture thereof and the solution may be cast on a protective or backing layer. The solvents are then evaporated to obtain a hydrogel film.

[0133] One method of filling the composition with the active agent is by applying the desired active agent, e.g., teeth whitening agent, in an aqueous solution to a hydrogel surface placed on a suitable support, or placing the active agent directly on the support. A protective layer is then applied to the composition to form a layered structure, and the solution containing the bleaching agent is absorbed into the composition due to its water swelling properties. Alternatively, the composition applied to the substrate may be immersed in a solution containing the desired concentration of bleaching agent and the solution absorbed into the composition. By measuring the mass increase rate during liquid absorption, the percentage filling of the composition with the active agent can be determined and controlled.

[0134] Another approach for filling the composition with the active agent is to add the active agent as a solid or solution to the composition dissolved in the solvent. The mixture is then cast in the usual manner on a suitable support and allowed to dry, although a lower drying temperature is desired in this filling method. The compositions prepared in this way can be dried at ambient temperature for a period from about 1 hour to several days.

[0135] Typical film thicknesses are from about 0.050 to 0.80 mm, preferably 0.25 to 0.50 mm. The thickness of the film is not critical and can be changed according to the concentration of whitening agent introduced into the film, the length of time the film contacts the teeth, the level of comfort desired by the user and the degree of discoloration to be removed.

V. METHODS OF APPLICATION [0136] In practice, the compositions can be used simply by removing the product from the packaging, removing the protective layer (if any) and applying an adhesive layer on the teeth that you want to whiten (or placing in any other moist or wet body environment) surface when another function of the composition is used or a different active agent is used). The systems described in this document can be provided in a variety of sizes, so that the composition can be applied to the entire tooth or part of it, to any number of teeth at once, or to any part of the mouth or other humid place.

[0137] The primer may be formulated to be sealed or impenetrable to the active agent to reduce or eliminate leakage of the active agent from the composition when the user wears the composition for a desired time, i.e. the composition will deliver the drug unidirectional, e.g. mucosa. Alternatively, the primer may be formulated to have a predetermined permeability to provide bi-directional drug delivery, e.g. towards the mucosal surface and towards the mouth. The level of permeability, i.e. its selective nature, can also be used to control the relative delivery rates towards the surface

- 30 mucous membranes and towards the mouth.

[0138] The composition can be held in the desired place for just a few minutes, several hours, all day or overnight, and then removed after achieving the desired degree of whitening or desired therapeutic or cosmetic effect. Alternatively, you can leave the composition in place and let it unfold completely. Consequently, in one embodiment of the invention, the teeth whitening method may simply include applying the composition to teeth in need of whitening, while in another embodiment the method may further include removing the composition after achieving the desired degree of whitening.

[0139] If desired, a translucent composition can be provided that is worn discretely and invisibly to others. This system can also be designed without the active ingredient and which is used as a protective layer on the oral surface, for example as a wound dressing.

[0140] The composition can be worn for a long time, but usually it will be worn for a predetermined period of about 10 minutes to about 24 hours, after which the composition can be removed or left to completely decompose. For teeth whitening, the preferred time is from about 10 minutes to about 8 hours (e.g. overnight), with 30 minutes to about 1 hour also being the preferred embodiment. For other active agents, the therapeutically or cosmeceutically effective time can easily be determined by the pressure on the active agent used as well as the ailment being treated.

[0141] In one embodiment, the hydrogel is a solid and is attached to the primer during production. As a result, the composition is applied in one step. Alternatively, the hydrogel may not be solid, and may be manufactured and packaged separately from the primer. In this case, the user first applies the hydrogel and then applies the primer to the outer surface of the hydrogel. In each of these embodiments, the user can form the composition around the upper or lower teeth or other oral tissues by applying ordinary hand pressure to the primer with the fingertips and thumb, optionally by slightly wetting the composition or body surface prior to application. Assuming that the average adult's finger or thumb area is approximately one square centimeter, the normal pressure generated by the tips of the fingers and thumbs is about 100,000 to about 150,000 pascals (i.e. about 3 pounds or 1.36 kg) per square centimeter. Pressure is usually applied to the composition with the tip of each finger and thumb for about one or two seconds. After removing the pressure of the fingertips and thumbs on the foundation, the composition retains its shape and remains glued to the surface of the teeth and surrounding soft tissue, where it was formed.

[0142] Once the user is ready to remove the composition, it can be removed simply by peeling the composition off the tooth surface or other surface of the mouth or body. If necessary, the composition can be glued again for an additional period of treatment. Any remaining debris is minimal and can be removed by conventional methods of cleaning your teeth or mouth.

[0143] In one embodiment of the invention, the composition is a solid and is

- 31 pressure sensitive adhesive and absorbs water.

[0144] The composition may also be used as a non-solid composition, for example applied as a liquid or gel. For example, the user can squeeze the composition from the tube onto the finger to apply it on the teeth or other body surface, squeeze the composition from the tube directly onto the teeth, apply the composition with a brush or other applicator, etc. The disintegrating foundation can then be applied in a separate step after application liquid or gel. After evaporation of the solvent, the liquid or gel composition dries to form a matrix-type polymer film or gel on the body surface. In one embodiment of this liquid or gel film-forming composition, the hydrogel contains sufficient water or another solvent to provide fluidity. In another embodiment of this composition, the polymeric components of the liquid or gel composition are soluble in the water-ethanol mixture at both ambient temperature and cooling temperatures from about 4 ° C and are miscible after evaporation of the solvent. In yet another embodiment of this film-forming liquid or gel composition, the polymeric composition has a lower critical dissolution temperature from about 36 ° C in an ethanol-water mixture. The resulting film (after evaporation of the solvent) is preferably insoluble or slowly soluble in saliva at body temperature to ensure long-term contact between hydrogen peroxide and tooth enamel. Finally, hydrogen peroxide should be stable in both liquid or gel compositions and in the polymer film after drying.

[0145] Practice of the invention will use - unless otherwise indicated - conventional techniques for polymer chemistry, binder production, and hydrogel preparation, which are within the prior art. These techniques are fully explained in the literature.

[0146] It should be understood that, while the invention has been described in connection with the preferred specific embodiments, the above description, as well as the following examples, are intended to illustrate and not limit the scope of the invention. Other aspects, advantages and modifications will be apparent to those skilled in the art to which the invention relates.

[0147] The following examples are presented to provide ordinary practitioners with a complete disclosure and description of how to make and use the compounds of the invention, and their purpose is not to limit the scope of what the inventors consider their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g. quantities, temperatures, etc.), but some errors and deviations should be considered. Unless otherwise indicated, the parts are mass parts, the temperature is given in degrees Celsius (° C) and the pressure is atmospheric or near atmospheric.

[0148] The following abbreviations and trade names are used in the examples:

Eudragit L 100-55 methacrylic acid copolymer (Rohm America Inc.)

Eudragit L 100

PEG

PVP methacrylic acid copolymer (Rohm America Inc.) polyethylene glycol 400

Kollidon® 90 polyvinylpyrrolidone (BASF)

EXAMPLE 1

EXAMPLES

RECEIVING A SOLID COMPOSITION [0149] One embodiment of the teeth whitening composition can be made from the following ingredients in a hot extrusion process:

Eudragit L 100-55 9 wt.

PVP 44 wt.

PEG 22 wt.

Hydrogen peroxide 6% by mass

Water, stabilizers, pH 19% modulators

[0150] The ingredients are melted in a Brabender single screw extruder as follows: Eudragit L 100-55 is added to the extruder first, followed by PVP and PEG at 100-150 ° C. The composition is extruded to a thickness of 0.35 mm between the protective layer of polyethylene terephthalate and the disintegrating primer made of Eudragit S 100, if necessary with a suitable plasticizer. A hydrogen peroxide solution is added to the extruded film.

EXAMPLE 2

OBTAINING A NON-SOLID COMPOSITION [0151] A tooth whitening composition is obtained from the following ingredients:

<td>Deionized water</td><td>35.0 mass%</td>

<td>Ethanol</td><td>35.0 mass%</td>

<td>Eudragit L 100-55</td><td>4.00 mass%</td>

<td>PEG</td><td>1.00 mass%</td>

<td>PVP</td><td>7.00% by mass</td>

<td>Carbamide peroxide</td><td>18.0 mass%</td>

<td>Sodium Citrate</td><td>0.13 mass%</td>

[0152] The composition is mixed in a high torque low speed Cole-Parmer laboratory mixer equipped with a teflon coated impeller (diameter 5.08 cm) as follows. Deionized water is mixed with ethanol, then PEG is added. Then sodium citrate is added under vigorous mixing. Powdered Eudragit L 100-55 is slowly added (over a period of 2-5 min.) While stirring intensively (500-600 rpm). After about 5-10 min. (no need to wait for Eudragit to dissolve) PVP powder is added slowly (within 5 min). The high stirring speed is maintained for 5-10 min. Powdered carbamide peroxide (within 1-2 min) and mixed the mixture until a homogeneous solution (approximately 30 minutes at 800-900 rpm). Then the solution is allowed to stand for 2-5 hours so that air bubbles are released.

[0153] This tooth whitening composition may be packaged for use with a disintegrating Eudragit RL 100 foundation.

EXAMPLE 3

OBTAINING A NON-SOLID COMPOSITION [0154] A tooth whitening composition is obtained from the following ingredients:

<td>Deionized water</td><td>35.0 mass%</td>

<td>Ethanol</td><td>35.0 mass%</td>

<td>Eudragit L 100-55</td><td>2.50 mass%</td>

<td>PEG</td><td>1.92% mass</td>

<td>PVP</td><td>6.00 mass%</td>

<td>Carbamide peroxide</td><td>18.0 mass%</td>

<td>Sodium Citrate</td><td>0.08 mass%</td>

<td>Methocel A4C</td><td>1.50 mass%</td>

<td colspan="2">[0155] The composition is mixed in a high torque low speed Cole-Parmer laboratory mixer equipped with a teflon coated impeller (diameter 5.08 cm). Deionized water is mixed with ethanol, then PEG is added. Then sodium citrate is added under vigorous mixing. Powdered slowly</td>

Eudragit L 100-55 (within 5 min), stirring intensively (500-600 rpm), then slowly adding (within 5 min) powdered Methocel A4C, stirring intensively (500-600 rpm). After about 10 minutes, powdered PVP is slowly added (over 5 minutes). The high stirring speed is maintained for 5-10 min. Powdered carbamide peroxide (within 1-2 min) and mixed the mixture until a homogeneous solution (approximately 3060 minutes at 500-800 rpm). Then the solution is allowed to stand for 2-5 hours so that air bubbles are released.

[0156] This tooth whitening composition may be packaged for use with a disintegrating Eudragit RS 100 foundation.

Prepared and verified

Danuta Stefani-Ivanov

Patent Attorney