CN111603401A

CN111603401A - Multi-film, multi-component tooth whitening, desensitizing, and/or remineralizing systems and methods of making and using

Info

Publication number: CN111603401A
Application number: CN201910131220.0A
Authority: CN
Inventors: 梁梅花
Original assignee: Individual
Current assignee: Individual
Priority date: 2019-02-22
Filing date: 2019-02-22
Publication date: 2020-09-01

Abstract

The invention discloses a preparation method of a multi-film multi-component tooth whitening, desensitizing and/or remineralizing system, which comprises the following steps: adding an activating compound or ingredient and/or a desensitizing agent and additional ingredients to the synthetic film polymer to form a dissolvable film by shaping and/or evaporating a portion of the added liquid; an insoluble film is provided in association with the dissolvable film, and a substance added to the dissolvable film activates the substance on the insoluble film when applied to the tooth surface. According to the invention, through the independent structural design of the soluble film and the insoluble film, the activating compound or component in the soluble film can activate the peroxy compound or component on the insoluble film, so that teeth can be whitened and remineralized, no premixing or waste of reagents and catalysts is needed, and teeth sensitivity can be better prevented.

Description

Multi-film, multi-component tooth whitening, desensitizing, and/or remineralizing systems and methods of making and using

Technical Field

The invention belongs to the field of tooth whitening health, and particularly relates to a multi-film multi-component tooth whitening, desensitizing and/or remineralizing system and a preparation and use method thereof.

Background

Teeth are composed of an inner dentin layer and an outer enamel layer with a protective layer, the outer layer is also called as a tooth surface film, and the outer enamel layer is a protein film formed on the surface of the tooth enamel. Pellicle and enamel may stain with time by foreign objects because the enamel layer of the tooth is porous, which means that any black pigment rich material, such as coffee, red wine, tobacco, tea and food, can be easily absorbed into the pores, accumulate on the enamel layer of the tooth and form a film on the tooth. Regular consumption of these particular foods can result in staining and permanent discoloration of teeth.

There are currently several single film based tooth whitening strips/sticks on the market, including both soluble and insoluble forms. Their peroxide concentrations range from 3-14% by weight. However, these ingredients are considered to be slow bleaching. These whitening patches have the disadvantage of being non-chemically activated and thus not effective in whitening teeth, requiring a long time of use, typically 30 minutes or more, by the user. If the user uses it for a short time, the peroxide contained in the whitening patch will not have enough time to decompose into bleaching radicals and achieve the whitening effect. However, prolonged use of whitening often causes or is accompanied by tooth sensitivity and/or demineralization, and therefore, after use, usually requires desensitization or remineralization.

Peroxy compounds have been used for many years in the field of tooth whitening because the decomposition of these compounds can generate free radicals to oxidize organic molecules and inorganic compounds. Peroxy compounds, for example, hydrogen peroxide, an oxidizing agent which is itself relatively weak under mild conditions: they may achieve some oxidation but for truly effective applications it needs to be activated in one way or another.

Decomposition of hydrogen peroxide has been extensively studied as a model reaction for the catalytic activity of various metal complexes, and has also been studied as a catalase model. Can accelerate H₂O₂Decomposition into H₂O and O₂Has been known by man for about a century. The rate of hydrogen peroxide decomposition increases with increasing temperature, concentration and Ph. The decomposition process can be catalyzed by a variety of compounds, including most transition metals and their compounds (e.g., manganese dioxide, silver, and platinum). Certain metal ions, e.g. Fe₂ ⁺Or Ti₃ ⁺This results in decomposition via different pathways, including the formation of free radicals (HO.) and (HOO.). Non-metallic catalysts include potassium iodide, which reacts particularly rapidly. The hydrogen peroxide can also be generated by peroxidationThe catalase is biologically decomposed.

Prior art whitening strips containing superoxide for tooth whitening include U.S. patent nos. 5891453, 7785572, 5891453, 6893629, 5879691, 6949240, 9149417 and 9149417.

U.S. patent No. 5891453, among others, discloses a one-component transparent flexible tape material that provides an adhesive tooth whitening substance. U.S. patent No. 5879691 discloses a one-component transparent tape material having a bending stiffness of less than about 50 g/cm and providing a tooth whitening substance. The similarities between us patent numbers 5891453 and 5891453 are not clear. However, it is apparent that the power required by us patent No. 5879691 is covered by us patent No. 5891453 for these mature tooth whitening strip technologies.

U.S. patent No. 7785572 discloses a one-part dry adhesive material device comprising a base gel layer containing a peroxide tooth whitening agent and a hydrophilic glassy polymer as base polymers, and a support layer. U.S. patent No. 6419906 discloses a one-component anhydrous hydratable ethylene oxide polymer matrix film containing a solid peroxide whitening agent which, after being placed on stained teeth, is hydrated by saliva and then whitens the teeth. U.S. patent No. 6949240 discloses a one-component tooth whitening strip that carries a tooth whitening peroxide at a concentration greater than about 7.5% and a hydrogen peroxide density of less than 1.3 mg/cm. In contrast, the tooth whitening, desensitizing and/or remineralizing strip system comprises at least two film strips that are separated from each other prior to use.

U.S. patent No. 6893629 discloses a one-component, dissolvable film made of a flexible castable polymeric material having a tooth whitening substance dispersed thereon, the film dissolving time being approximately one hour when the film is attached to the teeth, during which time the active tooth whitening substance will be released. U.S. patent No. 9149417 discloses a one-part multi-layer dissolvable tooth whitening strip in which the inner layer contains a solid whitening active and the dissolvable outer layer contains a mixed polymer that dissolves after a predetermined time, and an adhesive is formed between the tooth-contacting inner and outer layers by partial dissolution during the casting process.

U.S. patent No. 6682721 discloses a one-part multi-layer dry tooth whitening patch comprising a hydrated adhesive layer containing a stable peroxide tooth whitening agent and a peroxide compatible hydrophilic glass polymer as a support layer. In contrast, the multi-layer film tooth whitening, desensitizing and/or remineralizing strip system described herein comprises a layer of tooth contacting soluble adhesive film containing a peroxide-activated complex, a desensitizing agent and/or remineralizing agent and/or an anti-inflammatory agent, and an insoluble outer film strip containing a stabilized tooth whitening active ingredient and/or a desensitizing agent and/or a remineralizing agent and/or an anti-inflammatory agent and a liquid; the liquid of the outer membrane will dissolve the first layer of orally dissolvable membrane and the peroxide-activated complex of the first membrane will activate the peroxide complex on the second membrane and accelerate tooth whitening; the two layers of membrane strips are separated from each other until application.

TW200407169A discloses a tooth whitening strip comprising a film of two sides coated with a tooth whitening agent on one of the sides.

The above prior art patents can both play a certain whitening effect, but all have some problems, for example, the film structure is simply coated with a coating, but the single film structure cannot be tightly attached to the surface of the teeth, the contact time cannot be guaranteed, and the whitening effect can be seriously affected. At present, some products only have single whitening effect, do not help the protection and curing of enamel, and only have temporary effect on the surface, but do not last.

Disclosure of Invention

When a peroxide and a peroxide activator, which are generally incompatible with each other, are combined for the first time, such as transition metal salts or complex enzymes, electrolytes, alkaline substances and mixtures thereof, catalytic decomposition of hydrogen peroxide is caused and active bleaching radicals are released which rapidly whiten teeth. Catalytic decomposition is dependent on H₂O₂The concentration of the catalyst, the temperature and the pH of the reaction solution.

The multilayer film application system provides convenience while also providing additional advantages to the consumer. These additional advantages include tooth whitening, improved tooth remineralization without the need for mixing or wasting agents and catalysts, better prevention of tooth sensitivity, as the anti-sensitivity ingredients can be separated from the whitening ingredients prior to use and activated at the time of use, and can also reduce use time and improve comfort.

Based on the principle, the invention provides a preparation method of a multi-film multi-component tooth whitening, desensitizing and/or remineralizing system, which comprises the following steps:

synthesizing the activating compound or ingredient and/or desensitizing agent and additional ingredients into a film polymer, forming a dissolvable film by shaping and/or evaporating a portion of the added liquid;

an insoluble film is provided in association with the dissolvable film, and a substance added to the dissolvable film activates the substance on the insoluble film when applied to the tooth surface.

Preferably, the dissolvable film and the insoluble film are separate two-layer film structures, and the activation compound or composition added to the dissolvable film activates the peroxide compound or composition on the insoluble film when applied to the tooth surface.

Preferably, the peroxide compound or component on the insoluble film is hydrogen peroxide or carbamide peroxide, and when applied to the tooth surface, the activating compound or component added to the first soluble film activates the peroxide compound on the second insoluble film and accelerates the release of the effective factor to accelerate the whitening effect.

Preferably, the dissolvable film incorporates at least one activating compound or ingredient and/or desensitizing agent and/or remineralizing agent and/or anti-inflammatory agent.

Preferably, the above dissolvable film comprises 20 to 95% by weight of water-soluble film forming polymers including, but not limited to, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), pullulan, carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (Na-CMC), pectin, starch, gelatin, xanthan gum, polyvinylpyrrolidone (PVP), sodium alginate, chitosan derivatives, alone or in combination, having an average molecular weight of 5,000-.

Preferably, the dissolvable film (ODF) described above comprises from about 20% to 95% water-soluble film-forming polymer (by total film weight).

Preferably, the dissolvable film includes a water insoluble polymer, such as polyvinyl acetate (PVA), ethylene/ethylene copolymer (EVA), with a melt flow index in the range of 2 to 200.

Preferably, the dissolvable film (ODF) described above contains 0.1% to 10% water insoluble polymer (by weight of the total film).

Preferably, the dissolvable film includes desensitizing agents, sweeteners, flavoring agents, coloring agents, salivation promoting agents, surfactants, sweeteners, plasticizers and thickening agents, either alone or in combination.

Preferably, the above-mentioned dissolvable film (ODF) comprises at least one activator, such as a transition metal salt, e.g. iron, manganese, copper, etc.; a compound and/or complex; PH enhancers, such as sodium hydroxide, potassium hydroxide; ammonium hydroxide, triethanolamine, tris (hydroxymethyl) urethane, and the like; electrolytes, such as alkaline salts; biologically active enzymes, and the like, alone or in combination.

Preferably, the desensitizer is potassium nitrate, sodium citrate, calcium nitrate and the like, singly or in combination and/or a remineralizing agent, such as nano-hydroxyapatite, nano-fluorapatite, casein phosphopeptide-amorphous calcium phosphate (casein phosphopeptide-amorphous calcium phosphate), calcium hydrogen phosphate (fluoride) nano-complex (calcium phosphate), bioactive glass, sodium monofluorophosphate, potassium monofluorophosphate, magnesium monofluorophosphate, acidified fluorphosphate, amine fluoride, water-soluble fluoride salt, such as sodium fluoride, potassium fluoride, calcium fluoride, stannous fluoride, sodium fluorosilicate, bis-salicylato-bis-fluorotitanium (IV), fluorosilicate, calcium salt, phosphate, calcium salt/ionic fluoride source, zinc salt/phosphate, alone or in combination.

Preferably, the sweetener is sucralose, saccharin or xylitol; a flavoring agent selected from citrus flavor, mint flavor, chocolate flavor, berry flavor, and the like, either alone or in combination; colorants, salivation enhancers, surfactants, sweeteners, plasticizers and thickeners.

Preferably, the dissolvable film is substantially thin and comfortable.

Preferably, the thickness of the dissolvable film is 50 μm to 1mm, and the dissolvable film has a single-layer or multi-layer structure, and has both toughness and scalability.

Preferably, the dissolvable film comprises multiple but thin strips, stabilizers, humectants, thickeners, and the like; at least one of them is supported by inert polymers such as Polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), etc.; the whitening substance is in the form of a gel comprising a tooth whitening peroxy compound, such as hydrogen peroxide or carbamide peroxide.

Preferably, the insoluble film is substantially thin and comfortable.

Preferably, the thickness of the insoluble film is 50 μm to 500. mu.m.

Preferably, the above method comprises synthesizing the activating compound or ingredient and/or desensitizing agent and additional ingredients into a film polymer by solvent casting, semi-solid casting, Hot Melt Extrusion (HME), solid dispersion extrusion or rolling, and then forming the film by shaping and/or evaporating a portion of the liquid added.

Preferably, less than 20% by weight of the total film of liquid/solvent, such as water, alcohol, etc., alone or in combination, may be added during mixing to provide good dispersion of the ingredients. Preferably, part of the liquid added will evaporate during forming or casting.

Preferably, the above film-forming polymers, such as Hydroxypropylmethylcellulose (HPMC), Hydroxyethylcellulose (HEC), Hydroxypropylcellulose (HPC), pullulan, carboxymethylcellulose (CMC), sodium carboxymethylcellulose (Na-CMC), pectin, starch, gelatin, xanthan gum, polyvinylpyrrolidone (PVP), sodium alginate, chitosan derivatives, polyvinyl acetate (PVA), ethylene/vinyl copolymer (EVA), and the like, and mixtures thereof, are used as ODF matrices.

Preferably, the above process comprises from about 20% to 95% water soluble polymer and/or from about 0.1% to 10% water insoluble polymer by total film weight; or alternatively,

prepared by various processes including, but not limited to, solvent casting, semi-solid casting, Hot Melt Extrusion (HME), solid dispersion extrusion or rolling, which can embed a mesh layer to provide additional flexibility, breaking strength and tensile strength, wherein the mesh material is made of High Density Polyethylene (HDPE), Low Density Polyethylene (LDPE), Linear Low Density Polyethylene (LLDPE), polypropylene (PP), polyvinyl acetate (PVA) or a mixed polymer, and has an air permeability of 200cfm to 2000cfm, a thickness of 0.025mm to 0.25mm, and an areal density of 3.4g/m2 to 85g/m 2; the resulting film becomes essentially part of an Orally Dissolvable Film (ODF).

Preferably, at least one plasticizer is used, such as glycerol, propylene glycol, polyethylene glycol (PEG)200, 400, 600, polymer PEG, copolymers of polyoxyethylene and polypropylene oxide, and mixtures thereof.

Preferably, the method comprises activating compounds, or components containing transition metal salts, such as compounds and/or complexes of iron, manganese, copper, etc.; pH enhancers, such as sodium hydroxide, potassium hydroxide; ammonium hydroxide, triethanolamine, tris (hydroxymethyl) aminomethane, etc.; electrolytes, such as alkaline salts; biologically active enzymes, and the like, and mixtures thereof.

Preferably, the above method comprises desensitizing agents such as potassium nitrate, sodium citrate, calcium nitrate, and the like, alone or in combination, and/or remineralizing agents such as nano-hydroxyapatite, nano-fluorapatite, casein phosphopeptide-amorphous calcium phosphate (casein phosphopeptide-amorphous calcium phosphate), calcium hydrogen phosphate (fluoride) nanocomposite (calcium phosphate) (fluoride) nano-complex, bioactive glass, and the like, alone or in combination, and/or anti-inflammatory agents such as Bis-phenols (e.g., triclosan), cerolines (Cyclines), aloe vera, menthol, carboxymethyl cellulose (CMC) -prebiotics-OTF, elderberry (brucus nigra), garlic, tea polyphenols, alone or in combination.

Preferably, the above method comprises some additional ingredients including sweeteners, flavoring agents, coloring agents, salivation promoting agents, thickeners, and the like.

Preferably, the thickness of the film produced by the above method is generally between 100 μm and 1 mm.

A multi-film, multi-component tooth whitening, desensitizing and/or remineralizing system prepared according to the above method, comprising:

a first layer of soluble film made of a liquid-soluble or liquid-dispersed polymer system, to which at least an activating compound or ingredient is added, and a second layer of insoluble film to which a peroxygen compound or ingredient is added.

A method of using a multi-film, multi-component, tooth whitening, desensitizing and/or remineralizing system as described above, comprising:

placing a first dissolvable film on the tooth surface, waiting a few seconds (between 1 second and 59 seconds) or until the film absorbs saliva to become gelatinous, activating its adhesive properties, and then placing a second insoluble film on the first dissolvable film; alternatively, the first and second electrodes may be,

placing a first dissolvable film on the tooth surface and immediately thereafter placing a second insoluble film on the first dissolvable film; alternatively, the first and second electrodes may be,

the first dissolvable film is placed over the second insoluble film and then both films are placed on the tooth surface.

Preferably, the first dissolvable film is placed on the tooth surface and immediately hydrates, becoming gel-like upon contact with saliva.

Preferably, the active substance on the first soluble film contacts the tooth whitening peroxy compound on the second insoluble film and accelerates the release of active bleaching radicals, so that the teeth are whitened quickly.

Preferably, the dissolution of the hydrogen peroxide activated complex in the first dissolvable film is controlled by interaction with the liquid containing whitening component of the second insoluble film.

A multi-film, multi-component tooth whitening, desensitizing and/or remineralizing system comprising:

a first dissolvable film made of a liquid soluble or liquid dispersible polymer system incorporating at least one calcium compound or ingredient;

a separate second insoluble film containing at least one phosphate compound or component and at least one fluid or liquid for dissolving the first soluble film, wherein when the two separate films are placed together on the tooth surface, the calcium compound or component added to the first soluble film reacts with the phosphate compound or component on the second insoluble film to form hydroxyapatite for remineralizing the tooth.

Preferably, the calcium compound or component on the first dissolvable film is calcium carbonate, calcium silicate, calcium sulfate, calcium phosphate, calcium gluconate, calcium oxide, calcium lactate, calcium hydride, calcium carboxymethylcellulose, calcium alginate, calcium citrate, alone or in combination.

Preferably, the phosphate compound or component on the insoluble membrane of the second layer is sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium pyrophosphate, tetrasodium pyrophosphate, sodium tripolyphosphate, sodium hexametaphosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, tripotassium phosphate, alone or in combination.

Compared with the prior art, the multi-membrane multi-component tooth whitening and desensitizing system and the preparation and use methods thereof provided by the invention have the advantages that through the double-layer structure design of the dissolvable membrane and the insoluble membrane, the activating compound or component in the dissolvable membrane can activate the peroxy compound or component on the insoluble membrane, so that tooth remineralization and tooth whitening can be improved, premixing or waste of reagents and catalysts is not needed, and tooth sensitivity is better prevented.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required to be used in the embodiments of the present invention will be briefly described below, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

FIG. 1 is a schematic diagram showing key factors in the preparation of an ODF by a solvent casting method;

FIG. 2 is a key process diagram for manufacturing an ODF using a Hot Melt Extrusion (HME) method;

FIG. 3 is a schematic diagram of an alternative process for the fabrication of an oral dissolvable film ODF by embedding a mesh layer 32 and using film winding;

FIGS. 4-8 illustrate an embodiment of the present invention;

FIGS. 9-11 illustrate another embodiment of the present invention;

FIGS. 12-17 illustrate another embodiment of the present invention;

fig. 18-20 illustrate another alternative embodiment of the present invention.

The labels in the figure are: 1-a feeding motor; 2-a feeder; 3-rotating the barrel; 4-a heater; 5-a segmented screw; 6-an extrudate; 7-driving a motor; 8-a gearbox; 9-molding; 10-a film; 11-a roller; 12-a dryer; 13-doctor blade; 14-membrane raw material; 15-mesh and support layers; 21-an administration system; 22-a first dissolvable film; 24-a release film; 25-a second insoluble film; 26-a whitening substance; 27-produced/finished film; 28-a release film; 30-a second insoluble film; 32-a mesh layer; 34-activating compounds (or calcium compounds); 36-a peroxy compound; 38-adjacent teeth; 40-gingival tissue.

Detailed Description

Features and exemplary embodiments of various aspects of the present invention will be described in detail below, and in order to make objects, technical solutions and advantages of the present invention more apparent, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not to be construed as limiting the invention. It will be apparent to one skilled in the art that the present invention may be practiced without some of these specific details. The following description of the embodiments is merely intended to provide a better understanding of the present invention by illustrating examples of the present invention.

It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising … …" does not exclude the presence of other identical elements in a process, method, article, or apparatus that comprises the element.

The present embodiment provides a method for preparing a multi-film multi-component tooth whitening and desensitizing system, comprising:

In some embodiments, the dissolvable film and the insoluble film are separate two-layer film structures, and the activation compound or composition added to the dissolvable film activates the peroxide compound or composition on the insoluble film when applied to the tooth surface.

In some embodiments, the peroxide compound or composition on the insoluble film is hydrogen peroxide or carbamide peroxide, and when applied to the tooth surface, the activating compound or composition added to the first dissolvable film activates the peroxide compound on the second insoluble film and accelerates the release of the effective factor to accelerate the whitening effect.

In some embodiments, the dissolvable film is pre-loaded with at least one activating compound or ingredient and/or desensitizing agent and/or remineralizing agent and/or anti-inflammatory agent.

In some embodiments, the dissolvable film comprises 20% to 95% by weight of a water soluble film forming polymer including, but not limited to, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), pullulan, carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (Na-CMC), pectin, starch, gelatin, xanthan gum, polyvinyl pyrrolidone (PVP), sodium alginate, chitosan derivatives, alone or in combination, having an average molecular weight of 5,000 and 500,000.

In some embodiments, the dissolvable film (ODF) comprises from about 20% to 95% water-soluble film-forming polymer (by total film weight).

In some embodiments, the dissolvable film includes a water insoluble polymer, such as polyvinyl acetate (PVA), ethylene/ethylene copolymer (EVA), with a melt flow index in the range of 2 to 200.

In some embodiments, the dissolvable film (ODF) contains 0.1% to 10% water insoluble polymer (by total film weight).

In some embodiments, the dissolvable film includes one or a combination of desensitizing agents, sweeteners, flavorants, colorants, salivation promoting agents, surfactants, sweeteners, plasticizers, and thickeners, alone or in combination.

In some embodiments, the dissolvable film (ODF) comprises at least one activator, such as a transition metal salt, e.g., iron, manganese, copper, and the like; a compound and/or complex; PH enhancers, such as sodium hydroxide, potassium hydroxide; ammonium hydroxide, triethanolamine, tris (hydroxymethyl) urethane, and the like; electrolytes, such as alkaline salts; biologically active enzymes, and the like, alone or in combination.

In some embodiments, the desensitizing agent is potassium nitrate, sodium citrate, calcium nitrate, and the like, alone or in combination and/or as a remineralizing agent, such as nano-hydroxyapatite, nano-fluorapatite, casein phosphopeptide-amorphous calcium phosphate (casein phosphopeptide-amorphous calcium phosphate), calcium hydrogen phosphate (fluoride) nano-complex (calcium phosphate), bioactive glass, sodium monofluorophosphate, potassium monofluorophosphate, magnesium monofluorophosphate, acidified fluorphosphate, amine fluoride, water-soluble fluoride salt, such as sodium fluoride, potassium fluoride, calcium fluoride, stannous fluoride, sodium fluorosilicate, bis-salicylato-bis-fluorotitanium (IV), fluorosilicate, calcium salt, phosphate, calcium salt/ionic fluoride source, zinc salt/phosphate, alone or in combination.

In some embodiments, the sweetener is sucralose, saccharin, xylitol; a flavoring agent selected from citrus flavor, mint flavor, chocolate flavor, berry flavor, and the like, either alone or in combination; colorants, salivation enhancers, surfactants, sweeteners, plasticizers and thickeners.

In some embodiments, the dissolvable film is substantially thin and comfortable.

In some embodiments, the dissolvable film has a thickness of 50 μm to 1mm, is a monolayer or multilayer structure, and is both flexible and stretchable.

In some embodiments, the dissolvable film contains multiple layers but is very thin strips, stabilizers, humectants, thickeners, and the like; at least one of them is supported by inert polymers such as Polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), etc.; the whitening substance is in the form of a gel comprising a tooth whitening peroxy compound, such as hydrogen peroxide or carbamide peroxide.

In some embodiments, the insoluble film is substantially thin and comfortable.

In some embodiments, the insoluble film has a thickness of 50 μm to 500 μm.

In some embodiments, the method comprises synthesizing the activation compound or ingredient and/or desensitizing agent and additional ingredients into a film polymer by solvent casting, semi-solid casting, Hot Melt Extrusion (HME), solid dispersion extrusion, or rolling, and then forming the film by shaping and/or evaporating a portion of the liquid added.

In some embodiments, less than 20% of the total film weight of liquid/solvent, such as water, alcohol, etc., alone or in combination, may be added during mixing to provide good dispersion of the ingredients. Preferably, part of the liquid added will evaporate during forming or casting.

In some embodiments, the above film-forming polymers, such as Hydroxypropylmethylcellulose (HPMC), Hydroxyethylcellulose (HEC), Hydroxypropylcellulose (HPC), pullulan, carboxymethylcellulose (CMC), sodium carboxymethylcellulose (Na-CMC), pectin, starch, gelatin, xanthan gum, polyvinylpyrrolidone (PVP), sodium alginate, chitosan derivatives, polyvinyl acetate (PVA), ethylene/vinyl copolymer (EVA), and the like, and mixtures thereof, are used as ODF matrices.

In some embodiments, the above method comprises from about 20% to 95% water soluble polymer and/or from about 0.1% to 10% water insoluble polymer by total film weight; or alternatively,

in some embodiments, the web material is made using a variety of processes including, but not limited to, solvent casting, semi-solid casting, Hot Melt Extrusion (HME), solid dispersion extrusion, or rolling, which can embed a web layer to provide additional flexibility, breaking strength, and tensile strength, wherein the web material is made using High Density Polyethylene (HDPE), Low Density Polyethylene (LDPE), Linear Low Density Polyethylene (LLDPE), polypropylene (PP), polyvinyl acetate (PVA), or a mixed polymer, and has an air permeability of 200cfm to 2000cfm, a thickness of 0.025mm to 0.25mm, and an areal density of 3.4g/m2 to 85g/m 2; the resulting film becomes essentially part of an Orally Dissolvable Film (ODF).

In some embodiments, at least one plasticizer is used, such as glycerin, propylene glycol, polyethylene glycol (PEG)200, 400, 600, polymeric PEG, copolymers of polyoxyethylene and polypropylene oxide, and mixtures thereof.

In some embodiments, the method comprises activating a compound, or a composition comprising a transition metal salt, such as a compound and/or complex of iron, manganese, copper, and the like; pH enhancers, such as sodium hydroxide, potassium hydroxide; ammonium hydroxide, triethanolamine, tris (hydroxymethyl) aminomethane, etc.; electrolytes, such as alkaline salts; biologically active enzymes, and the like, and mixtures thereof.

In some embodiments, the methods include desensitizing agents, such as potassium nitrate, sodium citrate, calcium nitrate, and the like, alone or in combination, and/or remineralizing agents, such as nano-hydroxyapatite, nano-fluorapatite, casein phosphopeptide-amorphous calcium phosphate (calcium phosphate), calcium hydrogen phosphate (fluoride) nanocomposite (calcium phosphate) nano-complex), bioactive glass, and the like, alone or in combination, and/or anti-inflammatory agents, such as Bis-phenols (e.g., triclosan), cerolines (Cyclines), aloe vera, menthol, carboxymethyl cellulose (CMC) -prebiotic-OTF, Sambucus nigra, garlic, tea polyphenols, alone or in combination.

In some embodiments, the method comprises some additional ingredients, including sweeteners, flavoring agents, coloring agents, salivation-promoting agents, thickening agents, and the like.

In some embodiments, the method produces a film thickness typically between 100 μm and 1 mm.

The present embodiments provide a multi-film, multi-component tooth whitening and desensitizing system, comprising:

a first layer of soluble film made of a liquid-soluble or liquid-dispersed polymer system, pre-loaded with at least an activating compound or component, and a second layer of insoluble film pre-loaded with a peroxygen compound or component.

The present embodiments provide a method of using a multi-film, multi-component tooth whitening and desensitizing system, comprising:

Wherein the first dissolvable film is immediately hydrated upon placement on the tooth surface and becomes gelatinous upon contact with saliva. The active substance on the first layer of the dissolving film contacts the tooth whitening peroxy compound on the second layer of the non-dissolving film and accelerates the release of active bleaching free radicals, so that the teeth are whitened quickly. The dissolution of the hydrogen peroxide activated complex in the first dissolvable film may be controlled by interaction with the liquid containing whitening component of the second insoluble film.

The present embodiments also provide a multi-film, multi-component tooth whitening and desensitizing system, comprising:

a first dissolvable film made of a liquid soluble or liquid dispersible polymer system pre-loaded with at least one calcium compound or ingredient;

The calcium compound or component on the first soluble film is calcium carbonate, calcium silicate, calcium sulfate, calcium phosphate, calcium gluconate, calcium oxide, calcium lactate, calcium hydride, carboxymethyl cellulose calcium, calcium alginate, calcium citrate, or their mixture.

The phosphate compound or component on the insoluble membrane of the second layer is sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium pyrophosphate, tetrasodium pyrophosphate, sodium tripolyphosphate, sodium hexametaphosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate and tripotassium phosphate, which are singly or in combination.

Figures 4, 5, 6, 7 and 8 show a preferred embodiment of the invention, designated 21. Embodiment 21 represents a multi-component teeth whitening, desensitizing and/or remineralizing, multi-layer film application system. The first layer of orally dissolvable film 23 of the application system 21 has one orally dissolvable film 22 and one release film 24, both films being flat, preferably rounded; the second insoluble film 25 of the application system 21 has a strip of film material 30 which is the same shape as the first orally dissolvable film 22, and a release film 28 is attached to the strip of film material 30 by the whitening substance 26. The peroxide activating compound (or calcium compound) 34 is uniformly and uniformly dispersed throughout the orally dissolvable film 22, as shown in fig. 5. The orally dissolvable film 22 has sufficient flexibility and tensile strength to form a curved shape between adjacent teeth; upon hydration of the dissolvable film 22 by contact with the user's saliva or the liquid contained in the whitening substance 26 on the second insoluble film 30, it becomes gelatinous and conforms perfectly to the tooth surface. Once the release film 28 is removed, strips of film material 30 carrying the whitening substance 26 are applied to the first layer of film 22.

In an alternative embodiment of the invention shown in fig. 9, 10 and 11, the first layer of orally dissolvable film 22 comprises or is embedded in a mesh layer 32, providing a finished film with toughness, resistance to fracture, and tensile strength, wherein the mesh material is made of High Density Polyethylene (HDPE), Low Density Polyethylene (LDPE), Linear Low Density Polyethylene (LLDPE), polypropylene (PP), polyvinyl acetate (PVA), or a blend of polymers; the film 27 thus produced is essentially an Orally Dissolvable Film (ODF) with a mesh layer 32, which is the only residue after application and dissolution.

Fig. 12 shows a first layer of an orally dissolvable film 22 and an activating compound (or calcium compound) 34 of an application system 21 of the present invention applied to the front and back surfaces of adjacent teeth 38, and to gingival tissue 40 adjacent the front surfaces of the teeth. Adjacent gingival tissue is defined herein as soft tissue surrounding the tooth, including: mastoid, marginal gingiva, gingival ravines, inner gingiva, lingual surface, and buccal surface gingival structures.

Fig. 13 shows a second layer of insoluble film 30 and whitening substance 26 of the application system 21 of the present invention applied over the first layer of orally dissolvable film 22 with the whitening substance 26 on the side of the film material 30 opposite the first layer of orally dissolvable film 22.

Fig. 14 shows the reaction between the peroxide activating compound (or calcium compound) 34 in the first layer of orally dissolvable film 22 and the peroxide complex (or phosphate compound) in the whitening substance 26 on the second layer of insoluble film 30, accelerating the release of active bleaching radicals (HO) for fast whitening₂-,OH-,O₂-,O-,O₂). Dissolution of the first film 22 is controlled by the interaction of the user's saliva or the liquid contained in the whitening substance 26 on the second film 30.

Fig. 15 is a cross-sectional side view of fig. 12 taken along line 16-16 showing the first layer of orally dissolvable film 22 of the present invention engaging the teeth and adjacent gum tissue and absorbing saliva through the orally dissolvable film 22 and becoming gelatinous and adhesively attached to the sides of the teeth.

Fig. 16 is a cross-sectional side view of fig. 13 taken along line 17-17 showing the application of a second insoluble film 30 of the present invention to the first orally dissolvable film 22 while conforming to the teeth and adjacent gum tissue and adhesively attached to both sides of the teeth by a substance 26 located between the first dissolvable film 22 and the insoluble film 30.

Fig. 17 is a cross-sectional side view of fig. 14 taken along line 18-18 showing the reaction between the peroxide activating compound (or calcium compound) 34 in the first layer of dissolvable film 22 and the peroxide compound 36 on the second layer of film 30 to accelerate the release of active bleaching radicals (HO) for fast whitening₂-,OH-,O₂-,O-,O₂). This figure shows a cross-sectional side view showing the reaction between the calcium compound 34 in the first soluble film 22 and the phosphate compound 36 on the second insoluble film 30, accelerating the release of active bleaching radicals (HO) for fast whitening₂-,OH-,O₂-,O-,O₂)。

Fig. 18, 19 and 20 show an alternative method of using the multilayer film application system 21 of the present invention: placing a first dissolvable film 22 containing a peroxide activating compound (or calcium compound) 34 over a second non-dissolvable film 30 carrying a whitening substance 26 containing a peroxide compound 36 and then placing the two films over the tooth surface, the peroxide activating compound (or calcium compound) 34 in the first film 22 and the peroxide compound 30 on the second film 30 react to accelerate the release of active bleaching radicals (HO) for rapid whitening₂-,OH-,O₂-,O-,O₂)。

In one aspect, the present invention provides a multi-component tooth whitening, desensitizing and/or remineralizing, multilayer film application system wherein a first layer of an Orally Dissolvable Film (ODF)22 is preloaded with at least one activating compound or ingredient (or calcium compound) 34 and/or desensitizing agent and/or remineralizing agent and/or anti-inflammatory agent, and a separate second layer of an insoluble plastic or polymeric film 30 comprises insoluble single or multilayer thin film strips 30 made of inert polymers such as Polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), etc., wherein the whitening substance 26 is in the form of a gel containing a tooth whitening peroxide compound 36 such as hydrogen peroxide, urea peroxide or sodium perborate; stabilizers and thickeners. After the two films are applied to the tooth surface, the activating compound (or calcium compound) 34 on the first film 22 activates the peroxy compound 36 on the second film 30 and accelerates the release of the active factor for whitening, while the film components desensitize and/or remineralize the teeth. As shown in fig. 14 and 17.

In some embodiments, the Orally Dissolvable Film (ODF)22 is based on water soluble film forming polymers including, but not limited to, Hydroxypropylmethylcellulose (HPMC), Hydroxyethylcellulose (HEC), Hydroxypropylcellulose (HPC), pullulan, carboxymethylcellulose (CMC), sodium carboxymethylcellulose (Na-CMC), pectin, starch, gelatin, xanthan gum, polyvinylpyrrolidone (PVP), sodium alginate, chitosan derivatives, and the like, alone or in combination. ODF consists essentially of about 20% to 95% (by weight) of the water-soluble polymer.

In some embodiments, the ODF consists of a blend of different low/high molecular weight polymers as described above. For ODF, mixtures of different molecular weights can provide additional advantages, such as good mechanical properties, which can facilitate subsequent processing and conversion to the product produced. Preferably, such a mixture comprises at least one polymer having a molecular weight of less than 20,000 and a second polymer or mixture having a molecular weight of greater than 50,000.

In some embodiments, the ODF comprises less than 10% water-insoluble film-forming polymers, such as polyvinyl acetate (PVA), ethylene/ethylene copolymers (EVA), preferably having a melt flow index from 2 to 200.

In some embodiments, the average molecular weight of the film-forming polymer is between 5,000 and 500,000.

In another aspect, the ODF comprises at least one peroxide activating compound (or calcium compound) 34 and/or a desensitizing agent and/or a remineralizing agent and/or an anti-inflammatory agent. Other ingredients included include plasticizers, sweeteners, flavoring agents, coloring agents, salivation promoting agents, surfactants, and thickeners.

Peroxide activating compounds (or calcium compounds) 34 are defined herein as transition metal salts or transition metal complexes containing a transition metal compound and a chelating agent, and/or a pH enhancer and/or an electrolyte and/or a biologically active enzyme, etc., alone or in combination, that are capable of activating a peroxy compound by producing an active bleaching molecule.

The amount of peroxide activating compound (e.g., transition metal compound/complex and/or pH enhancing agent and/or electrolyte and/or biologically active enzyme, etc., alone or in combination) or calcium compound (e.g., calcium carbonate, calcium silicate, calcium sulfate, calcium hydrogen phosphate, calcium gluconate, calcium oxide, etc., alone or in combination) 34 contained in the first layer dissolvable film 22 of the multi-component multi-layer film application system for tooth whitening, desensitization, and/or remineralization of the present invention will depend on the amount of peroxide 36 contained in the second layer insoluble film 30.

In professional use, the second insoluble film 30 contains a relatively high concentration of peroxide compound, i.e., about 9% to 40% by weight, and the peroxide activating compound (or calcium compound) 34 content in the first insoluble film 22 is between 0.1% and 10%, preferably between 0.2% and 5% by weight. For self-use, the concentration of the peroxide compound 36 on the second layer insoluble membrane is between 0.1% and 15% by weight, for example, a lower concentration of the peroxide activating compound (or calcium compound) 34 between 0.01% and 5% is included in the first layer soluble membrane 22, preferably 0.02% to 1% by weight of the activator is used.

In addition, the surfactant may be used to disperse the peroxide activating compound/complex and enhance the diffusion of free radicals, thereby achieving an effective whitening effect. Preferred polymeric surfactants include polyethylene glycol having a molecular weight greater than 2,000, polyoxyethylene/polyoxypropylene block copolymers, polyvinylpyrrolidone (PVP), polyvinyl alcohol, and the like.

On the other hand, the first layer of the orally dissolvable film, ODF, is thin and comfortable to use, wherein the film is typically between 50 μm and 1mm thick and preferably has some tensile strength or toughness. The design can be a single layer to a multi-layer system.

In addition, the invention provides a technology for manufacturing the ODF, which is called as the technology of the oral dissolvable film. The orally dissolvable film techniques include combining the active compound or ingredient and/or desensitizing agent, and other ingredients within the film forming polymer together by mixing and/or grinding, and then forming a film by modeling and/or casting or evaporating portions of the liquid.

In one aspect, the first layer of Orally Dissolvable Film (ODF)22 may be prepared by one or a combination of the following processes: solvent casting, semi-solid casting, Hot Melt Extrusion (HME), solid dispersion extrusion, and rolling. The most common methods of making films are solvent casting and hot melt extrusion. Table 1 is a comparison of the solvent casting and hot melt extrusion processes.

TABLE 1 comparison of solvent casting and Hot melt extrusion methods

Production process	Solvent casting	Hot melt extrusion
			Selected API	Thermal decomposition and thermal stabilization	Thermal stabilization
Required solvent	Is that	Whether or not
			Process for the preparation of a coating	Hydration of	Without water
Required equipment	Roller/film coating machine	Hot melt extruder
			Enlarging production	May cause problems to occur	May not be difficult
Probability of air inhalation	High probability	Small probability of

ODF, on the other hand, is preferably prepared by solvent casting, i.e. the water soluble ingredients are dissolved and form a clear and viscous solution. The other ingredients are uniformly dissolved or dispersed in the liquid dispersant. This mixture is then added to another aqueous viscous solution. Entrapped air was removed by vacuum. Degassing must be performed to obtain consistent film properties and thickness. The final solvent is cast into a film, dried, and cut into the desired shape.

The properties of the film-forming polymer play a crucial role in the selection of a suitable solvent. The physicochemical properties of the film-forming polymer should be considered. These properties include compatibility of the film-forming polymer with other film-forming excipients, compatibility with solvents, polymorphism in the film-forming polymer selected, and temperature sensitivity.

More deeply, ODF is prepared using no more than 20% total membrane weight of liquids/solvents such as water, alcohol, etc., alone or in combination. Solvents may be added during mixing to provide good dispersion of the ingredients.

In some embodiments, a portion of the liquid added is evaporated during forming or casting.

As shown in fig. 1, is a key element in the preparation of an orally dissolvable film by a solvent casting process.

Hot Melt Extrusion (HME): HME is commonly used to prepare granules, sustained release compositions, transdermal and transmucosal administration systems. The HME process has recently gained popularity in the pharmaceutical industry. As shown in fig. 2, a key process for manufacturing ODF using Hot Melt Extrusion (HME) method, based on knowledge from the plastics industry, formulators can extrude the active ingredient, polymer and plasticizer into various final forms to achieve the desired release effect. The processing of films by this technique is the molding of a polymer into a film by a thermal process rather than by conventional solvent casting. In the HME process, the active ingredient and other adjuvants are mixed in the dry state, heated initially, and the melt is extruded from a hot melt extruder. The advantage of this process is the complete absence of solvent. The film is cooled and then cut to the desired size and shape. The high temperatures used in the process make it suitable for heat resistant components. Temperature sensitive ingredients cannot be used in this process.

In some embodiments, at least one plasticizer, such as glycerol, propylene glycol, polyethylene glycol (PEG)200, 400, 600, polymeric PEG, copolymers of polyoxyethylene and polypropylene oxide, and mixtures thereof, is used in the preparation of the above ODFs. The amount of plasticizer used may vary from 0.1% to 40%, preferably from 0.5% to 10% by weight.

Moisture has a great influence on the stability of the film and its mechanical properties. Another factor that needs to be tightly controlled is temperature. Temperature conditions need to be controlled to maintain the viscosity of the solution and the temperature sensitivity of the active ingredient. A special type of equipment, such as a roller, is required to inject the solution into the inert substrate. The gap between the roller and the substrate will determine the thickness of the film. And finally, drying the membrane, removing the solvent and obtaining a finished product. Typically, glass, plastic or teflon plates are used as inert substrates for the cast film. In the final drying process, a suitable type of dryer is selected. Production and packaging of ODF requires special precautions to be taken to avoid the effects of moisture.

Orally dissolvable film technology is a polymer film that may contain agents or other active materials that erode or dissolve at a predetermined rate upon contact with a biological or other liquid. This is an effective medium for stabilizing sensitive agents, providing therapeutic agents or dispersing pigments.

The carriers used to prepare the single layer films of the multi-component tooth whitening, desensitizing, remineralizing and anti-inflammatory strip systems of the present invention are completely different. The first layer of orally dissolvable film 22 is made of a single or multiple layer film forming polymer, such as hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), pullulan, carboxymethyl cellulose (CMC), pectin, starch, polyvinyl acetate (PVA), gelatin, sodium alginate; with other ingredients included including plasticizers, sweeteners, flavoring agents, coloring agents, salivation promoting agents, and thickening agents. The second insoluble film 30 is made of a single or multiple layers of inert polymer such as Polyethylene (PE), polypropylene (PP), nylon, polyvinyl chloride (PVC), and the like. The carrier required for the composition 26 used to prepare the second insoluble film 30 comprises water and/or a suitable humectant such as glycerin, propylene glycol, polyethylene glycol or any suitable mixture. Water is the preferred humectant in the practice of the present invention.

An alternative method of making the first layer of orally dissolvable film 22 is to embed a mesh layer 32 that provides additional flexibility, breaking strength and tensile strength, wherein the mesh material is made of High Density Polyethylene (HDPE), Low Density Polyethylene (LDPE), Linear Low Density Polyethylene (LLDPE), polypropylene (PP), polyvinyl acetate (PVA) or a blend of polymers, and the mesh material has an air permeability of 200cfm to 2000cfm, a thickness of 0.025mm to 0.25mm, and an areal density of 3.4g/m2 to 85g/m 2; the resulting film 27 becomes essentially part of an Orally Dissolvable Film (ODF), the only residue after application and dissolution being the mesh layer 32. Fig. 3 shows an alternative process for ODF fabrication by embedding the mesh layer 32 and using film winding. An alternative process of manufacturing by ODF employs a mesh layer 22 and rollers.

On the other hand, on the second insoluble film 30, there is a gelatinous whitening substance containing a tooth whitening peroxy compound, such as hydrogen peroxide or carbamide peroxide, stabilizers, thickeners, and the like.

The peroxide compounds used in the composition of the present invention include hydrogen peroxide, urea peroxide, metal peroxides such as calcium peroxide, sodium peroxide, strontium peroxide, magnesium peroxide, and perborates, perphosphates and percarbonates such as sodium perborate, potassium perbenzoate and sodium percarbonate. The most effective peroxy compounds of the present invention are hydrogen peroxide and carbamide peroxide. An effective range of peroxy compounds is between about 0.1% to about 35% (by weight). A preferred range is between about 1% to about 20% by weight. The amount of peroxy compound in the second insoluble film 30 of the multi-component teeth whitening, desensitizing and/or remineralizing multi-film application system of the present invention will vary from application to application.

The peroxy compound is stabilized by the addition of a whitening gel stabilizer selected from the group consisting of ethylenediaminetetraacetic acid (EDTA) and salts thereof, potassium stannate, sodium stannate, etidronic acid, phosphoric acid, sodium pyrophosphate. The thickener is important to obtain a tacky glue so that it adheres to the second film before application and adheres to both films after application. The thickener is derived from a mixture of crosslinked polyacrylic acid, polyvinylpyrrolidone (PVP), a copolymer of polyethylene oxide and polypropylene oxide.

On the other hand, the two films are placed separately until applied to the teeth, wherein the peroxide activating compound (or calcium compound) 34 on the first orally dissolvable film 22 reacts with the peroxide compound on the second film 30 to accelerate the rapid release of the active ingredient from the peroxide compound 36, which is very effective for tooth whitening, as shown in fig. 14 and 17. The present invention provides the following advantages: premature decomposition of the peroxy compound 36 is avoided and a large amount of active bleaching molecules are rapidly generated, thereby reducing the use time of the user, and the effect is better, the comfort is greatly improved, and the use by professionals such as dentists is more convenient.

In some embodiments, the present invention provides a method of using a multi-film application system of a multi-component tooth whitening, desensitizing, or remineralizing substance. As shown in fig. 12 and 13 (also fig. 15 and 16), the use method includes:

a) placing the first layer of orally dissolvable film 22 on the surface of the teeth, waiting a few seconds (between 1 second and 59 seconds) or until the film 22 absorbs saliva and becomes gelatinous, activating its adhesive properties, and then placing the second layer of insoluble film 30 on the first layer of orally dissolvable film 22; alternatively, the first and second electrodes may be,

b) placing the first layer of orally dissolvable film 22 on the surface of the teeth and immediately thereafter placing the second layer of insoluble film 30 on the first layer of orally dissolvable film 22; alternatively, the first and second electrodes may be,

c) the first dissolvable film 22 is placed over the second insoluble film 30, waiting for a few seconds (between 1 second and 59 seconds) or until the first film 22 absorbs liquid from the second film 30, thus becoming gelatinous, and activates the peroxide on the second film 30, which is then placed on the tooth surface.

In the present invention, the technical features "film", "membrane" and "membrane strip" may be used interchangeably.

In the present invention, the technical features "tooth whitening" and "tooth bleaching" may be used interchangeably.

It will be understood by those skilled in the art that an oral film Or Dissolvable Film (ODF) is a film comprising a film forming polymer, such as hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), pullulan, carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (Na-CMC), pectin, starch, gelatin, xanthan gum, polyvinylpyrrolidone (PVP), sodium alginate, and the like, alone or in combination.

It will be appreciated by those skilled in the art that the orally dissolvable film technology is one technique for preparing the above-described orally dissolvable film ODF, comprising combining the active compound or ingredient and/or desensitizing agent, and other ingredients within the film-forming polymer by mixing and/or grinding, and then forming the film by modeling and/or casting or evaporating portions of the liquid.

It will be appreciated by those skilled in the art that one method of using the multi-film application system of the multi-component tooth whitening substance: the first layer of orally dissolvable film is placed on the tooth surface and the second layer of insoluble film is placed immediately or shortly thereafter on top of the first layer of orally dissolvable film.

All percentages, ratios and proportions are by weight unless otherwise specified. All temperatures are in degrees Celsius (. degree. C.) unless otherwise indicated.

The multi-layer film tooth whitening, desensitizing and/or remineralizing application system provided by the present invention has the advantages over conventional one-component whitening strip systems in that:

1. the first dissolvable film 22 activates and catalytically decomposes the peroxy compound 36 on the second film 30 immediately upon contacting the second insoluble film 30.

2. The same or better whitening, desensitizing and remineralizing effects are achieved, while the use time is greatly reduced.

3. The separation of the whitening complex (active ingredient) 36 and the peroxide-activated complex or calcium compound 34 improves the stability and shelf life of the ingredients.

4. The separation of the calcium complex and the phosphate complex enables the generation of the in situ hydroxyapatite required for tooth formation.

5. The dry film further improves the stability of the reagent.

The invention also provides other embodiments.

In some examples, first layer ODF sample formulations were prepared containing xanthan gum, HPMC, and PVA as film forming polymers, transition metal salts, manganese gluconate as peroxide activator, PVP as surfactant, and the like. The film was prepared by solvent casting. The solvent ethanol was added to disperse the film-forming polymer, followed by evaporation.

In some embodiments, another sample formulation of the first layer ODF was prepared containing PVP with a molecular weight of 3,000 and PVP with a molecular weight of 36,000, PVA as a film forming polymer, transition metal salt, manganese gluconate as a peroxide activator, PVP as a surfactant, and the like. Propylene glycol was used as the liquid dispersant. The film was prepared by hot melt extrusion.

In some examples, sample formulations of the first layer ODF were prepared containing xanthan gum, PVP with a molecular weight of 3,000 and PVP with a molecular weight of 36,000, PVA as a film forming polymer, transition metal salts, manganese gluconate as a peroxide activator, and the like. The film is prepared by a combination of solvent casting and hot melt extrusion. The solvent ethanol was added to disperse the film-forming polymer, followed by evaporation.

It should also be noted that the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element.

The embodiments in the present specification are described in a progressive manner, and the same and similar parts among the embodiments are referred to each other, and each embodiment focuses on the differences from the other embodiments. In particular, for the system embodiment, since it is substantially similar to the method embodiment, the description is simple, and for the relevant points, reference may be made to the partial description of the method embodiment.

The above description is only an example of the present application and is not intended to limit the present application. Various modifications and changes may occur to those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the scope of the claims of the present application.

Claims

1. A method of making a multi-film, multi-component tooth whitening, desensitizing, and/or remineralizing system, the method comprising:

2. The method of claim 1, wherein the soluble film and the insoluble film are separate two-layer film structures, and wherein the activating compound or composition added to the soluble film activates the peroxide compound or composition on the insoluble film when applied to the tooth surface.

3. A method according to claim 1 or 2, wherein the dissolvable film incorporates at least one activating compound or ingredient and/or a desensitizing agent and/or a remineralizing agent and/or an anti-inflammatory agent.

4. The method according to claim 1 or 2, wherein the dissolvable film comprises 20-95% by weight of water soluble film forming polymers including but not limited to hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), pullulan, carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (Na-CMC), pectin, starch, gelatin, xanthan gum, polyvinylpyrrolidone (PVP), sodium alginate, chitosan derivatives, alone or in combination, with an average molecular weight of 5,000-.

5. The method of claim 1 or 2, wherein the dissolvable film comprises a water insoluble polymer and has a melt flow index in the range of 2 to 200.

6. The method of claim 1 or 2, wherein the dissolvable film comprises one or a combination of desensitizing agents, sweeteners, flavoring agents, coloring agents, salivation promoting agents, surfactants, sweeteners, plasticizers and thickeners, alone or in combination.

7. The method according to claim 1 or 2, wherein the dissolvable film has a thickness of 50 μm to 1mm in a single or multi-layer structure.

8. The method according to claim 1 or 2, wherein the insoluble film has a thickness of 50 μm to 500 μm.

9. A multi-film multi-component tooth whitening and desensitizing system prepared according to the methods of claims 1-8, wherein said system comprises:

10. A method of using the multi-film multi-component tooth whitening, desensitizing and/or remineralizing system of claim 9, wherein: the method comprises the following steps:

placing a first dissolvable film on the tooth surface, waiting a few seconds or until the film absorbs saliva to become gelatinous, activating its adhesive properties, and then placing a second insoluble film on the first dissolvable film; alternatively, the first and second electrodes may be,

11. The method of claim 10 wherein the first dissolvable film is hydrated immediately upon placement on the tooth surface and becomes gelatinous upon contact with saliva.

12. The method of claim 10, wherein the active substance on the first soluble film contacts the teeth whitening peroxy compound on the second insoluble film and accelerates the release of active bleaching radicals to rapidly whiten teeth.

13. The method of claim 10, wherein the dissolution of the hydrogen peroxide activated complex in the first soluble film is controlled by interaction with a liquid containing whitening composition in the second insoluble film.