Chewing solid form and method for introducing of active agent into occlusion dental surfaces

FIELD: method and composition for oral cavity care.

SUBSTANCE: claimed form contains a) 1-40 % of retaining agent, Selected from group containing water soluble hydrophilic resins, water soluble hydrophilic polymers or mixtures thereof, wherein retaining agent is capable of hydration under water or saliva action to produce retention coefficient of 1-4; and b) 60-90 % of local carrier. Moreover composition contains 65 wt.% of water-insoluble particles. Further disclosed is dental paste composition containing a) 30-65 % of water-insoluble particles as retaining agent, wherein solubility of retaining agent in water is less then 1 g/30 g at 25°C; b) 0.01-40 % of active agent for oral cavity care; c) 0.1-25 % of buffer agent. Claimed composition has retention coefficient of 1-4.

EFFECT: improved compositions for oral cavity care.

9 cl, 3 dwg, 5 ex

 

The technical field to which the invention relates.

This invention relates to compositions of solid chewable form of unit dosages and methods of delivery (especially long-term delivery in the oral cavity fluoride or other active agents for oral care mouth. The mechanical force when biting or chewing subject are used for applying and retaining the minimum quantity of this composition on the surface of the teeth, especially in the pits, fissures and occlusal surfaces of the teeth. These compositions contain inhibiting agent and optionally one or more agents, such as active agents for oral care mouth, abrasive material, foaming agent, flavoring agents/agents sensations and/or special buffer system. The present invention also relates to chewing solid compositions and methods for regulating the pH level on the surfaces of the teeth and in the mouth. These compounds include chewable tablets for cleaning teeth.

The level of technology

There have been many attempts to regulate or prevent both tooth decay and the formation of plaque. For example, use fluoride solutions or gels, and they are usually used in dental clinics, with periodic but infrequent intervals. Plaque turns to the Yes cause tooth decay bacteria, such as Streptococcus mutans, are United in colonies and form deposits on the surfaces of the teeth. The presence of bacteria and sediment damaging to teeth and gums and can lead to gingivitis, caries, periodontitis and tooth loss.

The existing prior art considers a variety of agents that help to alter the development of many States in the oral cavity, including agents, that provide effective against caries, bacteria, Tartar, as well as anesthetic, whitening and/or anti-inflammatory effect. In particular, it has long been known that supplying the fluorine compounds are safe and effective means of enhancing the recovery process of mineralization.

In addition, the existing prior art considers the use of tablet dosage forms for different purposes when taking care of your oral cavity. For example, in U.S. patent No. 4.753.792, issued June 28, 1988, disclosed pills for brushing your teeth. Specifically, this reference describes a pill for cleaning teeth, which foams and becomes cleansing during chewing, and which includes subspinipes double effervescent composition that allows the tablet to quickly form a foam when chewing without having to use a toothbrush. Further, U.S. patent No. 3.962.417, issued in the name of Howell et al, describes a pill that contains asuu approximately 70-75% by weight of acid neutralizer and approximately 17-20% by weight acid. The initial reaction neutralizer acid and acid is used to create effervescent action in the mouth, and the resulting alkaline solution is then neutralizes acid Bacillus Acidophilios. U.S. patent No. 5.496.541, issued March 5, 1996, describes dental products that may be in the form of tablets, using ternary surfactant system of poloxamers, anionic polysaccharides and non-ionic cellulose ethers for a significant increase in strength foaming.

Despite the above-described technology of the prior art for the treatment of conditions in the oral cavity, in the existing prior art does not fully assessed the benefits or problems associated with the delivery of active agents to care for the oral cavity to the surface of the teeth in the pits, fissures or occlusal surfaces of the teeth using a chewing solid forms of a single dosage. The present invention provides these advantages over mechanical cutting provided by biting or chewing chewing solid form of a single dosage, and by retaining agent. Retaining agent enhances the deposition and adhesion of the composition to the tooth surface. Also in the existing prior art was not offered adequate funds for maintenance of the pH at the tooth surface, especially in places where often formed cavities, AMC the x, fissures and occlusal surfaces of the teeth. These advantages are achieved, for example, by selecting ingredients and levels of the components of the present invention.

The invention

The present invention relates to a composition for caring for the oral cavity for local oral administration in humans or other animal, containing:

a retention agent from about 1% to about 40% by weight of the composition, selected from the group consisting of water-soluble hydrophilic resins, water-soluble hydrophilic polymers, and mixtures thereof, and the retaining agent has the hydrating property under the influence of water or saliva, which leads in part to the formation of healthy hydrated mass to ensure retention rates from about 1 to about 4; and

b) a safe and effective amount of local funds delivery of care for the oral cavity;

when this composition is nearisogenic solid chewing the form of a unit dosage; and the composition contains less than about 65% by weight of water-insoluble particles.

The present invention further relates to a composition for caring for the oral cavity that contains:

a retention agent of water-insoluble particles from about 30% to about 65% by weight of the composition, the solubility of retention agent in water is less than 1 g to 30 g PR is a temperature of 25° C;

b) a safe and effective amount of active agent to care for the oral cavity;

c) a safe and effective amount of surfactant;

d) a safe and effective amount of a buffering agent;

when this composition is a chewing purifying solid form of a unit dosage, nishibuchi, nearisogenic; and

the composition has a coefficient of deduction from about 1 to about 4.

The present invention further relates to a method for keeping pH in the saliva of the oral cavity or the environment, or on the surface of the teeth in need of this person or animal from about 7 to about 12 units for at least 2 minutes by implementing these structures, including a buffer agent, locally in the oral cavity.

The present invention further relates to a method for providing prolonged delivery of the active agent, flavoring agent, feelings or buffer in the oral cavity of a human or animal when their needs by implementing these structures locally in the oral cavity.

Brief description of drawings

The present invention will be better understood with reference to the subsequent detailed description of embodiments with accompanying drawings, in which similar positions indicate identical elements. Without intent to limit the invention, embodiments of to the present invention are described in more detail below.

Figure 1 is a photograph of a human molar, captured, respectively, after approximately 5, 15, 30, 45 and 60 minutes after people chewed the compressed tablet of the present invention, and then brushed his teeth brushed, spat and rinsed my mouth with water.

Figure 2 is a chart of the full set of human teeth, shown in red place of deposition of the material of the tablets after people have used the present invention. The photo directly below each graph represents a partial view of two real molars with tablets, marked on them. Chart and pictures taken, respectively, after approximately 5, 15, 30, 45 and 60 minutes after people chewed the compressed tablet of the present invention, and then brushed his teeth brushed, spat and rinsed my mouth with water.

Figure 3 is a chart of the full set of human teeth, shown in red place of deposition of the material of the tablets after people have used the present invention. The photo directly below each graph represents a partial view of a real molar with material tablets inflicted on him. Chart and pictures taken, respectively, after approximately 5, 15, 30, 45 and 60 minutes after people chewed compressed tablet according to the present from which bretania, and then I brushed my teeth brushed, spat and rinsed my mouth with water.

Detailed description of the invention

Definition

"Natural set of teeth", as used here, means a person with natural teeth, including not more than one or two substitutions or tabs in his teeth, in another embodiment no more than three substitutions or seals, and having at least 8 molars (including premolars). In addition, the subject must not have a filling material or porcelain crowns with a facet on the teeth, and the teeth are of normal morphology, such as the absence of relatively flat surfaces of the molars. The stitching of the teeth may lead to relatively flat surfaces of the molars, where the edge of the flattened teeth. Substitution include crowns and fillings.

"Composition for the care of mouth" or "oral composition"as used here, means the product must not intentionally proglatavetsa for the purposes of system of injection of therapeutic agents, but remains in the mouth for a sufficient time to come in contact with some or all surfaces of the teeth and/or mucous tissues in order to care for the oral cavity. In addition, these terms can mean a product that can intentionally proglatavetsa, but can't proglatavetsa for the purposes of system introduction terapeutiche is such funds.

"Status in the mouth", as used here, means diseases or conditions of the oral cavity, including caries, plaque, bad breath, erosion of the teeth, gingivitis and periodontitis. Condition in the oral cavity is further described in international application WO 02/02096 A2, published on 10 January 2002, Procter & Gamble.

"Effective and sufficient", as used here, means the number of component, high enough to significantly (positively) change the condition to be treated, or to obtain the desired action of anti-caries result, but low enough to avoid serious side effects (at a reasonable ratio benefit/risk) within a framework of sound medical/dental judgment. Safe and effective amount of a component will vary for specific conditions to be treated (for example, to initiate action of anti-caries activity or effect recovery of mineralization), for age and physical condition of the patient being treated, the severity of the condition, the duration of treatment, the nature of concurrent therapy, the specific forms being used and the particular environment with which this part applies.

"Toothpaste", as used here, means a product that should not intentionally program ativates for systemic injections of therapeutic agents, but remains in the mouth for a sufficient time to come in contact with some or substantially all surfaces of the teeth and/or mucous tissues in order to care for your mouth, unless otherwise noted.

"The surface of the tooth" or "teeth", as used here, means the pits, fissures, occlusal surface cracks, grooves, notches, grooves, gaps, irregularities, tooth surface and/or surface along the cervical part of the gums, smooth surfaces of the teeth and/or chewing or kostelny the surface of the tooth.

Here, the term "containing" means that others may be added operations and other ingredients that do not affect the final result. This term encompasses the terms "consisting of" and "consisting essentially of".

"The health of the entire body, as used here, means the total health system, characterized by reduction in the risk of major systemic diseases and conditions including cardiovascular disease, stroke, diabetes, acute respiratory infections, premature delivery and low weight of the baby at birth (including postnatal neurological disorder/personality features and the associated increased risk of mortality. It is believed that oral infections can lead to a systemic disease. Bacteria can spread from the mouth into the bloodstream and other parts of the body, thereby jeopardizing human health. Oral infections can contribute to the development of a certain number of serious conditions including heart disease, diabetes, respiratory disease, preterm delivery and low weight of the baby at birth. The health of the entire organism and its stimulation by treatment of infections of the oral cavity is further described in international applications WO 02/02063 A2, WO 02/02096 A2, WO 02/02128 A2, all of which were published on 10 January 2002.

All percentages and ratios used herein are listed by weight of the total composition, unless otherwise indicated.

All measurements are referenced, was carried out at a temperature of 25°C, unless otherwise noted.

All percentages, ratios and levels of ingredients, which here is referred to based on the actual amount of the ingredient, and do not include solvents, fillers and other materials with which the ingredient may be combined as a commercially available product, unless otherwise indicated.

All publications, patent applications and granted patents mentioned herein, included here in its entirety by reference. Quoting any material by reference is not an admission with respect to any determination of its availability as prior art to the claimed invention.

Retaining agent

p> The main ingredient of the present invention is a safe and effective amount of retention agent. Retaining agent operates to allow at least the minimum amount of structure imposed on some of the surfaces of the tooth for a minimum period of time after the person is bitten or chewed solid form of a single dosage (or once bitten and chewed, and then brushed his teeth using a solid form of a single dosage). The mechanical force when biting or chewing help to impose and apply some of the dosage forms on the tooth surface, especially in the pits and fissures. These structures using mechanical force, biting allowed or chewing superimposed or adjacent to the topology of some of the surfaces of the tooth and thereby can provide a temporary physical barrier or pad to protect the surface of the tooth from bacteria, acid, food coloring substances and other substances, and can also provide long-term delivery of active agents on care of the mouth directly to the surfaces of the teeth or in the mouth. The custodial agent shall have sufficient cohesive properties to attach to the tooth surface chemical and(or) physical way. In one embodiment, solid form a single desire the Ki toothpaste retaining agent must provide aesthetically pleasing viscous liquid mass, generated by use of the part of the dosing odds, which is not applied and not applied on the tooth surface. In one embodiment, the retaining agent should not provide negative feelings or presence in the mouth, such as not to be too sticky, viscous, viscous, etc.

In one embodiment, the composition and methods have an average retention rates (next LOC) from about 1 to about 4, in another embodiment from about 2 to about 4. KU is calculated as follows. First, choose at least about five people (in one embodiment at least about 10, and in another embodiment at least about 20 people)with a natural set of teeth. These people chew two tablets (one tablet on each side of the mouth) during the period from about 5 to about 30 seconds. Then people brush their teeth with a soft toothbrush with a flat head for about 30 seconds (in another embodiment, for about 1 minute). People then spit the liquid mass, resulting from brushing. Then people rinse the mouth with about 10 ml of water and spit again. After 5 minutes (in another embodiment, after about 8 minutes, and in one embodiment within about 10 minutes) all surfaces zu is impressive every person visually evaluated according to the following scale:

Retention ratesThe amount of printed matterThe number of surfaces of molars premolars with printed matterThe total time until the applied substance remains visible
0No00
1Enough to be visible2-3 surfaceFrom about 1 to about 60 minutes; in another embodiment from about 10 to about 35 minutes
2Enough to be visible4-5 surfacesFrom about 1 to about 60 minutes; in another embodiment from about 10 to about 35 minutes
3Enough to be visible6-7 surfacesFrom about 1 to about 60 minutes; in another embodiment from about 10 to about 35 minutes
4Enough to be visibleMore surfaces 7From about 1 to about 60 minutes; in another embodiment from about 10 to about 35 minutes

If a person has a substance deposited on a single surface of a single tooth, for example, the cervical part of the gums and in the hollow molar, these surfaces have itivity separately. "Visible" means that caused at least enough substance so that it was visible to the naked eye.

In order to measure the RL for white tablets or tablets that have a color that matches the color of human teeth after man spits the liquid mass, he/she is rinsing the mouth with water solution in an amount of 5 to 10 ml, containing a pigment or a contrast agent. Printed matter then will have a color contrasting with the color of teeth. It should also be noted, however, that the solid form of a single dosage can be of any color and shape.

In one embodiment, after the person has to explain it (and optionally after brushing your teeth), from about 0.5% to about 20% by weight of the initial composition is applied to some surfaces of the teeth, in another embodiment, from about 0.8% to about 15% by weight, in another embodiment from about 1% to about 10% by weight, and in one embodiment from about 1% to about 5% by weight of the initial composition. After the deposition of the teeth portion of the composition remains attached to the surface some tooth for at least about 2 minutes, in another embodiment at least about 5 minutes, in another embodiment, for ENISA least about 10 minutes, in another embodiment, from about 1 minute to about 1 hour, in another embodiment from about 10 to about 35 minutes, and in another embodiment from about 15 to about 30 minutes.

In one embodiment, the retaining agent is hydrophilic aqueous solution, the resin or polymer substance which will form gidratirovannuyu a lot of hydration water liquids (water or saliva). In one embodiment, the gel formation occurs within from about 1 to about 120 seconds, in another embodiment from about 5 to about 60 seconds after exposure to water or saliva. An adequate rate of hydration minimizes dissolution, disintegration or erosion of the substance deposited on the surface of the tooth and minimizes subsequent rapid penetration of water or saliva inside the applied substances. In one embodiment, the present composition contains a hydrophilic aqueous solution, the resin or polymeric retention agent in an amount of from about 1% to about 40%, in another embodiment from about 2% to about 40%, in another embodiment from about 7% to about 25%, in another embodiment from about 8% to about 20%, and in one embodiment from about 11% to about 18% in the su composition.

In one embodiment, the retaining agent is selected from the group consisting of acacia, resin karaya, guar resin, gelatin, alginic acid and its salts (such as sodium alginate, polyethylene glycol, polyethylene oxide, acrylamide polymers, linked polyacrylic acid, hydrophobically modified polymers, polyacrylic acid, polyvinyl alcohol, ethyleneoxide polymers, polyvinylpyrrolidone, cationic polyacrylamide polymers, cellulose derivatives such as carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose; xanthan resin, carrageenan, resin carob, gum Arabic, tragacanth resin, pullulan, pre gelatinising and partially pre-gelatinizing starch, hydrolyzed starch, dried maltodextrin and corn syrup, hydrogenated maltodextrin, hydrogenated products of hydrosilation starch, amylose, amylopectin, starch derivatives and mixtures thereof.

In another embodiment, the retaining agent is selected from the group consisting of acacia, resin karaya, guar resin, gelatin, alginic acid and its salts (e.g. sodium alginate), polyethylene oxide, acrylamide polymers, linked polyacrylic acid, polyvinyl alcohol, cation is s polyacrylamide polymers, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, xanthan resin, carrageenan, resin carob, gum Arabic, tragacanth resin, pullulan, pre gelatinising and partially pre-gelatinizing starch, hydrolyzed starch, dried maltodextrin and corn syrup, hydrogenated products of hydrosilation starch, amylose, amylopectin, starch derivatives and mixtures thereof.

In another embodiment, the retaining agent is selected from the group consisting of acacia, resin karaya, guar resin, alginic acid and its salts (such as sodium alginate, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carrageenan, resin carob, gum Arabic, tragacanth resin, pullulan and mixtures thereof.

In another embodiment, the retaining agent is chosen from the group consisting of hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose, carboxymethyl cellulose, hydroxyethyl cellulose and mixtures thereof.

In one embodiment, the retaining agent is a relatively hydrophilic polymer or resin, for example, having a higher relative level of substitution of hydrophilic groups (e.g., from about 7% to the ome 12% replacement hydroxypropyl) and a lower relative level of hydrophobic substitution (for example, from about 19% to about 24% substitution methoxyl)such as Methocel K (hypromellose type 2208 from Dow Chemical Co.), Methocel K4M Premium and K100LV Premium (Dow Chemical Company), etc.

In one embodiment, the retaining agent is a hydrophilic polymer or resin having a relatively small particle size, for example, at least 75% of the polymer passes through the filter 200 mesh, in another embodiment, at least 75% of the polymer passes through the filter 100 mesh, such as Methocel K (hypromellose type 2208 from Dow Chemical Co.), the polymers of cellulose, which have a high level hydroxypropyl substitution and low metaxylene replacement brand Methocel K4M Premium and K100LV Premium (Dow Chemical Company), etc.

In one embodiment, the retaining agent is a mixture of grades of Methocel K4M Premium and K100LV Premium (Dow Chemical Company) in a ratio of from 1:1 to 1:2,5 Methocel K4M Premium to K100LV Premium.

In another embodiment, the retaining agent is Methocel E (hypromellose type 2910 from Dow Chemical Co.), which have a level hydroxypropyl substitution equal to 7-12%, and the level metaxylene substitution equal to 28-30%.

In one embodiment, the composition contains from about 1% to about 20% by weight, in another embodiment from about 1% to about 18% by weight, and in one VA is iante implementation from about 3% to about 16% by weight retention agent, which is a water-soluble hydrophilic resin or a polymeric substance with a viscosity from about 80 to about 20,000 centipoise (CP), in another embodiment from about 100 to about 15000 centipoise, and in one embodiment from about 150 to about 10,000 centipoise. These viscosities are determined using the method described in USP Official Monorgaph (official Handbook of United States Pharmacopeia) for hydroxypropylmethylcellulose, and physical tests on the viscosity. In one embodiment, these substances with lower viscosity are mixed in a hydrogel of high viscosity (for example, with viscosities from about to about 21000 100000 SDR).

In one embodiment, the retaining agent is Natrasol 250, available from Aqualon company, or hydroxyethylcellulose medium or high viscosity, available from Aqualon company.

In one embodiment, the retaining agent is carboxymethylcellulose with high viscosity, such as Carboximetylcellulose 7H3, available from Aqualon company, having an average viscosity of 3000 centipoise, Carboximetylcellulose 9H4, available from Aqualon company, having an average viscosity of 4000 centipoise, and Aquasorb A500, available from Aqualon company.

In one embodiment, the retaining agent comprises a class of homopolymers of acrylic acid crosslinked with an alkyl ester of pentaerythritol or alkyl ester of sucrose, or carbama the s. Carbomer commercially available from BF Goodrich company in a series of Carbopol®. Particularly preferred carbopol include Carbobol 934, 940, 941, 956, and mixtures thereof.

Special sources above the retaining agents are the following. Acacia, guar gum, tragakant, xanthan gum, resin carob, guar gum and agar are available in various brands from the company Gumix Imtemational. Carrageenan and pectin available under the trademark Genu of the company Keico; resin Carrie (Keltrol® from Kelco company); konjac (from the firm FMC); gelatin (from the firm Kind and Knox); alginic acid and its salts, such as sodium alginate and propylene glycol alginate (Protanol® from the firm FMC and Kecoid/Kelgin® from Kelco company); polyethylene glycol (Carbowax®); altertoxin polymers, polyethylene oxide (Polyox® from the company Union Carbide), polyvinyl alcohol (Elvanol® from the firm Du Pont); polyvinylpyrrolidone and its derivatives (Plasdone® from the company ISP, Kollidone® from BASF); linked polyacrylic acid, their salts and derivatives (Carbopol® from the company and a Noveon Polycarbophil® from firms BF Coodrich/a Noveon); hydrophobic modified polymers of polyacrylic acid (sold as Carbopol® 1342 and 1382, Carbopol® ETD 2020 and Pemulen® TR-1, TR-2, 1621 and 1622, all of which are available from the company BF Coodrich), carboxymethycellulose (Cekol® from the company Metsa-Serla); hydroxyethylcellulose (Natrosol® from Aqualon company®/Hercules); hydroxypropylcellulose (Klucel® from Aqualon company®/Hercules); hypromellose (Methocel® from Dow); pre-relatively and partially pre-gelatinising starch (Unipuse®/National 78-1551 from company National Stach; Starch 1500 from Colorcon); hydrolyzed starch, dried maltodextrin and corn syrup (Maltrin® from company Grain Processing); hydrosylate hydrogenated starch (Hystar® from the firm SPI Polyols).

In another embodiment, the retaining agent may be holding agent of water-insoluble particles having a solubility in water of less than about 1 g to 30 g at a temperature of 25°With, in another embodiment less than about 1 g per 100 g at a temperature of 25°and in another embodiment less than about 1 g to 1000 g at a temperature of 25°C. the Level of the holding agent from the particles typically less than about 65% by weight of the composition, in another embodiment less than about 60%, in another embodiment from about 30% to about 65%, in another embodiment from about 30% to about 60%, and in another embodiment from about 35% to about 55% by weight of the composition. Examples of retention agents of the particles include calcium carbonate, mica, titaniumalloy mica, magnesium carbonate, talc (magnesium silicate), magnesium-aluminum-silicate, kaolin (aluminum silicate), titanium dioxide, oxide is zinc polyethylene powder, powder of polystyrene, bismuth oxychloride, and mixtures thereof.

In one embodiment, the retaining agent particles is selected from the group consisting of calcium carbonate, magnesium carbonate, talc (magnesium silicate), magnesium-aluminum-silicate, and mixtures thereof.

In one embodiment, the composition according to the present invention have less than about 5% by weight, in another embodiment less than about 2% by weight, and in one embodiment, are essentially free from starches, sugars, polysaccharides, or fermented sugars, which are known as cariogenic (for example, sucrose and the like). Possible cariogenic effects that may appear due to the use of the above starches as retention agents, can be countered by the inclusion in the present compositions of fluoride ions, buffers and/or use of nearisogenic polysaccharides.

In one embodiment, these compositions are not effervescent compositions. In one embodiment, the retaining agent is nearisogenic.

In one embodiment, these compositions are less than about 65%, in another embodiment less than about 60%, in another embodiment less than about 55% water-insoluble particles (e.g., dental abrasives or other media particles is similar), having a solubility in water of less than about 1 g to 30 g at a temperature of 25°in another embodiment, about 1 g to 100 at a temperature of 25°and in another embodiment less than about 1 g to 1000 g at a temperature of 25°C.

Modifiers retention

In one embodiment, to increase or decrease the retention properties of the composition, the composition may contain an optional modifiers retention level from about 0.5% to about 20%, in another embodiment from about 2% to about 18%, in another embodiment from about 2% to about 15% by weight of the composition. These properties hold is selected from the group consisting of bentonite, pectin, fats, waxes, shellac, ethyl cellulose, insoluble polymers, surfactants, alum, Zein, cyclodextrin (Kleptose, Roquette); proteins and hydrolyzed protein (for example, Crotein® from Croda), alkylvinyl ether maleic acid or anhydrous copolymer or salts and mixtures thereof. In addition, these properties hold can add hydrophobicity to the solid form of a unit dosage order to slow down the erosion or dissolution of the active agent from the precipitated substance. Alkylvinyl ether maleic acid or anhydrous copolymers used in the form of their free acids or partially or fully autralasian alkali metal salts (for example, zinc, iron, magnesium, calcium, strontium, potassium and sodium) or ammonium salts, and mixtures thereof, disclosed in U.S. patent No. 6.475.498 name Rajaiah et al., published November 2, 2002; U.S. patent No. 6.475.497 name Rajaiah et al., published November 2, 2002, and include Gantrez AN 139 (M.W. 500,000 in), A.N. 119 (M.W. 250,000 in), 169 and AN S-97 Pharmaceutical Grade (M.W. 70,000 tons) of GAF Corporation.

Optional bothersome agents and pH

The present compositions can optionally include a buffer agent. In one embodiment, the present invention relates to a composition and method whereby the saliva or the environment on or in the tooth surfaces is buffered to a pH of from about 7 to about 12. This bothersome the action of chewing solid forms of a single dosage of the present invention can provide improved performance against the formation careenage lesions in the oral cavity. Improved action of anti-caries efficacy can be achieved by direct neutralization of the acidic environment present on or in the tooth surfaces, especially in the pits, fissures or occlusal surfaces of the teeth, where in most cases is formed cavities.

Any suitable buffering agent may be selected for use here in a safe and effective amount. In one embodiment, the buffer agent can be selected from the group consisting of the water soluble buffering agents, such as sodium bicarbonate, sodium carbonate, phosphate buffer agents, amino acid buffer agents such as alanine and glycine, and mixtures thereof. In another embodiment, the buffer agent is selected from the group consisting of sodium bicarbonate, carbonate sodium triphosphate sodium diphosphate, sodium, sodium hydrogen phosphate, sodium dihydrophosphate, Tris(hydroxymethyl)aminomethane, tetrasodium pyrophosphate, deerfoot sodium, tetramerista potassium salts tripolyphosphates, and mixtures thereof. In another embodiment, a buffering agent is sodium bicarbonate, sodium carbonate and mixtures thereof. The buffer agent may also include water-soluble bothersome agent, for example, calcium carbonate.

In one embodiment, the present composition includes a buffering agent, from about 0.1% to about 25%, in another embodiment from about 1 to about 20%, and in one embodiment from about 5 to about 18% by weight of the composition.

Diphosphate sodium also known as dirtiest sodium, dibasic sodium phosphate, phosphate of soda and secondary sodium phosphate.

After chewing composition described herein containing a buffer agent, the pH of saliva and(or) environment, or when the tooth surface is from about 7 to about 12, in another embodiment from about 7.5 to about 0, in yet another embodiment, from about 8 to about 9. As used here, "environment or when the tooth surface" means the surface of the tooth, which is adjacent to the solid form of a unit dosage, affect or are deposited on the tooth surface, and does not directly matter, which affects the surface of the tooth. This pH is maintained for at least 2 minutes, in another embodiment at least 5 minutes, in another embodiment at least 15 minutes, and in another embodiment at least 30 minutes. In another embodiment, this pH is maintained from about 5 minutes to about 60 minutes, in another embodiment from about 5 minutes to about 30 minutes.

pH can be measured using the following procedure. Subject to natural teeth chew the form of a unit dosage of the present invention as long as this form of a unit dosage that will not be destroyed (for example, chews from about 5 seconds to about 30 seconds). Optionally, after this, the subject brush your teeth for about 30 seconds, in another embodiment, about 1 minute, manual soft toothbrush with a flat head. After that, the subject of the spits and optional spolaskivayut about 10 ml of water and spits again. Saliva is collected using covered on the rates sponge critical tampon. Sponge covered end is placed into the environment on or in the surface of the tooth. The handle of the swab is then cut to an approximate length of 1.5 mm, and then placed in a tube microcentrifuge (end of the tampon up). The samples are centrifuged for 10 minutes at 10.000 rpm Tampons are removed from the tubes, leaving only the remaining saliva. the pH of this saliva was measured using a micro pH electrode (for example, microlaminate No. 9810 BN from Thermo Orion)connected to the meter Model Corning 430 pH. The pH measurement can be performed at different time periods after chewing and deposition, i.e. at 5, 10, 15, 30 minutes.

Alternatively, the sample (2-5 mils) saliva is removed from the mouth, and the pH of the saliva samples was measured by an appropriate electrode pH.

Optional active agents for the care of the oral cavity

The present invention may optionally contain safe and effective amount of the active agent to care for the oral cavity selected from the group consisting of agent against plaque, the source of fluoride ions, antimicrobial agents, desensitizing tooth fabric agents, anesthetic agents, antifungal agents, anti-inflammatory agents, selective H-2 antagonists, action of anti-caries agents, reducing mineralization agents, whitening agents, anti-erosion agents, vitamins and minerals and is Mesa, and in another embodiment is selected from the group consisting of an agent against plaque, the source of fluoride ions, antimicrobial agents, the action of anti-caries agents, and mixtures thereof. These active agents for oral care mouth useful in the treatment of one or more States in the mouth.

Active agents for oral care of the mouth may be present in the composition in solid dosage forms suitable for single dosage amounts. These quantities are known in the art and are disclosed below.

In one embodiment, the advantage chewable forms of a single dosage of the present invention is that the composition can provide efficacy at lower doses of active agents for oral care mouth, rather than dose, traditionally known and used in the prior art. Lower than traditionally, the dosage can ensure efficiency because the dosage of active agent to care for the oral cavity is delivered directly to the tooth surfaces and stays there.

Action of anti-caries agents and a source of fluoride ions

This composition may optionally contain safe and effective amount of action of anti-caries agent recovery agent mineralization and mixtures thereof. In one embodiment, action of anti-caries the Gent is chosen from the group consisting of xylitol, a source of fluoride ions and mixtures thereof. The source of fluoride ions provides free fluoride ions in the process of chewing composition. In one embodiment, the source of fluoride ions selected from the group consisting of sodium fluoride, tin fluoride, fluoride India, organic fluorides, such as aminofluorides and monoftorfosfat sodium. Sodium fluoride is a source of fluoride ions in another embodiment. U.S. patent No. 2.946.725 in the name of Norris et al., issued July 26, 1960, and U.S. patent No. 3.678.154 name Widder et al., issued July 18, 1972, disclose such fluorine salts, and other, which can be used as a source of fluoride ions.

The advantage of chewing solid forms of a single dosage of the present invention is that the composition can provide efficacy at lower doses of the active agent to care for the oral cavity, because the dosage of active agent to care for the oral cavity is delivered directly to the tooth surfaces and remains on them sufficient time. For example, can be used lower doses of fluoride, thereby, possible safety advantage, by delivery of a source of fluoride ions directly on the tooth surface, and providing the means by which fluoride adheres directly to the area where a large h is the terrain of caries, especially pits, fissures and occlusal surfaces of the teeth.

In one embodiment, the source of fluoride ions is from about 5 ppm (parts per million) to about 3500 ppm, in another embodiment from about 10 ppm to about 3000 ppm, in another embodiment from about 50 ppm to about 2800 ppm, in another embodiment from about 10 ppm to about 2000 ppm, in another embodiment from about 300 ppm to about 1500 ppm, and in one embodiment from about 850 ppm to about 1100 ppm, or from about 200 ppm to about 300 ppm of free fluorine.

In one embodiment, the size of the tablets may be within the range of from about 250 mg to about 1500 mg, in another embodiment, from about 250 mg to about 1000 mg, and in another embodiment from about 250 mg to about 500 mg

In one embodiment, when the dosage of active agent to care for the oral cavity is provided with one pill, these tablets can keep score, and the subject divides the pill in half and puts 1/2 tablets on each side of the mouth before chewing. In one embodiment, when the dosage is provided by two tablets, the principal may place one tablet on each side of the mouth before chewing. Alternatively, when Osinovka is one tablet (twice a day), the subject can chew one tablet on one side of the mouth in the morning and one tablet on the other side of the mouth in the evening.

Restore the mineralization agents

Other optional action of anti-caries agents include those agents that restore the mineralization of enamel and dentin. These recovery mineralization agents prevent, treat and (or) reverse karisny process. Optional restore the mineralization agents are selected from the group consisting of a source of calcium ions, which are dissolved by saliva or becomes soluble with increasing heat or change in pH, and (or) a source of phosphate ions; complexes source of fluoride ions with insoluble or soluble source of calcium ions and their amorphous forms; complexes source of fluoride ions with insoluble or soluble source of phosphate ions and their amorphous forms; source of fluoride ions with insoluble or soluble source of calcium ions and phosphate and amorphous forms, amorphous forms; diphosphate calcium; hydroxapatite; nanohydroxyapatite; a combination of EDTA complex of strontium and soluble source of fluoride ions; glycomacropeptide casein, and mixtures thereof.

The combination of calcium, phosphate and / or fluoride disclosed in U.S. patent No. 5.037.639, issued August 6, 1991 in the name Tung, U.S. patent No. 6.000.341, issued December 14, 1999, n is the name Tung, U.S. patent No. 5.258.167, issued December 7, 1993 in the name Tung, U.S. patent No. 6.303.104, issued October 16, 2001 in the name of Winston et al., U.S. patent No. 6.159.449, issued December 12, 2000 in the name of Winston et al., U.S. patent No. 6.036.944, issued March 14, 2000 in the name of Winston et al., U.S. patent No. 5.895.641, issued April 20, 1989 in the name of Usen et al., U.S. patent No. 5.866.102, issued February 2, 1999 in the name of Winston et al., U.S. patent No. 5.858.333, issued January 12, 1999 in the name of Winston et al., U.S. patent No. 5.833.957, issued November 10, 1998 in the name of Winston et al., U.S. patent No. 5.817.296, issued October 6, 1998 in the name of Winston et al., U.S. patent No. 5.614.175, issued March 25, 1997, U.S. patent No. 5.605.675, issued February 25, 1997 in the name of Usen et al., U.S. patent No. 5.571.502, issued November 5, 1996 in the name of Winston et al., U.S. patent No. 6.120.754, issued September 19, 2000 in the name of Lee et al., U.S. patent No. 6.214.321, issued April 10, 2001 in the name of Lee et al.

Glycomacropeptide casein disclosed in U.S. patent No. 5.853.704, issued December 29, 1998 in the name of Zhang et al., U.S. patent No. 6.207.138, issued March 27, 2001 in the name of Zhang et al., U.S. patent No. 5.741.773, issued April 21, 1998 in the name of Zhang et al., U.S. patent No. 4.992.420, issued February 12, 1991 in the name of Nesser.

Revitalizing mineralization agent may contain a combination of the EDTA complex of strontium and soluble source of fluoride ions, such as disclosed in U.S. patent No. 4.978.522 name Barbera et al., issued December 18, 1989

Nanocrystalline hydroxyapatite, and eusi average particle size of 0.5 to 200 nm, disclosed in the international application W) 00/03747, published January 27, 2000 in the name of Dolci et al. Nanohydroxyapatite of the present invention may also include those disclosed in U.S. patent No. 5.833.959, issued November 10, 1998 in the name of Sangi Co., Atsumi et al., which examines the composition for use in dental tissues with hydroxyapatite having a particle size of up to about 1.0 microns, and in General in the range from about 0.05 microns to about 1.0 microns of at least 0.1% by weight. In the patent Atsumi et al. hydroxyapatite is also known as triple phosphate of calcium. Other hydroxyapatite substance described in U.S. patent No. 4.923.683 name Sakuma et al., assigned Sangi, issued may 8, 1990, and U.S. patent No. 5.135.396 name Kuboki, assigned Sangi, issued August 4, 1992

These recovery mineralization agents optionally used at a level from about 0.1% to about 20%, in another embodiment from about 0.5% to about 5%, and in one embodiment from about 1% to about 3% by weight.

Biological action of anti-caries agents

The present invention can also optionally contain safe and effective amount of the biological substance, for example, the type of bacteria in the mouth that cause or contribute to the development of caries, which are modified to represent less harm in Karinna by the CoE. For example, it is believed that the mutant Streptococcus is fundamentally pathogens in dental caries, the disease is characterized by destruction of the mineral portion of the tooth caused by acid, emerging from the interaction of bacteria on the tooth surface with carbohydrates. Modified bacteria include, for example, recombinant strains of Streptococcus mutant, characterized by the absence of production of lactic acid and production of recombinant alcohol dehydrogenase (RDS) (ADH), as described in U.S. patent No. 5.607.672, issued March 4, 1997 in the name of Hillman. Some of these mutant strains isolated from a strain of Streptococcus mutant BHT-2(str), which are characterized by a single point mutation in the structural gene for the enzyme L(+) lactate hydrogenase, and this enzyme in normal conditions reacts to the production of lactic acid by this bacteria. See, for example, U.S. patent No. 4.133.875, issued January 9, 1979 in the name of Hillman, and U.S. patent No. 4.324.860, issued April 13, 1982 in the name of Hillman. These recombinant strains of Streptococcus mutant suitable for use to prevent or treat dental caries.

Agents against Tartar

These compositions can optionally contain safe and effective amount of at least one agent against Tartar. This amount is mainly what constitutes from about 0.01% to about 40% weight of the composition, in another embodiment, from about 0.1% to about 25%, in another embodiment from about 4.5% to about 20%, and in yet another embodiment, from about 5% to about 15% by weight of the composition. An effective amount of an agent against dental stone is released from the solid form of a single dosage. Agent against Tartar should be largely compatible with other components of the composition.

Agent against Tartar is selected from the group consisting of polyphosphates and their salts; polyaminopropyl sulfonic acid (AMPS) and its salts; polyolefineheat and their salts; polyvinyl phosphates and their salts; polyolefin phosphates and their salts; diphosphonates and salts; phosphonocrotonate acid and its salts; polyphosphonates and their salts; polyvinylacetatove and their salts; polyolefineheat and their salts; polypeptides; and mixtures thereof. In one embodiment, the salts are salts of alkali metals. In another embodiment, the agent against Tartar selected from the group consisting of polyphosphates and their salts; diphosphonates and salts; and mixtures thereof. In another embodiment, the agent against Tartar selected from the group consisting of pyrophosphates, polyphosphates and their salts, and mixtures thereof.

Polyphosphate

In one embodiment of the present invention, the agent against the law of Ukraine is the main stone is a polyphosphate. In General it is considered that the polyphosphate consists of two or more phosphate molecules located mostly linear, although there may be some cyclic derivatives. Linear polyphosphates match (X PO3)nwhere n is from about 2 to about 125; preferably n is greater than 4, and X is, for example, sodium, potassium, etc. When n (X PO3)nless than 3, polyphosphates become brittle in nature. Counterions for these phosphates may be alkali metal, alkaline earth metal, ammonium ion, With2-C6alkanolamine and a mixture of salts. Polyphosphates are generally used as a fully or partially neutralized water soluble alkali metal salts, such as potassium, sodium, ammonium salts, and mixtures thereof. Inorganic polyphosphate salts include tripolyphosphate, alkali metal (e.g. sodium), metropolitical, salt metal dialkyldithiocarbamate acid (for example, disodium salt), salt of the metal trialkylphosphates acid (for example, trinacria salt), potassium phosphate, sodium phosphate, sodium hexametaphosphate alkali metal (e.g. sodium), and mixtures thereof. Polyphosphates more than Metropolitanate commonly found as brittle amorphous substance. In one embodiment, the polyphosphates are produced by FMC Corporation, which Izv the local commercial as Stavos (n≅ 6), Hexapod (n≅13), the Voice of N (n≅21), and mixtures thereof. Source polyphosphate will typically contain from about 0.5% to about 20%, in another embodiment from about 4% to about 15%, in another embodiment from about 6% to about 12% by weight of the polyphosphate composition.

Sources of phosphate are described in more detail in Kirk&Othmer, Encyclopedia of Chemical Technology., Fourth Edition, Volume 18, Wiley-Interscience Publishers (1996), pages 685-707, included here by reference in its entirety, including all references to Kirk&Othmer.

In one embodiment, the linear polyphosphates are "brittle" polyphosphates having the structure

HO(HRO3)nX,

where X is sodium or potassium, and n is from about 6 to about 125.

In one embodiment, when n is at least 2 in both of the two above formulas, the level of the agent against Tartar is from about 0.5% to about 40%, in another embodiment from about 2% to about 25%, in another embodiment from about 5% to about 15% by weight of the composition. Polyphosphates are disclosed in U.S. patent No. 4.913.895.

The pyrophosphate

Salt of pyrophosphate used in these compositions include pyrophosphates of alkali metals, di-, tri - and monosilane or sodium pyrophosphates, di-, tri-, tetrameristaceae salt SEL is cnyh metals and mixtures thereof. In one embodiment, salts of pyrophosphates are selected from the group consisting of nutritionalstatus, digidrogenfosfata sodium (Na2H2P2O7), deerfoot potassium, tetrasodium pyrophosphate (Na4P2O7), tetramerista potassium (K4P2About7) and mixtures thereof. Salts of pyrophosphate, described in U.S. patent No. 4.515.772, published may 7, 1985, and U.S. patent No. 4.885.155, published on 5 December 1989, both on the name Parran et al., included here by reference in its entirety, as disclosed in these references. Salt of pyrophosphate described in more detail in Kirk&Othmer, Encyclopedia of Chemical Technology., Third Edition, Volume 17, Wiley-Interscience Publishers (1982), pages 685-707.

In one embodiment, the compositions according to the present invention contain tetrasodium pyrophosphate. Tetrasodium pyrophosphate may be anhydrous salt form or decahydrate form or any other kinds, are stable in solid form in the present compositions. Salt is in the form of solid particles, which may be crystalline or amorphous state, and the size of the salt particles is preferably small enough so that they are aesthetically acceptable and instant during use.

Level pyrophosphate salt in the compositions of the present invention is any safe and effective amount in total is approx the RNO 1.5% to about 15%, in another embodiment, from about 2% to about 10%, in another embodiment from about 3% to about 8% by weight of the composition.

Azacycloheptane-2,2-diphosphine acid are disclosed in U.S. patent No. 3.941.772 published on March 2, 1976 in the name of Ploger et al., assigned Henkel, and in U.S. patent No. 3.988.443, published October 26, 1976 in the name of Ploger et al.

Optional agents to be used instead pyrophosphate salt or in conjunction with it, include such well-known substances as synthetic anionic polymers, including polyacrylates and copolymers of maleic anhydride or acid, and metilidinovy ether (e.g., Gantrez), as described, for example, in U.S. patent No. 4.627.977 name Gaffar et al., like, for instance, polyaminopropyl acid (PPSC), the trihydrate of zinc citrate, polyphosphates (e.g., tripolyphosphate, hexametaphosphate), diphosphonates (e.g., EGDF, AGF), polypeptides (such as poliasparaginovaya and polyglutamine acid) and mixtures thereof.

Anti-erosion agents

Tooth erosion is a permanent loss of tooth substance from the surface under the action of chemicals, such as coarse abrasives and acids, as opposed to subsurface demineralization or caries, is caused by bacterial action. Tooth erosion is a condition which does not include the bacterial Blas and, and so different from dental caries, which is a disease caused by acids produced by bacterial plaque. Tooth erosion can be caused by external or internal factors.

Anti-erosion agents may include, but are not limited to, polymeric mineral surface active agents selected from the group consisting of condensed phosphorylated polymers; polyphosphonates; polycarboxylates and carboxylester polymers; copolymers of phosphate - and postnationalism monomers or polymers with etileno unsaturated monomers, amino acids or other polymers selected from proteins, polypeptides, polysaccharides, poly(acrylate), poly(acrilamide), poly(methacrylate), poly(ethacrylate), poly(hydroxyethylmethacrylate), poly(vinyl alcohol), poly(maleic anhydride), poly(maleate), poly(amide), poly(ethylenimine), poly(ethylene glycol), poly(propylene glycol), poly(vinyl acetate) or poly(vinylbenzoate); and mixtures thereof. In one embodiment, anti-erosion agent is selected from the group consisting of polyphosphates, where n=21 (described above), tripolyphosphate and mixtures thereof. As anti-erosion agents useful ions of metals selected from tin, zinc, copper and mixtures thereof. Anti-erosion agents are further described in the application U.S. No. 2003/0165442, who published September 4, 2003

Antimicrobial agents

Antimicrobial agents from dental plaque can also be present in these compositions. Such agents may include, but are not limited to, triclosan, 5-chloro-2-(2,4-dichlorophenoxy)-phenol, as described in The Merck Index. 11-th ed. (1989), page 1529 (entry # 9573) in U.S. patent No. 3.506.720 and European patent application No. 0.251.591 Beecham Group, PLC, published January 7, 1988; chlorhexidine (Merck Index, No. 2090), alexidine (Merck Index, No. 222), hexetidine (Merck Index, No. 4624); sanguinarine (Merck Index, No. 8320); benzalkonium chloride (Merck Index, No. 1066); salicylanilide (Merck Index, No. 8299); domainbased (Merck Index, No. 3411); cetylpyridinium chloride (CPH) (Merck Index, No. 2024); tetradecylbenzene chloride (TNX); N-tetradecyl-4-ethylpyridinium chloride (TDAP); octenidine; delmopinol, Octafinal and other piperidinedione; effective antimicrobial amount of essential oils and their combinations, for example, lemon, geranium and combination of menthol, eucalyptus, thymol, and methyl salts of salicylic acid; antimicrobial metals and their salts, for example, those that provide zinc ions, tin ions, copper ions and / or their mixtures; bisbiguanide or phenols; antibiotics such as Augmentin, amoxillin, tetracycline, doxycycline, minocycline, and metronidazole; and analogs and salts of the above-mentioned antimicrobial agents against dental plaque; antifungal agents such as t is, what used to combat Candida albicans. If these agents are present, they in General are in a safe and effective amount of, for example, from about 0.1% to about 5% by weight of the compositions of the present invention.

Anti-inflammatory agents

Anti-inflammatory agents can also be present in the compositions of the present invention. Such agents may include, but are not limited to, non-steroidal anti-inflammatory agents such as aspirin, Ketorolac, flurbiprofen, ibuprofen, naproxen, indomethacin, aspirin, Ketoprofen, piroxicam and meclofenamic acid, inhibitors SOH-2, such as valdecoxib, celecoxib and rofecoksib and mixtures thereof. If anti-inflammatory agents are present, they in General be from about 0,001% to about 5% by weight of the composition of the present invention. Ketorolac is described in U.S. patent No. 5.626.838, published may 6, 1997.

Antagonists N-2

The present invention can also include a safe and effective amount of a selective antagonist N-2, including mixtures disclosed in U.S. patent No. 5.294.433 on the name of the Singer et al., issued March 15, 1994.

Whitening agents

Active teeth whitening agents that can be used in compositions for caring for the oral cavity according to the present invention contain a safe and effective amount otbelivanie what about the agent, which involves bleaching or oxidise agents, such as peroxidase, perborate, percarbonate, peroxyacids, persulfates, chlorites metals and their combinations. Suitable peroxide compounds include hydrogen peroxide, urea peroxide, calcium peroxide, and mixtures thereof. An example of percarbonate is percarbonate sodium. Other suitable bleaching agents include persulfates and perborate mono - and tetrahydrate potassium, ammonium, sodium and lithium, and the pyrophosphate peroksigidrat sodium. Suitable metal chlorites include chlorite calcium, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite and potassium chlorite. In one embodiment, the chlorite is sodium chlorite. Additional bleaching active substances can be hypochlorite and chlorine dioxide.

The levels of bleaching agents is in General from about 0.5% to about 15%, in another embodiment from about 1% to about 10% by weight of the composition.

Vitamins and minerals

The present invention may contain a safe and effective amount of vitamins and minerals. As used in this disclosure, the term "vitamin" refers to the residual organic substances that are required in the diet. For the purposes of the present invention, the term "vitamin(s)" includes, without limitation t is min, Riboflavin, nicotinic acid, Pantothenic acid, pyridoxine, Biotin, folic acid, vitamin B12, lipoic acid, ascorbic acid, vitamin a, vitamin D, vitamin E and vitamin K. the term "vitamin" are also included his deferment. Deferment represent specific chemical forms of vitamins. Deferment include thiamine pyrophosphates (CFT) (RTR)mononucleotide of cholelithiasis (CFM) (FMM), flamin adenine dinucleotide (FAD), nicotinamide dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADF), piroxicam phosphate deferment A (COA), biocytin, tetrahydrofolate acid, deferment B12, lipolysis, 11-CIS-retinal and 1,25-dihydroxycholecalciferol. The term "vitamin(s)" also includes choline, gamitin and alpha, beta and gamma carotenes.

As used in this disclosure, the term "mineral" refers to inorganic substances, metals and the like required in the human diet. Thus, the term "mineral"as used here, includes without limitation, calcium, iron, zinc, selenium, copper, iodine, magnesium, phosphorus, manganese, chromium and the like and mixtures thereof.

Vitamins and minerals also include oral supplements, such as amino acids, lipotropic substances, fish oil, and mixtures thereof, as disclosed in the publication Drug Facts and Comparisons (insert drug information SL is jby). Wolters Kluer Company, St. Louis, Mo., © 1997, pp.54-54e. Amino acids include, but are not limited to, L-tryptophan, L-lysine, methionine, threonine, l-carnitine or L-carnitine and mixtures thereof. Lipotropic substances include, but are not limited to, choline, betaine, linoleic acid, linolenic acid and mixtures thereof. Fish oil contains large amounts of polyunsaturated fatty acids Omega-3 (N-3), icosapentaenoic acid and docosahexaenoyl acid.

As used with reference to a vitamin or mineral, the term "effective amount" means an amount of at least 10% of the Recommended daily servings (RDP) ("RDA") of the U.S. this particular ingredient to the patient. For example, if appointed ingredient is vitamin C, an effective amount of vitamin C will include the amount of vitamin C sufficient to provide 10% or more of the RDP. Generally, if the tablet includes a mineral or vitamin, it will include a large amount, preferably about 100% or more from suitable for RDP.

CHEWING SOLID FORM of a UNIT DOSAGE

The term "chewing solid form of a unit dose"as used here, means chewing tablet, capsule, hard and soft candy, toffee, nougat, chewy candy, and the like. In one embodiment, Givat the global solid form of unit dosages are extruded tablets soft gelatin capsules, molded tablets, molded spheres or ellipsoids, made of a pharmaceutically acceptable filler, which can be melted or molded, forms a type of chewing gum, extruded solid forms, etc. In another embodiment, the chewing solid form of a unit dose is selected from the group consisting of compressed tablets and capsules. In one embodiment, the chewing solid form of a unit dosage represents a pressed tablet. The solid form of a unit dosage may be here a layered form, comprising one or more layers.

In another embodiment, the form of a unit dosage is pressed tablet of any shape or size, for example, spherical or elliptical tablet. The tablet is pressed using conventional equipment and processes, for example, see Lieberman, et al. Pharmaceutical Dosage Forms: Tablets [Pharmaceutical dosage forms: tablets] (1980) Chapter 3, pp.109-185. In one embodiment, the form of a unit dosage of the present invention contains a form of a unit dose from about 100 mg to about 5 grams total weight, in another embodiment, from about 250 mg to about 2 grams total weight, and in one embodiment from primer is 500 mg to about 1.5 grams total weight.

Dosage form may also contain, in one embodiment, the inert molded spherical or elliptical base. As used here, "molding" refers to a process in which molten or semi-inert pharmaceutically acceptable substance is injected into the molding cavity and left to harden. Thus the dimensions of the molding cavity determines the size of the basis. Suitable substances include, but are not limited to, accept food pharmaceutically acceptable waxes, such as beeswax, paraffin, Carnauba wax, and triglycerides with a melting point of about 50°such as tristearin. The active agent may be included in the base during the molding process or deposited on a molded base.

Another preferred form of a unit dosage is a solid capsule (i.e. grahamlowe, cellulose or gelatin hard capsules). KRAMAROVA capsule can be filled with solid form of the active agent, as described above. Preparation of tablets, capsules and hard and soft candy is well known in the art. In one embodiment, for the collection of the dental tablets should granulation dental abrasive for commonly used abrasives with small particles. Granulation is preferable to provide the treatment stream processing and to give compactness of these substances. Can be used following the wet granulation:

a) Mix the abrasive and sorbitol and / or mannitol (or other suitable volumetric filler).

b) to Prepare a binder solution by dissolving a coupling agent in water or other suitable solvent.

c) Add binding solution (b) to the powder mixture (a) with the corresponding mixing to the required moisture.

d) Optional grind wet substance for the destruction of large wet agglomerates.

e) Dried using a suitable tool to an acceptable water content/granulating solution (drying in a tray or drying of the liquefied layer, for example).

f) Optional grind wet granulation to obtain the appropriate particle size of the granules.

Wet granulation can be achieved by other means processing: for example, granulating the liquefied layer, the extrusion of the wet mass extrusion and spherizone, rotational processing of the liquefied layer and processing shugi.

In one embodiment, the granulation can be also achieved by a method of dry granulation as follows:

a) Mix the abrasive and sorbitol and / or mannitol (or other suitable volumetric filler).

b) Compressed into large tablets (drums press) or strips/briquettes (roller compactor).

c) to Dry the ground is already installed, b), in order to obtain an acceptable particle size granulation.

For both methods, dry and wet granulation - in this step may include other ingredients. For example, a powder mixture or binder solution may be added to the active agent, to ensure uniformity of content in a partial agent. Colors, flavors, surfactants, foaming agents, active agents, etc can also be added. In one embodiment, the final mixture for tableting are prepared as follows:

a) Combine the above granular form with all other components, except the lubricant, and mix accordingly to ensure homogeneity.

b) Add lubricant and mix as needed.

Tableting can be done by traditional means, for example, you can extrude the final powder mixture of the above on tabletirujut press to form compacts with the appropriate properties, such as sufficient hardness and fragility.

Alternatively, if a mixture of prescription components has enough fluid properties and can be molded acceptable CD, you can use the direct pressing, in which the components are simply with elevayta and pelletized without the need for the step of granulation.

The LOCAL MEDIA FOR the CARE of the oral CAVITY

In addition to the essential ingredients of the compositions of this invention contain in General the local media about the care of the oral cavity. As used here, "local media to care for the oral cavity or oral carrier" means one or more compatible solid or liquid filler diluents or encapsulating substances that are suitable for administration to a subject or suitable for local oral administration. The term "compatible", as used here, means that these ingredients are able to be mixed with the active agent or other necessary ingredients and with each other so that there is no interaction which would substantially reduce the effectiveness of the composition in normal use situations. Media in caring for the oral cavity should, of course, to be clean enough and sufficiently low toxicity to be considered suitable for introduction in the treated subject. Media in caring for the oral cavity can act to facilitate the introduction of the active agent in the dosage form, modify the output of the active agent from the dosage form, to stabilize the active agent or to enhance absorption of the active agent. Media in caring for the oral cavity should be safe for the intended imiportant at levels, used in the recipe. Formulation of the active agent and the media to care for the oral cavity is selected according to the criteria of well-known experts in the technique, in order to achieve the desired speed output, stability, absorption, and to facilitate the manufacture of dosage forms.

In one embodiment, the carrier for the care of mouth is nearisogenic and has a low hygroscopic property, or not have them at all.

Media in caring for the oral cavity in General include fillers or diluents, binders, disintegrating agents and lubricants. Fillers, for example, in General are selected from the group consisting of lactose, sucrose, dextrose, mannitol, sorbitol, xylitol, eritria, lactate, isomalt, maldita, trehalose, tagatose, calcium sulfate, dibasic calcium phosphate, triphosphate calcium, trehosnovnogo of calcium sulfate, starch such as corn starch, potato starch, hydrogenomonas hydrolysates of starch and sodium glycolate, starch, calcium carbonate, microcrystalline cellulose and mixtures thereof. In one embodiment, the filler is nearisogenic polysaccharide, isomalt and mixtures thereof. Cm. the above discussion concerning the use of cariogenic polysaccharides.

"Grease"as used is : here means a substance which can reduce the friction arising from the interaction of the tablets and the walls of the punch during the pressing and extraction. Lubricants can also be used to prevent sticking in the die and the wall of the stamp. The term "substances against adhesion" is sometimes used to refer specifically to substances that function during ejection. However, as used in this disclosure, the term "grease" is used generically and includes substances against sticking".

Lubricants can be internal and external. A lubricating substance that is applied directly to the surface tabletiruemogo tool in the form of a film, for example, by sputtering on the surface of the die cavity and / or stamp, known as external lubricating substance. Its use, however, requires complex application equipment and methods, which increase the cost and decrease performance. Internal lubricants are embedded in subject to pelletizing substance. Traditional internal lubricants include stearic acid, magnesium stearate and calcium stearate of zinc, hydrogenomonas and partially hydrogenomonas vegetable oils (e.g. peanut oil, sesame oil, olive oil, kukuruz the e oil and oil of Theobroma, Sterotex), animal fats, glycerin, polyethylene glycol, polyoxyethylene the monostearate, talc, light mineral oil, sodium benzoate, sodium lauryl sulfate, magnesium oxide and the like and mixtures thereof. Cm. the EPO application No. 0.275.834 in the name of Leal et al. and U.S. patent No. 3.042.531.

Internal lubricants according to the present invention can optionally be used in effective amounts, for example, up to 5 wt.%, in another embodiment, from about 0.25% to about 5%, in another embodiment from about 0.5% to about 2% by weight of the total composition.

Other local media for the care of the oral cavity include emulsifiers, such as Tweens®; moisturizing agents, such as sodium lauryl sulfate; coloring agents; tabletiruemye agents; stabilizers; antioxidants; preservatives; free from pyrogens water; isotonic saline; and phosphate buffer solutions. Tablet media described in Remington's Pharmaceutical Sciences, Mack Publishing Co. (19th edit. 1995); Modem Pharmaceutics, Vol.7 Chapter 9 & 10, Banker &Rhodes (1979); Lieberman, et al. Pharmaceutical Dosage Forms: Tablets (1981); and Ansel, Introduction to Pharmaceutical Dosage Forms, 2d (1976). Their choice will depend on secondary considerations like taste, cost, and stability during storage, etc. and can be easily made by experts in the technique.

Other types of local media to care for the oral cavity that may in order to be included in the compositions of the present invention, together with a particular non-limiting examples are:

Foaming agent (surfactant)

The present composition may also contain suitable foaming agents, such as those that are affordable, stable and foaming in a wide range of pH. Foaming agents include nonionic, anionic, amphoteric, cationic, zwitterionic, synthetic detergents, and mixtures thereof. Many suitable non-ionic and amphoteric surfactants are disclosed in U.S. patent No. 3.988.433 on the name Benedict; No. 4.051.234, published April 27, 1977, and many suitable nonionic surfactants are disclosed in U.S. patent No. 3.959.458 in the name of Agricola et al., published on 25 may 1976. In one embodiment, the ratio of the retention agent to surfactant is greater than 1, in another embodiment, is greater than 2, and in one embodiment is greater than 3.

This composition optionally contains a safe and effective amount of a blowing agent, in another embodiment, contains from about 0,001% to about 20%, in another embodiment from about 0.05% to about 6% and in another embodiment from about 0.1% to about 3% by weight of the composition of the surfactant. In one embodiment, a blowing agent wybir the Ute from the group consisting of cocamidopropylbetaine, alkylsulfate sodium, poloxamer, sorbitan of isostearate PEG-40 and mixtures thereof.

Anionic surfactants

Anionic surfactants herein include the water-soluble salts of alkyl sulphates having from 8 to 20 carbon atoms in Akilova the radical (for example, materialschlacht) and water-soluble salt of sulfate of monoglycerides of fatty acids having from 8 to 20 carbon atoms. Sodium lauryl sulfate and sulfonates nationalized coconut oil are examples of anionic surfactants of this type. Other suitable anionic surfactants are, like laurylsarcosine sodium, taurate, laurylsulphate sodium, laurelsatin sodium, eurekabuild and dodecylbenzenesulfonate sodium. Can also be used a mixture of anionic surfactants.

Abrasives

The present composition may also include a dental abrasive. Dental abrasives used in local oral carriers of the compositions of the present invention include many different substances. The selected material should be compatible with the composition and not overly erase hard tooth tissue. Suitable abrasives include, for example, silicas including gels and precipitates, insoluble input polymetaphosphate sodium, the hydrate of aluminum oxide, calcium carbonate, dihydrate dirtfoot calcium, calcium pyrophosphate, tricalcium phosphate, polymetaphosphate calcium and resinous abrasive materials such as condensation products of urea and formaldehyde in the form of particles.

Level optional abrasive in the compositions described herein, in General ranges from about 6% to about 70% by weight of the composition, in another embodiment it is from about 10% to about 60% of the abrasive, in another embodiment from about 15% to about 50%, and in another embodiment from about 15% to about 40% by weight of the composition.

In one embodiment, water-insoluble particles of the present invention (for example, some abrasives, fillers, etc. are less than about 65%, in another embodiment less than about 60%, in another embodiment less than about 50% by weight of the composition.

Another class of abrasives for use in the compositions are shrink-polymerized resin in the form of particles, as described in U.S. patent No. 3.070.510, issued in the name of Cooley & Graben-stetter 25 December 1962. Suitable resins include, for example, melanin, phenolic resins, urea -, melamine-urea, urea-formaldehyde, melamine-urea-formaldehydes, cross-linked epoxides and polyesters with the Popper is related links.

Silica dental abrasives of various types are preferred because of their unique benefits of exceptional dental cleaning cloth and indicators polishing without excessive abrasion of the tooth enamel or hard tissues of the teeth. Silica abrasive polishing agents mentioned here, as well as the other abrasives, generally have an average particle size ranging between about 0.1 and about 30 microns, and preferably from about 5 to about 15 microns. The abrasive can be a sedimentary silica or silica gel, such as the silica xerogels described in U.S. patent No. 3.538.230 name Pader et al., published on March 2, 1970, and U.S. patent No. 3.862.307 name DiGiulio, published on 21 January 1975. In one embodiment, silica abrasives are by silica xerogels marketed under the name "Syloid" company W.R. Grace&Company, Davison Chemical Division. In another embodiment, silica abrasives are sedimentary siliceous substances, such as those produced by J.M. Huber Corporation under the market name Seagent®in particular silica called Seagent 119®. The types of silica dental abrasives used in the toothpastes of the present invention, described in more detail in U.S. patent No. 4.340.583 on the name of the Wason, published on 29 July 1982.

In particular, preferred is a recreational sedimentary silica is silica, disclosed in U.S. patent No. 5.603.920, published on 18 February 1997, 5.589.160, published December 31, 1996, 5.658.553 published August 19, 1997, 5.651.958, published on July 29, 1997, which are all assigned Procter & Gamble Co.

Can be used a mixture of abrasives.

Flavoring and sweetening agents

Flavouring agents may also be added to the compositions. Suitable aromatizers agents include oil of Grushenka, peppermint oil, peppermint oil curly, oil of clove buds, menthol, anethole, methyl salt of salicylic acid, eucalyptus oil, 1-methyl acetate, sage, Myrtle oil, parsley, oxanol, Alvarion, marjoram, lemon, orange, propenyl Gaeta, cinnamon, vanillin, thymol, linalool, acetylcellulose glycerin, known as the LRA, and mixtures thereof. Flavoring agents are generally used in the compositions in amounts of from about 0,001% to about 5% by weight of the composition.

Sweetening agents which can be used optionally, include Sucralose, sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, some saccharine salts, thaumatin, aspargine, D-tryptophan, dihydrochalcones, Acesulfame and cyclamate salts, especially sodium cyclamate and sodium saccharin, and mixtures thereof. In one embodiment, the composition contains from about 0.1% to primer is 10% of these agents, in another embodiment, from about 0.1% to about 1% by weight of the composition.

In addition to flavouring and sweetening agents may be used fresheners, sljunootdelitelnye agents, warming agents, and causing numbness agents as optional ingredients in the compositions of the present invention. These agents are present in the compositions in amounts of from about 0,001% to about 10%, in another embodiment from about 0.1% to about 1% by weight of the composition.

Freshener may be any of a variety of substances. These substances include carboxamide, menthol, ketals, diols, and mixtures thereof. The preferred fresheners in these compositions are parameterbased agents, such as N-ethyl-p-Menten-3-carboxamide, known commercially as "WS-3", N,2,3-trimethyl-2-isopropylmalonic, known as "WS-23", and their mixtures. Additional preferred fresheners selected from the group consisting of menthol, 3-1-methoxypropane-1,2-diol known as TK-10 manufactured by Takasago, acetylimino glycerin, known as AMG, manufactured by Haarmann and Reimer, and Menthyl lactate, known as Prescolar®manufactured by Haarmann and Reimer. Terms menthol and Menthyl, as used here, includes right - and levogyrate isomers of these compounds and their racemic mixtures. TC-10 is described in U.S. patent No. 4.459.425, in the name of Amano et al., publ is forged on 10 July 1984. WS-3 and other agents described in U.S. patent No. 4.136.163 in the name of Watson et al., published on January 23, 1979.

Sljunootdelitelnye agents of the present invention include Jambu®manufactured by Takasago. Warming agents include esters of capsicum and nicotinate esters, such as benzyl nicotinate. Causing numbness agents include benzocaine, lidocaine, oil of clove buds and ethanol. Can be used mixtures of these agents.

Agents sensations/anesthetic agents

Pain or relieving sensitivity agents can also optionally be present in the compositions according to the present invention. Analgesics are agents that relieve pain by Central action to increase the pain threshold without impairment of consciousness or change other means of perception. Such agents may include, but are not limited to, strontium chloride, potassium nitrate, sodium nitrate, sodium fluoride, acetanilide, phenacetin, thiorphan, spiradoline, aspirin, codeine, thebaine, Levorphanol, hydromorphone, Oxymorphone, phenazocine, fentanyl, buprenorphine, butanol, nalbufin, pentazocine, natural herbs such as ink nut, ... May also be present anesthetic agents, or local analgesics, such as acetaminophen, salicylate sodium salicylate, trolamine, Lido is ain and benzocaine. These analgesic active substance are described in detail in the book, Kirk-Othmer, Encyclopedia of Chemical Technology, Fourth Edition, Volume 2, Wiley-Interscience Publishers (1992), pp.729-737.

Other media for the care of the oral cavity

Chewing solid form of a single dosage of the present invention in one embodiment less than about 5% dezintegriruetsja agents, in another embodiment less than about 3% dezintegriruetsja agents, and in one embodiment less than about 1%, or are practically free from dezintegriruetsja agents.

The use of a composition

These compositions can be used by the consumer at home. These compositions are used, in one embodiment, from about once per week to about four times per day, in another embodiment from about three times a week to about three times per day, in another embodiment from about once per day to about twice a day. The period of such treatment extends, generally, from one day to a lifetime. For specific diseases or conditions of the oral cavity, the duration of treatment depends on the severity treatable disease or condition specific forms of delivery and the patient's response to treatment. In one embodiment, the duration of treatment ranged from primer the 3 weeks to about 3 months but may be shorter or longer depending on the severity treatable condition, specific forms of delivery and the patient's response to treatment.

The present invention further relates to a method for providing prolonged delivery of the active agent into the oral cavity of the subject when his needs for treatment or prevention of conditions of the mouth alone, or to promote the health of the entire body by local injection of a composition for caring for the oral cavity that contains:

a) retaining agent from about 1% to about 40% by weight of the composition, selected from the group consisting of water-soluble hydrophilic resins, water-soluble hydrophilic polymers, and mixtures thereof, and the retaining agent has the property of hydrating under the influence of water or saliva, in one embodiment, leads to the formation in healthy hydrated mass to ensure retention rates from about 1 to about 4; and (b) a safe and effective amount of local media for the care of the oral cavity; however, the composition is nearisogenic solid chewing the form of a unit dosage; and the composition contains less than about 65% by weight of water-insoluble particles.

The present invention further relates to a method for providing prolonged delivery of the active agent into the oral cavity of a subject when it is rebnosci for the treatment or prevention of conditions of the mouth alone, or to promote the health of the entire body by local injection of the composition for the care of the oral cavity, containing: a) retaining agent of water-insoluble particles from about 30% to about 65% by weight of the composition, the solubility of retention agent in water is less than 1 g to 30 g at a temperature of 25°C; b) a safe and effective amount of active agent to care for the oral cavity; (C) a safe and effective amount of surfactant; (d) a safe and effective amount of a buffering agent; the composition is a chewing purifying solid form of a unit dosage, nishibuchi, nearisogenic; and the composition has a coefficient of retention from about 1 to about 4.

The present invention further relates to a method for ensuring long-term delivery of the flavor agent sensations or buffer in the oral cavity of a subject when it needs by introducing locally in the oral cavity composition for the care of an oral cavity, comprising: a) retaining agent from about 1% to about 40% by weight of the composition, selected from the group consisting of water-soluble hydrophilic resins, water-soluble hydrophilic polymers, and mixtures thereof, and the retaining agent has the property of hydrating under the influence of water or saliva, in one embodiment, leads to the formation in healthy hydrated mass, to ensure retention rates from about 1 to about ; and (b) a safe and effective amount of local media for the care of the oral cavity selected from the group consisting of a flavoring agent, feelings, buffers and mixtures thereof; the composition is nearisogenic solid chewing the form of a unit dosage; and the composition contains less than about 65% by weight of water-insoluble particles.

The present invention further relates to a method for ensuring long-term delivery of the flavor agent sensations or buffer in the oral cavity of a subject when it needs by introducing locally in the oral cavity composition for the care of an oral cavity, comprising: a) retaining agent of water-insoluble particles from about 30% to about 65% by weight of the composition, the solubility of retention agent in water is less than 1 g to 30 g at a temperature of 25°C; b) a safe and effective amount of active agent to care for the oral cavity; (C) a safe and effective the amount of surfactant; (d) a safe and effective amount of media on the care of the mouth, selected from the group consisting of a flavoring agent, feelings, buffers and mixtures thereof; the composition is a chewing purifying solid form of a unit dosage, nishibuchi, nearisogenic; and the composition has a coefficient of deduction from about 1 to about 4.

The compositions according to the present is obreteniyu used for human for other animals (e.g. Pets or animals in the zoo).

EXAMPLES

The following non-limiting examples describe preferred embodiments of the scope of this invention. Valid many changes to these examples without departing from the scope of the invention.

Example I

The following compressed chewable tablets containing sodium fluoride, produced by traditional methods of processing of tablets by mixing the following:

SubstanceNo. 1 wt.%No. 3 Wt.%No. 3 Wt.%No. 4 Wt.%No. 5 Wt.%
Sodium fluoride0,2430,08840,05520,110,11
Sodium lauryl sulfate1,51,51,5
Poloxamer 4077,5
Sorbitan diisostearate PEG-402
Silica202020
Calcium pyrophosphateÈA; 40
Diphosphate calcium40
Tetrasodium pyrophosphate555
Saccharin sodium0,50,40,40,4
Acesulfame potassium0,3
Sucralose0,1
Aspartame0,3
Flavor1,51,51,51,51,5
Sodium bicarbonate5510
Dibasic sodium phosphate5
Methocel K4M Premium (Hydroxypropylmethyl-cellulose)105
Methocel K100LV Premium (Hydroxypropylmethyl-cellulose)10
Natrocarbonatite-cellulose N Aqualon)615
Hydroxyethyl-cellulose (Klucel 250 M Aqualon)3
Xanthan gum2
Microcrystalline cellulose5105
Policyprovider33
Related noticebox-methyl-cellulose2
Linked polyvinylpyrrolidone122
Sorbitol3016,811619,44483323
Mannitol33,2570028,4922,49
Cetylpyridinium chloride0,5
Chlorhexidine gluconate0,5
The zinc stearate11111
Total100100100100100
1Plasdone XL from ISP

Example II

The following compressed chewable tablets containing monitoroff sodium, manufactured by traditional methods of processing of tablets by mixing the following:

td align="center"> 0,5
SubstanceNo. 1 wt.%No. 2 Wt.%
Monitoroff sodium0,8330,150
Sodium lauryl sulfate1,5
Sorbitan diisostearate PEG-402
Silica20
Diphosphate calcium40
Tetrasodium pyrophosphate5
Saccharin sodium0,5
Flavor1,51,5
Sodium bicarbonate10
Dibasic sodium phosphate5
Methocel K4M Premium (Hydroxypropylmethyl-cellulose)4
Methocel K100LV Premium (Hydroxypropylmethyl-cellulose)8
Natrocarbonatite-cellulose (Cekol 30000)7
Polimetilvinilovy/anhydride maleic acid (salt Ca/Zn)12
Microcrystalline cellulose5
Policyprovider33
Linked polyvinylpyrrolidone210
Sorbitol1520
Mannitol14,66714,35
Zinc chloride2,5
Chloride copper0,5
The zinc stearate0,51,0
Total100100
2Plasdone XL from ISP

Example III

Nijesleduyushee chewable tablets, containing fluoride tin, made by traditional methods of processing of tablets by mixing the following:

SubstanceNo. 1 wt.%No. 2 Wt.%
Fluoride tin0,4540,0825
Sodium lauryl sulfate1,5
Sorbitan diisostearate PEG-402
Silica2010
Aluminum oxide5
Polyphosphate sodium (Glass N)377
Saccharin sodium0,50,5
Flavor1,51,5
Sodium bicarbonate10
Dibasic sodium phosphate5
Methocel K4M Premium (Hydroxypropylmethyl cellulose)57,5
Methocel K100LV Premium (Hydroxypropylmethyl cellulose)107,5
Microcrystalline cellulose50
Policyprovider3,00
Linked Polyvinyl shall irreligion 422
Sorbitol12,04620
Mannitol2030,9175
Zinc chloride1
The zinc stearate11
Total100100
3n=21 from FMC
4Plasdone XL from ISP

Example IV

The following compressed chewable tablets not having a source of fluoride ions, produced by traditional methods of processing of tablets by mixing the following:

SubstanceNo. 1 wt.%No. 3 Wt.%No. 3 Wt.%
Sodium lauryl sulfate1,51,5
Cocamidopropylbetaine2
Silica20
Calcium carbonate40
Diphosphate calcium40
Tetrasodium pyrophosphate5
Sodium tripolyphosphate7
Polyphosphate sodium (Glass H)510
Saccharin sodium0,50,50,5
Flavor1,51,51,5
Sodium bicarbonate1057
Methocel K4M Premiwn (Hydroxypropylmethyl cellulose)56
Methocel K100LV Premium (Hydroxypropylmethyl cellulose)106
Sodium alginate (Protanol LF 200s)10
Microcrystalline cellulose5
Policyprovider1,21,2
Starch glycolate, sodium2
Sorbitol2027,55
Mannitol19,0227,5
Triclosan0,28
Cetylpyridinium chlorideÈA; 0,251
The zinc stearate111
Total100100100
5n=21 from FMC

Example V

The following compressed chewable tablets are manufactured by traditional methods of processing of tablets by mixing the following:

SubstanceNo. 1 wt.%No. 3 Wt.%No. 3 Wt.%
Sorbitol, NF (D-glucitol)15,000
Calcium carbonate46,87537,965
Sodium fluoride0,0880,1770,324
Isomalt (hydrogenomonas isomaltose)32,401
Mannitol, USP39,83734,250
Magnesium-aluminum silicate45,000
Hydroxypropylmethyl-cellulose3,150
Polyvinylpyrrolidone4,0993,308
Hydrox the ethyl-cellulose 2,000
Carboxymethyl-cellulose5,000
Powder alkylsulfate sodium1,5000,875
Cocamidopropylbetaine1,750
Sodium bicarbonate10,000
Saccharin sodium, USP1,0001,1000,850
Flavor1,5001,2501,600
Talc2,5011,950
Magnesium stearate2,3501,5000.800 to
Total100,000100,000100,000

Although described specific embodiments of the present invention, for specialists will be apparent various changes and improvements of the present invention without deviating from the essence and scope of the invention. The accompanying claims are intended to cover all such modifications that are within the scope of the present invention.

1. The composition for the care of the oral cavity, containing

a retention agent 1 is about 40%, preferably from 11 to 18%, by weight of the composition, selected from the group consisting of water-soluble hydrophilic resins, water-soluble hydrophilic polymers, and mixtures thereof, and the retaining agent has the property of hydrating under the influence of water or saliva, which leads to the formation in healthy hydrated mass to ensure retention rates from about 1 to about 4; and

b) the number of local media for the care of the mouth, selected from the range from 60 to 90%, preferably medium to care for the oral cavity selected from the group consisting of a flavoring agent, sensations, foaming agent, an abrasive, a buffer agent and mixtures thereof;

and optionally from 0.01 to 40% of the active agent to care for the oral cavity selected from the group consisting of agent against plaque, the source of fluoride ions, antimicrobial agents, desensitizing tooth fabric agents, anesthetic agents, antifungal agents, anti-inflammatory agents, the action of anti-caries agents, reducing mineralization agents, whitening agents, anti-erosion agents, vitamins and minerals, and mixtures thereof; the composition is nearisogenic solid chewing the form of a unit dosage.

2. The composition according to claim 1, in which the medium contains from 0.1 to 25% buffer the CSOs agent, selected from the group consisting of water soluble buffering agents, sodium bicarbonate, sodium carbonate, phosphate buffer agents, amino acid buffering agents, alanine, glycine, triphosphate sodium diphosphate, sodium, sodium hydrogen phosphate, sodium dihydrophosphate, three(hydroxymethyl) aminomethane, tetrasodium pyrophosphate, deerfoot sodium, tetramerista potassium salts tripolyphosphate and mixtures thereof.

3. Care set for oral cavity containing

a) the composition for the care of the oral cavity for local oral administration in a human or animal containing

1) retaining agent is from 1 to 40%, preferably from 7 to 30%, by weight of the composition, selected from the group consisting of water-soluble hydrophilic resins, water-soluble hydrophilic polymers, and mixtures thereof, and the retaining agent has the property of hydrating under the influence of water or saliva; and

2) from 60 to 90% of the local media to care for the oral cavity selected from the group consisting of a flavoring agent, sensations, foaming agent, an abrasive, a buffer agent and mixtures thereof;

b) capacity;

when this composition is nearisogenic chewing solid form of a unit dosage.

4. The composition according to claim 1, in which the retention rates ranging from 2 to 4.

5. The composition according to claim 1, in which from 0.5 to 20% by weight, the beginning is a high composition is deposited on some of the surfaces of the teeth after chewing the subject, such as pits, fissures on the occlusal surface, slits, grooves, notches, grooves, gaps, irregularities, tooth surface and/or surface along the cervical part of the gums, smooth surfaces of the teeth and/or chewing or kostelny the surface of the tooth.

6. The composition of claim 1, wherein the restraining agent is selected from the group consisting of acacia, resin karaya, guar resin, gelatin, alginic acid and its salts, tragakant, polyethylene glycol, politi-nanoxide, acrylamide polymers, linked polyacrylic acid, polyvinyl alcohol, ethyleneoxide polymers, polyvinylpyrrolidone, cationic polyacrylamide polymers, carboxymethyl cellulose, hydroxyethyl-cellulose, hydroxypropyl-cellulose, hydroxypropylmethyl-cellulose, xanthan resin, carrageenan, resin carob, gum Arabic, tragacanth resin, pullulan, pre gelatinising and partially pre-gelatinizing starch, hydrolyzed starch, solid maltodextrin and corn syrup, hydrogenated products of hydrosilation starch, amylose, amylopectin, and mixtures thereof; preferably hydroxypropylmethyl-cellulose, hydroxyethyl-cellulose, carboxymethylcellulose, linked polyacrylic acid, and mixtures thereof.

7. The way to keep the pH from 7 to 12 units, preferably the t 7.5 to 10 units, for at least 2 min by local injection in the oral care composition for oral cavity containing

a retention agent is from 1 to 40% by weight of the composition, selected from the group consisting of water-soluble hydrophilic resins, water-soluble hydrophilic polymers, and mixtures thereof, and the retaining agent has the property of hydrating under the influence of water or saliva; and

b) from 2 to 20% of a buffering agent; and

c) from 60 to 90% of the local media to care for the oral cavity;

when this composition is nearisogenic solid chewable

the form of a unit dosage, and the composition contains less than about 65% by weight of water-insoluble particles.

8. The composition or method according to claim 1 or 8, in which the composition is nishiuchi.



 

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FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with creating preparations of psychotherapeutic action. It has been suggested 5 variants of aromatic compositions for normalizing psychoemotional state: for normalizing psychoemotional state in persons with highly unsteady type of the higher nervous activity (HNA), emotionally active; for normalizing psychoemotional state in persons with highly unsteady type of HNA; for normalizing psychoemotional state in persons revealing melancholic, weak type of HNA; for normalizing psychoemotional state in persons with highly steady type of HNA; for normalizing psychoemotional state in persons with weak unsteady type of HNA. The preparations mentioned provide purposeful impact upon affected psychoemotional sphere in persons with different constitutional peculiarities of HNA.

EFFECT: higher efficiency.

5 cl, 15 ex

FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with creating preparations of psychotherapeutic action. It has been suggested 5 variants of aromatic compositions for normalizing psychoemotional state: for normalizing psychoemotional state in persons with highly unsteady type of the higher nervous activity (HNA), emotionally active; for normalizing psychoemotional state in persons with highly unsteady type of HNA; for normalizing psychoemotional state in persons revealing melancholic, weak type of HNA; for normalizing psychoemotional state in persons with highly steady type of HNA; for normalizing psychoemotional state in persons with weak unsteady type of HNA. The preparations mentioned provide purposeful impact upon affected psychoemotional sphere in persons with different constitutional peculiarities of HNA.

EFFECT: higher efficiency.

5 cl, 15 ex

FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with creating preparations of psychotherapeutic action. It has been suggested 5 variants of aromatic compositions for normalizing psychoemotional state: for normalizing psychoemotional state in persons with highly unsteady type of the higher nervous activity (HNA), emotionally active; for normalizing psychoemotional state in persons with highly unsteady type of HNA; for normalizing psychoemotional state in persons revealing melancholic, weak type of HNA; for normalizing psychoemotional state in persons with highly steady type of HNA; for normalizing psychoemotional state in persons with weak unsteady type of HNA. The preparations mentioned provide purposeful impact upon affected psychoemotional sphere in persons with different constitutional peculiarities of HNA.

EFFECT: higher efficiency.

5 cl, 15 ex

FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with creating preparations of psychotherapeutic action. It has been suggested 5 variants of aromatic compositions for normalizing psychoemotional state: for normalizing psychoemotional state in persons with highly unsteady type of the higher nervous activity (HNA), emotionally active; for normalizing psychoemotional state in persons with highly unsteady type of HNA; for normalizing psychoemotional state in persons revealing melancholic, weak type of HNA; for normalizing psychoemotional state in persons with highly steady type of HNA; for normalizing psychoemotional state in persons with weak unsteady type of HNA. The preparations mentioned provide purposeful impact upon affected psychoemotional sphere in persons with different constitutional peculiarities of HNA.

EFFECT: higher efficiency.

5 cl, 15 ex

FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with creating preparations of psychotherapeutic action. It has been suggested 5 variants of aromatic compositions for normalizing psychoemotional state: for normalizing psychoemotional state in persons with highly unsteady type of the higher nervous activity (HNA), emotionally active; for normalizing psychoemotional state in persons with highly unsteady type of HNA; for normalizing psychoemotional state in persons revealing melancholic, weak type of HNA; for normalizing psychoemotional state in persons with highly steady type of HNA; for normalizing psychoemotional state in persons with weak unsteady type of HNA. The preparations mentioned provide purposeful impact upon affected psychoemotional sphere in persons with different constitutional peculiarities of HNA.

EFFECT: higher efficiency.

5 cl, 15 ex

FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with creating preparations of psychotherapeutic action. It has been suggested 5 variants of aromatic compositions for normalizing psychoemotional state: for normalizing psychoemotional state in persons with highly unsteady type of the higher nervous activity (HNA), emotionally active; for normalizing psychoemotional state in persons with highly unsteady type of HNA; for normalizing psychoemotional state in persons revealing melancholic, weak type of HNA; for normalizing psychoemotional state in persons with highly steady type of HNA; for normalizing psychoemotional state in persons with weak unsteady type of HNA. The preparations mentioned provide purposeful impact upon affected psychoemotional sphere in persons with different constitutional peculiarities of HNA.

EFFECT: higher efficiency.

5 cl, 15 ex

FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with creating preparations of psychotherapeutic action. It has been suggested 5 variants of aromatic compositions for normalizing psychoemotional state: for normalizing psychoemotional state in persons with highly unsteady type of the higher nervous activity (HNA), emotionally active; for normalizing psychoemotional state in persons with highly unsteady type of HNA; for normalizing psychoemotional state in persons revealing melancholic, weak type of HNA; for normalizing psychoemotional state in persons with highly steady type of HNA; for normalizing psychoemotional state in persons with weak unsteady type of HNA. The preparations mentioned provide purposeful impact upon affected psychoemotional sphere in persons with different constitutional peculiarities of HNA.

EFFECT: higher efficiency.

5 cl, 15 ex

Massage agent // 2302854

FIELD: medicine cosmetic, in particular agent for treatment of cripple infant suffering from infantile cerebral paralysis.

SUBSTANCE: claimed agent contains cameline oil, dogrose oil, and mint oil. Said agent is uniformly distributed on skin, has good absorption, provides good sliding effect, increases blood circulation, relives muscle stress.

EFFECT: agent with increased feeding, anti-inflammation and immunostimulating action.

1 ex

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