Oral care composition containing tin ions and nitrate ions

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to oral hygiene preparations. An oral care composition contains a) an aqueous phase; b) stannous tin ions dissolved in the aqueous phase; c) nitrates in the aqueous phase; wherein total nitrates is that a molar amount of nitrogen measured as a nitrate in the aqueous phase makes 1.8-0.1 of the molar amount of stannous tin ions; and d) a flavouring agent. What is also presented is a method for storage and a storage container for this composition; using nitrate for stabilising oxidised stannous tin ions dissolved in the aqueous phase. What is also presented is also a version of the composition, wherein the composition is aqueous.

EFFECT: using the group of inventions stabilises oxidised stannous tin ions dissolved in the aqueous phase by the above molar ratio of nitrate and stannous tin ions.

17 cl, 2 tbl, 15 ex

 

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the priority of European patent application No. 10159201.2 entered in the register on 7 April 2010, the content of which is introduced in the present invention fully by reference.

The technical field TO WHICH the INVENTION RELATES

The present invention relates to compositions for caring for the oral cavity, in particular a means for mouthwash containing ions of divalent tin.

Ions of divalent tin is used in the field of compositions for caring for the oral cavity over decades. The original reason for the use of ions of divalent tin in the composition for the oral cavity was the fact that the fluoride added to it in the form of fluoride of divalent tin. Other reasons for applying ions of divalent tin themselves in compositions for caring for the oral cavity was their diminishing sensitivity effect, effect, protects from decay, and the effect of protecting against demineralization.

The addition of ions of divalent tin to compositions for caring for the oral cavity suffers from the drawback consisting in the fact that the ions of divalent tin is susceptible to oxidation by the oxygen of the atmosphere, particularly in a predominantly aqueous medium that is found in these compositions. Oxidation gives tetravalent ions�of tin, actively hydrolyzed in an aqueous medium, giving the insoluble hydroxo or oxide molecules, which leads to sedimentation and turbidity. This in particular is undesirable to compositions for caring for the oral cavity in the form of means for rinsing the oral cavity or means for rinsing the mouth that are supposed to be transparent, not containing precipitation solution and which, when data of precipitation or turbidity, become unacceptable to the consumer. Ions of tetravalent tin, to the extent that they remain dissolved in the composition, have lower efficiency than that of ions of divalent tin.

When possible packaging of the composition to care for the oral cavity in an atmosphere of inert gas, such as nitrogen, or in vacuum, the inert gas atmosphere or a vacuum ceases to exist when opening the packaging by the consumer. Compositions for the care of mouth cavity containing ions of divalent tin, thus, require some stabilizing system that protects ions of divalent tin from oxidation after opening and during the time of applying the composition, which is usually several weeks, such as three weeks.

Prior art

US 5004597 A describes that in compositions for the care for�awn mouth loss of ions of divalent tin due to the oxidation of ions of bivalent tin can compensate for a capacitance, contains ferrous gluconate tin.

EP 0 026 539 describes A stabilization of ions of divalent tin in the aquatic environment, such as in mouthwash, hydrohloride ammonium (amine fluorides such as OLAFLUR.

J. Chem. Soc. pp. 1996-2000 (1961) mentions that "dilute solutions of nitrate of tin (II) are stable to the extent feasible". This relates to an aqueous solution containing the nitrate of tin (II) and in which the mole ratio of nitrate ions to ions of divalent tin is exactly 2:1.

US 5693314 A and WO 99/53893 describe A two-component composition, one component containing a salt of divalent tin, and another component containing reducing the sensitivity of the quantity of potassium nitrate. These two components must be mixed before use. US 5693314 A also describes to compare a toothpaste that contains potassium nitrate and fluoride divalent tin. As in the two-component compositions US 5693314 A and WO 99/53893 A nitrate ion in a single component is present in a large molar excess compared with the ion of divalent tin in another component, i.e., the mole ratio of nitrate ions to ions of divalent tin is much greater than 2:1, the two components, when mixed with an appropriate ratio, such as approximately 1:1 (see in particular WO 99/53893, page 8, lines 31-32 and page 0, lines 15-19) give the composition, again with a large excess of nitrate relative to ions of bivalent tin. Mentioned comparative toothpaste US 5693314 contained A mole ratio of nitrate ions (from potassium nitrate) ions of divalent tin (from fluoride divalent tin), as calculated from these weights, 19,4:1. In US 5693314 A stated in column 2, lines 17-20 that "prolonged contact between the ion of divalent tin and nitrate ion in a single toothpaste causes reaction data of ions, causing the conversion of NO3in potentially toxic substances".

US 5603922 describes A one - or two-component compositions for remineralization. They contain calcium salt (which can be a nitrate) and a salt of another divalent cation which can be, but not necessarily, ion of divalent tin; salt itself, in the case of salt ion of divalent tin, can be a chloride or nitrate. In example 9 part a describe the composition comprising the molar ratio of nitrate ions (from calcium nitrate) ions of divalent tin (chloride of divalent tin), as calculated from these weights, 332,7:1. In example 12 part a describe the composition comprising the molar ratio of nitrate ions (from calcium nitrate) ions of divalent tin (from the chloride of divalent tin), as calculated from the�azannyh weights 464,5:1.

The present invention seeks to provide a composition containing an ion of divalent tin, to care for the oral cavity with enhanced stability ion of divalent tin to oxidation.

Summary of the INVENTION

The number of problems solved by a composition for caring for the oral cavity containing a) an aqueous phase; (b) ions of divalent tin dissolved in the aqueous phase; c) nitrates dissolved in the water phase; in which the total content of the above-mentioned nitrates is such that the amount in moles of nitrogen in the aqueous phase, measured in the form of nitrate, is 1.8-0.1 of the amount in moles of dissolved ions of divalent tin; and (d) a flavoring.

Other aspects of the present invention and the preferred embodiments of all aspects of the present invention are the same as in the formula of invention.

Unexpectedly, it was found that when the nitrate is mixed in aqueous solution with ions of divalent tin in a molar ratio of nitrogen measured in the form of free nitrate ions of divalent tin, which is less than 2:1, then, first, the nitrate does not react substantially with ions of bivalent tin. In addition, it has surprisingly been found that in this case, ions of divalent tin is also stabilized against oxidation by atmospheric air.

DETAILED DESCRIPTION AND�GAINING

Composition for caring for the oral cavity of the present invention can be any composition, such as toothpaste, tooth gel for, solution for teeth, mouthwash, and so forth. Preferably it is a means for rinsing the mouth.

Compositions for caring for the oral cavity of the present invention contains the aqueous phase. Thus, also referred to as synonymous with "water song". By "aqueous phase" is understood that this phase usually contains 30%-99%, preferably 40%-95% by weight, relative to the liquid phase, water. The aqueous phase can be liquid, which means that it has a dynamic viscosity at room temperature greater than 1000 MP. The aqueous phase may also be in the form of a gel or syrup, which can be obtained by adding water-soluble gelling agents or thickeners, acceptable to the composition to care for the oral cavity, or the addition of characterfile higher viscosity than water, such as glycerine or propylene glycol. It is clear that any insoluble solids are not part of the aqueous phase, such as abrasives, which can suspendirovanie, or dispergiermittel, or mixed with the aqueous phase and which can be separated from the composition for the care of mouth by physical methods of separation of solids and liquids, such as Phil�tration, sedimentation, flotation or centrifugation, optionally after dilution of the composition to care for the oral cavity in up to twenty-fold amount of water. The aqueous phase may also contain some quantity, such as 1-15% by volume, relative to the aqueous phase, ethanol. Preferably the aqueous phase is a liquid with the above-mentioned dynamic viscosity. the pH of the aqueous phase is typically in the range of 3.0 to 6.0, preferably in the range of 4.0 to 6.0 and most preferably in the range of 4.0 to 5.0.

Compositions for caring for the oral cavity of the present invention contain ions of divalent tin dissolved in the aqueous phase". It is assumed that this term includes all types of ion tin with nominal oxidation state +II in the liquid phase. Examples of these types of tin are dissolved ions of divalent tin, soluble ionic or non-ionic complexes of ions of divalent tin ion and the hydroxo complexes of ions of divalent tin. The amount of dissolved ions of divalent tin is usually 100 to 2,500 ppm, preferably 150-1000 ppm, more preferably 150-500 ppm of dissolved ions of divalent tin relative to the water phase. Dissolved ions of divalent tin can be determined potentiometrically (see example 10). Dissolved inadvancing tin can be derived from pharmaceutically acceptable salts of divalent tin. Examples are chloride of divalent tin, fluoride divalent tin hydroxide, divalent tin, ferrous sulfate tin and fluoride divalent tin is preferred. What was labeled on the above level of technology as the nitrate divalent tin", not as a separate ion source of divalent tin and simultaneously separate source of nitrate ions, as this will give the composition for the oral cavity in a molar ratio of nitrogen measured in the form of nitrate ions of divalent tin 2:1, which is not in accordance with the present invention.

Compositions for caring for the oral cavity of the present invention contain in their aqueous phase dissolved nitrates. The term "nitrates" includes all water-soluble inorganic particles containing one or more Ν3-particles each (coordinated with the cation or as counter ions (counterions)). Examples of nitrates are nitrate complexes of metal cations present in the aqueous phase of the composition for the oral cavity, such as ions of divalent tin, dissolved nitrate counterions and undissociated nitric acid. Assume that the dissolved nitrate anions are nitrate anions, solvated by water molecules, and containing predominantly nesac�miksovannye cations, such as the cations of sodium, potassium or the cation of an amine fluoride (see below) as counterions. Since all these nitrates are usually in thermodynamic equilibrium with each other, you can determine the amount in moles of each of these nitrate separately. The common feature of all of these nitrates is, however, that alkalinization when they become dissolved nitrate anions by deprotonation of nitric acid and/or precipitation of metal cations from any nitrate complex in the form of insoluble hydroxides or oxides. Significant for the purposes of the present invention is that the total number of all data of nitrate dissolved in the aqueous phase of the composition for the oral cavity, i.e. the amount in moles of nitrogen contained in it, and measured after alkalizing (but without any other or further chemical transformations such as oxidation) in the form of nitrate anions (see example 11) was two times less than the amount in moles of ions of divalent tin dissolved in the aqueous phase. Assuming that nitrate is dissolved in the aqueous phase contain only one NO3-each particle (or coordinated as anion), then the amount in moles of the data NO3-particles and, thus, the amount in moles themselves dissolved nitrate is �I mentioned the amount in moles of nitrogen. In this case, referred to the ratio of the moles of nitrogen measured in the nitrate form, solvated ions of divalent tin is also called for brevity "is the mole ratio of nitrate ions to divalent tin".

Mentioned nitrates can be obtained by adding sodium nitrate or potassium hydroxide to the aqueous phase of the composition. You can also apply the nitrate of divalent tin" prior art, but then in combination with another salt of divalent tin to obtain a molar ratio of nitrogen measured in the nitrate form, solvated ions of divalent tin, less than 2:1, which is consistent with the present invention. The nitrate ions and ions of divalent tin in a molar ratio of approximately 0,66:1 can be added simultaneously from a crystal of the so-called "basic" nitrate divalent tin (consider that he has the formula Sn3(OH)4(NO3)2), particularly if the aqueous phase to which it is added, was previously acidified with a small amount of acid to prevent hydrolysis to a hydrated oxide of tin (II). Then, this composition can be done free from sodium and potassium. This salt can be obtained in crystalline form and is stable at room temperature; while at higher temperatures it can� to explode. Nitrates can also be obtained in the aqueous phase of the composition by adding silver nitrate to the aqueous phase, in which ions of divalent tin dissolved after addition of chloride of divalent tin. In this way any added silver ions can be quantitatively precipitated in the form of silver chloride, provided that a significant amount of chloride present in the aqueous phase. The remainder of significant amounts of chloride in the method is the equivalent of a significant amount of chloride of divalent tin, not yet exchanged for nitrate divalent tin, which, in turn, is consistent with the requirements of the present invention that the amount in moles of nitrogen, measured in the form of nitrate, was 1.8 to 0.1 of the amount in moles of ions of divalent tin. For brevity, this means that as silver chloride may precipitate when adding silver nitrate, the amount in moles of nitrogen, measured in the form of nitrate, is 1.8-0.1 of the amount in moles of ions of divalent tin according to the present invention.

Compositions for caring for the oral cavity of the present invention also contain a flavoring. This flavoring is preferably dissolved, dispersed or emulsifies in the aqueous phase. An exemplary subclass of flavour, the members of which may be contained in a composition for caring for the oral cavity we�Mr sage of the invention, is:

(i) essential oils and extracts from plant sources, such as oil, Basil oil, bitter almond oil, camphor oil, citronella oil, citrus oils, extracts of Apple, eucalyptus or peppermint, oil of lemon eucalyptus, eucalyptus oil, anise oil, anethole, oils of chamomile, mint oil, lime oil, Mandarin oil, clove oil, orange oil, citrus oil, peppermint oil, peppermint oil, sage oil, thyme oil, vanillin, oil of Wintergreen, oil of cinnamon or oil of cinnamon bark;

(ii) natural or synthetic compounds that cause the feeling of "heat" or "heat". Their examples include capsaicin, dihydrocapsaicin, gingerol, paradol, shogaol, piperine, paprika powder, red chilies, extracts of paprika, extracts of paprika, extracts of chili pepper; extracts from ginger root, extracts from delegatskogo pepper, extracts of cress oil, extracts of galangal small, extracts from alpinia galanga, N-vanillylamide carboxylic acids, in particular N-vanillylamide nonanoic acid, amides of 2-nonanalog acid, in particular, N-isobutyramide 2-nonanalog acid and N-4-hydroxy-3-methoxybenzylamine 2-nonanalog acid, alkyl ethers of 4-hydroxy-3-methoxybenzylamine alcohol, in particular n-butyl ether 4-hydroxy-3-methoxybenzylamine alcohol, alkyl ethers of 3-hydroxy-4-methoxybenzyl�tion of alcohol, alkyl ethers of 3,4-dimethoxybenzyl alcohol, alkyl ethers of 3-ethoxy-4-hydroxybenzylated alcohol, alkyl ethers of 3,4-methylenedioxybenzyl alcohol, amides (4-hydroxy-3-methoxyphenyl)acetic acids, in particular N-n-octylated (4-hydroxy-3-methoxyphenyl)acetic acid, nicotinamide, methylnicotinate, propylaniline, 2-butoxyaniline, benzylsuccinic and 1-acetoxyphenyl;

(iii) natural or synthetic compounds having "cooling" effect. Their examples are primarily 1-menthol, but also metaglidasen, Mantellate, substituted amides of Menthyl-3-carboxylic acid (for example, N-ethylamide of Menthyl-3-carboxylic acid), 2-isopropyl-N,2,3-trimethylbutyramide, substituted amides cyclohexanecarbonyl acid, 3-methoxypropane-1,2-diol, 2-hydroxyethylmethacrylate, 2-hydroxypropylmethacrylate, N-acetylcholinesterase ether, esters methylhydrocinnamic acid (for example, Menthyl 3-hydroxybutyrate), monomethylamine, 2-mercaptothiazoline, Menthyl 2-pyrrolidin-5-noncarboxylic, 2,3-dihydroxy-p-Mentana, 3,3,5-, 3-Menthyl 3,6-di - and tri-oxyalkylated, 3-methylmethacrylat, icillin and 1-ontimetravel the air.

Composition for caring for the oral cavity of the present invention may contain one or more fragrances, such as AP�mitigatory, described above. The type and amount of flavoring(s) depends on the taste that you expect to receive for the composition to care for the oral cavity. The approximate aggregate amount of flavors be 0.01%-0,5%, preferably of 0.03% to 0.3% by weight relative to the composition to care for the oral cavity.

Flavoring or flavoring agents may be soluble in water, in this case a simple dissolution will be used to sulfatirovnie of these substances in the aqueous phase. Alternatively, they may not dissolve in water or do not dissolve in water, in this case they can be dissolved by applying suitable characterial, such as the aforementioned 1-15% by volume relative to the water phase of ethanol. It is also possible to dissolve, disperse or emulsify using standard surfactants, as is known in the field of compositions for caring for the oral cavity. Preferred subclasses of surfactants include non-ionic (such as hydrogenated castor oil), cationic (such as salts of joining acids, fatty amines or floridino) and zwitterionic surfactants (such as cocamidopropylbetaine).

Industrial company for the production of flavourings such as Symrise, Mane Fils, Givaudan, Firmenich or International Fragrances provide ready-to-use cm�xiami flavors, which can be used in compositions for the care of the oral cavity.

Composition for caring for the oral cavity of the present invention may preferably also contain fluoride. The content of fluoride in the compositions for the care of the oral cavity is usually from 50 to 2000 ppm relative to the composition, preferably from 100 to 1000 ppm. Preferably, the fluoride is dissolved in the liquid phase of the composition. The content of fluoride in a composition for caring for the oral cavity can be determined potentiometrically using a fluoride selective electrode (see example 12). Fluoride can be added to the composition to care for the oral cavity in the form of any source of fluoride ion, usually used in compositions for caring for the oral cavity, e.g., in the form of fluoride divalent tin, sodium fluoride or amine fluoride. The latter is preferable; examples of suitable amine fluorides are those described in US 3083143 A, WO 98/22427 A and WO 2009/130319 A, and these three publications included in the present invention by reference. Especially preferred is hydrofloric amine, obtained by adding mole equivalent of hydrofluoric acid to N,N'n'-Tris(2-hydroxyethyl)-N-octadecenyl-1,3-diaminopropane free base, in which the known as amine fluoride Olaflur.

Composition for caring for the oral cavity of the present�present invention may contain dyes, acceptable to compositions for caring for the oral cavity. However, preferably practically not include dyes having the properties of sensitization of singlet oxygen are examples of these dyes are triarylmethane dyes and their derivatives, in particular patent blue V (E131; sodium or calcium salt of hydroxide [4-(α-(4-diethylaminophenyl)-5-hydroxy-2,4-desulfoviridin)-2,5-cyclohexadien-1-ylidene]diethylamine, inner salt). "Practically do not insert" is meant that the composition for the oral cavity contains less than 0.05% by weight, preferably less than 0.001% by weight in the amount of dyes, sensitizing singlet oxygen. "Practically do not insert" may indicate that these dyes are not present at all, or that there is a minimum, equal to zero, the number of these dyes, and the minimum amount is usually 0,00001% by weight.

Composition for caring for the oral cavity of the present invention may also contain noncariogenic sweeteners sugar alcohols. Examples include erythritol, threitol, arabitol, xylitol, sorbitol, ribitol and maltitol. The standard range for the total content of sugar alcohols is 5%-45% by weight relative to the composition to care for the oral cavity. These sugar alcohols are preferably �astonaut in the liquid phase.

A composition for caring for the oral cavity of the present invention can be adjusted to a physiologically acceptable pH values in the range from 3.0 to approximately 6,0, preferably from about 4.0 to about 6,0, more preferably from about 4.0 to about a 5.0. This can be accomplished using standard buffers, such as buffers based on digitaltruth/monohydrocalcite; lactic acid/lactate or gluconic acid/gluconate. Exact desired pH of the composition to care for the oral cavity can be adjusted by adding acid (such as hydrochloric acid) or base (such as sodium hydroxide).

The compositions of the present invention, when they are a means for rinsing the mouth, are mostly transparent solutions, preferably do not contain suspended or settled solids may or may not have clouding.

Additional optional components for all types of compositions for caring for the oral cavity of the present invention can be, for example, as follows:

- sweeteners, particularly artificial sweeteners, such as saccharin, Acesulfame, neotame, cyclamate or Sucralose, natural high intensity sweeteners, such as thaumatin, stevioside or glycyrrhizin, and sugar alcohols, ex�title from C (3-5)a sugar alcohol such as sorbitol, xylitol, maltitol or mannitol. They may be present in amounts of 0%to -0.2%, preferably of 0.005%-0,1% by weight, relative to the composition;

- antibacterial agents and/or preservatives, such as chlorhexidine, triclosan, Quaternary ammonium compounds (such as benzalkonium chloride) or parabens (such as methyl or propyl paraben). The amount of antimicrobial agent in the composition to care for the oral cavity is usually from 0 to about 0.5%, preferably from 0.05 to 0.1% by weight relative to the composition to care for the oral cavity;

- emulsifiers or soljubilizatory, mainly in mixtures with the above-mentioned flavoring(s) and/or antibacterial agents, which often have low solubility in aqueous medium. Examples of these emulsifiers are natural surfactants (such as polyoxyethylene hydrogenated castor oil or fatty acids sugars), anionic surfactants (such as sodium lauryl sulfate), cationic surfactants (such as ammonium cations of the formula (I)) or zwitterionic surfactants. These surfactants or soljubilizatory can usually be present in amounts from 0% to 2%, preferably from 0.2% to 1.5% by weight relative�tive composition for caring for the oral cavity;

- thixotropic agents, such as soluble granules hydroxypropylmethylcellulose, hydroxyethylcellulose or Mucins, in an amount effective to give the composition for caring for the oral cavity thixotropic properties;

stabilizers, such as polyvinylpyrrolidone.

Additional optional components of compositions for caring for the oral cavity of the present invention, which are solid phase, such as in particular toothpastes or gels for teeth are abrasives, such as inorganic abrasives (for example, silicon oxide, aluminum oxide, calcium carbonate, calcium phosphate, calcium pyrophosphate or pyrophosphate of divalent tin) or organic abrasives (such as polyethylene, polyvinyl chloride, polystyrene, polycarbonate, copolymers of (meth)acrylates and other olefin monomers, polyamides, urea-formaldehyde resins, melamine-formaldehyde resins, phenol-formaldehyde resin, cured, powdered epoxy or polyesters).

Since it was found that the ions of divalent tin are stabilized in aqueous solution relative to the oxidation of dissolved nitrate, the purpose of the present invention is to provide this method of stabilization. The present invention also relates to a single-chamber container in which the composition is stored for �stroke for the oral cavity of the present invention, or stored and then dispersed. Since it was found that the ions of divalent tin substantially stabilized relative to the oxidation of these nitrates, it became possible to ensure a long stored compositions for caring for the oral cavity (e.g., within three weeks), containing ions of divalent tin and nitrate ions in the same component of the container; and it became possible to manipulate these compositions for caring for the oral cavity, not observing safety precautions relative to gaseous oxygen. Thus, it is possible, but not necessary, to subject the composition to degassing to remove dissolved oxygen gas before filling the storage container or container for the storage and dispersion of the present invention. Possible, but not necessary, to subject the ingredients for the composition to care for the oral cavity, such as in particular the abrasives used for toothpaste of the present invention, prior to degassing. These abrasives are quite porous and have a large specific surface area and can contain a noticeable amount of gaseous oxygen or air, which is difficult to remove after adding data abrasives for toothpaste. Thus, the care composition according�spine of the mouth of the present invention, after filling the storage container or container for the storage and dispersion of the present invention, may contain some amount of dissolved gaseous oxygen. Perhaps, but no longer need nor purging the storage container or container for the storage and dispersion of the present invention, nitrogen or other inert gas or discharge it before and/or after filling them in compositions for caring for the oral cavity of the present invention. Their only camera can completely fill composition for caring for the oral cavity of the present invention. Usually, however, their only camera not completely fill composition, but it also contains a gas phase. This gas phase can represent, as it is traditionally in the art, a protective gas atmosphere such as pure nitrogen, or vacuum. Preferably, however, the gas phase consisted of just the air.

Examples of single-chamber storage containers of the present invention are storage tanks, bottles, containers or receptacles, received manufacturing equipment or equipment for packaging. Examples of single-chamber containers for the storage and dispersion, containing particularly preferably, the means for rinsing the mouth or the solution for W�BOV present invention, are cylinders or bottles with cap in which the cap, that when removed from the cylinder, can simultaneously serve as a cap to highlight certain aliquots, for example, 10 ml of a composition for caring for the oral cavity. The walls of this container can be "layered" wall, which means that they consist of several layers of different materials to reduce permeability of oxygen; or they may be "single-layer" walls consisting of only one substance, such as plastic. Examples of single-chamber containers for the storage and dispersion, containing particularly preferably a toothpaste or tooth gel for the present invention are compressible tubes. All data containers are preferably closed when they contain the composition of the present invention. The closure can be, but need not be gas-tight. The closure is preferably impervious to liquids.

The present invention will be hereinafter further explained with the following non-limiting examples.

Examples

Examples 1-9: the Compositions of funds for mouthwash

In the following examples, the amount of all ingredients listed in the table are percentages by weight relative to all funds mouthwash.

Example 10: measurement of the amount in moles of ions of divalent tin dissolved in the aqueous phase of the composition to care for the oral cavity of the present invention

Applied a combined platinum electrode type 6.1204.310 Metrohm, Switzerland and the potentiometer 809 Titrando Metrohm, Switzerland. Calibration of the electrode was performed according to the instructions.

10,0000 g of the composition to care for the oral cavity accurately weighed (±0.1 mg) into a 100 ml container and was added 40 ml of water, 5 ml of 32% by weight HCl and is known aliquot v (in ml) of standard 0.05 M KI3solution, so that the iodine is added in excess relative to the tin with a nominal oxidation state +II, contained in the sample (normal volume for v is 5 ml).

The electrode is immersed in the sample solution, and the remaining iodine, have not yet been restored to the I-tin with nominal oxidation state +II was titrated back with standard 0.1 M Na2S203the solution to the equivalence point during the titration. The applied amount of Na2S203solution in ml used as v1.

The number of ions of divalent tin contained in the sample, in parts per million relative to compositions for the oral cavity, [Sn+II], was obtained as

[Sn+II]=593,45 (v-v1).

If the composition for the oral cavity consisted of an aqueous phase and did not contain any solids, collicello in moles of ions of divalent tin, dissolved in the above 10,0000 g of the composition to care for the oral cavity, Sn2+water.(in millimoles, obtained from the above [Sn+II]

Sn2+water.=8,425×10-5×[Sn+II].

Alternatively, if the composition for the oral cavity contains aqueous phase and solid matter, other 10,0000 g of the composition to care for the oral cavity was dissolved in 40,0000 g of water, was filtered, the filtered solids were dried to constant weight. The weight of the dried solids, in grams, denoted as ms. The amount in moles of ions of divalent tin dissolved in the aqueous phase above 10,0000 g of the composition to care for the oral cavity, Sn2+water.(in millimoles, obtained from the above [Sn+II]

Sn2+water.=8,425×10-6×(10-ms)×[Sn+II].

Example 11: Measurement of nitrate content in compositions for caring for the oral cavity of the present invention

1,0000 g±0.1 mg of the composition to care for the oral cavity accurately weighed in a container and water was added to obtain the total weight 20,0000 g±0.1 mg. Determination was performed by ion chromatography with 20 ál of the sample supernatant layer of the solution.

Instrument: Dionex IC 25 ion chromatograph with automatic sampler AS 50 eluent generator EG 40 with EluGen KOH Cartridge.

Column: Dionex Ion Pac AS 14, V. D. 4 mm, �Lina 250 mm with precolonial Ion Pac AG14A, V. D. 4 mm, length 50 mm.

Suppressor: Dionex Anion self-regulating suppressor, (ASRS-ULTRA II V. D. 4 mm).

Eluent: 40 mm potassium hydroxide solution. The alkaline eluent transformed, upon contact with the sample, all of the nitrates contained therein, in the nitrate anions.

Flow rate: 0.9 ml/min.

The amount in moles of nitrate anion {NO3-} obtained in 20 µl of the sample was evaluated from the area of the nitrate peak in the ion chromatogram of the sample using the calibration curve the amount in moles of nitrate relative peak area. This calibration curve is obtained by measuring under the same conditions of ion chromatography 20 μl aliquots of solutions containing known, but changing the amount in moles of potassium nitrate in a suitable range.

If the composition is to care for the oral cavity consists only of the water phase, and {NO3-} given in micromolar, the amount in moles of nitrogen in the above 1,0000 g of the composition to care for the oral cavity, measured in the form of nitrate, which is denoted as {N} (in millimoles), is directly equal to {NO3-}.

Alternatively, if the composition for the oral cavity consisted of a liquid (water) phase and solids (e.g., abrasives), other 1,0000 g of the composition to care for the oral cavity diluted to 20,0000 g of water, filtered and the filtered solids were dried to a post�permanent volume. The weight of the dried solids, in grams, is designated as ms. The amount in moles of nitrogen, measured in the form of nitrate (in millimoles) in the aqueous phase above 1,0000 g of the composition to care for the oral cavity, which is denoted as {N} (in millimoles), prepared from above {NO3-}

If we assume that the dissolved nitrates present in the water phase, contain NO3-each particle (or coordinated as anion), then the amount in moles of the data NO3-particles and, thus, the amount in moles themselves nitrate, is equal to {N}.

Example 12: Potentiometric determination of the concentration of fluoride in a composition for caring for the oral cavity of the present invention

Used fluoride selective electrode type 6.0502.150 Metrohm, Switzerland, pH/Ion-meter 692, Metrohm, Switzerland and Ag/AgCl reference electrode type 6.0750.100, Metrohm, Switzerland.

The required buffer solution to adjust the total ionic strength (TISAB), and it was received as follows: a solution of 160 mg of NaOH in 2 liters of water (solution 1); 25 g of 1,2-diaminocyclohexane-N,N,N',N'-vs acid, 290 g of NaCl and 285 ml of glacial acetic acid was dissolved in 2 liters of water (solution 2); then the solutions 1 and 2 were mixed and added to 5 liters of water.

Calibration of the fluoride-selective electrode was performed with�their instructions pH/Ion-meter.

1,0000 g + 0.1 mg of the composition to care for the oral cavity accurately weighed, in 50 ml plastic container, and supplemented with water to weight 20,0000 g + 0.1 mg and added to 20 ml of the above-mentioned TISAB buffer. Fluoride-selective electrode and a reference electrode immersed in the sample and the potential was recorded after 5 minutes according to the manual pH/Ion-meter. The concentration of fluoride in parts per million was calculated by multiplying the measured value of the response by 40 (the total dilution factor from the composition to care for the oral cavity to be measured of the sample) and dividing by the sample weight of the composition to care for the oral cavity in

Example 13: Stability of ions of divalent tin in the absence of nitrate and in the presence of 1 molar equivalent of 2-molar equivalent of nitrate

Received three aqueous solution of 211 mg SnF2in 400 ml of distilled water. Thus, these solutions contained the original 400 parts per million of dissolved Sn2+. The first solution did not contain potassium nitrate; the second solution was added 136 mg of potassium nitrate (= 1 molar equivalent relative to ions of divalent tin), and the third was added 272 mg of potassium nitrate (=2 molar equivalent relative to ions of divalent tin). Obtaining the solutions were implemented without any additional protection from air. The content of Sn2+measured obijnikavaries by titration with sodium thiosulfate, and a known excess of iodine (see example 10) and carried out in duplicate during the time interval of 21 days. The solutions were kept at room temperature in the dark. The change in the concentration of Sn2+(in parts per million) in these solutions over time is shown in the following table

Both solutions 2 and 3 were completely stable within experimental error within 21 days. In contrast, the solution of 1 was oxidized with an average speed of about 11 ppm Sn+2water.a day oxygen dissolved air in water solution. Therefore, we can conclude that one molar equivalent of added nitrate ions relative to divalent tin (solution 2) is also effective for stabilization of ions of divalent tin as a two molar equivalent of nitrate relative to ions of divalent tin (solution 3). The stoichiometric ratio of nitrate ions to divalent tin during the observed time interval of approximately 3 weeks, apparently, has no effect on the stabilization of nitrate ions.

Example 14: Stability of solutions of ions of divalent tin in various storage conditions

Received three aqueous solution with an initial content of ions of divalent tin 400 ppm (fluoride dvukhvalentnogo� tin). The first solution did not contain nitrate, but the second and third solutions contained 340 ppm nitrate (potassium nitrate, 1 molar equivalent of nitrate relative to ions of divalent tin). Table 1 shows in the second column on the left of the time dependence of the concentration of ions of divalent tin (in parts per million) in the first storage solution without degassing and without taking any other measures against oxygen under normal sunlight in a transparent bottle. The third left-most column of table 1 shows the time dependence of the concentration of ions of divalent tin in the second storage solution without degassing and without taking any other measures against oxygen under normal sunlight in a transparent bottle. Right column of table 1 shows the time dependence of the concentration of ions of divalent tin in the third storage solution without degassing and without taking any other measures against oxygen, but in the dark.

You can see that in the first solution, the amount of dissolved ions of divalent tin is reduced at least 21 days to approximately one tenth of the initial level (second column from left). In the second concentration of ions of divalent tin is reduced to half the original value during the period� storage for 21 days (the third column from the left). In the third solution was not observed decrease the concentration of ions of divalent tin in the storage period of 21 days (right column).

Example 15: Stability means mouthwash at different storage conditions

Received three rinses of the mouth, similar to the solution Merida funds mouthwash sold by the applicant of the present invention (the composition was similar to the composition of example 7 of the present invention). First means for rinsing the mouth did not contain nitrate, but the second and third means for mouthwash contained 340 ppm nitrate (potassium nitrate, 1 molar equivalent of nitrate relative to ions of divalent tin). Table 2 shows in the second column on the left of the time dependence of the concentration of ions of divalent tin (in parts per million) in the first storage means for mouthwash without degassing and without taking any other measures against oxygen under normal sunlight in a transparent bottle for 21 days. The third left-most column of table 2 shows the time dependence of the concentration of ions of bivalent tin second means for rinsing the mouth in the same storage conditions. Right column of table 2 shows the time dependence of the concentration of ions of divalent tin in the third storage means for p�of Ascania mouth in the dark, again not taking any precautions against oxygen gas, again in the storage period of 21 days. The values in table 2 in all cases represent mean values plus standard deviation of six independent measurements (see example 10).

The properties of these three funds mouthwash are similar to the properties of the three solutions of example 14.

1. Composition for the care of mouth cavity containing
(a) the aqueous phase;
(b) ions of divalent tin dissolved in the aqueous phase;
(c) nitrate dissolved in the aqueous phase; where the total content of nitrates is such that the amount in moles of nitrogen in the aqueous phase, measured in the form of nitrate, is 1.8-0.1 of the amount in moles of dissolved ions of divalent tin; and
(d) a flavoring.

2. Composition for the oral cavity according to claim 1, where in the aqueous phase of the total content of dissolved nitrates is such that the amount in moles of nitrogen in the aqueous phase, measured as free nitrate, is preferably of 1.5 to 0.75, more preferably 1.1 to 0.9 times the amount in moles of dissolved ions of bivalent tin.

3. Composition for the oral cavity according to claim 1 in which the aqueous phase contains 100 to 2,500 ppm, preferably 150-1000 ppm, more preferably 150-500 parts per Milli�n dissolved ions of bivalent tin.

4. Composition for the oral cavity according to claim 1, wherein the aqueous phase contains 50-2000 ppm of dissolved fluoride ions.

5. Composition for the oral cavity according to claim 1, containing an aqueous phase and a means for rinsing the mouth.

6. Single-chamber container for storage or single-chamber container for storing and dispersing, each of which contains a composition for caring for the oral cavity according to one of claims. 1-5.

7. Single-chamber container for storage or single-chamber container for storing and dispersing according to claim 6, where the composition is to care for the oral cavity contains dissolved oxygen gas.

8. Single-chamber container for storage or single-chamber container for storing and dispersing according to claim 6 or 7, further comprising a gas phase, where the gas is air.

9. The method of storage of the composition for caring for the oral cavity according to one of claims. 1-5, which includes stages
(a) filling composition according to one of claims. 1-5 in a single-chamber container for storing and dispersing, where
A1) a composition not dehaired before filling into the container, or
A2) the container is not purged with inert gas before filling composition, or
A3) the container does not drain before filling composition, or
A4) the container is not purged with inert gas after filling composition, or
A5) the container does not drain after �of zapolneniya composition;
(b) the closing of a container received in a); and
(c) the premises of the container obtained in (b), for storage.

10. A method according to claim 9, in which stage (a):
A1) a composition not dehaired before filling into the container, and
A2) the container is not purged with inert gas before filling out
composition, and
A3) the container does not drain before filling composition, and
A4) the container is not purged with inert gas after filling composition, and
A5) the container does not drain after filling composition.

11. The method of stabilization of ions of divalent tin dissolved in the aqueous phase, from oxidation comprising contacting the dissolved ions of divalent tin nitrate, provided that the total amount of nitrate is such that the amount in moles of nitrogen in the aqueous phase, measured as free nitrate, is 1.8-0.1 of the amount in moles of dissolved ions of bivalent tin.

12. A method according to claim 11, which used the total amount of nitrate is such that the amount in moles of nitrogen in the aqueous phase, measured as free nitrate, is preferably of 1.5 to 0.75, more preferably 1.1 to 0.9 times the amount in moles of dissolved ions of bivalent tin.

13. The use of nitrate for the stabilization of ions of divalent tin dissolved in the aqueous phase, from oxidation,where applicable, the total amount of nitrates is such that what amount in moles of nitrogen in the aqueous phase, measured as free nitrate, is 1.8-0.1 of the amount in moles of dissolved ions of bivalent tin.

14. The use according to claim 13, wherein the applied amount of nitrate is such that the amount in moles of nitrogen in the aqueous phase, measured as free nitrate, is preferably of 1.5 to 0.75, more preferably 1.1 to 0.9 times the amount in moles of dissolved ions of bivalent tin.

15. Composition for the care of mouth cavity containing
(a) ions of divalent tin;
(b) nitrate, in which the mole ratio of nitrate ions to divalent tin is 0.1 to 1.8; and
c) flavor,
where the composition is water.

16. Composition for the oral cavity according to claim 15, where the molar ratio of nitrate ions to divalent tin is preferably of 0.75 to 1.5, more preferably 0.9 to 1.1.

17. Composition for the oral cavity according to claim 15 or 16, where the ions of divalent tin contained in an amount of 100 to 2,500 ppm, preferably 150-1000 ppm, more preferably 150-500 ppm.



 

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FIELD: chemistry.

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17 cl, 3 dwg, 12 tbl, 106 ex

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FIELD: medicine, pharmaceutics.

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2 cl, 2 tbl, 8 ex

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12 cl, 1 tbl, 5 ex, 1 dwg

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41 cl, 11 ex, 11 tbl

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11 cl, 8 tbl, 12 dwg

FIELD: chemistry.

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9 cl, 1 tbl, 16 ex

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9 cl, 4 ex

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7 cl, 4 dwg, 5 tbl, 13 ex

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4 cl, 2 tbl, 1 ex

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2 ex, 18 dwg

FIELD: medicine.

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2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to methods of purification and health improvement of an organism. For this purpose therapeutic starvation for not fewer than 5 days in case of a 7-day programme and for not fewer than 7 days in case of a 9-day programme is carried out. The duration of a recovery period constitutes two days. Food intake is realised nine times per day each day both in the process of therapeutic starvation and in the recovery period. In the period of therapeutic starvation the first food intake includes bee products "APIGRANULES 2" in a dose of one teaspoon, "KHINAZI balm" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "APITOK" in a dose of one teaspoon, "Antihelm phyto" - one capsule and still mineral water - one glass. The second food intake includes a drink with ginger, lemon juice, garlic and mint, honey - one teaspoon and one glass of apple-carrot juice. The third food intake supposes an intake of bee products "APIGRANULES 2" in a dose of one teaspoon, "KHINAZI balm" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "Antihelm phyto" - one capsule and still mineral water - one glass. The fourth food intake includes a drink with ginger, lemon juice, garlic and mint, honey - one teaspoon and one glass of apple-carrot juice. The fifth food intake consists of tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The sixth food intake consists of bee products "APIGRANULES 2" in a dose of one teaspoon, "A-P-V" in a dose of one teaspoon, "Antihelm phyto" - one capsule and one glass of still mineral water. The seventh food intake includes tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The eighth food intake supposes an intake of tea black or green with ginger, one teaspoon of honey and one glass of apple-carrot juice. The ninth intake of food includes depressant tea, including mint grass, valerian root, fennel seeds, cumin seeds, epilobium or strawberry leaves and one glass of apple-carrot juice. In the recovery period in 1-st, 2-nd, 3-rd, 4-th and 6-th intakes of food the composition of products remains the same as in the process of starvation. For the fifth intake of food the patients take tea black or green with ginger, one teaspoon of honey and vegetable soup. For the seventh intake of food the patients take tea black or green with ginger, "MILK COCKTAIL WITH CHITOSAN". The eighth intake of food includes tea black or green with ginger, one teaspoon of honey, "APICAMPA" cereal. The ninth intake of food for the recovery period includes a baked apple, depressant tea. In addition, a number of procedures are carried out after each food intake during the period of therapeutic starvation and the recovery period. After the first food intake gymnastics "5 Tibetan pearls" is realised. After the second food intake exercises on training apparatuses, procedures of press-therapy, electrolypolysis and myostimulation are realised. After the third food intake exercises of therapeutic physical training or aerobics are performed. After the fourth food intake a rest in form of a walk, a halotherapy session, combined with a session of relaxation therapy are realised. After the fifth food intake a course of strip-plastic is carried out. After the sixth food intake massage by manual application with a peloid-based mixture or manual massage with honey is carried out. After the seventh food intake an infra-red sauna, shower, phytobath with medicinal herbs, honey, ginger, lemon juice is taken. After the eighth food intake a shower is taken.

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3 tbl, 7 ex

FIELD: medicine.

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4 dwg, 1 ex

FIELD: chemistry.

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EFFECT: preparations, obtained on the base of composition, possess higher transparency.

17 cl, 3 dwg, 12 tbl, 106 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing shea oil microcapsules. Said method is characterised by that shea oil is dissolved in dimethyl sulphoxide, the obtained mixture is dispersed in a suspension of sodium alginate in butanol in the presence of E472c, followed by addition of isopropanol and water, filtering and drying the obtained suspension of microcapsules, wherein the nucleus/polymer ratio in the microcapsules is 1:1 or 1:3.

EFFECT: invention provides a simple and fast process of producing shea oil microcapsules and increases mass output.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to using medicinal plant Gelsemium elegans Benth. and Datura metel L. blossom in preparing a therapeutic agent for eliminating or relieving acute and persistent withdrawal symptoms caused by taking a dependence-producing substance. The invention refers to pharmaceutical compositions (versions) for eliminating or relieving acute or persistent withdrawal symptoms caused by taking the dependence-producing substance, and containing Gelsemium elegans Benth. and Datura metel L. blossom in certain relations.

EFFECT: pharmaceutical compositions containing Gelsemium elegans Benth and Datura metel L. blossom are effective for the individuals suffering drug dependence.

15 cl, 12 ex

FIELD: medicine, oncology, amino acids.

SUBSTANCE: invention relates, in particular, to the development of an antitumor preparation based on natural substances. Invention relates to an amino acid preparation comprising at least one modified essential amino acid obtained by treatment of amino acid by ultraviolet radiation (UV) at wavelength 250-350 nm for 12-80 h at temperature 15-30oC or with ozone at temperature 15-25oC. The modified amino acid has no toxicity for health cells. Also, invention relates to a method for preparing such preparation. Invention provides the development of an antitumor preparation based on modified amino acids and expanded assortment of antitumor preparations being without cytotoxicity for normal cells.

EFFECT: valuable medicinal antitumor properties of preparation.

8 cl, 4 tbl, 2 dwg, 4 ex

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