Compositions for treating teeth hypersensitivity

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to chemical-pharmaceutical industry and represents composition for oral cavity care, containing: a) at least one compound of formula M1-A-M2-B-M3, where: M1 and M3 represent Ti or titanium (Ti) oxide; A and B represent C2-C6 dibasic acid; and b) at least one orally acceptable solvent; where composition contains less than 5% of water.

EFFECT: invention provides creation of composition for treatment of teeth hypersensitivity, which effectively seals open dentin canals.

7 cl, 8 tbl, 12 dwg, 1 ex

 

Field of the INVENTION

The invention relates to such compositions for the treatment of sensitive teeth, which have a relationship to the dentin and effectively seal open dentinal tubules.

Background of the invention

Many people suffer from sensitive teeth, and this condition is often called increased dentinal sensitivity, which is a common problem among the adult population. It is defined as ongoing pain that occurs in the naked dentin, typically in response to chemical, thermal, tactile or osmotic stimuli that cannot be explained any other defects or diseases of the teeth. Erosion of the exposed surface (enamel) of the tooth and/or gingival recession often leads to exposure of dentinal tubules, creating lines of communication between the oral cavity and nerve fibers in the pulp. It has been shown in-vivo that the dentin has a gradient of pressure of liquid in the outward direction. Violation or increasing the current of fluid occurs in response to tactile, thermal (heat or cold) and osmotic stimuli (large amounts of sugar, etc.), and it is assumed, leads to the response of mechanoreceptors nerve fibers in the pulp, which is felt as pain. To treat sensitive teeth use�itary desensibilization nerves and substances occluding dentinal tubules. Special toothpastes containing potassium nitrate and/or biostable, amorphous calcium phosphate, etc., are regularly used by consumers suffering from increased dentinal sensitivity. Other occluding material that is also used to treat tooth sensitivity is potassium oxalate. However, none of these occluding substances is not completely effective to reduce dentinal sensitivity, since the effective blockage of the dentinal tubules is dependent on various variables. Thus, there remains a need for compositions for the treatment of sensitive teeth, which have high affinity to dentin and effectively sealed dentinal tubules.

Brief description of the invention

It is established that the above-mentioned goal can be achieved by selecting special compounds that form a protective barrier for teeth and/or effectively clogs Nude dentinal tubules, thereby reducing the sensitivity of the teeth. In some embodiments of the present invention proposed a composition for caring for the oral cavity that contains:

a) at least one compound of the formula I

M1-A-M2-B-M3 (I)

where: M1and M3represent independently a monovalent or divalent metal; M2a polyvalent metal or metal oxide; and A and B are independently selected from the group comprising C2-C6dibasic, and tribasic chetyrehskatnye acid;

(b) alternatively, flavoring;

c) alternatively, the sweetener;

(d) alternatively, a pH buffer; and

e) at least one orally acceptable solvent,

wherein the composition for caring for the oral cavity has a pH greater (or at least equal) to 2.0 (or approximately 2).

In other embodiments, the compositions of the present invention relate to compositions for caring for the oral cavity that contains:

a) at least one compound of the formula I

M1-A-M2-B-M3(I)

where: M1and M3represent independently a monovalent or divalent metal; M2a polyvalent metal or metal oxide; and A and B are independently selected from the group comprising C2-C6dibasic, and tribasic chetyrehskatnye acid; and

(b) at least one orally acceptable solvent;

where a composition according to codestone contains water.

In other embodiments, the compositions of the present invention relate to compositions for caring for the oral cavity that contains:

a) at least one compound of the formula I

M1-A-M2-B-M3(I)

where: M1and M3represent independently a monovalent or divalent metal; M2a polyvalent metal or metal oxide; and A and B are independently selected from the group comprising C2-C6dibasic, and tribasic chetyrehskatnye acid;

(b) at least one desensibilization; and

c) at least one orally acceptable solvent.

In another embodiment of the compositions of the present invention relate to a method for treating sensitive teeth comprising at least two sequential use on sensitive teeth composition containing:

a) at least one compound of the formula I

M1-A-M2-B-M3(I)

where: M1and M3represent independently a monovalent or divalent metal; M2a polyvalent metal or �xed metal; and A and B are independently selected from the group comprising C2-C6dibasic, and tribasic chetyrehskatnye acid; and

(b) at least one orally acceptable solvent,

moreover, the application should be made at intervals of not more than (or less than) 12 (or about 12 hours.

In other embodiments, the compositions of the present invention relate to a method of plugging dentinal tubules of teeth comprising at least two successive applying to the teeth a composition containing:

a) at least one compound of the formula I

M1-A-M2-B-M3(I)

where: M1and M3represent independently a monovalent or divalent metal; M2a polyvalent metal or metal oxide; and A and B are independently selected from the group comprising C2-C6dibasic, and tribasic chetyrehskatnye acid; and

(b) contact of the teeth with the composition for a period of at least (or greater than) 10 (or about 10) seconds

the tubules are plugged at least (or greater than) about 5%.

In other embodiments, the compositions of the present invention relate to a method Zach�of pariwana dentinal tubules of the teeth, comprising at least two sequential applying to the teeth a composition containing:

a) at least one compound of the formula I

M1-A-M2-B-M3(I)

where: M1and M3represent independently a monovalent or divalent metal; M2a polyvalent metal or metal oxide; and A and B are independently selected from the group comprising C2-C6dibasic, and tribasic chetyrehskatnye acid; and

(b) contact of the teeth with the composition in the presence of calcium for at least 20 seconds,

thus, the connection forms on the teeth or near the precipitate with calcium that at least (or greater than) 30% (or approximately 30%) of the formed precipitate remains on the teeth after dispersion with ultrasound for 2 (or about 2) minutes.

In other embodiments, the compositions of the present invention relate to a method for the deposition of precipitate on the teeth and/or dentinal tubules of teeth comprising at least two successive applying to the teeth a composition containing:

a) at least one compound of the formula I

M1-A-M2-B-M3(I)

where: M1and M3represent independently a monovalent or divalent metal; M2a polyvalent metal or metal oxide; and A and B are independently selected from the group comprising C2-C6dibasic, and tribasic chetyrehskatnye acid; and

(b) contact of the teeth with the composition in the presence of calcium for at least (or greater than) 20 (or about 20) seconds

where M2present in the precipitate at a concentration of at least (or greater than) 5% (or approximately 5%) of the deposited precipitate.

Brief description of the drawings

Fig.1 shows an image of the cut dentin treatment must be performed, using scanning electron microscope after 7 treatments with 0.5% composition of potassium oxalate and demonstrates a minimum precipitation of oxalate on the cut surface of the dentin and/or plugging dentinal tubules after treatment.

Fig.2 shows an image of the cut dentin treatment must be performed, using scanning electron microscope after 14 treatments with 0.5% composition of potassium oxalate and demonstrates a minimum precipitation of oxalate on the cut surface of the dentin and/or plugging dentinal tubules after clicks�processing.

Fig.3 is an image of the cut dentin treatment must be performed, using scanning electron microscope after 21 treatment with 0.5% composition of potassium oxalate and demonstrates a minimum precipitation of oxalate on the cut surface of the dentin and/or plugging dentinal tubules after treatment.

Fig.4 shows an image of the cut dentin treatment must be performed, using scanning electron microscope after 28 treatments with 0.5% composition of potassium oxalate and demonstrates a minimum precipitation of oxalate on the cut surface of the dentin and/or plugging dentinal tubules after treatment.

Fig.5 shows an image of the cut dentin treatment must be performed, using scanning electron microscope after 7 treatments with 0.5% composition of potassium oxalate, titanium oxide, indicating the strong precipitation of oxalate of titanium oxide on the cut surface of the dentin and/or virtually complete blockage of dentinal tubules after treatment.

Fig.6 shows an image of the cut dentin treatment must be performed, using scanning electron microscope after 14 treatments with 0.5% composition of potassium oxalate, titanium oxide, indicating the strong precipitation of oxalate of titanium oxide on the cut surface of the dentin and/or FAK�automatically complete blockage of dentinal tubules after treatment.

Fig.7 shows an image of the cut dentin treatment must be performed, using scanning electron microscope after 21 treatment with 0.5% composition of potassium oxalate, titanium oxide, indicating the strong precipitation of oxalate of titanium oxide on the cut surface of the dentin and/or virtually complete blockage of dentinal tubules after treatment.

Fig.8 shows an image of the cut dentin treatment must be performed, using scanning electron microscope after 28 treatments with 0.5% composition of potassium oxalate, titanium oxide, indicating the strong precipitation of oxalate of titanium oxide on the cut surface of the dentin and/or virtually complete blockage of dentinal tubules after treatment.

Fig.9 shows an image of the cut dentin treatment must be performed, using scanning electron microscope after treatment with a composition comprising the same ingredients that were used for the treatment of dentin slices in Fig.1-8, but they contain no potassium oxalate or potassium oxalate, titanium oxide and there is no difference in the precipitation on the cut surface of the dentin and/or blockage of the dentinal tubules before and after treatment composition.

Fig.10 shows an image of the cut dentin treatment must be performed, using scanning of electroneuromyography after 28 treatments composition includes the same ingredients that were used for the treatment of dentin slices in Fig.1-8, but they contain no potassium oxalate or potassium oxalate, titanium oxide and there is no difference in the precipitation on the cut surface of the dentin and/or blockage of the dentinal tubules before and after treatment composition.

Fig.11 shows obtained by scanning electron microscope image of a cut dentin treatment must be performed, who has been 28 treatments composition containing 0.5% potassium oxalate (composition B), and then the dispersion with ultrasound for 2 minutes using an ultrasonic disperser under normal impulse.

Fig.12 presents obtained by scanning electron microscope image of a cut dentin treatment must be performed, who has been 28 treatments composition containing 0.5% potassium oxalate titanium oxide (composition D), and then the dispersion with ultrasound for 2 minutes using an ultrasonic disperser at normal pulse. Compare these images of the dentin slices in Fig.11 and 12 with the corresponding images after 28-day treatment shown in Fig.4 and 8, illustrate the increased stability of the precipitates formed by composition with potassium oxalate titanium oxide, in comparison with real-time d�Oia, containing potassium oxalate.

Detailed description of the invention

The compositions according to the present invention can include, consist of, or consist primarily of essential elements and features of the invention described in this document and any additional or used for the selection of ingredients, components or features of the invention described herein.

All documents are fully incorporated herein by reference, is included only in the part in which they do not conflict with these technical requirements.

All percentage concentrations, parts and ratios are based on total weight of the composition according to the present invention, unless otherwise indicated. All these weight related to listed ingredients are based on the active level and, therefore, do not include carriers or by-products that may be included in commercially available materials, unless otherwise indicated.

The term "safe and effective dose" as used herein means that dose of a compound or composition of local or systemic action, sufficient to bring significant benefits, for example to cause a decrease teeth sensitivity, but low enough to avoid serious side effects, i.e. to provide a reasonable rela�oszenia the risk/benefit within the sound judgment of a specialist in this field.

The terms "blocked" or "clogging" as used herein means that the open holes in the dentinal tubules or openings in the dentinal tubules partially, substantially or completely closed.

The compositions of the present invention contain at least one compound of the formula I

M1-A-M2-B-M3(I)

where: M1and M3represent independently a monovalent or divalent metal; M2a polyvalent metal or metal oxide; and A and B are independently selected from the group comprising C2-C6dibasic, and tribasic chetyrehskatnye acid, as an option - C2-C4dibasic or tribasic acid, as an option - C2-C3dibasic or tribasic acid or as an option - C2dibasic acid.

Examples of suitable monovalent metals include among other things Na, K and Li; is Na or K; or as an option - K.

Examples of suitable divalent metals include among other things, Mg, Ca, Sr, Ba and Zn; as an option - Mg, Ba and Zn; or as an option - Mg.

Examples of suitable divalent metals include among other things, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Tc, Re, Os, Ir, Hg, Ce, Sn, Eu, Yb, Pa, and U; to�to option - Ti, Sn, Mn and Fe; or as an option - Ti.

Examples of suitable metal oxides include, among other things, the corresponding oxides of Ba, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Tc, Re, Os, Ir, Hg, Ce, Sm, Eu, Yb, Pa, and U; as an option, the corresponding oxides of Ba, Ti, Sr, Sn, Zr, Mn and Fe; as an option, the corresponding oxides of Ba, Ti, Sr, Sn, Zr; or, alternatively, the corresponding Ti oxide.

In some embodiments, M1and/or M3independently selected from the group consisting of Na, K and Li. As an option, and M1and M3represent K.

In some embodiments, M2selected from the group consisting of Ti, Sr, Sn, Mg, Ca, Mn, and Zr. Alternatively, M2selected from the group consisting of oxides of Ti, Sr, Sn, Mg, Ca, Mn, and Zr. In other embodiments, M2selected from the group consisting of Ti or Ti oxide.

Examples of suitable dibasic acids include inter alia, oxalic acid, succinic acid, pyruvic acid, diglycolic acid, glutaric (i.e. pentanedionato) acid, 3,5,5-trimethylpentanediol acid, hexandiol acid, 3,5,5-trimethylhexanoic acid, 2,4,4-trimethylhexane acid, decandido acid, undecadienal acid, dodecadienol acid, 1,4-cyclohexanecarbonyl acid, cyclohexane-1,4-diuksusnoi acid, maleic acid, Tarakanova acid, Iacono�Yu acid, fumaric acid, oxalic acid, terephthalic acid, phthalic and isophthalic acid, hydroxypentanal acid, malonic acid, adipic acid, sabotinova acid and tartaric acid, optionally, oxalic acid, succinic acid, or, alternatively, oxalic acid.

Examples of suitable tribasic acids include inter alia citric acid.

Examples of suitable chetyrehspalnyh acids include inter alia 1,1,2,2-atinternational acid; 1,1,2,3-propanetricarboxylic acid; 1,1,4,4-butanetetracarboxylic acid; 1,2,4,5-benzotriazolyl acid and ethylenediaminetetraacetic acid, or alternatively, 1,1,2,2-atinternational acid.

In some embodiments, the compound of formula I is selected from the group consisting of potassium oxalate, titanium oxide (KTO) (also known as titanium oxalate, potassium), potassium citrate, titanium oxide, titanium-calcium oxalate and potassium calcium titanium oxalate, alternatively, potassium oxalate, titanium oxide (KTO), potassium citrate, titanium oxide, or alternatively, potassium oxalate, titanium oxide (KTO).

The compositions of the present invention include, based on the total weight of the composition from 0.01% (or about 0.01%) to 10.0% (or approximately 10.0 per cent); alternatively, from 0.1% (or 0.1%) to 7.0% (or about 7, percent); or, alternatively, from 1% (or approximately 1%) to 5.0% (or about 5.0% of at least one compound of formula I.

In some embodiments, compositions comprise an orally acceptable solvent. Orally acceptable solvents include inter alia water; ethanol; n-propanol; polyhydric alcohols such as glycerin, sorbitol and polyethylene glycol; and any mixtures thereof and can be present in concentrations from about 0.1% to about 99.9 percent, alternatively from about 1% to about 90%, or alternatively from about 10% to about 75% of the orally acceptable solvent.

In some other embodiments, the compositions according to the present invention substantially does not contain water. The term "substantially free" as used herein means a composition with a water content of less than 5% (or approximately 5%); alternatively, at least 3% (or approximately 3%); as an option - less than 1% (or approximately 1%); as an option - less than 0.5% (or about 0.5%); as a variant - zero (or anhydrous).

In some embodiments, the compositions of the present invention have a pH value equal to at least 2 (or approximately 2); alternatively from 2.5 (or 2.5) to 7.0 (or approximately 7.0); as an option from 3.5 (or about�individual 3,5) to 6.0 (or approximately 6,0); or, alternatively, from 3.2 (or approximately 3.2) to 4.5 (or approximately 4.5).

In some embodiments, the pH for the compositions of the present invention create (app is buffering) using traditional acid-salt systems. Conventional buffer systems include phosphoric acid and phosphate salt or citric acid and sodium citrate. Suitable for use in the present invention combinations of acids/acid salts include citric acid-sodium citrate, phosphoric acid-metafictionally sodium, primary sodium acid phosphate, secondary sodium acid phosphate, acetic acid-sodium acetate, succinic acid-sodium succinate, Aconitum acid-aconitate sodium and benzoic acid-benzoic acid sodium at doses up to about 1% weight percent; alternatively, from about 0.05 percent weight percent to 0.75% weight percent of the composition; and/or, alternatively, about 0.1% percent by weight to 0.5% weight percent of the composition.

Additional components

In some embodiments, compositions according to the present invention further comprise other desensibilization that reduce the sensitivity of teeth. Examples of additional desensibilization include among other things, potassium citrate, potassium chloride, nitrate �Aliy, citric acid, salts of citric acid, strontium chloride, and mixtures thereof. Also suitable are biologically active glass materials described in U.S. patents 5735942; 5891233; 6086374; 6244871; 6338751; 6365132, every one who, by virtue of this reference is fully included in the present application, and phosphopeptide described in U.S. patents 5015628; 5981475; 6448374; 6780844, each of which in virtue of this reference is fully included in the present application.

In some embodiments, additional desensibilization is potassium nitrate. In some embodiments, the additional concentration of desensitizer to reduce tooth sensitivity is 0.1% (or about 0.01%) to 10% (or approximately 10%); alternatively, from 0.1% (or 0.1%) to 8% (or approximately 8%); or, alternatively, from 1% (or approximately 1%) to 7% (or approximately 7%) by weight of the composition.

The sources of fluoride ions are well known as anti-caries active substances in the compositions for the care of the oral cavity and may also be included in compositions according to the present invention. Fluoride ions are present for this purpose in a number of compositions for caring for the oral cavity, specifically in toothpastes. These toothpastes are described, for example, in U.S. patents 3538230; 3689637; 3711604; 3911104; 3935306; 4040858,every one who, by virtue of this reference is fully included in the present application.

The application of fluoride ions to the tooth enamel protects the teeth from decay. As sources of soluble fluoride in the compositions of the instant action, you can use a wide range of materials containing fluoride ions. Examples of suitable materials containing fluoride ions as described in U.S. patent No. 3535421 issued by Briner et al. October 20, 1970, and U.S. patent No. 3678154 issued to Widder et al. July 18, 1972, both patents are entirely incorporated in this application by reference. In some embodiments, sources of fluoride ions for the purposes of the present invention include dottorato tin, monitoringstate, sodium fluoride, potassium fluoride and ammonium fluoride. In other embodiments of included sodium fluoride. In some embodiments, the compositions of the present invention provide from about 50 to 10,000 ppm; alternatively, from about 100 to 3000 parts per million of fluoride ions in aqueous solutions that contact the surface of the teeth.

In the compositions of the present invention can also be used phosphates. Among the phosphates include pyrophosphates, polyphosphates, polyphosphonates and mixtures thereof. Pyrophosphates are among the products that are best known for use in dentistry. The ion source of pyrophosphato coming to the teeth, serve pyro�osbornia salt. Protostoria salts suitable for use in existing compositions include protostoria salt displacing metals, protophormia salt tetralone metals and mixtures thereof. Dihydrogenphosphate dynatree (Na2H2P2O7), tetrasodium pyrophosphate (Na4P2O7) and potassium pyrophosphate (K4P2O7in non hydrated and hydrated form are the preferred types of compounds. In some embodiments, the pyrophosphate salt is tetrasodium pyrophosphate.

Pyrophosphate salts are described in more detail in the encyclopedia Kirk & Othmer, Encyclopedia of Clinical Technology Third Edition, Volume 17, Wiley-Interscience Publishers (1982), fully incorporated into the present application by reference, including all references contained in the encyclopedia Kirk & Othmer. Additional substances that prevent the formation of Tartar, include pyrophosphates or polyphosphates disclosed in U.S. patent 4590066; polyacrylates and other polycarboxylates, for example, disclosed in the U.S. patents 3429963; 4304766; and 4661341; polyepoxide the succinates (salt of succinic acid), for example, disclosed in U.S. patent 4846650; ethylenediaminetetraacetic acid, disclosed in British patent No. 490384 of 15 February 1937; nitrilotriacetic acid and related compounds disclosed in U.S. patent 3678154; polyphosphonate disclosed in the us Pat�max USA 3737533; 3988443; and 4877603; all of these patents are fully incorporated in this application by reference. In some embodiments, the phosphates include pyrophosphates, potassium and sodium; sodium tripolyphosphate; diphosphonates, such as ethane-1-hydroxy-1,1-diphosphonate, 1-azacycloheptane-1,1-diphosphonate and diphosphonates linear Akilov; tricalcium phosphate, linear carboxylic acids; double sodium citrate-zinc and mixtures of any of the above phosphates. In some embodiments, the phosphate is tricalcium phosphate plus sodium lauryl sulfate, as described in application for U.S. patent 20080187500 A1, published August 7, 2008 Karlinsey, Robert L., and this publication is fully incorporated into the present application by reference.

Phosphates included in compositions according to the present invention, may be present in concentrations from about 0.01% to 10%; optionally about 0.1% to 7%; and optionally from about 0.5% to 5%.

In some embodiments, the compositions of the present invention include essential oils. Essential oils are volatile aromatic oils that are synthetic or derived from plants by distillation, extraction or extraction. Essential oils usually pass the smell or flavor of the plant from which they are derived. When using�Denmark in the composition means for brushing your teeth according to the present invention the essential oils have protivovirusnym action. Some essential oils also act as flavoring agents. Essential oils according to the present invention include but not limited to, thymol, menthol, methyl salicylate (wintergrove oil) and eucalyptol.

Thymol, with the chemical formula 5-methyl 2-(1-methylethyl) phenol, is obtained from the essential oil of Thymus vulgaris Labiatae and Monarda punctata Labiatae. Thymol is a white crystalline powder with an aromatic odor and taste. Thymol is soluble in organic solvents but only slightly soluble in deionized water.

Menthol is isolated mainly from Mentha arvensis oil. In commercial form menthol is available in the form of crystals of L-menthol, obtained with the help of the technological process, including the cooling oil. Fractional distillation of mint oil, which typically contains from about 40% to 65% of menthol, represents another important source of menthol. Also available synthetic sources of L-menthol.

Eucalyptol obtained from a eucalyptus tree. With camphor smell and cooling taste, this essential oil is then combined with other essential oils such as menthol, in the composition of medicinal substances with a sweet filler for the purpose of giving the latter treatment modality. The combination of menthol with eucalyptol widely used. Specifically, preferred embodiments of the ISPO�of isawanya combination with menthol eucalyptol include according to the present invention for cleaning teeth, such as toothpastes or gels.

Methyl salicylate is the main ingredient in many essential oils, accounting for approximately 99% of the oil in Wintergreen (Gaultheria procumbens) and birch globalistas (Betula lenta). Methyl salicylate, which has a characteristic refreshing flavor, is widely used in liquids for mouth rinses, chewing gums and other oral and pharmaceuticals.

The number of essential oils that can be used in the compositions according to the present invention may be from 0.001 (or about 0,001 to 1% (or approximately 1%) of thymol, from about 0.001 (or about 0,001 to 1% (or approximately 1%) methyl salicylate, from about 0.001 (or about 0,001) to 15% (or approximately 15%) of menthol, and from about 0.001 (or about 0,001 to 1% (or approximately 1%), eucalyptol, and these doses have clinical efficacy, necessary to suppress the development of gingivitis. As a variant, the composition according to the present invention contains approximately of 0.064% thymol, about is 0.060% methyl salicylate, about 0,042% menthol and about 0,092%, eucalyptol, and these doses have clinical efficacy, necessary to suppress the development of gingivitis.

Instead of or in addition to essential oils compositions of the present invention may also containing�ü an effective amount of an antimicrobial agent, selected from the group including zinc salts of polyphenols (e.g., triclosan), tin fluoride, chlorhexidine, hexetidine, sanguinarine, benzalkonium chloride, salicylanilide, domiphen bromide, cetylpyridinium chloride, tetradecylbenzene chloride (TPC), N-tetradecyl-4-ethylpyridine chloride (TDEPC), octenidine, delmopinol, Octafinal and other piperidine derivatives, preparations Nizina, drugs with ions of zinc/tin, antibiotics such as Augmentin, amoxicillin, tetracycline, doxycycline, minocycline, and metronidazole, and analogs and salts of the above preparations, essential oils, including eugenol, geraniol, carvacrol, citral, hinokitiol, catechol, hydrogen peroxide, metal salts of chlorite, or any combination of the foregoing.

Can also be used a mixture of any of the above substances.

The compositions according to the present invention can also contain a surfactant selected from anionic, nonionic, amphoteric, betaine, cationic surfactants and mixtures thereof. Suitable anyonne surfactants include alkylsulfate, alkylamine sulfates, sulfosuccinates, isetionate, acylamide, alcelaphinae the carboxylates and alkyl phosphates in which the alkyl group has from about 6 to about 30 carbon atoms. Suitable katianne surfactants include cetylpyridinium chloride. The total dose su�of factant(s) which are suitable for use in compositions according to the present invention can be based on the total weight of the whole composition from about 1% to about 50%; alternatively from about 5% to about 40%; or alternatively from about 8% to about 25%.

Types of nonionic surfactants that are suitable for use in the present invention include ethoxylate acids or amides, ethoxylate of monoglycerides, ethoxylate ether of sorbitol fatty alcohols and alkyl polyglycoside. These nonionic surfactants can be used in the compositions according to the present invention in doses based on the total weight of the composition, from about 0.0% to about 30%, for example from approximately 0.1% to approximately 20% and approximately 0.1% to approximately 15%.

Classes of amphoteric surfactants that are suitable for use in the present invention include alkylenediamines, alcelaphinae (mono - or di-), alkylamidoamines (mono - or di-), alkylamidoamines (mono - or di-), N-alkyl-β-aminopropionic acid, alkylaminocarbonyl and the phosphorylated imidazoline. These amphoteric surfactants can be used in the compositions of the present invention in doses based on the total weight of the composition, from about 0.1% to about 2%, for example, from about 0.1% to about 15% and from approximately 0.1% to approximately 10%.

Types of betinov, which are suitable for use in the present invention include alkylbetaine, alkylamidoamines, alkylsulfanyl and alkylimidazole in which the alkyl group has from about 6 to about 30 carbon atoms, with the preferred number of carbon atoms from about 10 to about 14. These betamovie surfactants can be used in the compositions of the present invention in doses based on the total weight of the cleaning composition, from about 0.1% to about 15%, for example from about 0.1% to about 10% and from approximately 0.1% to approximately 8%.

Classes of cationic surfactants that are suitable for use in the present invention include alkyl Quaternary amines (mono-, di - or tri-), benzyl Quaternary amines (for example, cetylpyridinium chloride), essential Quaternary amines, ethoxylated Quaternary amines, alkyl amines and mixtures thereof in which the alkyl group has from 6 to 30 carbon atoms, with the preferred number of carbon atoms from about 8 to about 22. These cationic surfactants can be used in the compositions of the present invention in doses DOS�bathrooms on the total weight of the composition, from about 0.01% to about 20%, e.g., from about 0.05% to about 15% and from approximately 0.1% to approximately 10%.

The compositions according to the present invention may also include one or more additional ingredients, including but not limited to, thickening agent, humectants, chelating agents, and additives such as flavorings, preservatives and the like.

Commercially available thickening agents, which are capable of imparting the appropriate viscosity to the compositions suitable for use in the present invention. Examples of suitable thickeners include, among other things mono or dietary 1) polyethylene glycol of formula: HO-(CH2CH2O)zH, where z is an integer from about 3 to about 200; and 2) fatty acids containing from about 16 to about 22 carbon atoms; esters of fatty acids and ethoxylated polyols; ethoxylated derivatives of mono and diapirov fatty acids and glycerol; hydroxyethylcellulose; alkylaryl; hydroxyethylcellulose and mixtures thereof. Preferred thickeners include ether of polyethylene glycol, are preferred over distearate PEG-150 delivered by Stepan Company, Norfield, Illinois, USA, or Comiel, S. p.A. Bologna, Italy, under the trade name "PEG 6000 DS".

In some embodiments, is�the performance of the thickeners can be included in compositions according to the present invention at concentrations of from about 0.01% to about 10%, optionally from about 0.1 to about 5%, or alternatively from about 0.2% to approximately 2.0%.

Commercially available humectants suitable for use in the present invention because of its moisturizing properties, in addition to the use as potential solvents, as noted above. The humectant may be present in an amount of from about 0% to about 10%, preferably from about 0.5% to about 5%, and more preferably from about 0.5% to about 3% based on the total weight of the composition. Examples of suitable humectants include, among others: 1) water soluble liquid polyols selected from the group including glycerin, propylene glycol, hexyleneglycol, butyleneglycol, dipropyleneglycol and mixtures thereof; 2) polyalkylene glycols of the formula: HO-(R”O)b-H, where R” is alkylenes group containing from about 2 to about 3 carbon atoms, and b represents an integer from about 2 to about 10; 3) ether of polyethylene glycol and methylglucose formula CH3-C6H10O5-(OCH2CH2)c-OH, where c is an integer from about 5 to about 25; 4) urea; and 5) mixtures thereof, the preferred humectant is glycerin.

� some embodiments, the humectants can be included in compositions according to the present invention at concentrations from about 0.1% to about 40%, alternatively, from about 1.0 to about 30%, or alternatively from about 5% to about 25%.

In some embodiments, the chelating agents can be included in compositions of the present invention. Examples of suitable chelating agents include those agents that are able to protect and preserve the compositions of the present invention. As an option, in addition to potential use as chetyrehosnuju acid in the compound(s) of formula I, ethylenediaminetetraacetic acid ("EDTA") can be used as a chelating agent. In some embodiments, the chelating agent is tetranitro EDTA, commercially available Dow Chemical Company, Midland, Michigan, under the trade name "Versene 100XL", which may be present in amounts, based on the total weight of the composition, and ranges from approximately 0 to approximately 0.5%; and alternatively from about 0.05% to approximately 0.25%.

Suitable preservatives include benzoic acid sodium and Polysorbate and are present in the composition in an amount, based on the total weight of the composition may range from about 0 to about 0.2%, and preferably from about 0.05% to about 0,10%.

The compositions of the present invention can be in the form of fluids are�her funds and mouthwash, means for brushing your teeth, pastes, such as toothpastes, powders, such as dentifrices, gels, pills, medicinal lozenges, microcapsules, sprays, lacquers or strips (such as remineralizers strips disclosed in U.S. patent 20070128130 Kropt et al., issued June 7, 2007, which is fully included in the present application by reference, either peroxide or superoxide strips for teeth whitening, as disclosed in U.S. patent 20080003248 Georgiades et al., issued January 3, 2008, and in U.S. patent 6949240 issued WEBERS et al. September 27, 2005, both of the patent document is fully incorporated in this application by reference), coatings for such strips and the like. Speaking of the above listed funds, the compositions of the present invention can also be applied using conventional devices to care for the oral cavity, including toothbrushes, floss, interdental floss, dental spray guns or sprayers and dental syringe pen, described in U.S. patent 20080044363, Montgomery, issued February 21, 2008, which is fully included in the present application by reference.

The compositions of the present invention may also be suitable as a coating or as impregnating substances for impregnation dental devices selected from the group consisting of toothbrushes (manual or mechanical), a slit�monk toothbrush, interdental thread, toothpicks and the like. The compositions of the present invention may also be useful as coatings or impregnating substances for dental composite materials, dental fillings and the like.

The method of use of compositions of the present invention

The invention illustratively disclosed herein, can be applied in the absence of any component, ingredient, or step which is not disclosed here, specifically.

In some embodiments, the compositions of the present invention are applied to sensitive teeth by using at least two sequential applications; as an option with at least (or more than) and 7 (approximately 7) consecutive applications; or as an option - 14 (or approximately 14) consecutive applications; or -21 (or approximately 21) consecutive applications; or as an option - 28 (approximately 28) consecutive applications.

When applied to the sensitive tooth (or teeth) in some embodiments, the composition is left in contact with sensitive teeth for a period of at least (or greater than) 10 (or about 10) seconds; - 20 (or about 20) seconds; as an option 30 (or about 30) seconds; as an option 50 (or about 50) seconds; or as your request�iant - 60 (or about 60) seconds.

In some embodiments, the time interval between consecutive applications should be no more than (or less than) 12 (or about 12 hours; alternatively - 8 (or about 8) hours; as a variant - 4 (or about 4) hours; as a variant - 2 (or about 2) hours, or, alternatively, one (or approximately one) hour.

In some embodiments, the compositions of the present invention is applied to sensitive teeth so that the compounds of formula I form on the teeth such deposits of precipitates containing calcium, at least (or greater than) 5% (or approximately 5%) of the dentinal tubules of the teeth occluded; as an option - 25% (or approximately 25%) occluded dentinal tubules; as an option - 40% (or approximately 40%) occluded dentinal tubules; as an option - 60% (or approximately 60%) occluded dentinal tubules; as a variant - 75% (or approximately 75%) occluded dentinal tubules; as an option 85% (or approximately 85%) of the dentinal tubules occluded; or as an option - 95% (or 95%) of the dentinal tubules occluded.

In some embodiments, M2formula I is present in the deposition of precipitate formed by the compound(s) of formula I and calcium in the late�entrale at least (or greater than) 5% (or approximately 5%); as an option - 10% (or approximately 10%), as an option - 20% (or approximately 20%); or, alternatively, 35% (or approximately 35%).

After the formation of the teeth is provided such stability adjournment(s) precipitate containing the compound of formula I and calcium that at least (or greater than) 5% (or approximately 5%); as a variant - 30% (or approximately 30%); as a variant - 35% (or approximately 35%); as a variant - 50% (or approximately 50%); as a variant - 75% (or approximately 75%); or, alternatively, 90% (or approximately 90%) remains on the teeth after ultrasonic treatment for 2 (or about 2) minutes using ultrasonic sonicator CD-4800 digital ultrasonic cleaner [CD-4800] produced by Best And More Electronics [Shenzhen] Co., Ltd., China) at the normal pulse frequency of about 42 kHz. At this frequency, sonicator usually provides more force than in normal use ultrasonic or manual toothbrushes. The phrase "deposition of(I) precipitates" as used herein means the deposition, which is formed on the teeth and/or clog the tubules of the teeth by precipitation of the compound(s) of formula I with calcium present in the fluids of the oral cavity after application of compositions containing compound(I) of formula I, as disclosed in the present claims�. To initiate or facilitate the formation of deposits(th) precipitates with compound(s) of formula I may also separate the addition of calcium in the oral cavity in the form of water soluble salts of calcium before or after the addition of the compositions of the present invention containing compound(I) of formula I. Examples of water-soluble calcium salts include among others calcium chloride, calcium nitrate, calcium bromide, dihydrogenphosphate calcium and mixtures thereof. The amount of water-soluble calcium salts must exceed, in molar proportions, the amount of compound(s) of formula I contained in the compositions of the present invention.

Below are some examples to further illustrate the invention and the method of its implementation.

Examples

The compositions of the present invention described in following examples illustrate specific examples of the practical application of the compositions of the present invention, but are not limited to these examples. Other modifications can be made by a person skilled in the art without departing from the scope of the present invention and a retreat from its essence.

Preparation of the compositions of funds for mouthwash

Compositions were prepared liquid funds mouthwash and evaluated the effectiveness of clogging the dentin compositions based on potassium ox�Lata titanium oxide ("KTO"). The method of preparation is described as follows.

In a container for the preparation of the composition was added and mixed until dissolved water, KTO, benzoic acid and poloxamer. After dissolution poloxamer added alcohol, n-propanol, sorbitol, water and benzoic acid sodium, then mixing them to dissolve. Checked the pH and found it to be equal to approximately 4.2.

To this mixture was added menthol, thymol, eucalyptol, methyl salicylate, mixing until a homogeneous condition. After a homogeneous solution was added sodium saccharin and FDC green No. 3 (1% solution, adjustable according to the degree of purity). Drug composition was mixed until uniform. The final pH of the composition was equal to 4.2.

The composition of the liquid formulations of funds mouthwash are presented in table 1.

Preparation of samples of dentin and artificial saliva

The efficiency of trapping of dentin compounds and compositions based on the KTO was demonstrated as follows:

The dentin slices (polished and untreated) were obtained from Dental product testing, unit Thermametric technologies Inc., Indianapolis, Indiana, USA. The dentin slices were protravlivanie for complete removal of smear layer (or a layer of sawdust formed by the cutting of the dentin or enamel) by propityvanie� dentin slices in 6% citric acid during the time interval to 2 minutes then were rinsed and subjected to sonication in deionized water.

Potassium oxalate (KO) was obtained from Fluka, St. Louis, Missouri, USA, (lot No. 430462/1). Potassium oxalate, titanium oxide (KTO), dihydrate was obtained from Sigma, St. Louis, Missouri, USA (lot # 51740).

Artificial saliva was prepared using the traditional equipment and protocols used in the laboratory according to the traditional method and had a composition shown in table 2:

Table 2
IngredientConcentration
Sodium chloride0,381 g/l
The dihydrate of calcium chloride0,213 g/l
Primary acid phosphate potassium0,738 g/l
Potassium chloride1,114 g/l
Gastric mucus2.20 g/l
pH=7,0

Control and analysis of method comparison

All samples of the etched dentin slices (total of 10) were arranged in random order and section�NY five treatment groups. In order to control blockage of tubules and surface deposition under the action of the compositions KTO were performed scanning electron microscopy (SEM) and chemical analysis of surfaces using electronic dispersion spectroscopy (EDS). Five treatment groups included:

Group 1: treatment with composition A

Group 2: treatment with composition B

Group 3: treatment with composition C

Group 4: treatment with composition D

Group 5: treatment with composition E (i.e. not KTO and not KO)

The processing scheme for groups 1-5 were as follows:

1. Processing samples of slices in each group with 20 ml of the appropriate therapeutic compositions with shaking for 30 seconds.

2. Rinse samples of slices in each group using deionized H2O within 1 minute.

3. Dip samples of slices in artificial saliva between treatments, and a day was made not more than two treatments.

4. Repeat steps 1-3 until you run 28 treatments.

5. The dentin samples were analyzed using SEM and/or EDS after 7, 14, 21 and 28 treatments. Before analysis the sections were rinsed with deionized H2O for 3 minutes and subjected to air drying for analysis by SEM.

Data obtained by analysis of EMF for 2 samples of slices (slice 1 and slice 2), are summarized in tables 3 and 4 presented lower�.

Table 3
EMF after 7 treatments
CompositionS (%)K (%)P (%)Ca (%)Ti (%)
ASlice 139,05,412,543,1X
Slice 237,96,213,542,4X
BSlice 116,99,317,256,6X
Slice 217,79,718,054,6X
CSlice 15,712,0 21,734,626,0
Slice 24,612,419,635,228,2
DSlice 1X11,628,028,332,1
Slice 2X12,525,7a 33.328,5
ESlice 148,2Xof 13.038,8X
Slice 247,7X13,239,1X

Table 4
EMF after 14 treatments
Composite� S (%)K (%)P (%)Ca (%)Ti (%)
ASlice 130,68,412,548,5X
Slice 229,59,011,350,2X
BSlice 16,813,516,060,5X
Slice 28,7the 15.418,457,5X
CSlice 11,810,2to 27.426,326,7
Slice 22,111,729,4 25,828,4
DSlice 1X18,722,126,432,8
Slice 2X20,917,730,0of 31.4
ESlice 147,5X13,638,9X
Slice 248,1X12,739,2X

After 7 treatments the samples treated with 0.5% KTO (composition D) demonstrate the highest degree of affinity to the etched dentin surface, as is evident from the decrease of the percentage of sulphur found in the EMF readings (usually EDS spectra etched surfaces of dentin contain about 45-50% sulfur). The percentage detected reduced sulfur as sulfur on the surface of the cut dentin coating�recover or masked by deposition on the surface, occur after treatment with composition KTO. Although sulfur is not completely absent, its percentage decreases dramatically in the sample treated with 0.1% KTO (composition C). After 14 treatments, the percentage of detected sulfur remains low in the sample treated with 0.5% KTO (composition D), and decreased more significantly in the sample treated with 0.1% KTO (composition C).

Scanning electron microscopy performed on these samples indicate the beginning or the formation of surface precipitation on the surface of the dentin samples treated with composition D, the degree of blockage of tubules increases with the number of treatments.

To conduct semi-quantitative comparison of the effectiveness of blockage of the dentinal tubules of various compositions performed SEM analysis, image classification and calculation of blockage of tubules in percent. Methods and calculations for data analysis, SEM, image classification and receive a percentage of occluded tubules were performed in accordance with methods described in the work

West NX, Addy M, Hughes, J. (1998) J. Oral Rehabil, 25, 885 and confirmed by the methods described in the work of Lee SY, Kwon HK, Kim BI (2008) J. Oral Rehabil, 35, 847. On the basis of the above-described data analyses SEM was calculated percentage of occluded tubules for composite� A-E 7, 14, 21 and 28 treatments, are shown in table 5 below.

Table 5
The percentage of occluded tubules
Composition7 treatments14 treatments21 treatments28 treatments
A5%15%25%40%
B20%35%45%60%
C25%35%55%75%
D40%65%85%>99%
E0%5%5%5%

Comparing the analyzed data to Miroshnikov obtained before and after treatment using scanning electron microscopy at different points BP�menny cycle times and at different concentrations KTO (as shown in table 5 and Fig.1-4 (processing KO), 5-8 (processing KTO) and 9-10 (treatment without oxalate)), clearly demonstrates the increased surface precipitation leading to increased blockage of tubules and increase its efficiency.

Definition of substantively for deposits formed precipitates

To determine substantively (or the ability of the precipitate to remain on the surface of the dentin) precipitate KTO deposited on samples of dentine slices in the loop processing, the following tasks have been completed. Slices of dentin treated with composition B (0,5% KO) and composition (D (0,5% KTO), after 28 treatments were subjected to dispersion with ultrasound for 2 minutes (the time may be approximately 2 minutes) using ultrasonic sonicator CD-4800 with normal heart rate (approximately 42 kHz). Comparing images processed by sonication slices (Fig.11 and 12) with the corresponding images after 28-day treatment shown in Fig.4 and 8, demonstrates that the deposition of precipitates obtained by KTO, proved to be more resistant to sonication (approximately 92% of the precipitate obtained by KTO, remained on the sample cutoff) than the precipitates obtained by KO (approximately 38% of the precipitate obtained by KO, remained on the sample slice), indicating that the deposition of precipitates obtained with POM�means of KTO, provide enhanced stability in comparison with the deposits of precipitates obtained by KO. In the absence of theoretical restrictions can be assumed that this improved the stability of the deposits of precipitates formed by the compounds of formula I, not only provides an increased degree of reduction of tooth sensitivity, but longer duration of the effect.

In tables 6 and 7 shows examples of F-O illustrating additional examples of liquids for rinsing of a mouth on the basis of the compositions of the present invention. Examples F-O can be prepared using the methods described above for examples A-E

Table 8 shows examples of P-S, illustrating the means for brushing your teeth on the basis of the compositions of the present invention. Examples of P-S can be prepared using conventional mixing technology tools for cleaning teeth. Example S illustrates the anhydrous dentifrice as variant implementation of the present invention.

Table 8
IngredientsPQRS
(weight percent %)(weight percent %)(weight percent %)(weight percent %)
Water15,0012,5010,00---
99.7% glycerin, USP23,0023,0023,0028,00
Carboxymethylcellulose sodium0,600,600,600,60
Sorbitol (70%)24,9624,9624,9629,96
Saccharin sodium0,200,200,200,20
Sucralose0,800,800,800,80
Sodium fluoride0,240,240,240,24
The silicon hydroxide20,0020,0020,0020,00
Nitrate potassium0,005,005,005,00
The titanium oxalate, potassium (KTO)5,002,505,005,00
Synthetic amorphous silicon dioxide6,506,506,506,50
Lauroylsarcosinate sodium1,001,001,001,00
Lauryl glucoside1,001,001,001,00
Cocamidopropylbetaine0,500,500,500,50
Flavoring1,201,201,20
Total100,00100,00100,00100,00

1. Composition for caring for the oral cavity that contains:
a) at least one compound of the formula I
M1-A-M2In M3(I),
where:
M1and M3are To;
M2represents Ti or titanium oxide (Ti);
A and b are C2-C6dibasic acid; and
(b) at least one orally acceptable solvent; where the composition comprises less than 5% water.

2. A composition according to claim 1, wherein the compound of formula I is potassium oxalate, titanium oxide.

3. A composition according to claim 1, wherein the composition is in the form of liquid or rinses mouth for cleaning teeth, paste, powder, gel, tablets, medicinal lozenges, microcapsules, strips or coatings to the strip.

4. A composition according to claim 1, wherein the composition is a coating or impregnating substance for dental devices selected from the group consisting of toothbrushes, the bristles of the toothbrush, interdental filaments and toothpicks.

5. A method of treating sensitive teeth comprising the step of contacting with sensitive teeth compositional�according to claim her 1 for at least 10 seconds.

6. Composition for caring for the oral cavity that contains: a) at least one compound of the formula I
M1-A-M2In M3(I),
where:
Μ1and Μ3are To;
Μ2represents Ti or titanium oxide (Ti);
A and b represents C2-C6dibasic acid; and
(b) at least one additional desensibilization; and
c) at least one orally acceptable solvent; where the composition comprises less than 5% water.

7. A composition according to claim 6, where the additional desensibilization selected from the group consisting of potassium citrate, potassium chloride, potassium nitrate, citric acid, salts of citric acid, chloride of strontium, bioactive glass materials, phosphopeptides and mixtures thereof.



 

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9 cl, 4 ex

FIELD: medicine.

SUBSTANCE: 0.5% dihydroquercetin is instilled into the rectum of a patient with temporary colostomy until he/she starts feeling intestinal inflation. The procedure is performed twice a day, daily up until the restorative surgery.

EFFECT: method reduces a rate and a degree of colitis manifestations by the local antioxidant, anti-inflammatory effect, unfolding the excluded colon.

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to cosmetic industry and represents a cosmetic product which has the following composition in each specific case calculated using the total composition: at least 0.1 wt % of at least one hydrophilic softening product, 2 to 40 wt % of at least one surfactant specified in a group of fatty alcohol ethoxylates, fatty alcohol ether sulphates and salts of sulphated and/or sulphonated fatty acids, 30 to 90 wt % of water, 1 to 30 wt % of one or more abrasives with the total ingredients making 10%; the product contains at least 0.1 wt % of at least one hydrophilic softening product with a hydrophilic-lipophilic balance ≥8 and flour thermally treated by saturated vapour; the flour is natural flour of shell or kernels characterized by a light absorption at wave length 660 nm of less than 1 prepared by reacting the flour 1 g with a solution prepared of water 10 ml and 0.1% aqueous methylene blue 1 ml.

EFFECT: invention provides the lower effect on viscosity, possesses the high cleaning action and high tolerability.

16 cl, 5 ex, 3 tbl

Foaming detergent // 2543713

FIELD: chemistry.

SUBSTANCE: invention relates to aqueous foaming composition for hands, containing castor oil maleate in amount from 0.1 to 1% of composition weight, PEG-7 glyceryl cocoate in amount from 0.05 to 0.3% of composition weight, glycerol in amount from 0.5 to 6% of composition weight, PEG-6 of glycerides of caprylic/capric acid in amount from 0.05 to 1% of composition weight and SAS. Glycerol is present in amount greater than amount of castor oil maleate or glyceryl cocoate PEG-7, and said composition has viscosity from 1 to 100 mPa·s (sP).

EFFECT: obtaining aqueous foaming composition for hands, which is capable of providing foam stability, has lower tendency for flowing and soiling when applied and creates more pleasant sensations for skin.

7 cl

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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