Link:  Pharm/Biotech Resources

Title:  Stomatic composition

United States Patent:  6,919,070

Issued:  July 19, 2005

Inventors:  Rudin; Vsevolod Nikolaevich (Moscow, RU); Zuev; Vladislav Petrovich (Moscow, RU); Komarov; Vladimir Fedorovich (Moscow, RU); Melikhov; Igor Vitallevich (Moscow, RU); Minaev; Vladimir Vasillevich (Moscow, RU); Orlov; Andrei Yurlevich (Moscow, RU); Mishin; Anatoly Aleksandrovich (Moscow, RU); Bozhevolnov; Viktor Evgenievich (Moscow, RU)

Assignee:  Zakrytoe Aktsionernoe Obschestvo "OSTIM" (Moscow, RU)

Appl. No.:  529742

Filed:  October 17, 1997

PCT Filed:  October 17, 1997

PCT NO:  PCT/IB97/01634

371 Date:  June 24, 2000

102(e) Date:  June 24, 2000

PCT PUB.NO.:  WO99/20237

PCT PUB. Date:  April 29, 1999

A stomatic composition has particles of hydroxyapatite with an average particle size in length (l), width (d) and thickness (h) of: l from 0.2 μm to about 0.01 μm, d from about 0.1 μm to about 0.001 μm and h from about 0.1 μm to about 0.001 μm.

SUMMARY OF THE INVENTION

It is an object of the present invention to create a stomatic composition comprising compounds capable to cure microdefects of the basic substance of the dental enamel to combat caries developing (e.g. to provide an anti-caries activity) and to prevent the spread of such inflammable-destructive diseases of paradentium tissues as paradenitis and paradentosis, and also compounds capable to stimulate reparative osteogenesis processes and possessing high bioactivity and specific pharmacological activity.

It is a further object of the invention to create a stomatic composition being identic to the basic substance of the dental enamel in its substance contents and crystalline parameters, as the acid formed in the materials covering dental surfaces causes destruction of mineral hydroxyapatyte out of which enamel is composed and has a result due to which calcium ion loss occurs.

DETAILED DESCRIPTION OF THE INVENTION

The task surprisingly has been solved in a composition characterised in that it comprises particles of hydroxyapatite with an average particle size in length (l), width (d) and thickness (h) of: (l) from about 0.2 μm to about 0.01 μm, (d) from about 0.1 μm to about 0.001 μm, and (h) from about 0.1 μm to about 0.0001 μm with the particles of hydroxyapatite having a specific surface of hydroxyapatite from 100 m²/g to 150 m²/g.

A preferred composition having a more pronounced effect in view of the improvements obtained according to the invention comprises particles of hydroxyapatite with an average particle size in length (l), width(d) and thickness(h) of about 1=0,06 im +/-;50%,

d=0,015im +/-;50% and h=0,005 im +/-;50%.

A most preferred composition having a surprisingly superior effect in view of the improvements obtained according to the invention comprises particles of hydroxyapatite with an average particle size in length (l), width(d) and thickness(h) of 1 about 0,06 im, d about 0,015 im, h about 0,005 im.

Being introduced into the composition, HA possesses osteo-reparative properties and contains preferably about 100% Ca₁₀(PO₄)₆(OH)₂.

The specific surface of HA used in the composite advantageously is 100 to 150 m²/g.

U.S. Pat. No. 6,254,855 column 2, line 30 to column 4, line 35 which is based on WO 98/18719 (of the same inventor) are hereby incorporated by reference into the present application. The pages of U.S. Pat. No. 6,254,855 describe a method for producing a suspension of hydroxyapatite as described in this application.

The amount of HA present in the oral composition of the present invention is in the range of 0,1% to 50%, preferably from 0,1% to 25%, and most preferably from about 0,2% to 20% by weight of the oral composition.

The composition reacts to a change in the biochemical environment, for instance a rapid dissolvement of ultra finely divided HA occurs when the pH is decreasing, that provides an active utilization of Ca and PO₄-ions in the osteogenesis process: the size and configuration of the inventive crystals are adapted to the maximum to the dental enamel structure, which is mostly composed of HA that suggests its use in the osteo-reparative process as a building material.

The ultra finely divided HA possesses a high adhesive-sorption activity to the dental enamel and to microdefects on its surface, that favour the preventive measures preventing the spread of caries disease and also possesses a high sorption activity in respect to proteins and aminoacids of paradentium tissues, that stimulates an active preventive treatment of the inflammable-destructive diseases such as paradenitis and paradentosis.

Moreover, the stomatic composition of the present invention will contain other conventional ingredients in addition to HA possessing osteo-reparative properties, whose introduction into the composition depends on the form of he product. For instance, in the case of an oral product in the form of dentifrice paste, cream or gel, the product will comprise a liquid phase containing humectants and binding thickeners which act to maintain the particulate solid abrasive and HA crystals in the form of stable suspension in the liquid phase.

Surfactants and flavouring agents are also usual ingredients for various inventive embodiments of oral compositions.

The humectants usually used are glycerol or sorbitol. However, other humectants may be used according to the invention including polyethyleneglycol, propyleneglycol, lactitol and hydrogenated corn syrop. The amount of hunctant will generally range from about 0% to 85% by weight of product. The remainder of the liquid phase will consist substantially of water. The liquid phase can be water or a non-aqueous composition.

As binding agents and thickeners, various substances can be used such as sodium carboxymethylcellulose, sodium hydroxyethytcellulose and xanthan gum. Natural gum bindings can be included such as gum tragacanth, gum karaya of Irish moss, etc. Any mixture of binding agents and thickeners can be also used. The amount of bindings and thickeners usually included into the oral composition is in the range of 0% to 10% by weight of the oral composition.

Moreover, any materials as widely disclosed in the literature generally also might be used for the invention as surfactants, i.e. surfactants like sodium lauryl sulphate, dodecylbenzene sulphonate and sodium lauryl sarcosinate. Other anionic surfactants also can be used as well as cationic and amphoteric and non-ionic surfactants. Surfactants are generally present in the composition in the amount of 0% to 5% by weight of the oral composition.

Flavours that are generally used in the oral compositions are those based on oils of spearmint and peppermint and might be used for the invention. Examples of other flavouring materials used are menthol, clove, wintergreen, eucalyptus and aniseed. A preferable amount of flavours is from 0% to 5% by weight in respect to the oral composition.

As abrasive materials, silica dioxide of various modifications, aluminium oxide, calcium carbonate, dicalcium phosphate anhydrite, dicalcium phosphate dihydrate, sodium metaphosphate insoluble in water, and thereof mixtures may be used. The amount of abrasive materials ranges from 0.0% to 25%. The oral composition may include a wide variety of optional ingredients. These include antimicrobiaI and anti-plaque agents for example chlorhexidine or 2,4,4-trichloro-2hydroxy-diphenyl ether, or zink compounds (see EPA-161898) anti-tartar ingredients such as condensed phosphates, e.g. alkali et al pyrophosphates, hexametaphosphatesor polyphosphates (see U.S. Pat. No. 4,515,772 and U.S. Pat. No. 4,627,977) or zinc citrates (see U.S. Pat. No. 4,100,269), sweetening agents such as saccharin. Preservatives such as formalin, sodium benzoate. colouring agents (for instance titanium dioxide) or pH-controlling agents, such as acid base or buffer agents the oral composition may also include agents enhancing the gingivitis system of the mouth cavity and representing extracts of various natural plants such as urtica, millefolium, chamomilla hypericum, salvia, etc. in the aqueous or aqueous-alcoholic forms.

The stomatic composition depending on its form (dentifrice paste, cream or gel) is maintained in contact with the tissue of the oral cavity from 15 sec to 12 hours.

The following examples of dentifrice pastes and gel comprising synthetic ultra finely divided HA possessing osteo-reparative properties as described above illustrate the invention. Percentages and parts of the components are by weight.

Below-standing preferred embodiments of the invention are shown in its composition.

EXAMPLES N1 AND 2.

Toothpaste prepared from the following ingredients.

EXAMPLES N 3 TO 7

Toothpaste prepared from the following ingredients.
 

EXAMPLES N8 AND 9

Gel preventing paradenitis.

Claim 1 of 9 Claims

1. A stomatic composition characterised in that it comprises particles of hydroxyapatite with an average particle size in length (l), width (d) and thickness (h) of: (1) from about 0.2 μm to about 0.01 μm, (d) from about 0.1 μm to about 0.001 μm, and (h) from about 0.1 μm to about 0.0001 μm with the particles of hydroxyapatite having a specific surface of hydroxyapatite from 100 m²/g to 150 m²/g.

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