GB1563828A - Composition for bucco-dental usage - Google Patents

Description

(54) NOVEL COMPOSITION FOR BUCCO-DENTAL USAGE (71) I, JEAN-JACQUES GOUPIL of 30 Avenue du President Wilson 94230 Cachan, France, of French Nationality, do hereby declare the invention, for which I pray that a patent may be granted to me, and the method by which it is to be performed, to be particularly described in and by the following statement :- The significant role played by dental plaque in buccodental health is well known. Dental plaque or bacterial plaque is an adherent coating derived from the saliva, rich in polysaccharides and mucoproteins, which rapidly forms a deposit on the gingival edge of the teeth, constituting a veritable culture center where infection and caries-generating microorganisms proliferate.

The thickness of this coating increases and the quality of the bacteria is modified with ageing.

The initial aerobic germs are gradually replace by a strict anaerobic flora, which increases the pathogenic power of the dental plaque on the gum.

In fact the presence of microorganisms which are living and developing in the absence of oxygen, such as Actinomyces viscosus, Ntaeslandi, Fusospirochetes vibrions, and Veillonella is considered to be responsible for acute or chrontc infections to the periodontium.

As a rule the saliva acts a natural antiseptic owing to its antibodies and enzymes and to the fact that it contains traces of dissolve oxygen as well as an oxidase and a peroxidase. But this is insufflclent and the saliva alone can not usually play a prophylactic and curative role in the infectious and inflammatory states of the bucco-lingual and bucco-gingival mucousa.

It is known that oxygen, present in the saliva in insufficient quantities, is a biogenetic element which is essential to the life of the cell and that it possesses an antimicrobal action.

The aim of the present invention therefore is to reinforce the natural functions of the saliva by effecting a local oxygenation of the buccal cavity by means of an influx of oxygen produced at the level of the tissues themselves, in order to obtain a tonic action increasing the tissues'defensive response, and an antimicrobal and deodorising action on the anaerobic flora of the dental plaque and if necessary on the lesions in the periodontium.

The present invention has as its object useful compositions for prophylaxis and the treatment of buccodental infections, characterised in that they are capable of liberating nascent oxygen at the level of the buccal cavity.

Chemical compounds which are capable of liberating nascent oxygen and which are compatible with the desired internal usage are referred to herein as "superoxygenated products"and are the superoxygenated salts such as the peroxy salts and the peroxides. These compounds are, however, usually unstable and often incompatible with the chemical nature of the excipients (presence of water, humidity, organic matters).

According to the present invention, the idea has been formulated of making compositions which contain simultaneously a stable superoxygenated body in a suitable excipient, and a product liable to release nascent oxygen from the superoxygenised body by placing it in contact but these two components being isolated from each other in the composition so that the overall product remains stable during packaging.

The present invention therefore provides a composition the prophylaxis and treatment of bucco-dental infections, characterised in that it comprises two active parts which are separately contained in pharmaceutically acceptable excipients and isolated one from another by the said excipients, the first active part consisting of a stable superoxygenated product (as herein defined) which is insoluble in water and the second active part consisting of a pharmaceutically acceptable mineral or organic acid and/or a pharmaceutically acceptable acid salt, and in that the two active parts are placed in contact by chewing the composition in the humid buccal cavity thereby reacting upon each other and liberating nascent oxygen.

Preferably the stable superoxygenated product which is insoluble inwater is chosen from metallic peroxides and peroxide salts which only liberate nascent oxygen at ambient temperature in the presence of an acid.

A superoxygenated product which is insoluble in water, which does not liberate its oxygen unless in the presence of an acid is chosen and it is coated in a suitable neutral excipient; a pharmaceutically acceptable acid or acidic salt is chosen, it is coated in a suitable excipient, and the two coatings obtained are juxtaposed. When the composition which has thus been obtained is subjected to mixing in the humid buccal cavity, the superoxygenated product and the acid come into contact and the chemical reaction which generates nascent oxygen is produced at the actual level of the gum and the tooth.

The selected excipients are advantageously chewirg gums which have the advantage of leading to masticatory gymnastics of some duration, permitting one on the one hand to achieve the desired chemical reaction of release of oxygen, and on the other hand to lead to a gingival massage and a mechanical excercise which is favorable for the good health and toning of the teeth and gums.

The gums used are the classical products used regularly in the composition of chewing gum.

The preferred stable peroxide which is insoluble in water, according to the present invention is magnesium peroxide. The product which is available in the commercial world contams 50% active and pure matter and is perfectly suitable for the operation of the present invention.

The products which are liable to release the oxygen produced from the peroxides and peroxy salts can be the acids or acidic salts which are pharmaceutically compatible with the desired internal usage, that is to say nontoxic. The acids currently used in pharmacy and in the food industry can be quoted, for example, phosphoric acid, tartaric acid, citric acid, malic acid, etc. The acidity of the acid part of the composition must be between pH = 2 and pH = 3. In these conditions the pH of the saliva which is normally of the order of 6.7 is advantageously rendered during mastication of the composition of the invention to a pH between 3 and 4.

The preferred excipients are of a gum and sugar base. The proportion of acid in the excipient of the acid part is between 5 and 8% in weight. The proportion of magnesium peroxide at 50/in the excipient of the super oxygenated part is between 5 and 10% in weight.

The invention is described in detail in the following examples given as an illustration and not a limitation to the invention.

The mass containing the peroxide or peroxy salt is prepared separately from the mass containing the acid product.

Mass containing the peroxide or peroxy salt The peroxide used is magnesium peroxide MgO2 at 50% active matter.

The proportion of magnesium peroxide in the mass of the excipient is between 5 and 10% inclusive in weight.

The excipient consists of a base which contains the gum and sugars. A composition without cariogenic sugars may be made by introducing a certain proportion of sorbitol.

Examples of composition and respective proportions are given below. The proportion ranges are given in percentages in weight in proportion to the total weight of the excipient.

Normal Formula Hypocariogenic Formula PortionRanges Constituents in % Portion Ranges in % Base 5-20 20-25 Massed glucose 20-30 0 Powdered dextrose 10-20 0 Icing 30-400 Sorbitol at 70% 0-5 15-25 Powdered Sorbitol 0 42 - 65 Powdered Mannitol 0 0 - 3 Ftavouring q. s. q. s.

The proportion of the base containing the gum can vary between 5% and 20% of the total weight of the excipient. It has been noted that there was an advantage in choosing a proportion near to 5% in order to facilitate the disintegration of the oxygen. The more the super oxygenated product is submerged in an excipient which is rich in gum, the more difficulties the oxygen has to release itself.

The following tables give examples of formulae of the peroxide part of the composition according to the invention.

Con sti tuents with sugars in weight % % % Mg0, 50% 5 5 10 10 Base 5 20 5 20 Massed glucose 30 25 30 25 Dextrose20101010 Icing sugar 35 40 40 30 Sorbitol 70% 5 0 5 5 q. s. q. s. q. s. s.

Hypocariogenic % constituentsin weight%%% 48 2 50% 5 10 10 Base 5 25 5 25 Sorbitol 70% 25 20 25 20 PowderedSorbitol 65 47 60 42 Mannitol 0 3 0 3 Flavouring q. s. q. s. q. s. q. s.

Mass containing the acid product The acid used is citric acid. The proportion of acid in the mass of the excipient is between 5 and 8% inclusive in weight.

The excipient consists of a base containing the gum and sugars. A composition without cariogenic sugars may be made by replacing them with a suitable quantity of sorbitol.

The examples below give the composition and the proportions respectively of the excipients which may be used in the present invention. The ranges of proportions are given in percentages in weight in relation to the total weight of the excipient.

NormalFormula Hypocariogenic Formula Ranges of Ranges of Proportion Constituents Proportion in % in % Base 20-30 20-25 Massed Glucose 20-25 0 Powdered Glucose 2-15 0 Icing Sugar 35-40 0 70% Sorbitol 0 2025 Powdered Sorbitol 0 40-50 Powdered Mannitol 0 0-3 Flavouring q. s. q. s.

In the acid part of the composition of the invention the proportion of gum is advantageously larger than in the super oxygenated part.

The base proportion containing the gum is between 20 and 30% inclusive. The following tables give examples of the formulae of the acid part.

Constituents % with sugars in weight % % % Citric acid5588 Base 20 30 20 30 Massed glucose 20 25 20 25 Powdered dextrose 15 5 12 2 Icing sugar 40 35 40 35 Flavouring q. s. q. s. q. s. q. s.

Hypocariogenic % constituents in weight % % % Citric acid 5 5 8 8 Base 20 25 20 25 Sorbitol 70aXc 25 20 25 20 Powdered sorbitol 47 50 44 47 Powdered mannitol 3 0 3 0 flavouring q. s. q. s. q. s. q. s.

The preferred formula for chewing-gum may be quoted as the formula below :

Superoxygenated Part Acid Part Constituents%% Base 26 Massedglucose 24 20 Powderedsaccharose 42. 6 40 Dextrose 20 7. 7 Magnesium peroxide 8. 4 0 Citric acid 0 6. 3 Flavouring q. s. q. s.

The preparatory process for the various formulae above, acid and superoxygenic, hypocariogenic or not, is the same; is produced in a mixer at a temperature not exceeding 60 C.

The base containing the gum is introduced by mixing in a Werner type mixer with a water bath maintained at 60 C, then, according to the formulae, the different constituents are progressively added, discerningly alternating the pastey, syrupy and powdery raw materials, in order to obtain a perfectly homogeneous paste after sufficient mixing, in which the active principles, peroxide in one case, acid in the other, are incorporated.

Each of the masses is passed separately into a press so that two rolls of the appropriate diameter are obtained which are then divided and shaped into slabs by joining and juxtaposition of the smallest contact area. The preferred relative proportions of each of the masses forming the specified unit are, for a total mass of 3.75 g, for the acidic mass 2.50 g and for the peroxide mass 1. 25 g, that is around 66% of acidic mass for 33% of peroxide mass.

This gives the relative proportions of the weights of acid and of peroxide present in the specified unit of : 0.156 g of citric acid for 0. 105 g of magnesium oxide at 50%.

By applying this percentage to the preferred formula given above, the following ranges of acidic and peroxidic concentration per specified unit are obtained.

Acid Content of the Acid content of the Acid acidic mass at 5% acidic mass at 87c Citric acid 0. 125 g 0. 200 g Tartaric acid 0.135 g 0.216 g Malic acid 0.120 g 0. 190 g Phosphoric acid 0. 100 g 0. 160 g De 1. 7 Peroxide content of Peroxide content of the peroxide mass the peroxide mass P eroxide, at 5% at 10% MgO, 50% 0.0625 g 0. 125 g The composition of the invention having thus been prepared, the active principe of each mass cannot react on the other until it is in the mouth, owing to the masticatory mechanical mixing. During storage the oxygen generator remains stable. Once in the mouth, after a few seconds'mastication, the release of oxygen begins as a reaction, owing to the aqueous salivory medium (the saliva contains approximately 99.5% water) of the acid on the peroxide.

The control of release of oxygen in the saliva is effected by a simple and quick method which allows the concentration of oxygen liberated in the saliva to be tested"in vivo", both qualitatively and quantitatively.

1. Principe The majority of peroxy salts, peroxides either in a neutral medium or in an acidic medium, liberate iodine in potassium iodide.

In the case of magnesium peroxide, after an acid attack and in the presence of the salivary water, hydrogen peroxide is produced according to the reaction MgO2 + H, SO4= H202 + MgSO4 which, upon contact with the mucouses readily liberates its oxygen, which can be shown by potassium iodide in the presence of dilute sulphuric acid (H202 + 2KI + H, S04 = 11 + K, SO, + 2H, 0) The quantity of displaced iodine is proportional to the quantity of displaced oxygen and allows its quantity to be determined.

2. Technique Since the saliva contains traces of dissolved oxygen as well as an oxidase and a peroxidase, an operation takes place in relation to a sample consisting of 10 ml of . filtered saliva, resulting from 3 minutes'mastication of the quantity of chewing gum containing the magnesium peroxide only. The same procedure takes place masticating this time the entire product-same quantity of gum with peroxide plus the acid gum-and after three minutes a volume x of saliva is collecte and filtered and 10 ml is taken in order to test the oxygen concentration.

The following constituents are incorporated simultaneously in two test tubes: Sample hbe Experimental Trwbe a) 10mlsalivaMgO2filtered a) 10 ml saliva MgO2 + filtered acid b) X drops N H, SO, b) X drops N H, SO, c) V drops KI solution at 20% c) V drops KI solution at 20% After shaking, the libration of iodine increases proportionally to the oxygen concentration.

The speed and intensity of the reaction, which reaches a maximum after half an hour, permits a very clear visual appreciation (brown colour) of the quantity of oxygen dissolve in the saliva after three minutes'mastication, in proportion to the sample. It is obvious that this rapid method only constitutes a test and that the classical analytic techniques maintain their entire value.

The compositions according to the present invention are extremely useful in prophylaxis and in the treatment of bucco-dental infections.

The presence of a chewing gum based excipient leads to masticatory gymnastics, which have a toning effect on the mucouses, a mechanical self-cleaning of the surfaces of the teeth and the gums, an increase in the salivary cleaning and it contributes to the protection of teeth against decay.

The release of nascent oxygen at the level of the gums themselves acts on the anaerobic flora of the dental plaque and gives the composition of the invention the following properties: bucco-dental antisepsis, deodorisation of the breath (particularly useful for heavy smokers), prophylaxis and treatment for improving infectious and inflammatory bucco-dental states such as gingivitis, stomatitis, pyprrhea, recession of the gums, prophylaxis of caries.

Claims (12)

1. WHAT I CLAIM IS- I. A composition for the prophylaxis and treatment of bucco-dental infections, characterised in that it comprises two active aprts which are separately contained in pharmaceutically acceptable excipients and isolated one from another by the said excipients, the first active part consisting of a stable superoxygenated product (as herein defined) which is insoluble in water and the second active part consisting of a pharmaceutically acceptable mineral or organic acid and/or a pharmaceutically acceptable acid salt, and in that the two active parts are placed in contact by chewing the composition in the humid buccal cavity thereby reacting upon each other and liberating nascent oxygen.
2. 2. A composition according to Claim l, wherein the stable superoxygenated product (as herein defined) which is insoluble in water is chosen from metallic peroxides and peroxide salts which only liberate nascent oxygen at ambient temperature in the presence of an acid.
3. 3. A composition according to Claim I or Claim 2, wherein the superoxygenated product is magnesium peroxide.
4. 4. A composition according to any of Claims I to 3, wherein the pharmaceutically acceptable acid is chosen from phosphoric, citric, malic, and tartaric acids.
5. 5. A composition according to any of Claims 1 to 4, wherein during mastication said composition brings the pH of the saliva from pH = 6.7 to 3 < pH < 4.
6. 6. A composition according to any of the preceding claims, wherein the part thereof based on a superoxygenated product contains between 5 and 10% by weight of superoxygenated product in proportion to the excipient chosen for the coating of said part.
7. 7. A composition according to any of the preceding claims, wherein the part based on an acid contains between 5 and 8% by weight acid in proportion to the excipient chosen for the coating of said part and has a pH of the order of from 2 to 3.
8. 8. A composition according to any of the preceding claims, wherein the excipients contain chewing gum.
9. 9. A composition according to Claim 7, wherein the excipient of the superoxygenated part of the composition contains between 5 and 20% by weight of a base containing a gum.
10. 10. A composition according to Claim 9, wherein the superoxygenated part of the composition contains between five and ten percent by weight of a base containing a gum.
11. I 1. A composition according to Claims 7,9 or 10, wherein the excipient of the acid part contains between 20 and 30 percent by weight of a base containing a gum.
12. 12. A composition as claimed in Claim I substantially as herein described.