Title:
Mouth cleansing preparation
United States Patent 3886265
Abstract:
The use of at least one ene-diol compound having at most 6 carbon atoms and selected from the group consisting of ascorbic acid, isoascorbic acid, dihydroxymaleic acid, dihydroxyfumaric acid, and reductic acid, or salts or derivatives thereof, and an oxidizing agent in the form of a water soluble peroxide selected from the group consisting of alkali metal percarbonate, alkaline earth peroxide, carbamide peroxide, and hydrogen peroxide in the manufacture of preparations effective against bad breath, preferably in the form of peroral dosage units.
Inventors:
Evers, Hans Christer Arvid (Sodertalje, SW)
Fischler, Max (Enskede, SW)
Fischler, Max (Enskede, SW)
Application Number:
05/375615
Publication Date:
05/27/1975
Filing Date:
07/02/1973
View Patent Images:
Export Citation:
Assignee:
Astra Lakemedel Aktiebolag (Sodertalje, SW)
Primary Class:
International Classes:
A61K8/22; A61K8/67; A61K9/00; A61K9/46; A61Q11/00; A61K8/19; A61K8/30; A61K7/16
Field of Search:
424/49-58
Primary Examiner:
Huff, Richard L.
Attorney, Agent or Firm:
Brumbaugh, Graves Donohue And Raymond
Claims:
We claim
1. A composition effective in combatting bad breath consisting essentially of an ene-diol compound selected from the group consisting of ascorbic acid and isoascorbic acid, said compound being present in an amount of at least 10 mg, and an oxidizing agent in the form of a water soluble peroxide selected from the group consisting of alkali metal percarbonates, alkaline earth peroxides and carbamide peroxide, wherein said oxidizing agent is present in an amount corresponding to active oxygen in an amount of at least 1 mg., in each case per peroral dosage unit.
2. A composition according to claim 1 wherein the ene-diol compound is ascorbic acid.
3. A composition according to claim 1 wherein the ene-diol compound is ascorbic acid present in an amount at least 10 mg and the oxidizing agent is sodium percarbonate present in an amount corresponding to active oxygen in an amount of at least 1 mg, in each case per peroral dosage unit.
4. A composition according to claim 1, wherein the oxidizing agent is sodium percarbonate.
5. A method of inhibiting bad breath by administering perorally at least 10 mg. of an ene-diol compound selected from the group consisting of ascorbic acid, isoascorbic acid, and salts or derivatives thereof, together with an oxidizing agent in the form of a water soluble peroxide selected from the group consisting of alkali metal percarbonates, alkaline earth peroxides, carbamide peroxide, and hydrogen peroxide, in an amount corresponding to active oxygen in an amount of at least 1 mg., in each case per peroral dosage unit.
1. A composition effective in combatting bad breath consisting essentially of an ene-diol compound selected from the group consisting of ascorbic acid and isoascorbic acid, said compound being present in an amount of at least 10 mg, and an oxidizing agent in the form of a water soluble peroxide selected from the group consisting of alkali metal percarbonates, alkaline earth peroxides and carbamide peroxide, wherein said oxidizing agent is present in an amount corresponding to active oxygen in an amount of at least 1 mg., in each case per peroral dosage unit.
2. A composition according to claim 1 wherein the ene-diol compound is ascorbic acid.
3. A composition according to claim 1 wherein the ene-diol compound is ascorbic acid present in an amount at least 10 mg and the oxidizing agent is sodium percarbonate present in an amount corresponding to active oxygen in an amount of at least 1 mg, in each case per peroral dosage unit.
4. A composition according to claim 1, wherein the oxidizing agent is sodium percarbonate.
5. A method of inhibiting bad breath by administering perorally at least 10 mg. of an ene-diol compound selected from the group consisting of ascorbic acid, isoascorbic acid, and salts or derivatives thereof, together with an oxidizing agent in the form of a water soluble peroxide selected from the group consisting of alkali metal percarbonates, alkaline earth peroxides, carbamide peroxide, and hydrogen peroxide, in an amount corresponding to active oxygen in an amount of at least 1 mg., in each case per peroral dosage unit.
Description:
The present invention relates to the use of an oxidizing agent together with at least one ene-diol compound having at most 6 carbon atoms, in the manufacture of preparations which are effective against bad breath.
The object of the present invention is to eliminate fetor ex ore, bad breath, without influencing the natural micro flora of the mouth.
Bad breath is a great social handicap to many people and therefore there is a demand for preparations which can eliminate it. Although frequent tooth brushing is carried out it has been shown that bad breath persists. The flavoring and aroma agents present in tooth paste, such as menthol, mask bad breath for a period immediately following brushing, but this is temporary, because the bad breath is caused primarily by methyl mercaptan formed in the mouth cavity, and also to a less extent by dimethylsulphide, ethanol and n-propanol.
Other mouth-washes intended to be used against bad breath are known. However, such mouth-washes do not reduce the amount of e.g. methyl mercaptan but only mask it.
It has been previously known (see U.S. Pat. No. 3,065,139) to use bactericide preparations containing an ene-diol compound, a peroxide, and a metal ion catalyst for infections in the mouth cavity, such as gingivits and stomatitis. The present inventors have shown that such preparations have a certain effect against bad breath by reducing the amount of methyl mercaptan. Such preparations have, in order to obtain an acceptable antibacterial effect, been used in an amount of 170 mg calculated on the active compounds for each administration.
It has now surprisingly been found possible to reduce the amounts of compounds creating bad breath by preparing and using mouth cleansing preparations containing a peroxide and an ene-diol compound, preferably without a metal ion catalyst.
According to a preferred embodiment of the invention ascorbic acid and sodium percarbonate are used.
As suitable ene-diol compounds besides ascorbic acid, isoascorbic acid, dihydroxymaleic acid, dihydroxyfumaric acid, or reductic acid (2,3-dihydroxy-2-cyclopenten-1-one), may be used, or salt thereof, such as the sodium, potassium or calcium salt, or derivatives thereof such as the esters of fatty acids having 2-18 carbon atoms, such as the acetate, palmitate or stearate. As a peroxide besides sodium percarbonate, other alkali percarbonates, alkaline earth peroxides, carbamide peroxide (carbamide crystallized with H 2 O 2 instead of H 2 o), and hydrogen peroxide may be used.
Furthermore, in the preparation of solid preparations, inert filling agents and lubricants known per se are used.
Such filling agents are e.g. mannitol, sodium bicarbonate, tartaric acid and starch.
As lubricants, magnesium stearate, and paraffin may be used.
Binding agents used in the granulation of the compounds prior to the manufacture of e.g. tablets and the like are e.g. polyvinylpyrrolidone and gelatin.
If a special flavor is desired, flavoring agents may be added. Suitable flavors are spearmint, peppermint, menthol, spiced fruits, orange, lemon, lime, etc.
In the utilization of a preparation according to the present invention, one obtains a considerable reduction in the amount of compounds creating bad breath, a weak interference with the micro flora of the mouth cavity and moreover a cheaper and more storage stable product than previously known products.
The preparation ready for use in the form of tablets, pellets or granules is chewed, whereby a reaction between the two active components, the ene-diol compound and the oxidizing agent is obtained and a destruction of the bad smelling compounds takes place. The amount of active oxygen produced per occasion of administration is at least 1 mg, preferably 3 mg, and the amount of the ene-diol compound is at least 10 mg. The administration takes place 3 to 4 times per day. The preparation may also be manufactured as soaking tablets, lozenges, chewing gum or in aerosol or spray form. Tablets may be chewed, or dissolved in water to produce a mouth wash. The amount of ene-diol compound should not exceed 200 mg per occasion of administration and the amount of peroxide should thus not exceed 20 mg as active oxygen.
The present invention will be described more in detail below with reference to the examples given.
EXAMPLE 1
Chewable tablets were prepared containing Ascorbic acid 100 mg Sodium percarbonate corresponding to active oxygen 9 mg Sodium bicarbonate 50 mg Tartaric acid 80 mg Cetyl pyridinium chloride 0.05 mg Flavoring agents q.s. Mannitol ad 750 mg
The tablets were prepared by granulating the mannitol and the sodium percarbonate with a solution of gelatin in water. The sodium bicarbonate was granulated with a 50% solution of polyvinylpyrrolidone in ethanol. Thirdly, the ascorbic acid and tartaric acid were granulated with a solution of polyethylene glycol in ethanol. After drying, the different granulates were passed through an oscillating granulator where the granulates are mixed with flavoring agents. Finally, tablets were pressed in a common tablet punching machine.
EXAMPLE 2
Effervescing granules were prepared and packed in dosage units, whereby each dose contained
Ascorbic acid 10 mg Sodium percarbonate corresponding to active oxygen 1 mg Sodium bicarbonate 4 mg Tartaric acid 5 mg Polyvinyl pyrrolidone 0.02 mg Flavoring agents q.s. Coloring agents q.s. Mannitol 0.03 g
The granules were prepared in accordance with the tablets above, excluding the tableting step.
EXAMPLE 3
Effervescing tablets were prepared containing
Ascorbic acid 50 mg Sodium percarbonate corresponding to active oxygen 5 mg Tartaric acid 5 mg Sodium bicarbonate 25 mg Starch 10 mg Polyvinyl pyrrolidone 2.5 mg Flavoring agents q.s. Coloring agents q.s.
The tablets were prepared in accordance with the tablets of Example 1.
EXAMPLE 4
Chewable tablets were prepared containing
Isoascorbic acid 35 mg Sodium percarbonate corresponding to active oxygen 3.5 mg Sodium bicarbonate 20 mg Tartaric acid 5 mg Cetyl pyridinium chloride 0.02 mg Flavoring agents q.s. Mannitol ad 300 mg
The tablets were prepared in accordance with the tablets of Example 1.
The reducing effect of the above preparations on bad breath has been studied in vitro. Morning saliva from a number of tested persons was incubated at 36°C for 5 to 12 hours until great amounts of methyl mercaptan had been formed, whereupon the saliva was divided into samples each containing 3 ml in 20 ml injection flasks, which were deep-frozen in a Dewer-vessel using CO 2 -ice. The different compared preparations were then added in the amounts stated by opening the capsule of the deep-frozen flasks, introducing the preparation, rapidly removing the air by sweeping with nitrogen gas, and closing the flasks again. Thereupon, the flasks were thawed and after 20 minutes at 36°C a sample was taken and analyzed on a gas chromatograph.
The results are given in Table 1 below, where the values for A, a control sample; B, a preparation according to the invention, based on ascorbic acid as described above in Example 1; C, a preparation according to the invention containing in addition 0.2% of a heavy metal catalyst in the form of copper sulphate calculated on the ene-diol compound; and D, a known mouth-wash containing menthol as masking agent are given. In Table 2 a comparison between a control sample A, and the preparations B and C and in addition, E, a liquid antibacterial iodine composition having oxidizing properties is given. The results are given in mm peak height of the gas chromatograms.
Table 1 ____________________________________________________________ ______________ Compound in MeSH EtOH n-PrOH MeSSMe the breath Preparation Mean SD xx ) Mean SD Mean SD Mean SD value value value value ____________________________________________________________ ______________ A 3584 224.0 336 40.6 84 6.1 -- -- C 10 mg 69 85.7 360 17.4 88 1.0 29 10.0 B 10 mg 23 18.8 368 13.9 88 2.6 33 12.2 D 10 μl 1872 -- 4160 x ) -- 83 -- 18 -- ____________________________________________________________ ______________ x ) The preparation contained ethanol xx ) Standard Deviation
Table 2 ______________________________________ Compound in the breath MeSH n-PrOH MeSSMe Preparation ______________________________________ A 1600 50 2 C 50 mg 86 48 5 B 50 mg 30 45 5 E 10 μ1 840 48 2 ______________________________________
As evident from Tables 1 and 2 above, a marked decrease in the amount of methyl mercaptan present after the addition of a preparation of the invention was obtained. Thus, the preparation of the invention shows an even better result than the corresponding preparation containing a heavy metal ion catalyst. The great decrease i.e. from 3584 mm peak height in the blank to 23 mm peak height is to be noted.
The object of the present invention is to eliminate fetor ex ore, bad breath, without influencing the natural micro flora of the mouth.
Bad breath is a great social handicap to many people and therefore there is a demand for preparations which can eliminate it. Although frequent tooth brushing is carried out it has been shown that bad breath persists. The flavoring and aroma agents present in tooth paste, such as menthol, mask bad breath for a period immediately following brushing, but this is temporary, because the bad breath is caused primarily by methyl mercaptan formed in the mouth cavity, and also to a less extent by dimethylsulphide, ethanol and n-propanol.
Other mouth-washes intended to be used against bad breath are known. However, such mouth-washes do not reduce the amount of e.g. methyl mercaptan but only mask it.
It has been previously known (see U.S. Pat. No. 3,065,139) to use bactericide preparations containing an ene-diol compound, a peroxide, and a metal ion catalyst for infections in the mouth cavity, such as gingivits and stomatitis. The present inventors have shown that such preparations have a certain effect against bad breath by reducing the amount of methyl mercaptan. Such preparations have, in order to obtain an acceptable antibacterial effect, been used in an amount of 170 mg calculated on the active compounds for each administration.
It has now surprisingly been found possible to reduce the amounts of compounds creating bad breath by preparing and using mouth cleansing preparations containing a peroxide and an ene-diol compound, preferably without a metal ion catalyst.
According to a preferred embodiment of the invention ascorbic acid and sodium percarbonate are used.
As suitable ene-diol compounds besides ascorbic acid, isoascorbic acid, dihydroxymaleic acid, dihydroxyfumaric acid, or reductic acid (2,3-dihydroxy-2-cyclopenten-1-one), may be used, or salt thereof, such as the sodium, potassium or calcium salt, or derivatives thereof such as the esters of fatty acids having 2-18 carbon atoms, such as the acetate, palmitate or stearate. As a peroxide besides sodium percarbonate, other alkali percarbonates, alkaline earth peroxides, carbamide peroxide (carbamide crystallized with H 2 O 2 instead of H 2 o), and hydrogen peroxide may be used.
Furthermore, in the preparation of solid preparations, inert filling agents and lubricants known per se are used.
Such filling agents are e.g. mannitol, sodium bicarbonate, tartaric acid and starch.
As lubricants, magnesium stearate, and paraffin may be used.
Binding agents used in the granulation of the compounds prior to the manufacture of e.g. tablets and the like are e.g. polyvinylpyrrolidone and gelatin.
If a special flavor is desired, flavoring agents may be added. Suitable flavors are spearmint, peppermint, menthol, spiced fruits, orange, lemon, lime, etc.
In the utilization of a preparation according to the present invention, one obtains a considerable reduction in the amount of compounds creating bad breath, a weak interference with the micro flora of the mouth cavity and moreover a cheaper and more storage stable product than previously known products.
The preparation ready for use in the form of tablets, pellets or granules is chewed, whereby a reaction between the two active components, the ene-diol compound and the oxidizing agent is obtained and a destruction of the bad smelling compounds takes place. The amount of active oxygen produced per occasion of administration is at least 1 mg, preferably 3 mg, and the amount of the ene-diol compound is at least 10 mg. The administration takes place 3 to 4 times per day. The preparation may also be manufactured as soaking tablets, lozenges, chewing gum or in aerosol or spray form. Tablets may be chewed, or dissolved in water to produce a mouth wash. The amount of ene-diol compound should not exceed 200 mg per occasion of administration and the amount of peroxide should thus not exceed 20 mg as active oxygen.
The present invention will be described more in detail below with reference to the examples given.
EXAMPLE 1
Chewable tablets were prepared containing Ascorbic acid 100 mg Sodium percarbonate corresponding to active oxygen 9 mg Sodium bicarbonate 50 mg Tartaric acid 80 mg Cetyl pyridinium chloride 0.05 mg Flavoring agents q.s. Mannitol ad 750 mg
The tablets were prepared by granulating the mannitol and the sodium percarbonate with a solution of gelatin in water. The sodium bicarbonate was granulated with a 50% solution of polyvinylpyrrolidone in ethanol. Thirdly, the ascorbic acid and tartaric acid were granulated with a solution of polyethylene glycol in ethanol. After drying, the different granulates were passed through an oscillating granulator where the granulates are mixed with flavoring agents. Finally, tablets were pressed in a common tablet punching machine.
EXAMPLE 2
Effervescing granules were prepared and packed in dosage units, whereby each dose contained
Ascorbic acid 10 mg Sodium percarbonate corresponding to active oxygen 1 mg Sodium bicarbonate 4 mg Tartaric acid 5 mg Polyvinyl pyrrolidone 0.02 mg Flavoring agents q.s. Coloring agents q.s. Mannitol 0.03 g
The granules were prepared in accordance with the tablets above, excluding the tableting step.
EXAMPLE 3
Effervescing tablets were prepared containing
Ascorbic acid 50 mg Sodium percarbonate corresponding to active oxygen 5 mg Tartaric acid 5 mg Sodium bicarbonate 25 mg Starch 10 mg Polyvinyl pyrrolidone 2.5 mg Flavoring agents q.s. Coloring agents q.s.
The tablets were prepared in accordance with the tablets of Example 1.
EXAMPLE 4
Chewable tablets were prepared containing
Isoascorbic acid 35 mg Sodium percarbonate corresponding to active oxygen 3.5 mg Sodium bicarbonate 20 mg Tartaric acid 5 mg Cetyl pyridinium chloride 0.02 mg Flavoring agents q.s. Mannitol ad 300 mg
The tablets were prepared in accordance with the tablets of Example 1.
The reducing effect of the above preparations on bad breath has been studied in vitro. Morning saliva from a number of tested persons was incubated at 36°C for 5 to 12 hours until great amounts of methyl mercaptan had been formed, whereupon the saliva was divided into samples each containing 3 ml in 20 ml injection flasks, which were deep-frozen in a Dewer-vessel using CO 2 -ice. The different compared preparations were then added in the amounts stated by opening the capsule of the deep-frozen flasks, introducing the preparation, rapidly removing the air by sweeping with nitrogen gas, and closing the flasks again. Thereupon, the flasks were thawed and after 20 minutes at 36°C a sample was taken and analyzed on a gas chromatograph.
The results are given in Table 1 below, where the values for A, a control sample; B, a preparation according to the invention, based on ascorbic acid as described above in Example 1; C, a preparation according to the invention containing in addition 0.2% of a heavy metal catalyst in the form of copper sulphate calculated on the ene-diol compound; and D, a known mouth-wash containing menthol as masking agent are given. In Table 2 a comparison between a control sample A, and the preparations B and C and in addition, E, a liquid antibacterial iodine composition having oxidizing properties is given. The results are given in mm peak height of the gas chromatograms.
Table 1 ____________________________________________________________ ______________ Compound in MeSH EtOH n-PrOH MeSSMe the breath Preparation Mean SD xx ) Mean SD Mean SD Mean SD value value value value ____________________________________________________________ ______________ A 3584 224.0 336 40.6 84 6.1 -- -- C 10 mg 69 85.7 360 17.4 88 1.0 29 10.0 B 10 mg 23 18.8 368 13.9 88 2.6 33 12.2 D 10 μl 1872 -- 4160 x ) -- 83 -- 18 -- ____________________________________________________________ ______________ x ) The preparation contained ethanol xx ) Standard Deviation
Table 2 ______________________________________ Compound in the breath MeSH n-PrOH MeSSMe Preparation ______________________________________ A 1600 50 2 C 50 mg 86 48 5 B 50 mg 30 45 5 E 10 μ1 840 48 2 ______________________________________
As evident from Tables 1 and 2 above, a marked decrease in the amount of methyl mercaptan present after the addition of a preparation of the invention was obtained. Thus, the preparation of the invention shows an even better result than the corresponding preparation containing a heavy metal ion catalyst. The great decrease i.e. from 3584 mm peak height in the blank to 23 mm peak height is to be noted.