US 3886265 A
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.
Description (OCR text may contain errors)
United States Patent 1 Evers et al.
[ May 27, 1975 MOUTH CLEANSING PREPARATION  Assignee: Astra Lakemedel Aktiebolag,
Sodertalje, Sweden 22 Filed: July 2,1973
21 Appl.No.: 375,615
 Foreign Application Priority Data June 30, 1972 Sweden 8597/72  US. Cl. 424/49  Int. Cl ..A61k 7/16  Field of Search 424/49-58  References Cited UNITED STATES PATENTS 3,065,139 11/1972 Ericsson et al. 424/130 Primary ExaminerRichard L. [Huff Attorney, Agent, or Firm--Brum.baugh, Graves, Donohue and Raymond [5 7] 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.
5 Claims, N0 Drawings MOUTH CLEANSING PREPARATION 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 feror 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 eg methyl mercaptan but only mask it.
It has been previously known (see US. 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, dihydrox yfumaric acid, or reductic acid (2,3-dihydroxy 2- cyclopenten-l-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-l8 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 instead of H 0), 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 com pounds 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.
5 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 mg as active oxygen.
The present invention will be described more in detail below with reference to the examples given.
EXAMPLE 1 The tablets were prepared by granulating the mannito] 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 l0 mg Sodium percarbonate corresponding to active oxygen 1 mg Sodium bicarbonate 4 mg Tartaric acid 5 mg Polyvinyl pyrrolrdone 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 The preparation contained ethanol "Standard Deviation -Continued Table 2 Sodium bicarbonate 25 mg Starch 10 g Polyvinyl pyrrolidone 2.5 mg Compound m the breath MeSH n-PrOH MeSSMe Flavoring agents q. pfepurmmn Coloring agents q.s.
A 1600 51) 2 C 50 86 48 5 The tablets were prepared in accordance with the 350 mg 30 45 5 tablets of Example 1. E 43 2 E EXAMPL 4 As evident from Tables 1 and 2 above, a marked decrease in the amount of methyl mercaptan present after Chewable tablets were prepared Comdmmg the addition of a preparation of the invention was obtained. Thus, the preparation of the invention shows an lsoascorbic acid 35 mg even better result than the corresponding preparation Sodium Percarbonale corrfisponding s containing a heavy metal ion catalyst. The great deag sl hg f m :2 crease i.e. from 3584 mm peak height in the blank to Tartaric acid 5 mg 23 mm peak height is to be noted. Cetyl pyridinium chloride 0.02 mg W6 Claim. Flavorin a ents q.s. Mannitol g ad 300 mg l. A composition effective in combattmg bad breath consisting essentially of an ene-diol compound selected The tablets were prepared in accordance with the from the group consisting of ascorbic acid and isotablets of Example 1. ascorbic acid, said compound being present in an The reducing effect of the above preparations on bad amount of at least 10 and oxldlzmg agent m the breath has been studied in vitro. Morning saliva from form of a w Solubl? peroxlde Selected from i a number of tested persons was incubated at for group consisting of alkali metal percarbonates, alkaline 5 to 12 hours until great amounts of methyl mercaptan f Peroxldes f carbalmde Peroxlder wherein sflld had been formed, whereupon the saliva was divided OXd1Z mg agent Present an amount corresp ondmg into samples each containing 3 ml in 20 ml injection to acme Oxygen m an amolfm of at least 1 each flasks, which were deep-frozen in a Dewer-vessel using Case Per peroridosage coricg The different Compared preparations were 2. composition according to claim 1 wherein the then added in the amounts stated by opening the capcne'dlol P H ascorbic acid sule of the deep-frozen flasks, introducing the preparacomposltlon aFCOrdmg P claim 1 the tion, rapidly removing the air by sweeping with nitro ene'dlol compound ascorbl? f f f" an gen gas and closing the flasks again. Thereupon, the amount at least 10 mg and the oxidizing agent is sodium flasks were thawed and after 20 minutes at 36C a samperFarbonate Present m an amount corresponfimg to ple was taken and analyzed on a gas chromatograph. actwe Oxygen m an amounf of at least 1 each The results are given in Table 1 below, where the valg g i z i g z g gh t 1 i 1 wh th ues for A, a control sample; B, a preparation according oxiizin a is g f s g ig gs g erem e i to the invention, based on ascorbic acid as described g g p 0 5. A method of inhibiting bad breath by administerabove In Example 1; C, a preparation according to the in Oran at 1 st 10 m f l d invention containing in addition 0.2% of a heavy metal g per y ea ah chelo h h catalyst in the form of copper sulphate calculated on Selecteh the group cohslshhg of hscorblc acid the ene diol compound and D a known mouthwash ascorbic acid, and salts or derivatives thereof, together containing menthol as masking agent are given. In with h Oxlchzmg agent In the form Water soluble? Table 2 a comparison between a control sample A, and peroxlde selected from group cohslshhg of alkah the preparations B and C and in addition, E, a liquid meial percaibohates alkhhhe earth. perhxldes carbantibacterial iodine composition having oxidizing prophhhde perohlde ahdhydrogeh heroxlde m an amount erties is given. The results are given in mm peak height corresphhdmg to achve Oxygen m an hmohht of at least of the g chromatograms 1 mg., in each case*per*perkorai dtlsage unit.
Table 1 Compound in MeSH EtOH n-PrOl-l MeSSMe the breath Preparation Mean SD 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 l().() B 10 mg 23 18.8 368 13.9 88 2.6 33 12.2 D 10 1.1.1 1872 4160 83 l8