MOUTH CARE PRODUCTS

Abstract: Mouth-care products containing an oxidoreductase and a combination of an 8-hydroxy-quinoline and a com­ pound yielding zinc ions.

Description: The invention relates to tooth-cleaning agents containing an oxidoreductase, and process for the preparation thereof, as defined in the appended claims Dutch Patent Specification 150,332 describes tooth-cleaning agents which, in addition to the ingredients which are usual for said agents, also contain an enzyme which yields hydrogen peroxide on breaking down a substrate. Depending on the nature of such an oxidoreductase, the relevant substrate and/or another enzyme which can convert compounds present in the mouth or on the tooth surface into a substrate for the oxidoreductase used are also added to the tooth cleaning agent. Use is made of such an enzyme system yielding hydrogen peroxide to achieve normalization of the mouth flora via the lactoperoxidase (saliva peroxidase) present in the saliva and the hypothiocyanite additionally formed, as a result of which the formation of harmful acids is prevented. According to this principle, the acid-forming bacteria are not killed but a temporary inactivation takes place of the enzymes which occur in said bacteria and which are responsible for the acid formation. It has been found, however, that under certain circumstances said inactivation does not take place, or takes place to a reduced extent, which depends, inter alia, on the nature of the food and the frequency at which it is consumed. A large number of articles have previously proposed adding bactericidal substances to tooth-cleaning agents in order to kill the acid-forming bacteria. The great disadvantage thereof is that this may lead to the production of resistant strains and the growth of undesirable micro-organisms. If bacteria are killed but not removed, autolysis of the dead cells will also occur as a result of which the surviving cells have additional nutrient substances at their disposal which is the very thing which promotes harmful acid formation. Surprisingly, it has now been found that the use of a combination of zinc ions and an 8-hydroxyquinoline in concentrations in which each of the two components separately and also in combination have no bactericidal action increases the inactivation of the acid-forming bacteria in an oxidoreductase-containing tooth-cleaning agent, even under the unfavourable conditions outlined above. The invention therefore relates to oxidoreductase-containing tooth-cleaning agents, optionally containing a substrate for such an oxidoreductase and/or an enzyme which can yield said substrate, characterized by the presence of an oxidoreductase yielding hydrogen peroxide, an hydroxyquinoline in a concentration between 5 x 10⁻⁵ and 10⁻¹% by weight, and a compound yielding zinc ions in a concentration, calculated as zinc in ionic form, of between 10⁻⁵ and 10⁻¹% by weight. As stated, the combination of zinc ions and an 8-hydroxyquinoline is used in such concentrations that neither the components separately nor the combination has a bactericidal action. The 8-hydroxyquinoline concerned is used in a concentration which is between 5 x 10⁻⁵ and 10⁻¹ % by weight of the tooth-cleaning agent, and zinc (in ionic form) in a concentration which is between 10⁻⁵ and 10⁻¹ % by weight. It has been found that the use of the 8-hydroxyquinoline concerned in a concentration of 5 x 10⁻⁴ to 10⁻³ % by weight and of zinc (ions) in a concentration of 10⁻⁴ to 5 x 10⁻³ has an especially effective action. The zinc compound to be used may be any pharmaceutically acceptable, water-soluble zinc compound derived from inorganic or organic acids such as zinc sulphate, zinc citrate, zinc gluconate, zinc acetate etc., but usually the zinc salt of the 8-hydroxyquinoline is used. The 8-hydroxyquinoline to be added may be 8-hydroxyquinoline itself, or derivatives thereof, such as substituted derivatives, esters, for example the acetate or sulphate, or acid addition salts thereof. Of the substituted derivatives, consideration is preferably given to the halogenated derivatives, such as the 5-halo, 7-halo, and 5,7-dihalo derivatives. The combination of zinc ions and an 8-hydroxyquinoline described above is added to an oxidoreductase-containing tooth-cleaning agent. Said oxidoreductase may be any oxidoreductase yielding hydrogen peroxide, such as lactate oxidase, glucose oxidase, pyruvate oxidase, xanthine oxidase etc. The quantity of oxidoreductase is usually between 0.01 and 500 units per gram/millilitre of the tooth-cleaning agent. A unit of enzyme is understood to mean the quantity which breaks down 1 µmol of substrate per minute at 30 °C and under standard conditions. One or more other enzymes, preferably hydrolases, such as carbohydrases and proteases, can also be added in addition. Preferably glucose oxidase is used as oxidoreductase, optionally in the presence of amyloglucosidase as hydrolase, and/or glucose as substrate. The effect of the combination according to the invention was manifestly demonstrated by means of human saliva, the mouth flora of which has been stimulated, i.e. has acquired an increased resistance to inactivation, by treatment with glutathion. Said saliva was introduced into a number of small containers, 1% of fructose being added, and the acid formation was measured by titration at a certain pH and temperature after adding a substance to be determined. From the table below it is then evident that adding one of the components comprising zinc, 8-hydroxyquinoline and glucose oxidase, and combinations of two of the said components does not slow down the acid formation, while the total combination does in fact do this. 1. ZnSO₄.7 H₂O 10⁻³ % by weight acid formation 2. 8-hydroxyquinoline 10⁻³ % by weight acid formation 3. ZnSO₄.7 H₂O + 8-hydroxyquinoline combination of 1 and 2 acid formation 4. Glucose oxidase (see Dutch Patent Specification 150,332) acid formation 5. Combination of 1 + 4 acid formation 6. Combination of 2 + 4 acid formation 7. Combination 3 + 4 no acid formation The tooth-cleaning agents according to the invention can be converted to various forms, such as to the form of a toothpaste, mouthwash, tablet, chewing gum or other conventional form. In addition to the components according to the invention, said tooth-cleaning agents may also contain the other usual excipients, such as abrasing and polishing agents, thickening agents, colourants, sweetening agents or fluorine compounds. The invention is illustratively explained in more detail by reference to the following compositions. Example 1 Toothpaste Sorbitol 22% (by weight) Silica 22% Ethoxylated fatty alcohol 3% Carragheen 1.5% Sodium benzoate 0.1% Flavouring 0.6% Sodium saccharinate 0.1% Amyloglucosidase 18 U/g Glucose oxidase 6 U/g Zinc sulphate 7 H₂O 10⁻³% 8-hydroxyquinoline 10⁻³% Water to 100% Example 2 Toothpaste Glycerol 15% (by weight) Aluminium oxide hydrate 35% Ethoxylated fatty alcohol 2.5% Carragheen 2% P.H.B. esters 0.15% Flavouring 1.2% Sodium fluoride 0.24% Mutanase 15 U/g Glucose oxidase 8 U/g Invertase 5 U/g Zinc gluconate 8 × 10⁻⁴% 5-chloro-8-hydroxyquinoline 10⁻³% Water to 100% Example 3 Mouthwash Glycerol 15% (by weight) Xylitol 15% Flavouring 0.05% Tween 80 2% Propyl p-hydroxybenzoate 0.1% Potassium thiocyanate 0.02% Sodium citrate 0.2% Amyloglucosidase 4 U/g Glucose oxidase 1 U/g Zinc citrate 2 × 10⁻⁴% 8-hydroxyquinoline sulphate 10⁻⁴% Water to 100% Example 4 Lozenge Sorbitol 1500 mg Encapsulated flavouring 10 Sodium stearate 10 Phosphate buffer pH = 7 50 P.V.P. 20 Zinc 8-hydroxyquinolate 0.16 mg Glucose oxidase 50 U Amyloglucosidase 100 U Example 5 Effervescent tablet NaHCO₃ 40mg Citric acid 20 P.V.P. 2 Sorbitol 24 Encapsulated flavouring 2 Glucose 2 Glucose oxidase 10 U Lactoperoxidase 100 U Potassium thiocyanate 1 Zinc 8-hydroxyquinolate 0.3 mg Dissolve in: 15 ml of water.

Claims: Oxidoreductase-containing mouthcare product, characterised by the presence of an oxidoreductase yielding hydrogen peroxide, an hydroxyquinoline in a concentration between 5 x 10⁻⁵ and 10⁻¹ % by weight, and a compound yielding zinc ions in a concentration, calculated as zinc in ionic form, of between 10⁻⁵ and 10⁻¹ % by weight. Product according to claim 1, characterized in that 8-hydroxyquinoline, or a derivative of 8-hydroxyquinoline substituted by one or more halogens, is used. Product according to claim 1 or 2, characterized in that a zinc salt of an 8-hydroxyquinoline is used. Process for the preparation of an oxidoreductase-containing mouthcare product, characterised in that in addition to an oxidoreductase yielding hydrogen peroxide, an hydroxyquinoline in a concentration between 5 x 10⁻⁵ and 10⁻¹ % by weight, and a compound yielding zinc ions in a concentration, calculated as zinc in ionic form, of between 10⁻⁵ and 10⁻¹ % by weight are added. Process according to claim 4, characterized in that 8-hydroxyquinoline, or a derivative of 8-hydroxyquinoline substituted by one or more halogens, is used. Process according to claim 4 or 5, characterized in that a zinc salt of an 8-hydroxyquinoline is used.

Inventors: HOOGENDOORN, HENDRIK
Applicants: DOUWE EGBERTS KONINKLIJKE TABAKSFABRIEK- KOFFIEBRANDERIJEN-THEEHANDEL N.V.
Application year: 1987
Main classification: A61K7
IPC codes: A61Q11, A61K8