DE19949575A1 - Fluoride and flavonoid combination, e.g. in chewing gum and toothpaste, for the prevention of caries and the treatment of dental disorders - Google Patents

Abstract

Products containing a combination of fluorides and flavonoids are effective in the prevention of caries and the treatment of dental disorders. Independent claims are included for the products (a) chewing gum, (b) chewable dragees, (c) sweets, (d) toothpaste, (e) mouthwash and (f) tablets, each containing a combination of fluorides and flavonoids is used for the prevention of caries and the treatment of dental disorders.

Description

The invention relates to a new combination of active ingredients of biologically highly effective Fluorides (amine fluoride (AmF) and / or zinc fluoride (SnF)) in combination with Flavonoids for tooth decay and dental prophylaxis and therapy of dental diseases such as B. Periodontal disease. The new combination of active ingredients can be administered, for example, in Application form as chewing gum, chewing gum, candy, toothpaste, mouthwash or in any other dosage form with or without sustained release function in the oral cavity.  

background dental care

Dental services account for approx. 10% of expenditure at the GKV (status 1996). 50-60% of patients receive one or two surfaces when they visit the dentist Tooth fillings due to tooth decay (the proportion is higher in the new federal states). Caries has had a consistently high prevalence in the population for years. Dental caries occurs at any age, but is a particular problem for the vulnerable child and youthful teeth. Caries infestation is in the early, here still reversible stage for the dentist cannot be seen with the naked eye because of the carious process on the sub-surface begins. In extreme cases, the lesion can remain invisible until it reaches the dentine. The aim must therefore be to use effective prophylactic measures at an early stage.

Another important and costly problem are diseases of the Oral mucosa, especially periodontitis (cause of more than 30% of all Visits to the dentist). Periodontal disease mainly affects older patients.  

Fluorides

Fluorine (F: 19.00) belongs to the 7th main group of the periodic table. Fluorine is found in the Nature in the form of various fluorides. Fluorides are effective enzyme poisons and affect especially phosphatases. Fluorides are quickly absorbed from the gastrointestinal tract. The daily intake of fluorine in the form of fluorides should not exceed 1-2 mg.

0.25 g is toxic to humans, 4-5 g are considered a lethal dose. From previous ones Knowledge is known that fluoride when used correctly (and in the correct chem. Composition) can offer optimal caries prophylaxis. Some have the potency to stop caries starting and to re-mineralize the tooth enamel. In addition, you can certain topically locally active fluoride combinations heal periodontitis promote or prevent their emergence. In combination with glucose / fructose Connections (especially in confectionery of all kinds) will the cariogenic potential of Sugar compounds decreased.

So far, there is no optimal application form of fluorides that matches the systemic with the combined topical application and a sufficient exposure time guaranteed. In particular cannot achieve a sustained release effect with conventional application forms of fluorides become.  

Flavonoids

Flavonoids are widely used dyes in plants. These are glycosides of flavanones, flavones, flavonols, aurones, isoflavones and redoids. Flavonoids can accumulate in animal membranes and accumulate in the vascular endothelium after oral administration. Flavonoids increase the permeability of the body vessels and reduce the capillary fragility. These effects are particularly attributed to rutin, hesperidin and naringin. They were recognized early on to have an edema-preventive effect as part of the therapy of chronic venous insufficiency in the leg area. In the animal model, flavonoids showed pain-relieving and antipyretic effects, which are said to be due to a cyclooxygenase and lipidoxygenase-inhibiting effect. The mitigating effect of flavonoids on allergic diseases is attributed to the inhibition of an ATPase in the membrane of the mast cell granules (stabilization of the mast cell membrane). Flavonoids form strong complexes with divalent heavy metal ions (Fe ²⁺ , Cu ²⁺ , Zn ²⁺ ) and can be easily oxidized. These properties make these compounds highly effective radical scavengers and antioxidants. Flavonoids synergistically support the ascorbic acid effect (e.g. formation of mesenchymal tissue).

Flavonoids are present in high concentrations in red wine. Red wine contains e.g. T. more than 1 g / l (especially flavonoids like catechins and anthocyanins), while white wine usually does not exceed 250 mg / l. A reason for that rare among the Mediterranean population occurring ischemic clinical pictures such as coronary heart disease and cerebral Strokes are related to those to a greater extent with food consumed flavonoids.  

Explanations of the previous fluoride applications toothpaste

Most toothpastes contain fluoride. Disodium fluorophosphate (NaO) ₂ PO (F) is often used for this. The main problem with this form of application is that the action time for fluorides is too short. Studies have shown that optimal caries prophylaxis can be achieved with fluorides in low concentrations and with a sufficient duration of action (therefore cleaning at least 3 minutes required). According to statistics, however, the average tooth brushing time is only 20 seconds. Common fluoride compounds cannot develop their effects optimally and have no long-term effect.

Mouthwashes

Are ineffective to ineffective due to the short duration of action.

Another problem is their alcohol content (ethanol). There is a risk of abuse given here. Due to the possibility of ingestion and the alcohol content for Unsuitable for children.  

Tablets

Actually only act systemically. Lozenges or chewable tablets are also unsuitable for an effective local caries prophylaxis, because here only in the oral cavity and on A sufficient fluoride concentration is achieved on the lingual side of the teeth. The The buccal approximal surfaces of the teeth are left out, as are the Interdental spaces and the buccal salivary glands (xerostomia).

Another problem with this dosage form is the fluoride concentration. Have studies shown that the optimal local caries prophylaxis only with fluorides in lower To achieve concentration. The concentration is too high for tablets. With children there is a potential risk of acute poisoning or chronic overdose (Fluorosis; recognizable by mottled teeth and brittle nails). The daily intake of fluorine in the form of fluorides should not exceed 1-2 mg.

The bioavailability of fluorides is reduced by simultaneous food intake (CaF ₂ formation with less absorption). It is best to take fluoride between meals. Exact dosing is hardly possible, especially for small children, where the intervals between food intake are small.

In older children and adults, systemic administration of fluoride led to an increased adsorption rate without significantly influencing the concentration in the tooth area. Local fluoride administration should therefore be the focus of caries and periodontal prophylaxis.
Example drugs: "Luride" (USA) corresponding to 1 mg fluoride from 2.2 mg NaF (1 OP with 120 tabs).
"Fluorettes" content per tablet 0.00055 g sodium fluoride = 0.00025 g fluorine.

salt

In Switzerland since 1983 with higher doses (0.025% instead of 0.009% fluoride) available.

Recently available in Germany in combination with iodide.

Drinking water

Very low average natural fluorine content in drinking water (e.g. Southern Germany 0.129 mg / l). So far, due to the legal situation, it is not nationwide Fluoridation provided. Drinking water fluoridation is otherwise done with alkali fluorides carried out.

Fluoride treatment by the dentist

Is in the v. a. carried out in the USA. But is considered ineffective and costly. The topical treatment in the form of a brush with 2% sodium fluoride solution is only 1-2 times / a carried out (lack of continuity). The fluoride doses used here are for local treatment too high, swallowed amounts can be significant.  

Explanations of the previous flavonoid applications

So far, flavonoids have only been used orally in gel form for the prophylaxis of periodontitis applied. A synergistic combination application of flavonoids and fluorides is not known. This is especially true in the additional combination with ascorbic acid (vitamin C). Flavonoids are used clinically in the treatment of chronic venous insufficiency in the Leg area administered orally.

Flavonoids are typically contained in high concentrations in red wine (approx. 1 g / l) and are consumed with food.  

Mode of action fluorides generally

• - Fluorides catalyze remineralization
• - Fluorides reduce the rate of demineralization
• - Hardening softened enamel and the histological repair is experimentally proven in humans
• - Influencing plaque:
  • - Inhibition of growth of microorganisms
  • - braking of glycolysis (especially AmF)
• - NaP gives complex born F in relatively low concentrations as fluoride.
• - F-administration (e.g. in drinking water) leads to significant in older people lower number of fractures in the femoral neck area.
• - In osteoporosis patients, Ca administration leads to continuous F administration significantly lower fracture rates (reg) (20 mg / d)
• - APF principle: low pH increases fluoride absorption in the enamel
• - Kidney excretion rate 50-80%

Amine fluoride (AmF)

• - lead to a higher F concentration on the enamel surface and build an F-depot on the enamel surface
• - have 4 × greater fluoride retention (toothpaste) than MFP
• - AmF / SnF ₂ synergistically inhibit plaque growth
• - longer stay in the plaque (compared to NaF 4 × longer), plaquophilia
• - more stable fluoride enrichment
• - Surfactant character, AmF attaches itself to the bacterial as a cation-active substance Cell membrane
• - has a bactericidal effect (germ reduction <95%)
• - antiglycolytic effect
• - Acidic pH promotes F-rich surface layer on the tooth enamel
• - 3-6 h effective, significantly slower oral fluorine clearance
• - reduces the acid solubility of the enamel surface
• - Formation of a bacteriophobic protective film that inhibits plaque formation

The special position of amine / zinc fluoride as a biologically particularly effective group of substances for the prophylaxis and therapy of dental diseases, especially dental caries is through numerous studies and the corresponding publications documented (H. Schmidt, chemistry and surface effects of amine fluorides, Dtsch. Dentist Z. 38, 1983, special issue 1; H.-J. Gülzow, Effectiveness of Amine Fluorides, Dtsch. Dentist Z. 38, 1983, special issue 1; F. Lutz, Mechanism of the Protected Amine Fluoride Effect, Dtsch. Dentist Z. 38, 1983, Special issue 1; Schmid R. and Mühlemann H. R .: Effects of organic and inorganic fluoride dentitrices on rat caries incidence. J. Dent. Res. 62 Abstr. 75, 506 (1983)).  

Mode of action flavonoids

Flavon derivatives reduce the increased permeability of the capillaries and thus normalize them Permeability. This reduces the risk of capillary fragility. In plants play phenolic flavone derivatives e.g. T. the role of redox catalysts. In the intestinal wall The red wine flavonoids effectively inhibit the enzyme phenolsulfotransferase (PST). This enzyme inactivates a wide range of phenols by conjugation with sulfate. The flavonoids could thus ensure that non-sulfated phenols are absorbed. As Therapeutic agents are used, for example, rutosides (= rutin). Because of her above Mode of action described flavonoids were previously used as an anti-permeability factor or as Called vitamin P. At first it was known that vitamin P synergistically ascorbic acid (Vitamin C) supports. Vitamin C deficiency leads to connective tissue diseases (lack of formation of mesenchymal tissue) such as scurvy. For the treatment of Periodontitis, also a disease of the connective tissue of the gums, therefore works Flavonoids combined with ascorbic acid synergistically. Rutoside u. a. out Buckwheat (Fagopyrum species, contain 1-4% rutoside) or from flower buds Japanese plant Sophora japonica (contain approx. 15% rutoside) or are with synthesized.

Table 1

Naturally occurring flavonoids

Many of these compounds are found in food components. they seem regarding their toxicity and side effects as harmless.  

The aim of the invention is to achieve a biologically highly effective combination of active substances Fluorides and flavonoids provide improved protection against tooth decay and periodontal disease. This object is achieved according to the invention by combining those described above Active ingredient combination z. B. in the application form as chewing gum / chewing gum / candy or Toothpaste / mouthwash.

Chewing candies / chewing gums or toothpastes preferred according to the invention enable one Long-lasting continuous release of active ingredients, which ensure an optimal fluoride effect on the Tooth is essential. Amine fluorides work better the lower the Active ingredient combination is dosed and the longer this on the enamel and in the Oral cavity can act. From various publications it is known that amine fluorides Promote reparative processes on the tooth (remineralization of teeth damaged by caries possible in the initial stage with the help of amine fluorides). The works here synergistically preventive effect of the flavonoids on the microcirculation of the gums. Because flavonoids the ascorbic acid effect supports synergistically, the treatment and healing of Periodontosis also with regard to the damaged connective tissue structure (lack of training of the mesenchymal tissue) of the gums. Because of the high effectiveness be the rutin (quercetin-3-rhamnoglucoside), hesperidin and naringin in natural or synthetic form (rutin derivatives such as troxerutin and monoxerutin) preferred. This The application form as chewing gum / chewing gum / candy or Toothpaste is only possible due to the long duration of action and can be applied in in a slow release form.

In addition, due to the antibiotic effect of the amine / zinc fluoride Causal diseases of the teeth (e.g. caries) and gums (e.g. periodontitis) fought (H. Schmidt, chemistry and surface effects of amine fluoride, Dtsch. Dentist Z. 38, 1983, special issue 1).

In confectionery of all kinds (incl. Sugar / alcohol-containing drinks), amine / zinc Fluorides neutralize the cariogenic breakdown products of glucose / fructose Links. These harmful cariogenic effects can thus be significantly reduced or even be canceled.  

Due to the action of the amine fluorides over an elongated flat profile (similar drinking water fluoridation), which is known to be short-term very high Concentrations (tablet fluoridation) is preferable, must be very low Fluoride concentration per chewing gum / chewing gum / candy in the interest more optimal Effectiveness should be sought. The amount of fluoride per unit should be less than 0.05 mg. The amount of flavonoids per unit can be very variable due to the harmlessness be considered. 10-50 mg already show a sufficient effect on the Microcirculation and synergistically support the ascorbic acid effect. The Ascorbic acid (vitamin C) cannot be overdosed. Amounts are sufficient here between 5-50 mg.

Exemplary recipes example 1 Chewing gum

Composition:
Chewing mass: Synthesis of rubbers e.g. B. styrene-butadiene, butyl
Sweeteners: e.g. B. Sorbitol (E420), Mannitol (E421), Xylitol (E967)
Antioxidants: e.g. B. Butyl
Amine fluoride 0.05 mg
Flavonoids e.g. B. a synthetic rutoside derivative (troxerutin or monoxerutin 50 mg)
Ascorbic acid 50 mg
Natural or nature-identical flavorings
Dyes

Example 2 sweet

Composition:
Hardened glucose syrup
Amine fluoride 0.05 mg
Flavonoids e.g. B. a synthetic rutoside derivative (troxerutin or monoxerutin 50 mg)
Ascorbic acid 50 mg
Natural or nature-identical flavorings
Dyes

Claims (19)

1. A chewing gum for caries provided with fluorides in combination with flavonoids and dental prophylaxis and therapy of dental diseases. 2. A chewing gum coated with fluorides in combination with flavonoids for caries and dental prophylaxis and therapy of dental diseases. 3. A candy for caries and with fluorides in combination with flavonoids Dental prophylaxis and therapy of dental diseases. 4. A toothpaste for caries provided with fluorides in combination with flavonoids and dental prophylaxis and therapy of dental diseases. 5. One with fluorides in combination with flavonoids Mouthwash / mouthwash for tooth decay and dental prophylaxis and therapy of Dental diseases. 6. A tablet for caries and with fluorides in combination with flavonoids Dental prophylaxis and therapy of dental diseases. 7. chewing gum according to claim 1 plus one or more additives, especially ascorbic acid (vitamin C). 8. chewing pills according to claim 2 plus one or more additives, especially ascorbic acid (vitamin C). 9. Candy according to claim 3 plus one or more additives, in particular Ascorbic acid (vitamin C). 10. toothpaste according to claim 4 plus one or more additives, in particular Ascorbic acid (vitamin C). 11. Mouthwash / mouthwash according to claim 5 plus one or more Additives, especially ascorbic acid (vitamin C). 12. Tablet according to claim 6 plus one or more additives, in particular Ascorbic acid (vitamin C). 13. Continuous, long-term release of fluorides in combination with flavonoids also via other forms of application (e.g. slow release form). 14. Claims 1 to 12 if the fluoride belongs to the group of amine fluorides. 15. Claims 1 to 12 if the fluoride belongs to the group of zinc fluorides. 16. Claims 1 to 12 if the fluoride belongs to the group of sodium fluorides. 17. Claims 1 to 12 when the fluoride in the group of amine fluorides in Combined with zinc fluoride or sodium fluoride.   18. Claims 1 to 12, if another chemical (organic and / or inorganic) active ingredient in combination with a fluoride and flavonoid is administered. 19. Claims 1 to 12, if another chemical (organic and / or inorganic) active ingredient in combination with a fluoride that belongs to the group of substances Amine and / or zinc fluoride and / or sodium fluoride in combination with one Flavonoid is heard, administered.