JPS635373B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to preparations for oral hygiene, in particular tooth and mouth care agents which are active against plaque formation and contain zinc aspartate and/or copper aspartate as active ingredients. The use of zinc compounds in oral hygiene preparations, inter alia to prevent or reduce the formation of dental plaque, has been well known for some time and is disclosed, for example, in Dutch Patent Application No. 7102432. According to this publication, zinc citrate is a particularly suitable zinc salt. The use of zinc citrate in combination with alkali salts and the application of zinc ammonium citrate or zinc alkali citrate in tooth and oral care preparations has already been reported in US Pat.
4325939 and German Patent Publication No.
It is described in the specification of No. 3021150. Using this complex salt should increase the solubility of the slightly water-soluble zinc citrate. Toothpastes containing zinc citrate as an active ingredient are also available on the market. However, the significant plaque-reducing effect of zinc citrate, as shown by clinical trials, could not be investigated in a double-blind manner (IADR
Abstracts of the British Division No.145,
Journal of Dental Research, Volume 59/Special
(See Issue D/Part (1981), p. 1827). Other zinc compounds, such as zinc salicylate, zinc lactate, zinc gluconate (published European Patent Application No. 74082)
), complex zinc compounds with carboxymethyloxysuccinic acid (Published European Patent Application No. 6708) and inter alia zinc acetate [Journal of the
American Dental Association, Vol. 27/No. 9 (1940), pp. 1379-1393]. To overcome the above-mentioned drawbacks and improve the efficacy against plaque, it is possible to achieve a synergistic effect by using zinc salts in a mixture with various active ingredients known to prevent plaque formation. It was suggested. In this regard, zinc salts, especially zinc fluoride and hexetidine [Schweizerische
Monatsschrift fu¨r Zahnheilkunde, Vol. 93 (1983), pp. 689-704 and Published European Patent Application No.
49830] should be noted. Furthermore, a synergistic effect was mentioned for the combination of tetradecylamine and zinc salt in US Pat. No. 4,146,607 and European Patent No. 11,663. Finally, issued UK Patent No. 2052978 discloses the combination of glycine with zinc compounds. However, despite all these different methods and combinations, Caries Research, Vol. 17 (1983), pp. 310-314, Scandinavian Journal of
Dental Research, Vol. 9 (1983), pp. 169-174,
and especially G.I. Although the primary utility of zinc compounds for this purpose is generally acknowledged, as can be seen from several scientific articles published in J. Afseth (Oslow, 1983), It has not been possible to prepare medicaments for oral hygiene containing stable zinc compounds that exhibit sufficient efficacy against oral hygiene. It has now been found that highly effective against dental plaque and stable compositions for oral hygiene containing zinc compounds can be prepared when using zinc aspartate as the zinc compound, and this is the object of the present invention. It is. Zinc aspartate can be applied as the sole zinc compound or used as a mixture with other zinc ion releasing components. However, in any case it is suitable that the zinc aspartate is present in an amount of more than 50% by weight of the possible mixture of zinc compounds. It is further known that copper cations prevent plaque formation when applied topically to tooth surfaces from solutions of copper compounds [AADR Abstracts 1979, 117]
No.: Caries Research, Volume 18 (1984), 434-439
page〕. This copper ion-releasing compound does not exhibit the well-known disadvantage of other antiplaque compounds, such as antimicrobial quaternary ammonium compounds or chlorhexidine salts, namely staining of the teeth and tongue after long-term application. However, the use of copper ion-releasing ingredients in toothpastes containing additional carrier materials and active and inactive ingredients may be difficult to achieve since they are inactivated by some of the ingredients or at the required PH value. could not be executed because it did not retain its activity. In European Patent Nos. 38867 and 38868,
Toothpaste compositions containing copper compounds in an active state have been described. This is achieved by optimal selection of the corresponding polishing agent. Although these compositions have been shown to be generally active against dental plaque, it is desirable not to be limited to certain ingredients or ranges in the selection of polishing agent and PH value, etc. Accordingly, there is a need for tooth and mouth care compositions having anti-plaque activity liberating copper ions which are not restricted to specific ingredients and whose activity is not diminished or inhibited by compounds normally present in such compositions. The problem to be developed must be solved. The solution to this problem was found to be the use of a copper salt of aspartic acid, copper aspartate, as the active ingredient that liberates copper ions. Copper aspartate is compatible with almost all polishes and other ingredients commonly used in dental and oral care products. Furthermore, this thing is about 4
It can be applied over a wide PH range between 10 and 10 and remains active. Copper aspartate and zinc aspartate may be added as such to the composition of the present invention, but they can be added to the composition by reacting aspartic acid with a soluble copper or zinc compound such as copper sulfate, copper chloride, zinc sulfate, etc. It is also possible to create it on the spot within the object itself. Particularly suitable percentages of copper aspartate and zinc aspartate are about 0.05 and about 5 of the total composition.
% by weight, especially between about 0.25 and about 2.5% by weight. The following animal studies described below show that the superior efficacy of zinc aspartate on the one hand and copper aspartate on the other hand was demonstrated by the superior efficacy of zinc citrate, zinc acetate, a "synergistic mixture" containing zinc citrate and hexetidine, or A comparison with a toothpaste containing copper sulfate is shown in comparison to an untreated control group. Test Report A 20-day-old Osborne-Mendel (Osborne-Mendel)
Mendel) rats were divided into 5 groups containing 16 animals in each group and fed a standard dental plaque diet for 2000 s. Initial plaque status was examined at the beginning of the study on each test animal. Next, the animal ACTINOMYCES viscosus
It was inoculated with 0.1 ml of a standardized bacterial suspension of OMZ105. Further inoculations were given each week. Treatment of test animals with the preparation to be investigated after birth
per test animal twice daily starting on day 23.
0.1 ml of the test preparation was applied with a syringe. 5 weeks later,
The animals were sacrificed and plaque formation was investigated on the first two buccal and first four lingual surfaces of upper molars 1 and 2, a total of 12 surfaces per animal. Evaluation is performed after staining with erythrosin according to the following schedule: 0: No plaque 1: Up to 1/3 of the surface is covered with plaque. 2: Up to 2/3 of the surface is covered with plaque. 3: More than 2/3 of the surface is covered with plaque. Add up the corresponding scores and calculate the average value. Result

[Table] Example A α-Alumina trihydrate 58.5 (wt%) Sorbitol solution (70%) 25.5 Xantham gum 0.6 Sodium monofluorophosphate 0.8 Sodium saccharin 0.1 Preservative 0.3 Sodium lauryl sulfate 0.4 Flavor mixture 0.1 Zinc aspartate 0.5 Water Adequate to 100.0 Toothpaste Composition Group 1: According to Example A, but with zinc aspartate 0.05% hexetidine and zinc citrate
It was replaced with 2H ₂ O0.5% (=Zn0.16%). Group 2: Follow example A, but replace zinc aspartate with zinc citrate _2H2O (=Zn0.16%) 0.5%
Replaced by Group 3: Toothpaste according to Example A. Group 4: Example A was followed, but zinc aspartate was replaced by 0.55% of zinc acetate 2H ₂ O (=Zn0.16%). Group 5: untreated control group. Equivalence of weight to 100% was achieved by varying the percentage of water. The results demonstrate the surprising superiority of zinc aspartate even over mixtures defined in the prior art as "synergistic mixtures" containing zinc compounds and hexetidine. Test report B results

[Table] Example A α-alumina trihydrate (particle size approximately 1 to 15 μm)
58.50% (by weight) Sorbitol solution (70%) 25.50 Xantham gum 0.60 Sodium monofluorophosphate 0.80 Sodium satucalin 0.10 Preservative 0.30 Sodium lauryl sulfate 0.40 Flavor mixture 0.10 Copper aspartate 0.26 Water Example of sufficient amount to make 100.00 B Synthetic zeolite A (Na ₁₂ (AlO ₂ ) ₁₂ (SiO ₂ ) ₁₂・
27H ₂ O 24.00% by weight Orthocalcium phosphate 10.00 Carboxymethyl cellulose 1.20 Sodium lauryl sulfate 2.00 Glycerin 6.00 Sorbitol 15.00 Preservatives 0.30 Flavor mixture 1.00 Colloidal silica 1.55 Satucalin sodium 0.05 Sodium monofluorophosphate 0.80 Asparagus Copper Ginate 0.25 Water 100.00 Example C Calcium carbonate 41.00% by weight Sodium lauryl sulfate 1.50 Hydroxymethylcellulose 1.30 Sorbitol 9.00 Sodium monofluorophosphate 0.80 Flavor mixture 1.00 Sodium saccharin 0.10 Preservative 0.25 Copper aspartate 0.25 Water Composition of enough toothpaste to make 100.00 Group 1: Follow example A. Group 2: Follow example B. Group 3: Follow example C. Group 4: Follow example C, but with copper aspartate
Replaced with 0.20% copper sulfate (=Cu0.05%). Group 5: untreated control group. Equivalent weight to 100% in group 4 was achieved by varying the percentage of water. This result shows the surprising superiority of copper aspartate over compositions containing copper sulfate at the same Cu concentration, even in the alkaline PH-range. The composition for oral hygiene according to the invention can be applied in various application formats. Toothpaste (either opaque or clear), mouthwash, and chewing gum are particularly good. However, different application forms such as oral sprays, suction or chew tablets, or toothpastes are also suitable carrier materials. As mentioned, the toothpaste can be opaque or transparent. Clear toothpastes contain a polishing agent that has the same refractive index as the carrier material. Particularly suitable polishing agents are aluminas, especially as trihydrates, such as .alpha.-alumina trihydrate and calcium carbonate, with particularly suitable particle sizes of between about 1 and about 20 .mu.m, especially about 10 .mu.m. Naturally, as polishing agents, e.g. alkali aluminum silicates, e.g. European Patent No. 2690
Zeolite A, various calcium phosphates such as dicalcium orthophosphate (as dihydrate or anhydrous), tricalcium phosphate, calcium pyrophosphate, insoluble alkali metaphosphates, various modifications, as described in No. 1 and No. 3023. It is also possible to prepare toothpastes based on other carrier materials, including silica, for example silica-xerogels, hydrogels or precipitated silicas, or polymethyl methacrylate powder plastic materials with a particle size distribution between about 0.5 and about 5 μm. It is. Of course, mixtures of suitable polishing agents can also be applied, such as mixtures of alpha-alumina hydrate and/or calcium carbonate with synthetic zeolite A in a ratio of approximately 1:1. The total polishing agent percentage in toothpastes according to the invention is preferably between about 20 and about 60% by weight of the total composition. Typical surfactants make up approximately
Can be used in amounts up to 2.5% by weight. Suitable synthetic surfactants are, for example, alkyl sulfates, alkyl ether sulfates, olefin sulfonates, sodium lauroylsarcosinate, or amphoteric, nonionic or cationic compounds or soaps, such as lauric acid, myristic acid, palmitic acid, Stearic acid or mixtures thereof, such as the alkaline salts obtained from coconut oil fatty acids or animal fatty acids. A review of toothpastes and suitable compositions for their manufacture is provided by M. S. Balsam (MS
Balsam)/E. Sagarin (E.Sagarin),
"Cosmetics-Science and Technology", 2nd
ed., volume 1, pages 423-533 (1972), the description of which is included as a citation. Toothpastes usually contain humectants in amounts between about 10 and about 35% by weight. A suitable humectant is glycerin,
Diols such as 1,4-butanediol or 1,2-propanediol, or sugar alcohols such as sorbitol, mannitol or xylitol, and also low molecular weight polyethylene glycols. Thickening agents are also included in the toothpaste, the amount of which in the toothpaste is about 0.25 and about 5% by weight of the total composition.
It is between. Suitable thickening agents include carboxymethylcellulose and its alkali salts, especially sodium carboxymethylcellulose, hydroxyalkylcelluloses such as hydroxymethylcellulose and hydroxyethylcellulose, methylcellulose, natural gums such as tragacanth, gum arabic, gum karaya, guar gum, xanthan gum, and iris gum. moss, synthetic polyelectrolytes such as alkali salts of polyacrylic acid, and inorganic thickening compounds, especially colloidal magnesium aluminum silicate or silica. Compositions for oral hygiene according to the invention may of course further contain other active ingredients. Particularly advantageous is the addition of the well-known anti-caries fluoride, preferably when the concentration of pure F in the composition is about F
Between 0.05 and about 1% by weight, especially between 0.1 and 1% by weight of the total composition.
It is preferable to add it in an amount between 0.5% by weight. Suitable fluorine components include various salts of monofluorophosphate, such as sodium, potassium, lithium,
Mono- and difluorophosphates of calcium and aluminum, and various ionic fluorides, especially alkali fluorides, such as sodium fluoride, lithium fluoride, potassium and ammonium fluoride, stannous fluoride, fluoride These include manganese, copper fluoride, zirconium fluoride, aluminum fluoride, and mixtures or adducts of these fluorides, such as manganese alkali fluoride. The oral hygiene agent according to the invention may further contain other plaque-inhibiting substances, ingredients such as ingredients that prevent the formation of tartar, such as hydroxyethane-1,1-diphosphonic acid or alkylene aminotetramethylene phosphonic acid and their water-soluble It may further contain salts, allantoin, azulene, etc. The following examples should characterize the principles of the invention.

[Table] Sufficient amount
Enough amount of Enough amount of Enough amount of Enough amount of Enough amount of Enough amount of Enough amount of
Example 9 Gargle concentrate flavor mixture 5.00 (% by weight) Zinc aspartate 3.30 Zinc citrate 2H ₂ O 0.25 Nonionic emulsifier 1.80 n-propanol 5.00 1-methoxypropanol 35.00 Glycerin 8.50 Phenyl salicylate 0.55 Satucalin sodium 0.30 Water 40.30 Before use Next, dilute the concentrate with water in a ratio of 1:4. Example 10 Chewing Gum Gum Base 30.00 Sorbitol 25.00 Xylitol 20.00 Satucalin Sodium 0.30 Zinc Acetate. 2H ₂ O 0.30 Zinc aspartate 2.40 Copper sulfate. 2H ₂ O 0.30 Glycerin 2.00 Flavor Mixture 3.70 Ascorbic Acid 1.00 Fructose 15.00 Example 11 Gargle Concentrate Flavor Mixture 5.00 (% by weight) Copper Aspartate 2.50 Zinc Citrate. 2H ₂ O 0.25 Nonionic emulsifier 1.80 n-propanol 5.00 1-methoxypropanol (-2)
35.00 Glycerin 8.50 Phenyl Salicylate 0.55 Satucalin Sodium 0.30 Water Enough to make 100.00 This concentrate is diluted with water in the ratio 1:4 before use. Example 12 Chewing Gum Gum Base 30.00 Sorbitol 25.00 Xylitol 20.00 Satucharin Sodium 0.30 Copper Fluoride 0.50 Copper Aspartate 2.20 Copper Sulfate. 2H ₂ O 0.30 Glycerin 2.00 Flavor Mixture 3.70 Ascorbic Acid 1.00 Fructose 15.00

Claims (1)

[Scope of Claims] 1. An oral hygiene composition characterized by containing zinc aspartate and/or copper aspartate. 2. Composition according to claim 1, containing from 0.05 to 5% by weight of zinc aspartate or copper aspartate, calculated on the total composition. 3 0.25 to 2.5% by weight calculated relative to the total composition
The composition according to claim 2, comprising zinc aspartate or copper aspartate. 4. Any one of claims 1 to 3 containing a polishing agent consisting of zinc aspartate and more than 50% hydrated alumina.
The composition described in Section. 5. Any one of claims 1 to 3 containing a polishing agent consisting of copper aspartate and more than 50% calcium carbonate.
The aqueous toothpaste composition described in .