Title: Precipitated silicas which contain an active substance
United States Patent: 6,214,383
Inventors: Esch; Heinz (Bonn-Duisdorf, DE); Kuhlmann; Robert (Erftstadt, DE); Neumuller; Matthias (Hasselroth, DE); Otto; Karin (Bonn, DE); Rausch; Ralf (Kreuzau, DE); Thomas; Klaus-Peter (Wolfersheim, DE)Assignee: Degussa-Huls AG (Frankfurt am Main, DE)
Appl. No.: 208453Filed: December 10, 1998
Foreign Application Priority Data: Dec 10, 1997[DE] (197 54 798); Jan 28, 1998[DE] (198 03 066)
A precipitated silica which contains an active substance with a characteristic, delayed release of active substance is prepared by adding the active substance during preparation of the precipitated silica. The precipitated silica containing the active substance may be added to oral hygiene agents such as toothpastes, topical fluoride preparations, dental materials or medicinal chewing gums.
SUMMARY OF THE INVENTION
The invention provides precipitated silicas which contain
an active substance and which are characterized by a characteristic,
delayed release of active substance.
The precipitated silica which contains an active substance may preferably
be characterized by:
the concentration of active substance
the release dynamics of the active substance.
In a preferred embodiment, the precipitated silica according to the
invention may have the following physico-chemical parameters
Moisture % 1-10, preferably 1-7 pH 2.5-8.5, preferably 6-8 N2 surface area m2 /g 25-800, preferably 25-400 Average particle 2-100, preferably 2-20 size (Malvern) .mu.mThe invention also provides a process for preparing precipitated silica with the ability to carry an active substance according to the invention which is characterized in that a precipitated silica is prepared in a known manner, wherein an active substance which is moderately to sparingly soluble in water is placed either in the precipitation recipient vessel or in the precipitation suspension or is dried together with the washed and optionally redispersed precipitated silica paste or is milled simultaneously with the dried material.
The preparation of amorphous silicas is described in a variety of ways. The common feature of all the methods is the reaction of an alkali metal silicate solution with mineral acid or Co2 while maintaining specific precipitating conditions, such as e.g. temperature, time, pH and solids content in the precipitation suspension. Then the pH is lowered by adding more acid. The mixture is stirred continuously during the precipitation and acidification phases. The suspension is filtered and the filter cake is washed, dried and milled.
Amorphous silicas according to the invention are prepared in such a way that a precipitated silica is prepared in a known manner, wherein an active substance which is moderately (0.1-1.0 molar) to sparingly (less than 0.1 molar) soluble in water either in the precipitation recipient vessel or in the precipitation suspension or is dried together with the washed and optionally redispersed silica paste or is milled simultaneously with the dried material.
Alkali metal fluorides, alkaline earth metal fluorides or fluoroapatite, for example, may be used as a component which contains fluoride ions, wherein fluorides from alkali metal compounds may also be bonded by adding alkaline earth metal ions. Further active substances may be: chlorhexidine, triclosan, hydroxyethane-1,1-diphosphonic acid, alkali metal pyrophosphates, zinc citrate, etc.
The precipitated silicas may be prepared in the ways described in the documents DE-A 44 23 493, DE-AS 14 67 019 and EP-B 0 272 380.
It has now been shown that a preferred form of preparation comprises placing the active substance in the precipitation recipient vessel or the spray dryer feed material. This ensures the most uniform and the finest distribution in the final product and the greatest retention effect. The therapeutically active amounts of fluoride are 0.001 to 10%, preferably 0.005 to 1.0%. The amount of triclosan is 0.1-1.0%, preferably 0.2-0.5%.
Any thickening, abrasive or bifunctional silica is suitable as a carrier silica. Synthetic, amorphous silicas are preferred, such as those described in EP 0 643 015 and obtainable from Degussa AG, Germany under the tradename SIDENT.RTM.. ZEODENT silicas from the J.M. Huber Corporation, Chemical Division, Havre de Grace, Md., TIXOSIL silicas from Rhone-Poulenc Chimie Les Mirroirs, La Defense 3 F-92400 Courbevoie, France; SORBOSIL silicas from Crosfield Chemicals, Warrington Cheshire, England or SYLOID silicas from Grace & Co., Davison Chemical Division, U.S.A. may also be used.
The precipitated silicas which are able to carry active substances according to the invention are preferably prepared by placing water and the active substance in a precipitation vessel, heating the mixture to a temperature of 50o to 100oC., preferably 80o to 90oC., adjusting the pH and the alkali metal concentration by adding sodium silicate solution while maintaining the temperature, and then adding sodium silicate solution and sulfuric acid, simultaneously, while keeping the pH and the alkali metal concentration constant, or one after the other, then acidifying to a pH of preferably 7 by adding further sulfuric acid, optionally stirring again, filtering, washing salt-free, redispersing the filter cake, drying with a spray dryer and milling the granular silica obtained.
The commercially available sodium silicate solution may have a concentration of, as a non-limiting example, 26.8% SiO2 and 7.85% Na2 O and a density of 1.352 g/ml.
The sulfuric acid may have a concentration of 50-96%.
Silicas according to the invention may be used in a conventional manner which is known to a person skilled in the art in oral hygiene preparations such as toothpastes, medicinal chewing gums and topical fluoride preparations as well as dental materials. In this case they may entirely or partly replace the silicas conventionally used there. A preferred area of use is in toothpastes. In addition, however, a combination with other, optionally soluble, active substances and the preparation of gel formulations etc., is also possible.
Dental care agents according to the invention containing (sic) one or more of the raw materials used according to the prior art, such as water, binders, such as e.g. cellulose derivatives such as carboxymethyl cellulose and their alkali metal salts, in particular sodium salts, hydroxyalkyl celluloses, xanthan gum, tragacanth gum, carragenates, alginates and gum arabica, etc., polishing substances (precipitated and pyrogenic silicas, dicalcium phosphate, chalk, aluminium hydroxide, etc.), moisture-retaining agents such as e.g. glycerol, sorbitol, propylene glycol, polyethylene glycols with low molecular weights, 1,4-butanediol, xylitol, etc., flavoring, surfactants such as e.g. alkyl sulfates, sodium lauryl sulfate, sarcosides, taurin fatty acid amides, monoglyceride sulfate, betains, etc., colorants and/or titanium dioxide, sweeteners, buffers, bases or acids, preservatives and active substances.
The dental care agents are prepared in accordance with the prior art. The ingredients, in a suitable form, are mixed, swollen and dispersed.
Precipitated silicas according to the invention may be used as an additive in toothpastes, in particular as a thickening and/or abrasive component which also releases active substances.
Precipitated silicas according to the invention have the following advantages:
Silicas according to the invention are used as a carrier for dentally active substances which are stored at the site of action and then release the active substance in small doses over a relatively long period of time (deposition effect, controlled release). The silicas thus act as active substance stores which contain the active substance in adsorbed, absorbed or chemisorbed form. Any form of silica, e.g. precipitated silicas or silica gels or pyrogenic silicas, may be used. Any sparingly soluble fluoride, such as e.g. CaF2 and sparingly soluble active substance such as e.g. triclosan or chlorhexidine may be used as an active substance.
The sparingly soluble active substances may be combined with readily soluble active substances, such as e.g. NaF, monofluorophosphate, etc. and then targeted adjustment of the active substance release dynamics, that is a targeted combination of the immediate and the deposition effect, is possible. The advantages of the silicas according to the invention are based on the longer availability and thus improved therapeutic efficacy, e.g. improved prevention of caries due to improving the resistance of teeth to demineralization. This means that small doses of active substances are possible and fewer side effects or lower toxicity would be expected. The addition of fluoride to drinking water, i.e. the compulsory provision of a medicament, may become unnecessary.
This application is based on German Applications DE 19754 798.2, filed Dec. 10, 1997, and DE 19803 066.5, filed Jan. 28, 1998, the disclosures of which are incorporated herein by reference.
Claim 1 of 7 Claims
What is claimed is:
1. A precipitated silica containing an active substance, having delayed
release of the active substance over a period of about two days.
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