ORAL DENTAL CARE COMPOSITION

Abstract: An oral dental care composition for inhibiting or preventing periodontoclasia and caries containing special sulfated polysaccharides, viz. xylan sulfate, dextran sulfate, starch sulfate or hyaluronic acid sulfate, in combination with a non-toxic carrier. The composition may e.g. have the form of a tooth cleaning agent, a suction or chewing tablet, a chewing gum, a rinsing solution or a solid or liquid concentrate intended to form a rinsing solution by dissolution or dispersion or suspension in water or another liquid or liquid mixture. Claimed is further the use of these sulfated polysaccharides as anti-periodontoclasia or anti-caries agents for oral administration.

Description: Oral Dental Care Composition Technical Field The present invention relates to oral dental care compositions containing special sulfated polysaccharides which inhibit the enzymatic degradation of collagen. It also relates to the use of these sulfated polysaccharides as anti- periodontoclasia agents (anti-tooth loosening agents). Background of the Invention Caries is a well known and wide spread tooth disease which affects people in all ages and which causes great economical losses both to the patient and the society, not to speak of the accompanying physical and mental suffering for the patient. Caries is caused i.a. by acid attacks on the hepatite layer of the tooth enamel exposing the tooth dentin, which is more easily subjected to bacterial growth than the enamel. The mouth-cavity with its environment is an excellent place of growth for various bacteria, and the dentin is also a good breeding ground or bacterial growth. Many attempts have been made to develop agents which inhibit the formation of caries and/or inhibit the development of already existing caries. Many of the prior proposals for solving the caries problems are directed to improving the acid resistance of the tooth enamel and the dentin, and to this end e.g. anti-caries agents containing certain tin compounds have been used. It has also e.g. been proposed to use anti-caries agents containing fluorine ions together with tin ions, whereby, in addition to improved acid resistance, inhibition of caries because the teeth have absorbed the fluorine has been achieved. The published European patent application 00S3Ψ86 discloses anti-caries compositions containing certain low molecular thiol and disulfide compounds, having collagenase-inhibiting activity. Because these compounds are low mole¬ cular they can be resorbed and certain toxicity problems can be expected when used as an oral dental care agent, wherein it is inherent in the nature of the treatment that the treated person may swallow comparatively great amounts of the compounds in question. Further, many low molecular thiols and disulfides have unpleasent smell and taste which can be difficult to hide. Furthermore, these prior art compositions are only intended for use as anti-caries agents, but there is no disclosure of any use thereof as anti-periodontoclasia agents. Although these and other prior art anti-caries agents have given certain positive results, there is still a great need for alternative or improved anti-caries agents. Tooth loosening - or parodental diseases - is i.a. caused by destruction of the tissue surrounding the necks of the teeth and of the parodental membranes, i.e. the fine filaments by means of which the teeth are suspended in the alveols. As far as we know, no anti-periodontoclasia agents are known, despite the fact that such agents would meet a very great demand. Ob fe t of the Invention The present invention aims at providing improved oral dental care 5 compositions which inhibit or prevent the formation and/or development of tooth-loosening and caries. The invention is based on an approach which is somewhat similar to that of the above mentioned European patent application 00-83486, viz. starting from the realization that certain bacteria, which are present in the mouth-cavity and 10 on the teeth, form collagen-degrading enzymes, such as coilagenase, elastase, etc. and that the presence of these enzymes play an important role for the formation and development of tooth-loosening and caries. In carles this effect is assumed to be related to the fact that these enzymes, when the collagen-rich dentin has been exposed by acid attack on the enamel, rapidly degrades the 1-5 collagen structure of the dentin, whereby the apatite loses its coupling with the collagen and therefore can be easily dissolved. In an analogeous manner tooth- loosening is assumed to be caused by the fact that these enzymes degrade the collagen filaments keeping the tooth attached to the tooth bone. It should, however, be underlined that this description of the assumed mechanism is not in 20 any way intended to limit the invention. Brief Description of the Invention The basic idea of the invention is to block or inhibit the collagen- degrading enzymes formed in the mouth-cavity and on the teeth, so that they become inactive and consequently lose the ability to enzymatically degrade the 25 root and tooth collagen. To this end the dental care agents according to the invention contain special sulfated polysaccharides which are non-toxic on oral administration and which preferably have a neutral or comparatively pleasant taste. These sulfated polysaccharides form a group of compounds which is known as such. 30 The sul ated polysaccharides used according to the invention are xyian sulfate, dextran sulfate, starch sulfate and hyaluronic acid sulfate. In contrast to the low molecular thiol and disulfide compounds disclosed in the above mentioned European patent application 0083486, these sulfated polysaccharides have relatively high molecular weights, are completely non-toxic, and are not 35 absorbed by the body even on considerable use in oral dental care compositions. Especially three first-mentioned sulfated polysaccharides, which are the pre¬ ferred ones, are cheap and readily available substances, which is a great advantage. They also exhibit a surprisingly good and extended effect, especially against tooth-loosening, which is assumed to result from a (more or less specific) binding to the mucous membranes in the mouth, e.g. in a tooth pocket between the teeth. The binding probably occurs with the sulfate groups turned outwards, whereby they are not inactivated by the binding. This capability of binding to the mucous membranes in the mouth probably depends on the special ring structure of the sulfated polysaccharides. The oral dental care compositions according to the invention may, in addition to the indicated sulfated polysaccharides and conventional inert carriers and/or diluents suitable for oral administration, also contain one or more other active dental care substances, provided that the same do not detrimentally affect the capability of the sulfated polysaccharides to inhibit collagen degradation. These inert carriers/diluents and other active dental care sub¬ stances respectively are, of course, chosen with regard to the special form of preparation and the intended method of use. In another aspect the invention relates to the use of the above indicated sulfated polysaccharides as anti-periodontoclasia agents and anti-caries agents. Description of Preferred Embodiments The sulfated polysaccharides which are especially preferred for use according to the invention are xylan sulfate, dextran sulfate, and starch sulfate. They are substantially non-toxic on oral administration in doses which inhibit the degrading of collagen, and they have a neutral or pleasant taste. The sulfated polysaccharides can be of any suitable molecular weight, but they preferably have a molecular weight in the interval about 2000-50,000, especially about 2000-20,000. As examples can be mentioned dextran sulfate of a molecular weight of about 2000-20,000, hyaluronic acid sulfate of a molecular weight of about 2000-50,000, starch sulfate of a molecular weight of about 2000-20,000, and xylan sulfate of a molecular weight of about 2000-15,000. As used herein the term "sulfated polysaccharides" also includes non-toxic salts, e.g. with such cations as metall ions (e.g. alkali metal, especially sodium salts), ammonium ions, and with organic bases such as amines. The sulfated polysaccharides used according to the invention, which for simplicity reasons will be called collagenase-inhibitors below, can be incorpo¬ rated into oral compositions by means of methods and means which are known as such, the formula of the composition, including the content of collagenase- inhibitor and the form of preparation, naturally being adapted to the intended method of use. The coilagenase-hinibitors can, e.g., be incorporated into tooth cleaning agents such as tooth paste, chewing gum or chewing tablets, mouth rinsing agents such as rinsing solutions, tablets or powders which are soluble in water or can be slurred in water, and the like. These oral preparations may contain well known inert adjuvants and/or other dental care agents. For example, tooth paste may contain suitable abrasives (such as silica), binders (such as hydroxy ethyl cellulose), etc. Rinsing tablets and powders, which are intended to be mixed with or dissolved/dispersed in e.g. water on use, can e.g. be prepared well known manner by means of well known vehicles (such as lactose and mannitol), binders (such as corn starch), etc. Chewing gums, suction or chewing tablets and the like may contain ingredients which are conventional for such products. The oral compositions according to the invention may urther contain e.g. sweeteners, taste improving agents, preserva¬ tives, thickeners, etc. The amount of collagenase-ϊnhibitor in the oral compositions according to the invention varies with regard to the chosen form of preparation, the specific collagenase-inhibitor used, the intended frequency of administration, the effect aimed at, etc. Very good results are achieved already at very low doses, e.g. of the order of 10 μg per 10 ml of a prepared rinsing solution, which is given 1 to 3 times daily with a rinsing time of one or a few minutes each time. This dosage can serve as a guideline for the dosage in the other forms of preparations, but it is not to be construed as any limitation of the invention, which is intended to comprise all dose levels giving the effect aimed at. The frequency of treatment normally ought to be at least once daily. The inhibiting effect on tooth-loosening and caries when using the coilagenase inhibitors according to the invention has been shown by the following test, in which teeth extracted from one and the same patient were used. Comparable teeth were paired in groups of two. An attack of caries was triggered by means of a coilagenase solution containing about 3 mg coilagenase per ml water. As a control that the coilagenase activity of the solution did not diminish with time, one drop of the solution was dropped onto a sheet of collagen every hour. A maintained coilagenase activity was observed during the entire test period by the ability of the solution to make a hole of drop size in the collagen sheet. As a model for demonstrating anti-tooth-loosening effect (Test 3) corresponding tests were carried out on extracted teeth having substantially intact collagen filaments and root cement. 5 mg of the preferred sulfated polysaccharide, viz. xylan sulfate, in 5 ml water was used as test solution. Test It Two first premoiars from the same mouth and with substantially uneffected enamel layer were kept immersed in coilagenase solution for 8 hours with and without (control) addition (5 ml) of the test solution. The teeth were examined with the naked eye, under microscope and mechanically with a spatula both before and after the test. The enamel layer of both teeth was substantially unchanged after the test, but a clear attack of caries on the control tooth was observed at the transition to the root. The test tooth was intact also in this area. Test 2; On two first premolars from the same mouth similar enamel damages were created mechanically. The same control and test solutions were used as in Test 1. One drop of each solution was applied to the respective enamel damage. On examination (with the naked eye, under microscope and by means of a spatula) after 8 hours the enamel damage was found to be unchanged on the test tooth, whereas the control tooth showed clear signs of beginning caries (discolouration, rough surface). Test 3; Two comparable premalars from the same mouth, having comparatively unaffected root cement and unaffected collagen filaments, were kept immersed in a coilagenase solution for hours. The test tooth had been pretreated by immersion in the above test solution (xylan sulfate) for 30 minutes. No pretreatment of the test tooth. After termination of the immersion in the coilagenase solution the teeth were examined under microscope. In the test tooth both the root cement and the collagen filaments were unaffected. In contrast both the root cement and the collagen filaments had been destroyed in the control tooth.

Claims: CLAIMS 1. An oral anti-tooth loosening and anti-caries composition, characterized in that it comprises a non-toxic, collagen degradation inhibiting amount of at least one sulfated poiysaccharide selected from the group consisting of xylan sulfate, dextran sulfate, starch sulfate, and hyaluronic acid sulfate, in combination with a non-toxic carrier. 2. The composition according to claim 1, characterized in that it is in the form of a tooth cleaning agent, a suction or chewing tablet, a chewing gum, a rinsing solution or a solid or liquid concentrate intended to form a rinsing solution by dissolution, dispersion or suspension in water or another liquid or liquid mixture. 3. The composition according to claim 1 or 2, characterized in that the sulfated poiysaccharide has a molecular weight in the interval about 2000-50,000, preferably about 2000-20,000. . The composition according to any one of claims 1 to 3, characterized in that the sulfated poiysaccharide is selected among xylan sul ate, dextran sulfate and starch sulfate. 5. Use of xylan sulfate, dextran sulfate, starch sulfate or hyaluronic acid sul ate as anti-tooth-loosening agents for oral administration. 6. Use of xylan sulfate, dextran sulfate, starch sulfate or hyaluronic acid sulfate as anti-caries agents for oral administartion. 7. Use according to claim 5 or 6, characterized in that the sulfated poiysaccharide has a molecular weight in the interval about 2000-50,000, especially about 2000-20,000. 8. Use according to claim 5 or 6, characterized in that the sulfated poiysaccharide is dextran sulfate, starch sulfate or xylan sulfate. 9. A method of inhibiting or preventing tooth-loosening, characterized by orally administering a periodontociasia-inhibiting amount of at least one sulfated poiysaccharide selected from the group consisting of xylan sulfate, dextran sulfate, starch sulfate, and hyaluronic acid sulfate, to a patient in need thereof. 10. A method of inhibiting or preventing caries, characterized by orally administering a caries-inhibiting amount of at least one sulfated poiysaccharide selected from the gorup consisting of xylan sulfate, dextran sulfate, starch sulfate, and hyaluronic acid sulfate, to a patent in need thereof.

Inventors: ANDERSSON BROR AXEL ERLING, LINDBLOM RAGNVALD ERIK, ANDERSSON, BROR, AXEL, ERLING, LINDBLOM, RAGNVALD, ERIK
Applicants: ANDERSSON A E BROR, LINDBLOM RAGNVALD ERIK, ANDERSSON, BROR, AXEL, ERLING, LINDBLOM, RAGNVALD, ERIK
Application year: 1984
Main classification: A61K7
IPC codes: A61K8, A61Q11