Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
  • A61K8/73—Polysaccharides
  • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

• 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).
• 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.
• the published European patent application 00S3 ⁇ 86 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.
• 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.
• no anti-periodontoclasia agents are known, despite the fact that such agents would meet a very great demand.
• the present invention aims at providing improved oral dental care
• 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
• 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
• 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
• 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.
• the sul ated polysaccharides used according to the invention are xyian sulfate, dextran sulfate, starch sulfate and hyaluronic acid sulfate.
• these sulfated polysaccharides have relatively high molecular weights, are completely non-toxic, and are not
• 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.
• active dental care substances provided that the same do not detrimentally affect the capability of the sulfated polysaccharides to inhibit collagen degradation.
• the invention relates to the use of the above indicated sulfated polysaccharides as anti-periodontoclasia agents and anti-caries agents.
• 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.
• dextran sulfate of a molecular weight of about 2000-20,000 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.
• 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.
• 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.
• the amount of collagenase- ⁇ nhibitor 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 ⁇ g 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.
• Test 2 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.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Cosmetics (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Birds (AREA)
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• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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• 1983
  • 1983-05-18 SE SE8302789A patent/SE8302789D0/xx unknown
• 1984
  • 1984-05-18 JP JP50220084A patent/JPS60501311A/ja active Pending
  • 1984-05-18 WO PCT/SE1984/000191 patent/WO1984004453A1/en not_active Application Discontinuation
  • 1984-05-18 EP EP19840902111 patent/EP0153925A1/de not_active Withdrawn

Non-Patent Citations (1)

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