A proposed new method for the treatment of dry mouth.

Introduction The number of described remedies for xerostomia (Dry Mouth) are witness to the difficulty in treating this condition. References 1-7 indicate a representative sample of the fluids that have been used from time to time in an attempt to alleviate dry mouth. A measure of success has been claimed for most of these fluids, as any aqueous solution is likely to alleviate the patient's symptoms transiently. Indeed even warm drinks are partially effective. The problem is the very temporary nature of the relief obtained unless the fluid is continuously applied, which usually means a considerable measure of social inconvenience. Attempts to produce artificial salivas have usually been based on cellulose derivatives, which exhibit near Newtonian viscosity in solution in the concentrations which have been used. These solutions have been found unsatisfactory as they caused irritant accumulations to form in the mouth and sometimes caused soreness of the mucosa. Some subjects complained of unpleasant taste and at best the effect lasted for only an hour. We have found such solutions of very limited value to our patients. 'S(Gravenmade et al (7) tried to develop saliva using a solution containing an extract of bovine salivary glands. This was found to give relief from about -1j to 4 hours and cause less mucosal irritation than the methylcellulose solution. The volume of solution used per day was 3.5 ml on average. A small volume is important to the patient as it is necessary to administer repetitive doses. Their solution is currently under clinical trials in the Netherlands and may be found to be of some value. In our initial observation of this material it has been found to exhibit viscous properties but appears to lack the viscoelasticity which is characteristically shown by human mucus solutions including saliva. One further problem with this material is the heterogenous nature of the bovine salivary glycoproteins from which the base is derived and the rather complex extraction techniques required to produce a more homogenous solution for patient use. (The material is produced on a small scale commercially under the name of Saliva Orthana). We have attempted to produce a salivary mucus substitute which is synthetic but possesses similar rheological properties to the natural secretion, i.e. non-Newtonian viscosity and elasticity. The latter physical property was considered to be most important and is related to the ability of natural saliva to be drawn out into threads and remain in contact with a mucosal surface for a period of time, whilst simultaneously holding water molecules. It is the 'elastic components' that allow the liquid to deform under stress without flowing off the surface. Physical (rheological) experiments on many aqueous solutions confirm that methylcellulose lacks any elasticity. It is certain that the peculiar physical properties of natural saliva are directly related to its mucus content. It was felt that in reproducing a mucus like base with similar rheological properties an adequate substitute could be formulated. A characteristic of the mucus glycoprotein molecules is their high molecular weight and very large effective volume of the water solvent pervaded. The shape of the molecule has been likened to that of a bottle brush, the 'bristles' representing the sugar groups attached to a central protein core. Building such a molecule artificially presents many technical problems in biochemistry. Therefore a synthetic substitute was sought.