WO2009078024A1

WO2009078024A1 - Device to supply artificial saliva

Info

Publication number: WO2009078024A1
Application number: PCT/IL2008/001638
Authority: WO
Inventors: Ora Kedem; Abraham Kedem
Original assignee: Yeda Research & Development Co. Ltd.
Priority date: 2007-12-18
Filing date: 2008-12-18
Publication date: 2009-06-25

Abstract

The present application provides a device (A) that supplies a continuous fluid flow to the mouth of a subject affected with dry mouth. Also provided, are v methods and composition that treat or improve dry mouth condition in a subject.

Description

DEVICE TO SUPPLY ARTIFICIAL SALIVA

FIELD OF THE INVENTION

[001] The invention provides devices, methods, and compositions for treating dry mouth.

BACKGROUND OF THE INVENTION

[002] Saliva is a complex fluid secreted by the major and minor salivary glands and the secretion is under the control of the autonomic nervous system. The three major salivary glands are parotid, sublingual and sub-mandibular. Daily secretion of saliva in human is about 1.5 liters and its normal pH is slightly alkaline (pH=7.4). Saliva contains organic aqueous medium. Besides glycoprotein, like mucin, it contains digestive enzymes such as lipase, amylase etc. Other compounds, such as lactoferrins, cystatin, histatin, thiocyanate ion and immunoglobulins are also present. Presence of lipids, both neutral and polar, has also been reported.

[003] Saliva has several distinct functions namely cleansing, lubrication, mucosal integrity, buffering, remineralisation, digestion and antimicrobial action. The saliva washes away the food particles from oral mucosa synchronously by the muscle activity, moving debris from teeth and soft tissues progressively towards the back of the mouth and eventually swallowing occurs. Glycoprotein's in saliva are responsible for the viscoelastic character of it giving a lubricative film, which enables free movement of oral tissues. The mucin and electrolytes in saliva maintains the oral mucosa in its hydrated state and thus providing mucosal integrity. The most prominent buffering agents in saliva are bicarbonate and phosphate ions and these agents protect the dentition from demineralization. Ions such as phosphate, calcium, and fluoride help for the remineralisation of teeth by promoting surface binding to the hydroxyapetite surface.

[004] Salivary gland dysfunction can be due to functional or morphological disorders resulting in qualitative and quantitative changes of saliva. Salivary gland dysfunction is a relatively common problem, which results in the symptoms of dry or scalded mouth, difficulties with speech, with eating, mucosal infections, denture intolerance, sialadenitis, increased dental caries and periodontal disease.

[005] Dry mouth (xerostomia) is a symptom. Although most frequently associated with alterations of salivary function, it is not synonymous with salivary gland disease. Xerostomia is not a reliable indicator of salivary hypo-function, and it should not be used as a diagnosis. One must distinguish between the symptom of oral dryness, signs of salivary dysfunction, and specific diagnoses of salivary disorders. The term xerostomia should be reserved for the description of the subjective impression of oral dryness and a specific diagnosis sought.

[006] Dry mouth in most, but not all, instances is related to reductions in salivary output. The most common causes of salivary hypo-function are medications, medical treatments, and systemic disease.

[007] Xerostomia can cause difficulty in speech and eating. It also leads to halitosis and a dramatic rise in the number of cavities, as the protective effect of saliva is no longer present, and can make the mucosa of the mouth more vulnerable to infection. Notably, a symptom of methamphetamine abuse usually called "meth mouth" is largely caused by xerostomia. Xerostomia may be a sign of an underlying disease, such as Sjogren's syndrome, poorly controlled diabetes, or Eaton-Lambert syndrome, but this is not always so.

[008] Other causes of insufficient saliva include anxiety, medications, or alcohol, trauma to the salivary glands or their ducts or nerves, dehydration, excessive mouth breathing, previous radiation therapy, and also a natural result of aging. The vast majority of elderly individuals will suffer xerostomia to some degree. Playing or exercising a long time outside on a hot day will often cause your saliva glands to simply dry up as your bodily fluids are concentrated elsewhere. Xerostomia is a common side-effect of various drugs, such as cannabis, dextromethorphan, and several antidepressants.

[009] Treatment involves finding any correctable causes and fixing those if possible. In many cases it is not possible to correct the xerostomia itself, and treatment focuses on relieving the symptoms and preventing cavities. Patients who have endured chemotherapy usually suffer from this post- treatment.

SUMMARY OF THE INVENTION

[0010] In one embodiment, the present invention provides a device for providing a substantially continuous fluid flow to the mouth of a subject, comprising: (a) a fluid container having a first end and a second end, with a mechanical pressure biasing means operably coupled to the container; and (b) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, wherein the fixing element is adapted for fixing said distal end of the tube in the mouth of a subject, and the proximal end of the tube is operably linked to the distal end of the container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed into the mouth of a subject.

[0011] In another embodiment, the present invention provides a device for providing a continuous fluid flow to the mouth of a subject, comprising: (a) a fluid container having a first end and a second end, with a mechanical pressure biasing means operably coupled to the container; and (b) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, wherein the fixing element is adapted for fixing said distal end of the tube in the mouth of a subject, and the proximal end of the tube is operably linked to the distal end of the container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed into the mouth of a subject.

[0012] In another embodiment, the invention further provides a device for providing a continuous fluid flow to the mouth of a subject, comprising: (a) a fluid container having a proximal end, a distal end, a basolateral end, and an apical end, with a pressure biasing means operably coupled to the container, wherein the basolateral end, and the apical end are connected by a pivot; and (b) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, wherein the fixing element is adapted for fixing the distal end of the tube in the mouth of a subject, and the proximal end of the tube is operably linked to the distal end of the container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed into the mouth of said subject.

[0013] In another embodiment, a continuous fluid flow is a substantially continuous fluid flow. In another embodiment, a substantially continuous fluid flow is continuous drip. In another embodiment, a substantially continuous fluid flow is perfusion. In another embodiment, a substantially continuous fluid flow is spatter.

[0014] In another embodiment, the invention further provides a method of providing a continuous fluid flow into the mouth of a subject comprising the step of applying a device for providing substantially continuous fluid flow of about 0.001-0.5 ml/minute to the mouth of a subject, wherein the device comprises: (a) a fluid container having a first end and a second end, with a mechanical pressure biasing means operably coupled to the container; and (b) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, wherein the fixing element is adapted for fixing the distal end of the tube in the mouth of a subject, and the proximal end of the tube is operably linked to the distal end of the container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed into the mouth of a subject, thereby providing a substantially continuous fluid flow to a subject.

[0015] In another embodiment, the invention further provides a method of providing a substantially continuous fluid flow into the mouth of a subject comprising the step of applying a device for providing a substantially continuous fluid flow of about 0.001-0.5 ml/minute to the mouth of a subject, wherein the device comprises: (a) a fluid container having a proximal end, a distal end, a basolateral end, and an apical end, with a pressure biasing means operably coupled to the container, wherein the basolateral end, and the apical end are connected by a pivot; and (b) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, wherein the fixing element is adapted for fixing the distal end of the tube in the mouth of a subject, and the proximal end of the tube is operably linked to the distal end of the container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of said subject, thereby providing a substantially continuous fluid flow to a subject.

BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is a schematic representation of a device for providing a substantially continuous fluid flow to the mouth-"device A". The device comprises a cylindrical container

(1) housing a spring (2) and an elongated rod (8) having a plunger (6). The external part of the rod (8) is thickened, thus forming a plug for the spring once it's compressed. Base (3) contains a tongue (7) which locks the spring's position. Tongue (7) can be displaced thus liberating the spring. A bag (4) filled with fluid is fitted into the cylindrical container (1). The bag has a circular plate (9). The tube (5) is fitted on the tube holder (11).

[0017] Figure 2 is a schematic representation of the tongue (7) based on a pivot. The pivot (12) allows the displacement of the tongue. Additionally, figure 2 provides a close-up of the biasing means comprising the spring (2) in a charged position.

[0018] Figure 3 is a schematic representation of a cross section of "device A" providing an insight into the junction of the bag's circular plate (9) connected to the tube holder (11). [0019] Figure 4 is a schematic representation showing placement of a device for providing a substantially continuous fluid flow to the mouth. Strap (17) attaches the device to a body part of the user. Tube 5 carries the fluid contained within the device into the mouth of a user.

[0020] Figure 5 is a schematic representation of a device using spiral springs as biasing means.

[0021] Figure 6 is a schematic representation of a device for providing a substantially continuous fluid flow to the mouth-"device C". Closing element (15) is attached to the base and closing niche (16) is situated near the edge of the top compartment. Pivot (13) connects the base and top portions of device C. The inner portion of the top compartment is equipped with an elastic layer (11) that balances the pressure exerted on the bag (4) containing the fluid. Closing element 15 on closing niche (16) actuates the biasing means which comprise all boundaries of device C. Pivot (13) connects the base and top portions.

[0022] Figure 7 is a schematic representation that provides an insight into "device C". Spring (2) balances the pressure exerted by connecting the top and the bottom compartment by closing element (15)-placing it on niche (16).

DETAILED DESCRIPTION OF THE INVENTION

[0023] In one embodiment, the invention provides a device for providing a substantially continuous fluid flow to the mouth of a subject, comprising: (a) a fluid container having a first end and a second end, with a mechanical pressure biasing means operably coupled to the container; and (b) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, adapted for fixing the distal end of the tube to the mouth of a subject, and the proximal end of the tube is operably linked to the distal end of the container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of said subject. In another embodiment, actuating the biasing means results in substantially constant and continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of said subject (figures 1, 2, and 5).

[0024] In another embodiment, the invention provides a device for providing a substantially continuous fluid flow to the mouth of a subject, comprising: (a) a container having a proximal end, a distal end, a basolateral end (bottom), and an apical end (top) (figure 7), with a pressure biasing means operably coupled to the container, wherein, the basolateral end, and the apical end of the container are connected by a pivot; (b) a bag comprised within the container; and (c) a tube serving as a flow regulator having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, and the proximal end of the tube is operably linked to the bag, wherein upon actuating the biasing means, a substantially continuous fluid flow is disposed to the mouth of a subject (figures 7-9).

[0025] In another embodiment, the invention provides a device for providing a substantially continuous fluid flow to the mouth of a subject, comprising: (a) a fluid container having a proximal end, a distal end, a basolateral end (bottom), and an apical end (top), with a pressure biasing means operably coupled to the container, wherein, the basolateral end, and the apical end are connected by a pivot; and (b) a tube serving as a flow regulator having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, and the proximal end of the tube is operably linked to the distal end of the container, wherein upon actuating the biasing means, a substantially continuous fluid flow is disposed to the mouth of a subject.

[0026] In another embodiment, the invention provides a device for providing a substantially continuous fluid flow to the mouth of a subject, comprising: (a) a container having a proximal end, a distal end, a basolateral end, and an apical end, with a pressure biasing means operably coupled to the container, wherein the basolateral end, and the apical end of the container are connected by a pivot; (b) a bag comprising fluid placed or housed within the container; and (c) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element. In another embodiment, the fixing element is adapted for fixing the distal end of the tube in the mouth of a subject. In another embodiment, the proximal end of the tube is operably linked to the bag. In another embodiment, upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of a subject (figures 7-9).

[0027] In another embodiment, the device is a square box. In another embodiment, the device is rounded. In another embodiment, the device is a rectangular, hi another embodiment, the device comprises any geometrical shape known to one of skill in the art.

[0028] In another embodiment, the device of the invention is disposable. In another embodiment, the device of the invention is reusable. In another embodiment, the device of the invention is reusable but comprises disposable parts. In another embodiment, disposable parts comprise a bag contained within the container. In another embodiment, the bag comprises a fluid. In another embodiment, a tube is disposable. In another embodiment, the term disposable comprises a single use. In another embodiment, the term disposable comprises 2-100 uses. In another embodiment, the term disposable comprises 2-10 uses. In another embodiment, the term disposable comprises 10-30 uses. In another embodiment, the term disposable comprises 20-50 uses. In another embodiment, the term disposable comprises 40-80 uses. In another embodiment, the term disposable comprises 60-100 uses.

[0029] In another embodiment, the pressure biasing means is coupled to the proximal end of the container. In another embodiment, the pressure biasing means is located at the proximal end of the container. In another embodiment, the pressure biasing located at the distal end of the container. In another embodiment, the pressure biasing means is connected to the device via a tube.

[0030] In another embodiment, the pressure biasing means comprises a spring (2) and an elongated rod (8) having a plunger (6) (Figures 1-3 and 5-6). In another embodiment, the pressure biasing means comprises a cap. In another embodiment, the external part of the rod (8) is thickened, thus forming a plug for the spring once it's compressed, hi another embodiment, the rod comprises a plunger on its proximal end. hi another embodiment, the rod comprises a cap on its distal end and a plunger on its proximal end. In another embodiment, the plunger is made of an elastic material. In another embodiment, the plunger is made of a hardened plastic material, hi another embodiment, the plunger is made of metal.

[0031] In another embodiment, a tongue (7) serves as a stopper. In another embodiment, the tongue serving as a stopper fixes the spring in a locked position. In another embodiment, the tongue serving as a stopper fixes the spring in a compressed position. In another embodiment, the tongue serving as a stopper fixes the spring in a position wherein the position is characterized by stored energy, hi another embodiment, the release of the tongue serving as a stopper initiates the pressure biasing means (see figures 1, 2, and 5).

[0032] In another embodiment, the spring is a flexible [elastic] object used to store mechanical energy. In another embodiment, the spring is made of hardened steel, hi another embodiment, the spring is a ferrous spring. In another embodiment, the spring is a non- ferrous metal spring. In another embodiment, the spring is made of phosphor bronze. In another embodiment, the spring is made of beryllium copper.

[0033] In another embodiment, the spring has a compliance of 0.01-10 mm/N. In another embodiment, the spring has a compliance of 0.01-0.05 mm/N. In another embodiment, the spring has a compliance of 0.02-0.08 mm/N. In another embodiment, the spring has a compliance of 0.07-0.12 mm/N. In another embodiment, the spring has a compliance of

0.12-0.18 mm/N. In another embodiment, the spring has a compliance of 0.18-0.5 mm/N. In another embodiment, the spring has a compliance of 0.5-1 mm/N. In another embodiment, the spring has a compliance of 1-3 mm/N. In another embodiment, the spring has a compliance of 3-5 mm/N. In another embodiment, the spring has a compliance of 5-10 mm/N.

[0034] In another embodiment, the spring is a coil spring. In another embodiment, the spring is a helical spring. In another embodiment, the spring is a tension spring. . In another embodiment, the spring is a compression spring designed to become shorter when loaded. In another embodiment, the spring is a volute spring. In another embodiment, the spring is a leaf spring.

[0035] In another embodiment, the pressure biasing means comprise an elastic layer pressed against the fluid, hi another embodiment, the pressure biasing means comprise an elastic layer pressed against a bag comprising fluid placed within the container (Figures 7- 9). In another embodiment, pressure is exerted through the use of a closing element such as but not limited to element 15 in figure 7. In another embodiment, one of skill in the art can use any known pressing apparatus as a pressure biasing means.

[0036] In another embodiment, an electrical pump is used as a pressure biasing means. In another embodiment, an electrical pump provides substantially continuous flow. In another embodiment, an electrical pump provides substantially constant and continuous flow. In another embodiment, the pump is a rotodynamic pump. In another embodiment, the pump is a positive displacement pump. In another embodiment, the pump is a compressed air- powered diaphragm pump. In another embodiment, the pump is a compressed air-powered double-diaphragm pump. In another embodiment, the pump is a kinetic pump. In another embodiment, the pump is a peristaltic pump.

[0037] In another embodiment, the pump is powered by alternating current. In another embodiment, the pump is powered by direct current. In another embodiment, an electrical system suitable to the device of the invention is well known to one of skill in the art.

[0038] In another embodiment the container is made of materials comprising plastic. In another embodiment the container is made of materials comprising rubber. In another embodiment the container is made of materials comprising metal.

[0039] In another embodiment, the container comprises a volume of 5-lOOOcc. In another embodiment, the container comprises a volume of 5-lOcc. hi another embodiment, the container comprises a volume of 10-20cc. In another embodiment, the container comprises a volume of 20-40cc. In another embodiment, the container comprises a volume of 30-60cc. In another embodiment, the container comprises a volume of 40-lOOcc. In another embodiment, the container comprises a volume of 70-120cc. In another embodiment, the container comprises a volume of 100-150cc. In another embodiment, the container comprises a volume of 120-180cc. In another embodiment, the container comprises a volume of 170-220cc. In another embodiment, the container comprises a volume of 200- 250cc. In another embodiment, the container comprises a volume of 250-300cc. In another embodiment, the container comprises a volume of 300-500cc. In another embodiment, the container comprises a volume of 400-600cc. In another embodiment, the container comprises a volume of 500-700cc. In another embodiment, the container comprises a volume of 600-800cc. In another embodiment, the container comprises a volume of 700- 900cc. In another embodiment, the container comprises a volume of 800-lOOOcc.

[0040] In another embodiment, the bag comprises a volume of 5-1000cc. In another embodiment, the bag comprises a volume of 5-10cc. In another embodiment, the bag comprises a volume of 10-20cc. In another embodiment, the bag comprises a volume of 20- 40cc. In another embodiment, the bag comprises a volume of 30-60cc. In another embodiment, the bag comprises a volume of 40-100cc. In another embodiment, the bag comprises a volume of 70-120cc. In another embodiment, the -bag comprises a volume of 100-150cc. In another embodiment, the bag comprises a volume of 120-180cc. In another embodiment, the bag comprises a volume of 170-220cc. In another embodiment, the bag comprises a volume of 200-250cc. In another embodiment, the bag comprises a volume of 250-300cc. In another embodiment, the bag comprises a volume of 300-500cc. In another embodiment, the bag r comprises a volume of 400-600cc. In another embodiment, the bag comprises a volume of 500-700cc. In another embodiment, the bag comprises a volume of 600-800cc. In another embodiment, the bag comprises a volume of 700-900cc. In another embodiment, the bag comprises a volume of 800-lOOOcc.

[0041] In another embodiment, the tube is connected to the container via a tube holder (11). In another embodiment, the tube holder has a conical shape. In another embodiment, the tube holder can fit various tubes having a diameter range that fits a conical tube holder. In another embodiment, the tube holder further comprises protrusions that further anchor the tube. In another embodiment the tube holder connects to an adapting device that connects the tube to the tube holder.

[0042] In another embodiment, the tube is 5-300 cm long. In another embodiment, the tube is 5-15 cm long. In another embodiment, the tube is 15-30 cm long. In another embodiment, the tube is 30-50 cm long. In another embodiment, the tube is 50-100 cm long. In another embodiment, the tube is 80-150 cm long. In another embodiment, the tube is 100-200 cm long. In another embodiment, the tube is 150-250 cm long. In another embodiment, the tube is 200-300 cm long.

[0043] In another embodiment, the proximal end of the tube is connected to the container. In another embodiment, the proximal end of the tube is connected to the distal end of the container. In another embodiment, the proximal end of the tube comprises an insertion end. In another embodiment, the insertion end comprises a spigot end.

[0044] In another embodiment, the proximal end of the tube is connected to the bag. In another embodiment, the bag comprises a proximal end and a distal end. hi another embodiment, the bag's proximal end and distal end are housed within the container in accordance with the container's proximal end and distal end. In another embodiment, the proximal end of the tube is connected to the proximal end of the bag. In another embodiment, the proximal end of the tube is connected to the distal end of the bag. In another embodiment, the proximal end of the tube comprises an insertion end. In another embodiment, the insertion end comprises a spigot end.

[0045] In another embodiment, the tube is made of non-toxic materials. In another embodiment, the tube is made of materials comprising plastic. In another embodiment, the tube is made of materials comprising MTSA PVC. In another embodiment, a tube comprising MTSA PVC has a density of 1.1-1.3 kg/m³. In another embodiment, the tube is made of materials comprising Styrene-ethylene/butylene-styrene copolymer (SEBS). In another embodiment, a tube comprising SEBS has a density of 0.8-1 kg/m³. hi another embodiment, the tube is made of materials comprising Poly (ethylene vinyl acetate) (EVA). In another embodiment, a tube comprising EVA has a density of 0.8-1 g/cm³. In another embodiment, the tube is made of materials comprising Polyethylene (LDPE). In another embodiment, a tube comprising LDPE has a density of 0.8-1 g/cm³. In another embodiment, the tube is made of materials comprising Ethylene/Polypropylene Statistical Copolymer. In another embodiment, a tube comprising Ethylene/Polypropylene Statistical Copolymer has a density of 0.8-1 g/cm³. In another embodiment, the tube is made of materials comprising Polyurethane thermoplastics (PUT). In another embodiment, a tube comprising PUT has a density of 0.9-1.6 g/cm³.

[0046] In another embodiment, the tube is a multi-lumen tube. In another embodiment, the tube is a multi-layered tube. In another embodiment, the tube is a bulb tube. In another embodiment, a bulb tube comprises variable cross-sections (the diameter expands over a restricted length). In another embodiment, the tube is a star-shaped tube. In another embodiment, a star-shaped tube comprises extruded sections that can be of almost any shape.

[0047] In another embodiment, the tube comprises an intermediate portion located in between the proximal and the distal ends of the tube. In another embodiment, the tube comprises an elastic deformable body arranged in a hollow in the tube wall. In another embodiment, the tube further comprises sealing elements concurring with the tube. In another embodiment, the tube is suitable to produce a flow passage for a fluid, such as a liquid, hi another embodiment, the tube is provides suitable means of flow passage for a fluid, such as a liquid. In another embodiment, the devices of the invention are provided with coupling elements which firmly mount the tube to the device. In another embodiment, coupling elements of the invention prevent fluid leakage from the device. In another embodiment, coupling elements seal the device. In another embodiment, coupling elements prevent contamination of the device and/or the fluid located in the container.

[0048] In another embodiment, the distal end of the tube comprises tapered end. In another embodiment, the proximal end of the tube portion is configured as a muff the bore of which converges conically inwards towards the device. In another embodiment, the size of the mentioned tapered parts is adapted to the material of the coupling elements in such a manner that the parts can remain in their coupled position by means of friction or gluing.

[0049] In another embodiment, the tube comprises a single wall, hi another embodiment, the tube comprises a first wall and flange constitute together with the corresponding recesses a labyrinth sealing which offers extraordinary strong sealing against leaking out of fluid from the flow passage or against leaking in of contamination into the flow passage. In another embodiment, if the fluid in the flow passage is under pressure it offers the advantage that the sealing elements comprise a second wall which extends parallel to the first wall and is configured to abut against the inner wall of the intermediate portion of the tube. In another embodiment, the fluid pressure pushes the second wall against the inner wall of the tube thus improving the sealing. In another embodiment, the invention provides that the tube serves as a flow regulator. In another embodiment, the invention provides a kit comprising a device and a set of tubes with varying physical characteristics that provide various flow rates.

[0050] hi another embodiment, the flow passage within the tube comprises a diameter of 0.1-1 cm. In another embodiment, the flow passage within the tube comprises a diameter of 0.1-0.2 cm. In another embodiment, the flow passage within the tube comprises a diameter of 0.2-0.3 cm. In another embodiment, the flow passage within the tube comprises a diameter of 0.3-0.4 cm. In another embodiment, the flow passage within the tube comprises a diameter of 0.4-0.5 cm. In another embodiment, the flow passage within the tube comprises a diameter of 0.5-0.6 cm. In another embodiment, the flow passage within the tube comprises a diameter of 0.6-0.8 cm. In another embodiment, the flow passage within the tube comprises a diameter of 0.8-1 cm.

[0051] In another embodiment, the tube comprises a diameter of 0.3-2 cm. In another embodiment, the tube comprises a diameter of 0.3-0.4 cm. In another embodiment, the tube comprises a diameter of 0.4-0.5 cm. In another embodiment, the tube comprises a diameter of 0.5-0.6 cm. In another embodiment, the tube comprises a diameter of 0.6-0.7 cm. In another embodiment, the tube comprises a diameter of 0.7-0.8 cm. In another embodiment, the tube comprises a diameter of 0.8-1.2 cm. In another embodiment, the tube comprises a diameter of 1.2-1.5 cm. In another embodiment, the tube comprises a diameter of 1.5-1.8 cm. In another embodiment, the tube comprises a diameter of 1.8-2 cm.

[0052] In another embodiment, the tube comprises a fixing element at its distal end. In another embodiment, the tube comprises a fixing element 1-15 cm before its distal end. In another embodiment, the tube comprises a fixing element 1-5 cm before its distal end. In another embodiment, the tube comprises a fixing element 5-10 cm before its distal end. In another embodiment, the tube comprises a fixing element 10-15 cm before its distal end.

[0053] In another embodiment, the fixing element maintains the tube in the mouth of a subject. In another embodiment, the fixing element holds the tube in the mouth of a subject. In another embodiment, the fixing element anchors the tube into the mouth of a subject. In another embodiment, the fixing element is found dental appliances. In another embodiment, the fixing element can be a metal within the tube that serves to shape the tube. In another embodiment, the fixing element is a metal within the tube that serves to shape the tube in a hook like shape, hi another embodiment, the fixing element is a mouth piece holding the proximal end of the tube in the subject's mouth. .

[0054] In another embodiment, the mouth piece is a spigot on the proximal end of the tube or fitting inserted into a bell mouth of another adjoining tube or fitting and held fixed by lead or the like. In another embodiment, the mouth piece is rigid. In another embodiment, the mouth piece permits or provide for angular deflection of the tube length. In another embodiment, the mouth piece is an annular resilient gasket disposed about the spigot, hi another embodiment, the gasket is held in compression between the spigot and bell mouth surfaces. In another embodiment, the spigot and bell mouth are held locked against lengthwise axial displacement by metal clips molded into the sealing gasket and co-acting upon being bent with grooves in the spigot to restrain separation of the tube sections.

[0055] In another embodiment, the mouth piece is a ball and socket joint. In another embodiment, the spigot is deformed into a convex cylindrical surface which seats with a complementary concave surface in the bell mouth. In another embodiment, an annular locking collar is provided on the spigot for locking engagement with the bell mouth.

[0056] In another embodiment, the mouth piece is an annular locking collar disposed about the spigot and co-acts with a bell mouth restraining flange to prevent axial separation of the pipe sections. The locking collar is mounted on the spigot to permit limited axial misalignment of the spigot and bell mouth longitudinal axis.

[0057] In another embodiment, the mouth piece provides an improved boltless type of tube joint which permits limited longitudinal axial misalignment of the spigot and bell mouths while at the same time providing a lock preventing lengthwise axial separation of the joint.

[0058] In another embodiment, the mouth piece is a restrainer assembly. In another embodiment, the restrainer assembly comprises an inner collar or retainer ring slidably disposed over the spigot and having a concave surface which engages the spigot ring. In another embodiment, the retainer ring is held fixed relative to the spigot ring by a snap ring which seats in a groove formed in the collar so that a flange projecting from the assembly underlies the lip about the bell mouth. In another embodiment, the provision of the concave surface accommodates limited axial misalignment of the spigot and bell mouth.

[0059] In another form of the invention the restraining assembly comprises a retainer ring and concentric outer sleeve disposed about the spigot. In another embodiment, the inner surface of the retainer ring is provided with a concave surface which engages the spigot ring fastened to the spigot as described above.

[0060] In another embodiment, the fixing element fixes the tube to the subject's head. In another embodiment, the fixing element comprises a tube clamping means which can be attached to the tube in a detachable manner, which tube clamping means is provided with positioning means connected thereto, which position the tube clamping means during use with the help of flexible, detachable securing means that arc to be arranged around the patient's head, the tube clamping means being designed such that it can be clamped around the tube after arranging the tube in the patient's mouth without disturbing the location of the tube.

[0061] In another embodiment, the fixing element has a body which is secured by a pair of non-stretchable, head encircling straps to overlie the subject's mouth and portions of the cheeks. In another embodiment, the straps, which are adapted to extend, one above and the other below, the subject's ears, have one-way tightening adjustability by pawl action. In another embodiment, the body is integrally molded to incorporate a quick-acting clamp having three integral hinges, one hinge pivotally connecting a pair of jaws of the clamp and the other two hinges supporting the jaws from resilient arms for snap-action between open and closed positions. In another embodiment, the clamp is operative to secure or release the tube while the straps retain the body in position on the mouth against dislodgment.

[0062] In another embodiment, the fixing element is a faceplate including a central, wide, closed-end slot, substantially equal in width to the width of the subject's mouth and the slot having spaced upper and lower edges generally in parallelism and equally spaced apart. In another embodiment, integral, oppositely disposed pairs of bendable prongs are provided along the edges of the slot to define a right side aperture, a central aperture and a left side aperture.

[0063] In another embodiment, a mouthpiece, preferably of plastic is mounted for sidewise sliding movement in the slot, held in place by front and rear flanges and having an axial bore generally normal to the face plate, a tubular bite block portion and a tubular guide portion. In another embodiment, the portion of the tubular mouthpiece between the front and rear flanges is flat at top and bottom to slide in the slot but to prevent turning.

[0064] In another embodiment, the mouthpiece of the stabilizer is not only slides sidewise in a central, wide, closed end, slot in the faceplate but itself is provided with a flared, full length, slot having an opening which is substantially smaller than the outside circumference of the compressible tube. In another embodiment, the tube may be compressed to pass the opening so that expansion to normal circumference retains the tube in the slot.

[0065] In another embodiment, the mouthpiece is straight and provided with an integral, outwardly projecting, fixation flange, in the intermediate portion of its length, the full length slot flaring out into the flange and there being tape holes in each quadrant around the flange for fastening tapes extending around the head of the patient.

[0066] In another embodiment, the tube is secured in place by any of a variety of means including adhesive tape applied to the facial area of the subject or a tube holder which includes a bite block that the patient grips in his teeth. In another embodiment, the bite block serves the purpose of allowing the subject something to bite on in normal response to the insertion and presence of the tube. In another embodiment, the fixing element comprises a tube lock means for securing the tube in place with respect to the face plate of the tube holder.

[0067] In another embodiment, the fixing element includes a faceplate configured to be positioned against a subject's face and adjacent the patient's mouth. In another embodiment, the faceplate includes an elongated guide track in a guide track portion therein, with the guide track portion configured to be positioned beneath the patient's mouth. In another embodiment, the tube holder also includes a tube platform attached to the guide track portion of the faceplate and configured to carry a tube thereon. In another embodiment, a slide means provided for moving the tube platform along the guide track. In another embodiment, a locking means is included for locking the endotracheal tube platform to one of a plurality of locations along the guide track.

[0068] In another embodiment, the faceplate can include a first side portion and a second side portion spaced therefrom. In another embodiment, the guide track portion extends between the side portions along their lower edges. In another embodiment, the side portions are substantially taller than the narrower guide track portion. In another embodiment, the faceplate forms a U-shaped structure which is configured such that the side portions contact a subject's cheeks on opposite sides of the subject's mouth and the guide track portion contacts the subject's chin.

[0069] In another embodiment, a resilient bite block can be attached to and aligned with the tube platform and configured to carry a tube thereon. In another embodiment, the bite block can include a pair of opposed resilient arms extending outwardly from a rear surface of the tube platform. In another embodiment, a securement means, such as a pair of opposed locking tabs, can be provided on the tube platform for securing an endotracheal tube thereto. In another embodiment, a mounting harness is attached to the faceplate and wraps around the patient's neck to securely attach the tube holder to the subject's face.

[0070] In another embodiment, the fixing element includes two separate parts, the face anchor and the tube cradle. In another embodiment, the face anchor has buckles which hold a head harness. In another embodiment, the face anchor is made of a material which allows it to conform to the contours of the face of the subject. In another embodiment, the face anchor also has a pivot hole to which the tube cradle is affixed by a pivot. In another embodiment, the tube moves transversely across the mouth due to the pivoting action of the tube cradle. In another embodiment, the tube cradle has a "living hinge" which allows the tube to move longitudinally.

[0071] In another embodiment, the fixing element comprises a ring made of metal. In another embodiment, the fixing element comprises a ring made of an elastic non-toxic material. In another embodiment, the ring fixes the tube to a tooth. In another embodiment, the ring fixes the tube to the tongue. In another embodiment, an elastic band fixes the tube to the tongue.

[0072] In another embodiment, the fixing element is removable. In another embodiment, the fixing element is disposable. In another embodiment, the fixing element is reusable. In another embodiment, the fixing element is inserted into the subject's mouth by a dentist. In another embodiment, methods and means for inserting a fixing element into a subject's mouth is known to one of skill in the art.

[0073] In another embodiment, the device of the present invention provides continues aerosol flow. In another embodiment, the device of the present invention provides continues droplet flow. In another embodiment, the device of the present invention provides a continuous spray. In another embodiment, the device of the present invention provides a continuous fluid flow.

[0074] In another embodiment, actuating the biasing means results in a substantially continuous fluid flow of about 0.001-0.5 ml/minute, hi another embodiment, actuating the biasing means results in a substantially continuous fluid flow of about 0.001-0.01 ml/minute. In another embodiment, actuating the biasing means results in a substantially continuous fluid flow of about 0.001-0.05 ml/minute. In another embodiment, actuating the biasing means results in a substantially continuous fluid flow of about 0.01-0.05 ml/minute. In another embodiment, actuating the biasing means results in a substantially continuous fluid flow of about 0.01-0.1 ml/minute. In another embodiment, actuating the biasing means results in a substantially continuous fluid flow of about 0.01-0.5 ml/minute. In another embodiment, actuating the biasing means results in a substantially continuous fluid flow of about 0.05-0.1 ml/minute. In another embodiment, actuating the biasing means results in a substantially continuous fluid flow of about 0. 1-0.5 ml/minute.

[0075] In another embodiment, the device further comprises a control means. In another embodiment, control means control the maximal flow rate. In another embodiment, control means control the minimal flow rate. In another embodiment, control means control the maximal and minimal flow rates. In another embodiment, the control means is the tube. In another embodiment, the tube elasticity provides the control means. In another embodiment, the tube diameter provides the control means. In another embodiment, the control means comprises plurality of mechanisms such as but not limited to a pump, and a tube.

[0076] In another embodiment, the control means is a physical assembly placed on or within the tube. In another embodiment, the physical assembly can increase the tube diameter thus increasing the flow rate. In another embodiment, the physical assembly can decrease the tube diameter thus decreasing the flow rate. In another embodiment, the physical assembly can both decrease and increase the tube diameter thus decreasing and increasing the flow rate, accordingly.

[0077] In another embodiment, the control means comprises controlling the pressure of fluids exerted on the tube. In another embodiment, the control means comprises controlling the pressure exerted by a pump. In another embodiment, the control means comprises controlling the pressure exerted on a plunger.

[0078] In another embodiment, the invention provides a bag filled with a fluid. In another embodiment, the invention provides that the bag is contained within the container. In another embodiment, the invention provides that the bag is placed in the container. In another embodiment, the bag's volume is adapted to the containers volume. In another embodiment, the bag's shape is adapted to the containers shape. In another embodiment, the invention provides that the bag comprises a port or an extension that connects to the tube. In another embodiment, the invention provides that the bag comprises a port or an extension that connects to a connecting element. . In another embodiment, the invention provides that the connecting element interconnects the bag and the tube.

[0079] In another embodiment, the bag is made of a medical grade material. In another embodiment, the bag is made of PVC. In another embodiment, the bag is made of silicon. In another embodiment, the bag is made of nitrile. In another embodiment, the bag is made of plastic. In another embodiment, the bag is further coated with a thermal insulation layer.

In another embodiment, the bag is disposable. In another embodiment, the bag is reusable.

In another embodiment the bag further comprises means for securing it to the container

(figure 1). In another embodiment the bag further comprises an elongated port which extends outwards and further connects to the tube. In another embodiment the bag is constructed according to methods known to one of skill in the art. [0080] In another embodiment the bag is elastic. In another embodiment the bag can withstand the pressure exerted on it by the pressure biasing means. In another embodiment, the bag further comprises a filling port that withstands the pressure exerted on it by the pressure biasing means. In another embodiment, the filling port is used to refill the bag with fluid. In another embodiment, the filling port is used to refill the bag with an active pharmaceutical ingredient. In another embodiment, the filling port is used to refill the bag with an excipient.

[0081] In some embodiments, the bag comprises a composition of the present invention. In some embodiments, the container comprises a composition of the present invention. In another embodiment, the composition of the present invention comprises water. In another embodiment, the composition of the present invention comprises mouth moisturizing solution or fluid. In another embodiment, the composition of the present invention comprises artificial saliva. In another embodiment, the composition of the present invention comprises isotonic fluid. In another embodiment, the composition of the present invention comprises a stabilizer. In another embodiment, the composition of the present invention comprises a preservative. ,

[0082] In one embodiment, the present invention provides combined preparations. In one embodiment, the term "a combined preparation" defines especially a "kit of parts" in the sense that the combination partners as defined above can be dosed independently or by use of different fixed combinations with distinguished amounts of the combination partners i.e., simultaneously, concurrently, separately or sequentially. In some embodiments, the parts of the kit of parts can then, e.g., be administered simultaneously or chronologically staggered, that is at different time points and with equal or different time intervals for any part of the kit of parts. The ratio of the total amounts of the combination partners, in some embodiments, can be administered in the combined preparation. In one embodiment, the combined preparation can be varied, e.g., in order to cope with the needs of a patient subpopulation to be treated or the needs of the single patient which different needs can be due to a particular disease, severity of a disease, age, sex, or body weight as can be readily made by a person skilled in the art.

[0083] In another embodiment, artificial saliva comprises water. In another embodiment, artificial saliva comprises glycoproteins. In another embodiment, artificial saliva comprises enzymes. In another embodiment, artificial saliva comprises antimicrobial substances. In another embodiment, artificial saliva comprises carboxymethylcellulose. In another embodiment, artificial saliva comprises xanthan gum. In another embodiment, artificial saliva comprises electrolytes. In another embodiment, artificial saliva comprises a muco- adhesive polymer. In another embodiment, artificial saliva comprises phospholipids, hi another embodiment, artificial saliva comprises mucin. In another embodiment, artificial saliva comprises potassium chloride. In another embodiment, artificial saliva comprises sodium chloride. In another embodiment, artificial saliva comprises magnesium chloride. In another embodiment, artificial saliva comprises cCalcium chloride. In another embodiment, artificial saliva comprises Di-potassium hydrogen orthophosphate. In another embodiment, artificial saliva comprises potassium di-hydrogen orthophosphate. In another embodiment, artificial saliva comprises sodium fluoride. In another embodiment, artificial saliva comprises sorbitol. In another embodiment, artificial saliva comprises methyl p- hydroxybenzoate. In another embodiment, artificial saliva comprises spirit of lemon.

[0084] In another embodiment, artificial saliva is a viscoelastic fluid with distinct surface activity. In another embodiment, artificial saliva is a Newtonian fluid, hi another embodiment, artificial saliva is a shear-thinning fluid. In another embodiment, artificial saliva comprises viscosity of 7.0 - 3.0 at shear rates 0.5 - 94.5 s-1. In another embodiment, the present invention provides that shear thinning property is essential to ensure proper flow and cleansing action. In another embodiment, artificial saliva comprises minimum surface tension of 30mN/m. In another embodiment, artificial saliva comprises minimum surface tension of 40mN/m. hi another embodiment, artificial saliva comprises minimum surface tension of 50mN/m. In another embodiment, artificial saliva comprises minimum surface tension of 60mN/m. hi another embodiment, artificial saliva comprises minimum surface tension of 70mN/m.

[0085] In another embodiment, the composition of the present invention further comprises a drug. In another embodiment, the drug is a xerostomia drug. In another embodiment, the xerostomia drug is fluoride. In another embodiment, the xerostomia drug is a re- mineralizing solution. In another embodiment, the xerostomia drug is an antifungal. . In another embodiment, the xerostomia drug is bromhexine. In another embodiment, the xerostomia drug is anetholetrithione. . In another embodiment, the xerostomia drug is pilocarpine hydrochloride. [0086] In another embodiment, the composition of the present invention further comprises a steroid. In another embodiment, the composition of the present invention further comprises a nonsteroidal anti-inflammatory drug. In another embodiment, the composition of the present invention further comprises an anti-rheumatic drug. In another embodiment, the composition of the present invention further comprises a cytokine. In another embodiment, the composition of the present invention further comprises an anti-cytokine reagent.

[0087] In another embodiment, the composition of the present invention further comprises an anti-cancer agent. In another embodiment, the composition of the present invention further comprises an immuno-modulating agent. In another embodiment, the composition of the present invention further comprises an anti-diabetic agent. In another embodiment, the composition of the present invention further comprises an agent treating the nervous system. In another embodiment, the composition of the present invention further comprises an agent treating the cardiovascular system. In another embodiment, the composition of the present invention further comprises an agent treating the gastrointestinal system. In another embodiment, the composition of the present invention further comprises an agent treating a dermatological disorder. In another embodiment, the composition of the present invention further comprises an anti-infective agent. In another embodiment, the composition of the present invention further comprises an agent treating the liver. In another embodiment, the composition of the present invention further comprises an agent treating the kidney. In another embodiment, the composition of the present invention further comprises an agent treating a metabolic disease. In another embodiment, the composition of the present invention further comprises an agent treating a wasting disease. In another embodiment, the composition of the present invention further comprises a gene therapy agent. In another embodiment, the composition of the present invention further comprises an agent treating the endocrine system. In another embodiment, the composition of the present invention further comprises vitamins. In another embodiment, the composition of the present invention further comprises stomatognathic agent. In another embodiment, the composition of the present invention further comprises urogenital agent. In another embodiment, the composition of the present invention further comprises behavior-modulating agent. In another embodiment, the composition of the present invention further comprises an agent treating the respiratory tract. In another embodiment, the composition of the present invention further comprises an agent treating the hemic system. In another embodiment, the composition of the present invention further comprises an agent treating the lymphatic system. In another embodiment, the composition of the present invention further comprises an agent treating a connective tissue. In another embodiment, the composition of the present invention further comprises an agent treating an ophthalmic disease. In another embodiment, the composition of the present invention further comprises any compound known to be effective in treating the condition of a subject by one of skill in the art. In another embodiment, the composition of the present invention further comprises any combination of compounds known to be effective in treating the condition of a subject by one of skill in the art.

[0088] In another embodiment, the invention provides a system comprising a xerostomia drug and a device of the invention. In another embodiment, the invention provides a system comprising a disposable pre-filled saliva bag and the device of the invention.

[0089] In another embodiment, the invention provides a kit comprising a xerostomia drug and a device of the invention. In another embodiment, the invention provides a kit comprising a drug of the invention and a device of the invention. In another embodiment, the invention provides a kit comprising a disposable pre-filled saliva bag and the device of the invention. In another embodiment, the invention provides a kit with multiple tubes of the invention providing different flow rates. In another embodiment, the invention provides a kit with multiple tubes of the invention providing different pre-selected flow rates.

[0090] In another embodiment, the invention provides a method of providing a substantially continuous flow of moisturizing fluid into the mouth of a subject comprising the step of applying a device for providing a substantially continuous fluid flow of about 0.001-0.5 ml/minute to the mouth of a subject, wherein the device comprises: (a) a fluid container having a first end and a second end, with a mechanical pressure biasing means operably coupled to the container; and (b) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element. In another embodiment, the fixing element is adapted for fixing said distal end of the tube in the mouth of a subject. In another embodiment, the proximal end of the tube is operably linked to the distal end of the container. In another embodiment, upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of a subject, thereby providing a substantially continuous fluid flow to a subject. [0091] In another embodiment, the invention provides a method of providing a substantially continuous fluid flow into the mouth of a subject comprising the step of applying a device for providing a substantially continuous moisturizing fluid flow of about 0.001-0.5 ml/minute to the mouth of a subject, wherein said device comprises: (a) a container having a proximal end, a distal end, a basolateral end, and an apical end, with a pressure biasing means operably coupled to a container, wherein the basolateral end (bottom), and the apical (top) end are connected by a pivot (see figure 7); (b) a bag housed within the container; and (c) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element. In another embodiment, the fixing element is adapted for fixing the distal end of the tube in the mouth of a subject. In another embodiment, the proximal end of the tube is operably linked to the bag. In another embodiment, the proximal end of the tube is operably linked to the distal end of the bag. In another embodiment, upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of a subject, thereby providing a substantially continuous fluid flow to a subject.

[0092] In another embodiment, applying a device of the invention comprises attaching a device of the invention to a body part. In another embodiment, applying a device comprises attaching a device of the invention to a subject's garment. In another embodiment, applying a device comprises attaching a device of the invention to any stationary element that can hold the device. In another embodiment, applying a device comprises attaching a device of the invention to any mobile element that can hold the device. In another embodiment, applying a device comprises attaching a device to furniture. In another embodiment, applying a device comprises attaching a device to a bed. In another embodiment, applying a device comprises attaching a device to a chair. In another embodiment, applying a device comprises attaching a device to a wheelchair. In another embodiment, applying a device comprises attaching a device to a stand. In another embodiment, applying a device comprises attaching a device to an infusion stand.

[0093] In another embodiment, attachment is achieved by fastening the device to a body part by an elastic band. In another embodiment, attachment is achieved by fastening the device to an object by an elastic band. In another embodiment, attachment is achieved by using a hook. In another embodiment, attachment is achieved by using a clip or a fastener. In another embodiment, attachment is achieved by any known means known to one of skill in the art.

[0094] In another embodiment, the subject is paralyzed thus a continuous fluid flow prevents dehydration of the subject, hi another embodiment, the subject is under the influence of anesthesia thus a continuous fluid flow prevents dehydration of the subject. In another embodiment, the subject is healthy subject that wishes to be treated with a continuous fluid flow. In another embodiment, the subject is diagnosed as a patient in need of a continuous fluid flow. In another embodiment, one of skill in the art will apply the method and device of the invention to a subject in need.

[0095] In another embodiment, the invention provides a method of treating dry mouth in a subject comprising the step of providing a substantially continuous fluid flow to the mouth of a subject, thereby treating dry mouth in a subject. In another embodiment, the invention provides a method of treating dry mouth in a subject comprising the step of providing a substantially continuous flow of moisturizing fluid to the mouth of a subject, thereby treating dry mouth in a subject. In another embodiment, the invention provides a method of treating dry mouth in a subject comprising the step of providing a substantially continuous flow of artificial saliva to the mouth of a subject, thereby treating dry mouth in a subject.

[0096] In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention (see figures 1-9). In another embodiment, the invention provides that the method of treating dry mouth comprises administering continuous flow of moisturizing fluid and a xerostomia drug. In another embodiment, the invention provides that the method of treating dry mouth comprises administering constant and continuous flow of moisturizing fluid and a xerostomia drug. In another embodiment, the invention provides that the method of treating dry mouth comprises administering continuous flow of moisturizing fluid and a drug of the invention. In another embodiment, the invention provides that the method of treating dry mouth comprises administering continuous flow of artificial saliva and a xerostomia drug use of the device of the invention. In another embodiment, the invention provides that the method of treating dry mouth comprises administering continuous flow of artificial saliva and a drug of the invention.

[0097] In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention during sleep of the affected subject. In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention over a period of 1-48 hours. In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention over a period of 1-3 hours. In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention over a period of 2-6 hours. In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention over a period of 4-8 hours. In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention over a period of 8-12 hours. In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention over a period of 10-20 hours. In another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention over a period of 15-30 hours, hi another embodiment, the invention provides that the method of treating dry mouth comprises the use of the device of the invention over a period of 20-48 hours.

[0098] In another embodiment, the invention provides a method of treating dry mouth wherein providing a substantially continuous fluid flow comprises the use of a device comprising: (a) a fluid container having a first end and a second end, with a mechanical pressure biasing means operably coupled to said container; and (b) a tube having a proximal end and a distal end, wherein the distal end of the tube comprises a fixing element, wherein the fixing element is adapted for fixing said distal end of the tube in the mouth of a subject, and the proximal end of the tube is operably linked to the distal end of the container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of a subject.

[0099] In another embodiment, a subject affected with dry when eating a meal is treated by the methods of the present invention. In another embodiment, a subject having difficulties swallowing any foods is treated by the methods of the present invention. In another embodiment, a subject that sips liquids to aid in swallowing dry foods is treated by the methods of the present invention. In another embodiment, a subject affected with little amount of saliva in his mouth is treated by the methods of the present invention. In another embodiment, a subject affected with Sjogren's syndrome is treated by the methods of the present invention. In another embodiment, a subject affected with an autoimmune disease is treated by the methods of the present invention. In another embodiment, a subject having elevated quantities of serum amylase is treated by the methods of the present invention.

EXPERIMENTAL DETAILS SECTION

EXAMPLE 1; TREATING A SUBJECT AFFECTED WITH DRY MOUTH

[00100] A device loaded with moisturizing fluid was assembled. The device was made of a cylindrical container, a spring, a bag, a thin tube and a strap with which the container was fixed to the subject's arm.

[00101] The cylinder was made of Perspex, inner diameter 20mm, length 100mm. One end of the cylinder (the upper end) was closed except a circular hole of 2mm diameter. The other end was closed by a cover which contained a spiral spring. The spring was compressed by a rod and an end plate (figure 1).

[00102] A thin walled silicon tube having 18mm diameter was cast for the device. Bags were prepared by closing off two ends of a 50mm length of the silicon tube between two stopcocks.

For the device one of the stopcocks carried a thin tube of 200 μm outer diameter, a so-called hollow fiber. The tube was 0.5 m long. A bag was introduced into the container so that the tube could be passed through the hole in the upper end.

[00103] The bag was filled with 9 ml of tap water (serving as a moisturizing fluid) by a syringe needle passed through the stopcock facing the open, lower, end of the cylinder. When the cover was screwed on, the end plate of the spring nearly touched the stopcock closing the bag.

[00104] The spring was released and exerted pressure on the bag. Water dripped from the free end of the thin tube at an initial rate of approximately 0.65 ml/hr. The rate of flow was between 0.6 and 0.75 ml/hr in a series of tests. In the different tests the open end of the tube was fixed in various positions relative to the cylinder, with a height difference of up to 25 cm.

EXAMPLE 2; TREATING A SUBJECT AFFECTED WITH DRY MOUTH WITH A DEVICE OF FIGURE 1

[00105] A subject affected with dry mouth is equipped before night sleep with a device as described in figure 1 having a cylindrical container (1) housing a spring (2) and an elongated rod (8) having a plunger (6). The external part of the rod (8) is thickened, thus forming a plug for the spring once it's compressed. The container contains a 50 cc disposable PVC bag (4) filled with commercially available artificial saliva-Salivart^®. A 100 cm MTSA PVC tube having a total diameter of 0.3 cm is used to connect the device and the mouthpiece.

[00106] The device is fixed on the arm of the subject (figure 4) with a flexible 2 cm wide elastic band. Once the biasing means is actuated, a substantially continuous fluid flow of about 0.05-0.1 ml/minute is disposed to the mouth of the subject through the mouthpiece.

[00107] The subject wakes after a 9 hours sleep without any symptoms of dry mouth.

EXAMPLE 3: TREATING A SUBJECT AFFECTED WITH DRY MOUTH WITH A

DEVICE OF FIGURE 6

[00108] A subject affected with dry mouth is equipped before night sleep with a device as described in figure 7 providing a substantially continuous fluid flow to the mouth.

[00109] The container contains a 50 cc disposable PVC bag (4) filled with commercially available artificial saliva-Salivart^®. A 100 cm MTSA PVC tube having a total diameter of 0.3 cm is used to connect the device and the mouthpiece.

[00110] The device is fixed on the arm of the subject (figure 4) with a flexible 2 cm wide elastic band. Once the top (apical portion) is closed thus actuating the biasing means, a substantially continuous fluid flow of about 0.05-0.1 ml/minute is disposed to the mouth of the subject through the mouthpiece.

[00111] The subject wakes after a 9 hours sleep without any symptoms of dry mouth.

Claims

What is claimed:

1. A device for providing a substantially continuous fluid flow to the mouth of a subject, comprising:

a. a fluid container having a first end and a second end, with a mechanical pressure biasing means operably coupled to said container; and

b. a tube having a proximal end and a distal end, wherein said distal end of said tube comprises a fixing element, wherein said fixing element is adapted for fixing said distal end of said tube in said mouth of said subject, and said proximal end of said tube is operably linked to said distal end of said container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of said subject.

2. The device of claim 1, wherein said pressure biasing means is coupled to said first end of said container.

3. The device of claim 1, wherein said container comprises a bag having a first end and a second end.

4. The device of claim 3, wherein said container comprises a bag anchoring means.

5. The device of claim 4, wherein said bag comprises a moisturizing solution.

6. The device of claim 5, wherein said moisturizing solution is artificial saliva.

7. The device of claim 4, wherein said bag further comprises a drug.

8. The device of claim 7, wherein said drug is a xerostomia drug.

9. The device of claim 1, wherein said container comprises a cylindrical shape.

10. The device of claim 1 , wherein said biasing means comprises a spring.

11. The device of claim 10, further comprising an elongated rod having a proximal end and a distal end housed within said spring.

12. The device of claim 11, wherein said rod comprises a plunger assembly on its proximal end.

13. The device of claim 11, further comprising a removable stopper, wherein said stopper locks said spring in a cocked position.

14. The device of claim 1 , wherein said fixing element is a mouth restraining muzzle.

15. The device of claim 1 , wherein said fixing element is attached to a tooth or a tongue.

16. A device for providing a substantially continuous fluid flow to the mouth of a subject, comprising:

a. a container having a proximal end, a distal end, a basolateral end, and an apical end, with a pressure biasing means operably coupled to said container, wherein said basolateral end, and said apical end are connected by a pivot;

b. a bag comprised within said container; and

c. a tube having a proximal end and a distal end, wherein said distal end of said tube comprises a fixing element, wherein said fixing element is adapted for fixing said distal end of said tube in said mouth of said subject, and said proximal end of said tube is operably linked to said bag, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of said subject.

17. The device of claim 16, wherein said pressure biasing means is coupled to said apical end of said container.

18. The device of claim 16, wherein said container comprises a bag having a proximal end and a distal end.

19. The device of claim 18, wherein said bag comprises moisturizing solution.

20. The device of claim 19, wherein said moisturizing solution is saliva.

21. The device of claim 18, wherein said bag further comprises a drug.

22. The device of claim 21, wherein said drug is a xerostomia drug.

23. The device of claim 16, wherein said container is a square box.

24. The device of claim 16, wherein said biasing means comprises a spring or an elastic material.

25. The device of claim 16, wherein said fixing element is a mouth restraining muzzle.

26. The device of claim 16, wherein said fixing element is a ring attached to a tooth or a tongue.

27. A system comprising a xerostomia drug and the device of claim 1.

28. A system comprising a disposable pre-filled saliva bag and the device of claim 1.

29. A system comprising a xerostomia drug and the device of claim 16.

30. A system comprising a disposable pre-filled saliva bag and the device of claim 16.

31. A method of providing a substantially continuous fluid flow into the mouth of a subject comprising the step of applying a device for providing said substantially continuous fluid flow of about 0.001-0.5 ml/minute to said mouth of said subject, wherein said device comprises:

b. a tube having a proximal end and a distal end, wherein said distal end of said tube comprises a fixing element, wherein said fixing element is adapted for fixing said distal end of said tube in said mouth of said subject, and said proximal end of said tube is operably linked to said distal end of said container, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of said subject, thereby providing a substantially continuous fluid flow to a subject.

32. A method of providing a substantially continuous fluid flow into the mouth of a subject comprising the step of applying a device for providing a substantially continuous fluid flow of about 0.001-0.5 ml/minute to said mouth of said subject, wherein said device comprises:

a. a container having a proximal end, a distal end, a basolateral end, and an apical end, with a pressure biasing means operably coupled to said container, wherein said basolateral end, and said apical end are connected by a pivot; b. a bag comprised within said container; and

c. a tube having a proximal end and a distal end, wherein said distal end of said tube comprises a fixing element, wherein said fixing element is adapted for fixing said distal end of said tube in said mouth of said subject, and said proximal end of said tube is operably linked to said bag, wherein upon actuating the biasing means, a substantially continuous fluid flow of about 0.001-0.5 ml/minute is disposed to the mouth of said subjectthereby providing a substantially continuous fluid flow to a subject.

33. The method of claim 31, wherein said moisturizing fluid is artificial saliva.

34. The method of claim 32, wherein said moisturizing fluid is artificial saliva.

35. A method of treating dry mouth in a subject comprising the step of providing a substantially continuous fluid flow into said mouth of said subject, thereby treating dry mouth in a subject.

36. The method of claim 35, wherein said substantially continuous flow is 0.001-0.5 ml/minute.

37. The method of claim 35, wherein said fluid is artificial saliva.

38. The method of claim 37, wherein said fluid further comprises a drug.

39. The method of claim 35, wherein said treating is performed during sleep of said subject.

40. The method of claim 35, wherein said providing a substantially continuous fluid flow of a moisturizing fluid comprises the use of a device comprising:

b. a bag comprised within said container; and

41. The method of claim 35, wherein said providing a substantially continuous fluid flow of a moisturizing fluid comprises the use of a device comprising: