A composition and methods for the treatment of symptoms due to disorders, disease or trauma that impairs normal function of die Eustachian tube and alters vital structures or tissues of the middle ear. This includes diseases and disorders of the Eustachian tube altered by tubal incompetence, inflammatory phenomenon as rhinitis, nasal allergies, infections by microorganisms, tympanic membrane rupture or trauma and variants. The composition is comprised of solution including L-Ascorbic acid and a pharmaceutically acceptable liquid carrier and delivery system. The administration of which is applied topically in appropriate composition and dosage for intranasal or trans tympanic route in the form of drops, spray, aerosol, rinse, douche, gel, or devices.

Description of the Invention

FIELD OF THE INVENTION

This invention relates generally to treatment of middle ear disorders and more specifically to a composition and treatment protocol for treatment of patulous Eustachian tube disorders of the middle ear and otitis media.

BACKGROUND

The Eustachian tube (ET) is an adnexa structure in the middle ear in man. It is a very narrow air passage in the wall of the middle ear which connects it to the nasopharynx, --a midline air filled space in the back of the nose. It is approximately 37 mm long and is slightly hour-glass shaped, flattened anterior-posteriorly. The small lumen of the eustachian tube permits the exchange of ambient gases between the middle ear and nasopharynx and the transport of middle ear secretions into the nasopharynx. The lateral one-third of the Eustachian tube (tympanic segment) is made of bone, while the medial two-thirds (pharyngeal segment) is cartilaginous. A constriction at the junction of the bony and cartilaginous segments, called the isthmus, may be as narrow as 1.0 mm by 1.5 mm. This tube regulates the intermittent exchange of air to or from the middle ear space to maintain equal pressure on both sides of the eardrum. The surface of the epithelium of the middle ear and eustachian tube is covered by a raucous blanket which is a defensive barrier against inhaled pollutants and a multitude of microorganisms. Middle ear secretions are normally eliminated through the ET.

In man, the Eustachian tube is a very unique structure that enables the middle ear pressure to adapt to various altitude changes and, and when closed it prevents the endogenous intraoral sounds of respiration and vocalization from reaching the middle ear to compete with and mask out the environmental sounds for reception and relay to the inner ear.

Normally, the Eustachian tube maintains an isobaric relationship between the middle ear space and the ambient air exchanged within the nasal passages during breathing. The critical opening pressure for the tube to ventilate the middle ear chamber is related to the surface tension and diameter of the ET opening onto the lateral wall of the nasopharynx. This is modified by the rheologic properties of the mucus blanket on the endothelial tissues. In its natural state, the Eustachian tube orifice is always closed, but may actively open spontaneously several times a minute or when swallowing or yawning. As integral part of the middle ear, the Eustachian tube functions to prevent and ameliorate the same inflammatory diseases such as otitis media etc. and its complications.

Incompetent Eustachian tube disorders refer to those conditions in which the closure of the facet at the orifice does not occur due to an increase in the diameter of the lumen of the Eustachian tube, a change in the surface tension of the secretions or fluid covering the mucous membrane, or a failure of the normal cartilage valve mechanism to passively relax for normal closure.

In this small sub set of individuals the Eustachian tube lumen is abnormally open continuously or intermittently. While the tube is open, it allows the respiratory sounds and speech of an individual to pass directly through the patent Eustachian tube to the middle ear sound-receiving mechanism. These individuals are very uncomfortable and frequently complain of a paradoxical symptom of a "clogged, plugged or stuffy ear" or a crackling or squeaking sound in actuality, there is a failure of the facet of Eustachian tube valve to passively collapse and seal the entrance at the nasopharynx. When they deny having a respiratory infection, further questioning may elicit a complaint of autophony (hearing their own breath sounds amplified in one's ear) and of hearing amphoric sounds in their ear similar to the sound of air being blown across the mouth of an uncapped empty bottle, or their voice sounding loud or strange. The symptom of autophony is pathognomonic of a patulous Eustachian tube disorder of the middle ear.

While the Eustachian Tube remains open, the continuous free flow of air from each respiration or vocal effort rushes to the middle ear causing the tympanum to resonate loudly. This uncontrollably amplifies the endogenous sounds (autophony) in one's ear. These forceful air currents, or acoustical energy, produced by breathing and vocalization generated within the approximate voice box, impact directly through the open Eustachian tube to the sensitive sound transmission system of the middle ear producing disturbing sounds and acoustical energy.

Unlike the symptoms of a common cold, PET symptoms totally disappear when lying down due to a shift of body fluids to the head increases local edema and passive closure of the tube. And so, to maintain closure, some patients spend the their day time hours supine, in bed.

The symptom of autophony--hearing the disturbing loud sounds from one's own breathing and voice, may be so disabling that many patients have considered suicide, and some attempts have been successful.

The patulous Eustachian tube syndrome and less severe variants such as a Patent, open, hyper-patent or semi-patulous Eustachian tube are variants of Eustachian tube incompetence.

In the past, different remedies have been recommended for the patulous Eustachian tube syndrome. These include sitting, and then bending over with ones head between the knees to increase nasal edema. Treatments included nasal insufflation of boric acid-salicylic acid power, local application of liquid silver nitrate, diathermy, Premarin hormonal or saturated solution of iodine (SSKI) drops. Another therapy has employed Kamikihi-To as reported by Jia-Wei-Gui-Pi-Tang. Some were impractical. None of these treatments have been consistently successful, nor are they without side effects, or serious complications.

In the inventor's previous related U.S. Pat. No. 5,470,587 (Nov. 28, 1995) which is herein incorporated by reference, the principle embodiment included hydrochloric acid (HCl), an inorganic acid. The invention sited above stimulated the necessary local edematous response to close the tube with the immediate, but short term, relief of symptoms due primarily to its pH effect. The properties of the novel invention and novel method of administration described herein stimulate both the immediate edema and the products essential for tissue healing, namely, dermatofibroblasts and pre-collagen fibers.

Surgical procedures have been advocated, including the injection of paraffin, Teflon, collagen, or Gelatin sponge injection into the wall around the Eustachian tube opening. Invasive surgery involving pterygoid hamulotomy has been performed or occlusion of the Eustachian tube lumen by a plug. Diathermy probe therapy has been used on the past. Laser-assisted endoscopic surgery or autologous fat grafting has been recommended for severely debilitating cases.

Additionally, among children in the US, 35 to 85 percent experience middle ear disease from otitis media in the first six months of life. Acute ear infections account for 15 to 30 million visits to the doctor each year in the U.S. In fact, ear infections are the most common reason why an American child sees the doctor. This is probably the result of prenatal deficiencies, and the infant or child's exposure to secondary smoke and respiratory viruses when their immune system is not fully developed.

Certain bacteria are reported to be the primary causes of acute otitis media (AOM) and are detected in about 60% of cases. The bacteria most commonly causing ear infections are: Streptococcus pneumoniae (also called S. pneumoniae or pneumococcus), the most common bacterial cause of acute otitis media, causing about 40% to 80% of cases in the U.S.; Haemophilus influenzae, the next most common culprit and is responsible for 20% to 30% of acute infections; and Moraxella catarrhalis, also a common infectious agent, responsible for 10% to 20% of Less common bacteria are Streptococcus pyogenes and Staphylococcus aureus.

A serious sequalae of bacterial chronic otitis media includes otitis media with effusion (OME) which is associated with complications such as a ruptured tympanic membrane (TM). The failure of the Eustachian tube to expel or eliminate the natural secretions, microorganisms, biofilms and toxic products result in destruction of the tissues, TM rupture and hearing loss. When the fluid becomes infected the increased pressure is very painful and causes the delicate tympanic membrane to rupture releasing the toxins into the external ear canal for elimination

The ideal treatment should involve a product that is first safe and free of side effects, non-toxic, exhibit high potency at a pH that facilitates host tissue defenses while at the same level is detrimental to the reproductive cycle of most microorganisms, and the biochemical or physical property to break down the protective biofilm barrier surrounding the microorganism or toxins. It would be advantageous if embodiment has anti oxidant properties to reduce free radical toxins on the damaged host tissue and participate in the production of the essential ingredients (pre-collagen) to complete the healing process of the tissue and improved function.

In the past, antibiotics have been the mainstay of eliminating bacterial microorganisms by direct biochemical interaction. Antibiotics can only treat the infection when and if the agent is capable of penetrating the biofilm barrier and altering the biochemistry of the microorganism internally. This is seldom the case now.

Of note, about 15% of these bacteria are now believed to be resistant to the first-choice antibiotics. With the overuse of antibiotics and the development of resistance by microorganisms, such treatment has become less effective and frequent side effects have become common.

More recently, because the chemical structure of the newer anti-infective agents are more complex, antibiotics are not absorbable in the gastrointestinal tract, necessitating that the medication be administered by intravenous injection which is further associated with serious side effects such as ototoxicity, hearing loss and tinnitus, allergic reactions. Scientific studies have identified prenatal markers, such as smoking, that predispose the infant to develop middle ear infections. Among the prenatal risk factors for early Otitis Media (OM) that can be modified, mother's intake of vitamin C and alcohol during pregnancy could have future health implications. Alcohol may stimulate the fetal liver to produce metabolic enzymes which degrade vitamin C producing deficiencies in both the fetus and the infant. Vitamin C--deficient animals have neutrophils with reduced bactericidal activity and ascorbic acid may also play a role in the fetal development of cartilage, bone, and the muscle of the Eustachian tube.

Recent discoveries have identified a universal mechanism by which disease is transmitted, established, perpetuated and flourishes despite antibiotic therapy. This is through the protective covering of biofilm. The organic matter adheres to the surface target organ and shields the penetration of the external membrane of the microorganisms by many forms of chemotherapy. To be effective, it is necessary the therapeutic agent to break down the biofilm, and then inactivate the microorganisms by establishing a pH environment which is detrimental to their survival.

The relative acidity of a solution or tissue is measured according to a pH scale that ranges from 0-14. Those registering above 7 function within an alkaline environment, those below 7 are acidic. A solution with a pH of 7 is considered neutral. The mathematical symbol pH represents the logarithm of the reciprocal of the hydrogen-ion concentration in gram atoms per liter of solution. The level of the pH regulates the biochemical availability of nutrients for the chemical processes of all vital tissues to survive.

It is therefore desirable to provide a composition for the treatment of the fundamental pathologic processes antecedent to patulous Eustachian tube disorders and to the dysfunctional tubal stenosis in middle ear diseases by employing an effective, non-toxic composition with known co-enzymatic and vital tissue healing properties.

SUMMARY

The embodiments of the invention disclosed herein provide a novel formulation and method for the prevention and relief of symptoms of inflammatory disease or functional disorders of the middle ear adnexa, the Eustachian tube, manifested by autophony or tubal tinnitus due to a severe form of Eustachian tube incompetence, patulous Eustachian tube syndrome, or deformity, acquired or following surgery, radiation or trauma. The inventive composition and method are further effective for the prevention and relief of symptoms related to primary inflammatory disease or functional disorders of the middle ear or such as may occur secondary to allergy, rhinitis or sinusitis, microorganisms, structural deformities or tubal dysfunction.

A method of treating the patulous Eustachian tube syndrome, and variants of Eustachian tube incompetence, includes the steps of: applying to a person's nasal mucosa a composition of at least of L-Ascorbic acid, with a pH level in the range of about 2.0 pH to about 2.5 pH, and a pharmaceutically acceptable liquid carrier and delivery system, the L-Ascorbic acid in the carrier at a concentration form about 25% to about 4% wt./volume.

A method of preventing and treating Middle Ear Diseases including Otitis Media (OM), Otitis media with effusion (OME), Tympanic Membrane (TM) or Eustachian Tube (ET) due to dysfunction or associated with allergy, rhinitis, sinusitis, and inflammatory disease from toxins, microorganisms, the biofilm and abiotic adhesin co-factors coating the surface of implanted devices, including the steps of applying a composition comprised of L-Ascorbic acid at a pH in the range of about 2.3 pH to 4.0 pH level in a pharmaceutically acceptable liquid carrier at a concentration from about 10. % to about 0.01% , wt./volume to the middle ear through the natural tubal stoma, an acquired opening or implants, to prevent or treat middle ear disease and its sequalae.

DETAILED DESCRIPTION

The embodiments described herein for the invention provide that when L-ascorbic acid is dissolved in an aqueous solution, the pH of that solution decreases sharply due to the dissociation of the hydrogen ion from the enediol group. The main contribution to the lowering of pH is the hydroxy group located on the number 3 carbon (C3). This composition provides a more flexible therapeutic pH range than HCL, is much safer, has no known toxicity, and is necessary for the production of collagen to support the strength and healing of these tissues. Unfortunately, man is unable synthesize L-Ascorbic acid due to the absence of the biochemical step in the liver of the species to convert L-gulonolactone which is required for the biosynthesis of L-ascorbic acid. Therefore, in man, the composition provided by the embodiment includes exogenous L-Ascorbic acid, an essential nutrient for tissue health. Further the embodiments of the composition and the methods described assure the availability of the composition directly to the tissue in obvious need.

The composition of the first exemplary embodiment has known antioxidant properties, scientifically established, that combat the build up of metabolic wastes. It restores the defensive bioactive reactions such as surface tension lowering substance (STLS) to combat the adherence or biofilm products of microorganisms.

Because man cannot synthesize ascorbic acid, it is a recognized essential nutrient that has to be provided by an exogenous source as referenced in [At this time, the Food and Nutrition Board of the U.S. National Research Council recommends a daily allowance of 60 mg in a 70 kg man to support certain vital functions.

The exemplary first embodiment employs this essential nutrient in the therapeutic form required by man for the production of pre-collagen necessary for the strength and healing process of the tubal tissues.

Unfortunately the early symptoms of PET may include those similar complaints that appear similar to those reported with the common cold, tubal stenosis, otitis media, environmental allergies, rhinitis or sinusitis. But in PET the fundamental cause is an OPEN TUBE, contrary to the inflammatory obstructive phenomenon of the middle ear congestion from a common cold etc. Therefore, it is essential to determine the exceptional diagnosis of PET and select the contrary therapy to relieve the disturbing cardinal symptoms of autophony. For anyone to recommend any of the conventional medications or non prescription decongestant remedies because of a misdiagnosis, it will invariably make the PET symptoms much worse.

OPERATION OF THE FIRST EXEMPLARY EMBODIMENT

The Patulous Eustachian Tube is abnormally open throughout the day when the individual is upright and about. The lumen of the tube remains open and the phenomenon of autophony, hearing one's amplified breath sounds and voice disturbingly loud, will persist throughout the day.

A novel composition for ameliorating patulous Eustachian tube symptoms, is provided by a solution of L-Ascorbic acid and a pharmaceutically acceptable liquid carrier in therapeutically effective amounts to normalize the surface tension of the luminal tissues of the eustachian tube, the solution having a pH level in the range of about 2 to 2.5 pH. The L-Ascorbic acid or comparable ingredient is in the form of U.S.P. grade, extra pure fine powder, granular powder or pure crystals. The L-Ascorbic acid employed in the embodiment is also known as Vitamin C, hexuronic acid, an antisorbutic vitamin, with chemical formula C.sub.6H.sub.8O.sub.6 and a molecular weight of 176.12, or its derivatives: Ester-C, Ascorbate, L-xyloascorbic acid, 3-oxo-L-gulofuranolactone, L-3-keto threo hexuronic acid lactone, or oxidation forms: dehydro-L-ascorbic acid, hydrophobic ascorbic acid, or 2-O-.alpha-D-glocopyranosyl-L-Ascorbic acid. For their synergistic effect to enhance the properties of the novel composition, specific antioxidants may be added. These include the flavon antioxidant, bioflavonoid, and the nutrient antioxidant, water solubilized vitamin E (alpha-tocopherol) and zinc salt(s) added to the L-Ascorbic acid composition.

For an exemplary embodiment, the liquid carrier is distilled water and the solution has a pH level in the range of about pH 1.9 to a pH of about 3.9. The L-Ascorbic acid is present in the carrier at a concentration from about 2% to about 25% wt./volume. The pH of Ascorbic acid produces the desired edema, as an immediate effect but also has co-enzyme and bioactive properties to combat the inflammatory reaction and facilitate the healing process.

A novel method to prevent or ameliorate the serious symptoms of middle ear disease due to impairment of its Eustachian tube function is accomplished by applying the composition through the natural orifices, or acquired openings, or implanted devices to normalize Eustachian tube function.

The solution is topically applied to the nasal mucosa, however in alternative embodiments of the method protocol, the solution is applied to the middle ear chamber mucosa. For application to the nasal mucosa, the solution is applied in drops into the nose, as a spray into the nose or in an aerosol into the nose. In one application, the solution is applied via an ET catheter to the nasopharyngeal stoma of the eustachian tube.

For application to the middle ear chamber mucosa, the solution is applied to the middle ear employing a syringe and needle, a tympanic membrane puncture or a myringotomy, by employing an implanted device in the middle ear chamber or bridging the defect of the tympanic membrane of the middle ear chamber.

In an exemplary first administration protocol, the composition is administered in the form of nose drops, the patient sniffs them through the ipsilateral nostril on the side of the symptomatic ear affected with the disorder. The number of drops administered can be titrated to the needs of the individual patient. The patient can sniff from two to four drops of the solution, and the drops are sniffed back into the nostril so as to deliver the medication to the Eustachian tube opening in the back of the nose. Administration of the drops may be repeated again in four to six hours. As desired, the daily dose maybe increased to 4 drops per administration.

The pH of Ascorbic acid produces the desired tubal edema, as an immediate effect but also has bioactive properties to combat the inflammatory reaction facilitating the healing process.

An exemplary nasal drop administration protocol has been developed for the first exemplary embodiment. To achieve normal closure of the lumen, 2-6 drops of the nasal supplement solution are applied to the stoma or opening of the Eustachian tube. It may take two weeks before changes in symptoms become apparent.

PatulEND.TM. nose drops are designed to increase the edema of the membrane at the stomal entrance of the Eustachian tube to the critical closing pressure level and seal the opening. When drops are instilled into the nasal chamber, they are slowly absorbed upon contact with the surface. It is important to sniff the nose drops so that they are drawn back to the opening of the Eustachian tube where they can be preferentially absorbed at the stoma. After using the supplement for several days one is usually able to master the technique and can identify the sensation associated with proper delivery of the drops to the Eustachian tube area.

Referring to the illustrations in FIGS. 1 and 2 (see Original Patent) for reference, after the patient been up for a period of time, symptoms begin as the tubal tissues lose fluid and the lumen increases. When the patient feels the symptom of autophony is about to occur, gently blowing the nose to clear any mucous is accomplished.

With the patient 10 lying with head 12 between 45 to 60 degrees above horizontal. The head is turned 45 to 60 degrees toward the affected ear 14, right as shown in FIG. 1 and left as shown in FIG. 2. This places the Eustachian tube stoma (opening) lower than the nostril 16. Gravity will allow the drops to flow to the back of the nose. Sniffing will draw the drops further info the nasal passage to the Eustachian tube before the semi-permiable membrane lining of the nasal passage can absorb them. Alternatively while sitting in a chair, the head is tilted back at approximately 45 degrees and then tilted toward the affected ear to place it almost below the nose.

For nasal administration, to instill the drops, put the dropper tip one-quarter inch (1/4'') into the lower nostril (affected side), closest to the symptomatic ear.

Instill 2-4 drops depending on individual anatomy. Sniffing briskly to draws the drops back approximately three inches (3'') to the location of the tube opening where they will be absorbed. The patient may feel a brief burning or stinging sensation when the drops are administered properly to stimulate the closure of the stoma of the tube. The patient then remains lying down in the administering position for ten (10) seconds.

The solution in the exemplary embodiment is devoid of pharmaceutical agents, astringent agents, hormones, alcohol, botanicals, yeast, wheat, soy, dairy products, sugar, salt, starch, and artificial coloring or dyes and is formulated without the uses of preservatives, artificial flavors or colors. It is light sensitive and oxygen sensitive.
 

Claim 1 of 21 Claims

1. A method of treating the patulous Eustachian tube syndrome, a severe variant, of Eustachian tube incompetence, comprising: applying to a person's nasal mucosa a composition of L-Ascorbic acid, in a highly acidic concentration of about 5% to about 20% wt/vol, within a range of about 2.4 to 2.0 pH level, in an aqueous solution, and a pharmaceutically acceptable liquid carrier and delivery system.

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