# Patent

## Title
Germicidal method for treating or preventing sinusitis

## Abstract

The method of treatment for a nasal or sinus tissue exhibiting a sinusitis or rhinosinusitis disease or condition in a diagnosed patient is disclosed. The method has the steps of activating an acoustic shock wave generator or source to emit acoustic shock waves; and subjecting the nasal or sinus tissue, or the entire nasal or sinus region of the patient to the acoustic shock waves stimulating said tissue, wherein the tissue is positioned within a path of the emitted shock waves. The method of treatment may further have the steps of administering one or more medicaments prior, during or after subjecting the patient to acoustic shock waves or testing the bacterial count or viability of the treated tissue or region of the diagnosed patient after exposure to one or more acoustic shock wave treatments; or subjecting a tissue or organ to a surgical procedure to remove or repair some or all of any defects or degenerative tissues. The method of treatment is for prevention of infectious disease and may be used with debridement. The treatment is particularly useful in eradicating and inhibiting biofilm formations.

## Background
RELATED APPLICATIONS
This application is a continuation in part of U.S. patent application Ser. No. 11/238,551 filed on Sep. 29, 2005 entitled “Germicidal Method for Eradicating or Preventing the Formation of Biofilms” and U.S. patent application Ser. No. 11/122,154 filed on May 4, 2005 now U.S. Pat. No. 7,470,240 entitled “Pressure Pulse/Shock Wave Therapy Methods and an Apparatus for Conducting the Therapeutic Methods” and U.S. patent application Ser. No. 11/071,156 filed on Mar. 4, 2005 entitled “Pressure Pulse/Shock Wave Apparatus for Generating Waves Having Nearly Plane or Divergent Characteristics” and also claims benefit of priority to U.S. Provisional Patent Application Ser. No. 60/693,369 filed Jun. 22, 2005; U.S. Provisional Patent Application Ser. No. 60/693,143 filed Jun. 23, 2005; U.S. Provisional Patent Application Ser. No. 60/621,028 filed Oct. 22, 2004 and of U.S. Provisional Patent Application Ser. No. 60/642,149 filed Jan. 10, 2005, the disclosures of which are incorporated herein by reference in their entirety.


FIELD OF THE INVENTION
The present invention relates to germicidal methods to treat sinusitis and to methods to prevent the formation of such conditions.
BACKGROUND OF THE INVENTION
According to the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, U.S. Department of Health and Human Services, Sinusitis simply means your sinuses are infected or inflamed, but this gives little indication of the misery and pain this condition can cause. Health care experts usually divide sinusitis cases into: acute, which last for 3 weeks or less; chronic, which usually last for 3 to 8 weeks but can continue for months or even years; and recurrent, which are several acute attacks within a year.
Health care experts estimate that 37 million Americans are affected by sinusitis every year. Health care providers report nearly 32 million cases of chronic sinusitis to the Centers for Disease Control and Prevention annually. Americans spend millions of dollars each year for medications that promise relief from their sinus symptoms.
Sinuses are hollow air spaces in the human body. When people say, “I'm having a sinus attack,” they usually are referring to symptoms in one or more of four pairs of cavities, or sinuses, known as paranasal sinuses 300. These cavities, located within the skull or bones of the head surrounding the nose, include the Frontal sinuses 306 over the eyes in the brow area, Maxillary sinuses 302 inside each cheekbone, Ethmoid sinuses 304 just behind the bridge of the nose and between the eyes and Sphenoid sinuses 308 behind the ethmoids in the upper region of the nose and behind the eyes.
Each sinus has an opening into the nose for the free exchange of air and mucus, and each is joined with the nasal passages by a continuous mucous membrane lining. Therefore, anything that causes a swelling in the nose—an infection, an allergic reaction, or another type of immune reaction—also can affect the sinuses. Air trapped within a blocked sinus, along with pus or other secretions may cause pressure on the sinus wall. The result is the sometimes intense pain of a sinus attack. Similarly, when air is prevented from entering a paranasal sinus by a swollen membrane at the opening, a vacuum can be created that also causes pain.
The location of your sinus pain depends on which sinus is affected. Headache when you wake up in the morning is typical of a sinus problem. Pain when your forehead over the frontal sinuses is touched may indicate that your frontal sinuses are inflamed. Infection in the maxillary sinuses can cause your upper jaw and teeth to ache and your cheeks to become tender to the touch. Since the ethmoid sinuses are near the tear ducts in the corner of the eyes, inflammation of these cavities often causes swelling of the eyelids and tissues around your eyes, and pain between your eyes. Ethmoid inflammation also can cause tenderness when the sides of your nose are touched, a loss of smell, and a stuffy nose. Although the sphenoid sinuses are less frequently affected, infection in this area can cause earaches, neck pain, and deep aching at the top of your head. Most people with sinusitis, however, have pain or tenderness in several locations, and their symptoms usually do not clearly indicate which sinuses are inflamed. Other symptoms of sinusitis can include fever, weakness, tiredness, a cough that may be more severe at night and runny nose (rhinitis) or nasal congestion.
In addition, the drainage of mucus from the sphenoid or other sinuses down the back of your throat (postnasal drip) can cause you to have a sore throat. Mucus drainage also can irritate the membranes lining your larynx (upper windpipe). Not everyone with these symptoms, however, has sinusitis. On rare occasions, acute sinusitis can result in brain infection and other serious complications.
Most cases of acute sinusitis start with a common cold, which is caused by a virus. These viral colds do not cause symptoms of sinusitis, but they do inflame the sinuses. Both the cold and the sinus inflammation usually go away without treatment in 2 weeks. The inflammation, however, might explain why having a cold increases your likelihood of developing acute sinusitis. For example, your nose reacts to an invasion by viruses that cause infections such as the common cold or flu by producing mucus and sending white blood cells to the lining of the nose, which congest and swell the nasal passages.
When this swelling involves the adjacent mucous membranes of your sinuses, air and mucus are trapped behind the narrowed openings of the sinuses. When your sinus openings become too narrow, mucus cannot drain properly. This increase in mucus sets up prime conditions for bacteria to multiply.
Most healthy people harbor bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae, in their upper respiratory tracts with no problems until the body's defenses are weakened or drainage from the sinuses is blocked by a cold or other viral infection. Thus, bacteria that may have been living harmlessly in your nose or throat can multiply and invade your sinuses, causing an acute sinus infection.
Sometimes, fungal infections can cause acute sinusitis. Although fungi are abundant in the environment, they usually are harmless to healthy people, indicating that the human body has a natural resistance to them. Fungi, such as Aspergillus, can cause serious illness in people whose immune systems are not functioning properly. Some people with fungal sinusitis have an allergic-type reaction to the fungi.
Chronic inflammation of the nasal passages also can lead to sinusitis. If you have allergic rhinitis or hay fever, you can develop episodes of acute sinusitis. Vasomotor rhinitis, caused by humidity, cold air, alcohol, perfumes, and other environmental conditions, also may be complicated by sinus infections.
Acute sinusitis is much more common in some people than in the general population. For example, sinusitis occurs more often in people who have reduced immune function (such as those with primary immune deficiency diseases or HIV infection) and with abnormality of mucus secretion or mucus movement (such as those with cystic fibrosis).
It can be difficult to determine the cause of chronic sinusitis. Some investigators think it is an infectious disease but others are not certain. It is an inflammatory disease that often occurs in patients with asthma. If you have asthma, an allergic disease, you may have chronic sinusitis with exacerbations. If you are allergic to airborne allergens, such as dust, mold, and pollen, which trigger allergic rhinitis, you may develop chronic sinusitis. An immune response to antigens in fungi may be responsible for at least some cases of chronic sinusitis. In addition, people who are allergic to fungi can develop a condition called “allergic fungal sinusitis.” If you are subject to getting chronic sinusitis, damp weather, especially in northern temperate climates, or pollutants in the air and in buildings also can affect you.
If you have an immune deficiency disease or an abnormality in the way mucus moves through and from your respiratory system (e.g., primary immune deficiency, HIV infection, and cystic fibrosis) you might develop chronic sinusitis with frequent flare-ups of acute sinusitis due to infections. In otherwise normal individuals, sinusitis may or may not be infectious. In addition, if you have severe asthma, nasal polyps (small growths in the nose), or a severe asthma attacks caused by aspirin and aspirin-like medicines such as ibuprofen, you might have chronic sinusitis.
Because your nose can get stuffy when you have a condition like the common cold, you may confuse simple nasal congestion with sinusitis. A cold, however, usually lasts about 7 to 14 days and disappears without treatment. Acute sinusitis often lasts longer and typically causes more symptoms than just a cold.
Doctors can diagnose sinusitis by listening to your symptoms, doing a physical examination, taking X-rays, and if necessary, an MRI or CT scan (magnetic resonance imaging and computed tomography).
After diagnosing sinusitis and identifying a possible cause, a doctor can suggest treatments that will reduce your inflammation and relieve your symptoms.
If bacteria cause your sinusitis, antibiotics used along with a nasal or oral decongestant will usually help. Your doctor can prescribe an antibiotic that fights the type of bacteria most commonly associated with sinusitis.
Many cases of acute sinusitis will end without antibiotics. If you have allergic disease along with sinusitis, however, you may need medicine to relieve your allergy symptoms. If you already have asthma then get sinusitis, you may experience worsening of your asthma and should be in close touch with your doctor.
In addition, your doctor may prescribe a steroid nasal spray, along with other treatments, to reduce your sinus congestion, swelling, and inflammation.
Doctors often find it difficult to treat chronic sinusitis successfully, realizing that symptoms persist even after taking antibiotics for a long period. As discussed below, many doctors treat with steroids such as steroid nasal sprays. Many doctors do treat chronic sinusitis as though it is an infection, by using antibiotics and decongestants. Other doctors use both antibiotics and steroid nasal sprays. Further research is needed to determine what is the best treatment.
Some people with severe asthma are said to have dramatic improvement of their symptoms when their chronic sinusitis is treated with antibiotics.
Doctors commonly prescribe steroid nasal sprays to reduce inflammation in chronic sinusitis. Although doctors occasionally prescribe these sprays to treat people with chronic sinusitis over a long period, doctors don't fully understand the long-term safety of these medications, especially in children. Therefore, doctors will consider whether the benefits outweigh any risks of using steroid nasal sprays.
If you have severe chronic sinusitis, your doctor may prescribe oral steroids, such as prednisone. Because oral steroids are powerful medicines and can have significant side effects, you should take them only when other medicines have not worked.
When medical treatment fails, surgery may be the only alternative for treating chronic sinusitis. Research studies suggest that the vast majority of people who undergo surgery have fewer symptoms and better quality of life.
In children, problems often are eliminated by removal of adenoids obstructing nasal-sinus passages.
Adults who have had allergic and infectious conditions over the years sometimes develop nasal polyps that interfere with proper drainage. Removal of these polyps and/or repair of a deviated septum to ensure an open airway often provides considerable relief from sinus symptoms.
The most common surgery done today is functional endoscopic sinus surgery, in which the natural openings from the sinuses are enlarged to allow drainage. This type of surgery is less invasive than conventional sinus surgery, and serious complications are rare.
At least two-thirds of sinusitis cases caused by bacteria are due to two organisms that can also cause otitis media (middle ear infection) in children as well as pneumonia and acute exacerbations of chronic bronchitis. NIAID is supporting multiple studies to better understand the basis for infectivity of these organisms as well as identifying potential candidates for future vaccines strategies that could eliminate these diseases.
Scientific studies have shown a close relationship between having asthma and sinusitis. As many as 75 percent of people with asthma also get sinusitis. Some studies state that up to 80 percent of adults with chronic sinusitis also had allergic rhinitis. NIAID conducts and supports research on allergic diseases as well as bacteria and fungus that can cause sinusitis. This research is focused on developing better treatments and ways to prevent these diseases.
Scientists supported by NIAID and other institutions are investigating whether chronic sinusitis has genetic causes. They have found that certain alterations in the gene that causes cystic fibrosis may also increase the likelihood of developing chronic sinusitis. This research will give scientists new insights into the cause of the disease in some people and points to new strategies for diagnosis and treatment.
Another NIAID-supported research study has recently demonstrated that blood cells from patients with chronic sinusitis make chemicals that produce inflammation when exposed to fungal antigens, suggesting that fungi may play a role in many cases of chronic sinusitis. Further research, including clinical trials of antifungal drugs, will help determine whether, and for whom, this new treatment strategy holds promise.
Dr. Jay M. Dutton, MD in a recent article for the American Rhinologic Society, “Complications of Sinusitis”, reports when sinusitis is managed properly, complications rarely occur. However, because of the close proximity of such structures as the intracranial cavity and the orbit, in certain circumstances these infections may spread and cause life-threatening sequelae. These complications may occur after either acute or chronic infections but do so more commonly after the former. The following list includes many of the potential complications of sinusitis, but is by no means exhaustive: Intracranial Complications—The frontal, ethmoid and sphenoid sinuses are separated from the intracranial cavity by a layer of bone. If the infection passes through this bone it may infect the tissue and fluid that lines the brain, causing “meningitis”. In even more severe cases the infection may spread to the brain itself causing an “abscess”, or collection of pus. These problems are life threatening and require prompt and aggressive treatment. Orbital Complications—The frontal, maxillary, ethmoid and sphenoid sinuses sit immediately above, below, between and behind the eyes, respectively (FIG. 13). For this reason, infections of any of the sinuses may spread to the orbit, causing a wide spectrum of complications from mild inflammation of the eyelid to abscesses with possible blindness. Vascular Complications—The carotid artery and cavernous sinus are two large vascular structures that border the sphenoid sinus. Infections that involve either of these structures may lead to aneurysms or infected blood clots in the intracranial cavity, both of which are potentially fatal. Asthma—A number of patients suffer from both asthma and chronic sinusitis and, for these individuals, flare-ups of the sinusitis can lead to asthma attacks. Many studies have shown that resolving the sinus condition will result in dramatic improvement of the asthma. Loss of Smell and Taste—Sinusitis may diminish the senses of smell and taste, since the two are interconnected. This may be either temporary or permanent, depending on the nature of the injury. In most cases, the cause is poor airflow to the olfactory nerve (which detects odors) and by improving the nasal airway the senses of smell and taste improve. This is particularly true in patients who suffer from nasal polyps. However, in some cases chronic sinusitis may permanently injure these nerve endings. Osteomyelitis—Some recent studies suggest that bone becomes actively involved during a chronic sinus infection, making the infection more difficult to treat. This may even cause the destruction of bone that leads to the intracranial and intraorbital complications discussed above.
Many patients are reluctant to undergo endoscopic sinus surgery for sinusitis but surgery may be imperative, as when one of these complications develops or to prevent one from occurring in the face of a chronic infection. While these complications are fortunately rare, their outcomes may be severe and tragic!
The common element in all cases of sinusitis is the presence of an infection caused by a combination of viral, bacterial or fungus deep within the sinus cavities and somewhat protected by the mucus that blocks normal drainage. This environment in the sinus cavities is precisely similar to that describing the formation of biofilms as is described in U.S. Pat. No. 6,777,223, entitled “Method for Eliminating the Formation of Biofilm”, the inventors describe biofilm as:

    
    
        biological films that develop and persist at the surfaces of biotic or abiotic objects in aqueous environments from the adsorption of microbial cells onto the solid surfaces. This adsorption can provide a competitive advantage for the microorganisms since they can reproduce, are accessible to a wider variety of nutrients and oxygen conditions, are not washed away, and are less sensitive to antimicrobial agents. The formation of the biofilm is also accompanied by the production of exo-polymeric materials (polysaccharides, polyuronic acids, alginates, glycoproteins, and proteins) which together with the cells form thick layers of differentiated structures separated by water-filled spaces. The resident microorganisms may be individual species of microbial cells or mixed communities of microbial cells, which may include aerobic and anaerobic bacteria, algae, protozoa, and fungi. Thus, the biofilm is a complex assembly of living microorganisms embedded in an organic structure composed of one or more matrix polymers which are secreted by the resident microorganisms.
    
    


Almost all of the prior art literature on the subject of eliminating or preventing biofilms suggests one or more drugs or chemical agents as the solution to this problem as well as well known cleaning procedures such as debridement in the practice of post surgery sinus treatments.
What is sorely lacking is a safe and reliable method to break down the cellular barrier properties of these complex architectural microbial structures called biofilms.
It is therefore an object of the present invention to provide such a method to reduce or eradicate microbial biofilms not only on surfaces, but within tissues and organs, such as the sinus cavities.
SUMMARY OF THE INVENTION
The method of treatment for a sinus or nasal tissue exhibiting a sinusitis or rhinosinusitis disease or condition in a diagnosed patient is disclosed. The method has the steps of activating an acoustic shock wave generator or source to emit acoustic shock waves; and subjecting the sinus or nasal tissue, or the entire sinus or nasal region of the patient to the acoustic shock waves stimulating said tissue, wherein the tissue is positioned within a path of the emitted shock waves. The emitted shock waves are either convergent, divergent, planar or near planar. Alternatively the emitted shock waves can be convergent having one or more geometric focal volumes or points at a distance of at least X from the generator or source, the method further comprising positioning the organ at a distance at or less than the distance X from the source.
The method of treatment may further have the steps of administering one or more medicaments prior, during or after subjecting the patient to acoustic shock waves or testing the bacterial count or viability of the treated tissue or region of the diagnosed patient after exposure to one or more acoustic shock wave treatments; or subjecting a tissue to a surgical procedure to remove or repair some or all of any defects or degenerative tissues. The treated sinus or nasal tissue may have an indication of one or more pathological conditions including a biofilm mass, inflammation or infection. The method of treatment is for prevention of infectious disease and may be used with debridement.
In most if not all cases the treatment includes the step of destroying biofilm in or on the treated tissue or region, wherein the treated tissue or region activates or otherwise stimulates stem cells or release of cellular growth factors in the sinus or nasal structure effecting a tissue repair or tissue regeneration.
DEFINITIONS
Acute rhinosinusitis: Symptoms of rhinosinusitis that begin suddenly, often about one week after a typical “cold”.
Barosinusitis: This is a sudden pain that develops in one sinus area as a result of sudden swelling and closure of the sinus opening (ostium).
Chronic rhinosinusitis: Patients are diagnosed with chronic rhinosinusitis when their rhinosinusitis symptoms persist for greater than 12 weeks despite medical treatment. Chronic sinus disease may be caused by anatomic sinus ostial narrowing, mucociliary disturbances or immune deficiency.
Cilia: Microscopic “hairs” on the surface of the sinus membranes that provide a sweeping action to move mucus out of the sinuses.
Concha bullosa deformity: This is a common “anatomic variant” characterized by an air-filled middle turbinate. If large, concha bullosa may contribute to impaired nasal breathing.
A “curved emitter” is an emitter having a curved reflecting (or focusing) or emitting surface and includes, but is not limited to, emitters having ellipsoidal, parabolic, quasi parabolic (general paraboloid) or spherical reflector/reflecting or emitting elements. Curved emitters having a curved reflecting or focusing element generally produce waves having focused wave fronts, while curved emitters having a curved emitting surfaces generally produce wave having divergent wave fronts.
“debridement” the surgical removal of lacerated, devitalized, or contaminated tissue. This includes removal of mucus and dead tissue post nasal or sinus surgery.
“Divergent waves” in the context of the present invention are all waves which are not focused and are not plane or nearly plane. Divergent waves also include waves which only seem to have a focus or source from which the waves are transmitted. The wave fronts of divergent waves have divergent characteristics. Divergent waves can be created in many different ways, for example: A focused wave will become divergent once it has passed through the focal point. Spherical waves are also included in this definition of divergent waves and have wave fronts with divergent characteristics.
Eosinophil: A type of white blood cell that usually comprises <5% of all white blood cells in the blood. Eosinophils are found in increased numbers in chronic rhinosinusitis, nasal polyps and asthma. They contribute to inflammation by production of inflammatory mediators, such as leukotriene C4.
“extracorporeal” occurring or based outside the living body.
Functional endoscopic sinus surgery (FESS): The most common type of sinus surgery. The goal of FESS is to remove blockages in the ostiomeatal complex thereby improving drainage from the ethmoid and maxillary sinuses.
A “generalized paraboloid” according to the present invention is also a three-dimensional bowl. In two dimensions (in Cartesian coordinates, x and y) the formula yn=2 px [with n being ≠2, but being greater than about 1.2 and smaller than 2, or greater than 2 but smaller than about 2.8]. In a generalized paraboloid, the characteristics of the wave fronts created by electrodes located within the generalized paraboloid may be corrected by the selection of (p (−z,+z)), with z being a measure for the burn down of an electrode, and n, so that phenomena including, but not limited to, burn down of the tip of an electrode (−z,+z) and/or disturbances caused by diffraction at the aperture of the paraboloid are compensated for.
Haller Cell: An “anatomic variant” that develops as an air cell from the ethmoid sinuses and develops into the floor of the orbit. If large, the haller cell may narrow maxillary and/or ethmoid ostia and contribute to the development of rhinosinusitis.
Middle meatus: An important drainage pathway through the ostiomeatal complex.
“necrosis” A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately CELL DEATH.
A “paraboloid” according to the present invention is a three-dimensional reflecting bowl. In two dimensions (in Cartesian coordinates, x and y) the formula y2=2 px, wherein p/2 is the distance of the focal point of the paraboloid from its apex, defines the paraboloid. Rotation of the two-dimensional figure defined by this formula around its longitudinal axis generates a defacto paraboloid.
“Plane waves” are sometimes also called flat or even waves. Their wave fronts have plane characteristics (also called even or parallel characteristics). The amplitude in a wave front is constant and the “curvature” is flat (that is why these waves are sometimes called flat waves). Plane waves do not have a focus to which their fronts move (focused) or from which the fronts are emitted (divergent). “Nearly plane waves” also do not have a focus to which their fronts move (focused) or from which the fronts are emitted (divergent). The amplitude of their wave fronts (having “nearly plane” characteristics) is approximating the constancy of plain waves. “Nearly plane” waves can be emitted by generators having pressure pulse/shock wave generating elements with flat emitters or curved emitters. Curved emitters may comprise a generalized paraboloid that allows waves having nearly plane characteristics to be emitted.
A “pressure pulse” according to the present invention is an acoustic pulse which includes several cycles of positive and negative pressure. The amplitude of the positive part of such a cycle should be above about 0.1 MPa and its time duration is from below a microsecond to about a second. Rise times of the positive part of the first pressure cycle may be in the range of nano-seconds (ns) up to some milli-seconds (ms). Very fast pressure pulses are called shock waves. Shock waves used in medical applications do have amplitudes above 0.1 MPa and rise times of the amplitude are below 100's of ns. The duration of a shock wave is typically below 1-3 micro-seconds (μs) for the positive part of a cycle and typically above some micro-seconds for the negative part of a cycle.
Ostiomeatal complex: The drainage area for the maxillary sinus and the anterior ethmoid sinus on each side. This area commonly becomes blocked by swelling of the sinus membranes leading to an infection and mucus accumulation in the maxillary and anterior ethmoid sinus.
Ostium (plural=ostia): The opening point at which each sinus empties into the nasal cavity. The frontal, maxillary and sphenoid sinuses each have a small sinus ostium. In contrast, the ethmoid sinuses have multiple small sinus ostia.
Rhinoscopy (nasal endoscopy): An examination of the nose and sinuses using a flexible or rigid endoscope. Also known as nasal or sinus endoscopy.
Rhinosinusitis: Inflammation of the sinus passages due to infection or other causes.
Septum: The vertical bone that separates the right from the left side of the nose.
Septoplasty: A surgical procedure designed to straighten the nasal septum.
Turbinate (inferior, middle, superior): Normal structures within the nasal cavity that help humidify and filter air as it passes through the nose. Each turbinate is also know as a concha.
Waves/wave fronts described as being “focused” or “having focusing characteristics” means in the context of the present invention that the respective waves or wave fronts are traveling and increase their amplitude in direction of the focal point. Per definition the energy of the wave will be at a maximum in the focal point or, if there is a focal shift in this point, the energy is at a maximum near the geometrical focal point. Both the maximum energy and the maximal pressure amplitude may be used to define the focal point.



BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be described by way of example and with reference to the accompanying drawings in which:
FIG. 1a is a simplified depiction of a pressure pulse/shock wave (PP/SW) generator with focusing wave characteristics.
FIG. 1b is a simplified depiction of a pressure pulse/shock wave generator with plane wave characteristics.
FIG. 1c is a simplified depiction of a pressure pulse/shock wave generator with divergent wave characteristics.
FIG. 2a is a simplified depiction of a pressure pulse/shock wave generator having an adjustable exit window along the pressure wave path. The exit window is shown in a focusing position.
FIG. 2b is a simplified depiction of a pressure pulse/shock wave generator having an exit window along the pressure wave path. The exit window as shown is positioned at the highest energy divergent position.
FIG. 2c is a simplified depiction of a pressure pulse/shock wave generator having an exit window along the pressure wave path. The exit window is shown at a low energy divergent position.
FIG. 3 is a simplified depiction of an electro-hydraulic pressure pulse/shock wave generator having no reflector or focusing element. Thus, the waves of the generator did not pass through a focusing element prior to exiting it.
FIG. 4a is a simplified depiction of a pressure pulse/shock wave generator having a focusing element in the form of an ellipsoid. The waves generated are focused.
FIG. 4b is a simplified depiction of a pressure pulse/shock wave generator having a parabolic reflector element and generating waves that are disturbed plane.
FIG. 4c is a simplified depiction of a pressure pulse/shock wave generator having a quasi parabolic reflector element (generalized paraboloid) and generating waves that are nearly plane/have nearly plane characteristics.
FIG. 4d is a simplified depiction of a generalized paraboloid with better focusing characteristic than a paraboloid in which n=2. The electrode usage is shown. The generalized paraboloid, which is an interpolation (optimization) between two optimized paraboloids for a new electrode and for a used (burned down) electrode is also shown.
FIG. 5 is a simplified depiction of a pressure pulse/shock wave generator being connected to a control/power supply unit.
FIG. 6 is a simplified depiction of a pressure pulse/shock wave generator comprising a flat EMSE (electromagnetic shock wave emitter) coil system to generate nearly plane waves as well as an acoustic lens. Convergent wave fronts are leaving the housing via an exit window.
FIG. 7 is a simplified depiction of a pressure pulse/shock wave generator having a flat EMSE coil system to generate nearly plane waves. The generator has no reflecting or focusing element. As a result, the pressure pulse/shock waves are leaving the housing via the exit window unfocused having nearly plane wave characteristics.
FIG. 8 is a simplified depiction of a pressure pulse/shock wave generator having a flat piezoceramic plate equipped with a single or numerous individual piezoceramic elements to generate plane waves without a reflecting or focusing element. As a result, the pressure pulse/shock waves are leaving the housing via the exit window unfocused having nearly plane wave characteristics.
FIG. 9 is a simplified depiction of a pressure pulse/shock wave generator having a cylindrical EMSE system and a triangular shaped reflecting element to generate plane waves. As a result, the pressure pulse/shock waves are leaving the housing via the exit window unfocused having nearly plane wave characteristics.
FIG. 10 is a simplified depiction of a pressure pulse/shock wave (PP/SW) generator with focusing wave characteristics shown focused with the focal point or geometrical focal volume being on an organ, the focus being targeted on the location X0.
FIG. 11 is a simplified depiction of a pressure pulse/shock wave (PP/SW) generator with the focusing wave characteristics shown wherein the focus is located a distance X, from the location X0 of an organ wherein the converging waves impinge the organ.
FIG. 12 is a simplified depiction of a pressure pulse/shock wave (PP/SW) generator with focusing wave characteristics shown wherein the focus is located a distance X2 from the mass location X0 wherein the emitted divergent waves impinge the organ.
FIG. 13 shows a patient being treated extracorporeally with shock waves being transmitted through the skin tissue to the sinus or nasal region of the head to be treated.



DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to the use of various therapeutic pressure pulse wave patterns or acoustic shock wave patterns as illustrated in FIGS. 1-12 for treating various nasal or sinus related diseases or conditions or for preventing such conditions from occurring. Each illustrated wave pattern will be discussed later in the description, however, the use of each has particularly interesting beneficial features that are a remarkably valuable new tool in the fight against sinus diseases.
With reference to FIG. 13, a view of a patients head showing the nasal or sinus region 200 is shown.
The current preventive procedure used to eliminate viral, fungal or bacterial infections is the use of antibiotics or nasal sprays having steroids to reduce inflammation and swelling of the nasal passages. The next step in current treatment is surgery.
Shock waves are a completely different technology and a quantum leap beyond current treatments. The mechanism of shock waves is far from being understood, but is known to cause new blood vessels to grow in an area of treatment and regenerate bony tissue. In the present invention shock waves are used to treat nasal or sinus disease by causing the structure of the tissue architecture to be regenerated. This is a phenomenal advancement over the current approach which includes difficult surgery. If surgery could be replaced in many cases, it would save millions of dollars, gain wide acceptance (non-invasive) and be a tremendous boon to patient's world wide. The aerobic or anaerobic bacteria are thought to be the major culprit in infectious sinusitis diseases. These bacteria are commonly found in nasal biofilms formed in the mucus of blocked passages in the sinus region.
Ideally the treatments to remove the bacterial laden mucus would not only eradicate the bacteria, but would also provide or stimulate a germicidal protective feature that would inhibit the bacteria from re-colonizing these regions.
As was mentioned the use of antibiotics has its own detrimental drawbacks and is thus far more complicated and less effective than needed in the area of treating these complex nasal biofilms.
The present invention employs the use of pressure pulses or shock waves to stimulate a germicidal cellular response that kills the bacteria laden mucus or biofilms while stimulating a tissue regenerative healing process that activates the tissue cells to defend against these microbial agents.
In the pressure pulse or shock wave method of treating an olfactory tissue, with a risk of exposure to a sinus infection or post-occurrence of such infection requires the host patient to be positioned in a convenient orientation to permit the source of the emitted waves to most directly send the waves to the target site to initiate pressure pulse or shock wave stimulation of the target area with minimal, preferably no obstructing features in the path of the emitting source or lens. Assuming the treatment region is accessible through the mouth then the shock wave head 43 can be inserted and placed directly on the treatment region. Alternatively the shock wave head 43 can be placed externally on the skin and transmit the emitted shock wave patterns 200 through the cheek tissue 116 for example and into the adjacent nasal or sinus tissue 100 to be treated, as shown in FIG. 13. Preferably the outer skin tissue 116 is pressed against the sinus treatment region 300 to insure the transmission loss is minimal. Assuming the infected or inflamed target area or site is within a projected area of the wave transmission, a single transmission dosage of wave energy may be used. The transmission dosage can be from a few seconds to 20 minutes or more dependent on the condition. Preferably the waves are generated from an unfocused or focused source. The unfocused waves can be divergent, planar or near planar and having a low pressure amplitude and density in the range of 0.00001 mJ/mm2 to 1.0 mJ/mm2 or less, most typically below 0.2 mJ/mm2. The focused source preferably can use a diffusing lens or have a far-sight focus to minimize if not eliminate having the localized focus point within the tissue. Preferably the focused shock waves are used at a similarly effective low energy transmission or alternatively can be at higher energy but wherein the tissue target site is disposed pre-convergence inward of the geometric focal point of the emitted wave transmission. In treating some hard to penetrate infections or biofilms or cancerous tumors or masses 102, the pressure pulse more preferably is a high energy target focused wave pattern which can effectively attack the biofilm or mass outer structure or barrier shield causing fractures or openings to be created to expose the colonies of microorganisms within the biofilm or malignant cell to the germicidal effects of the pressure pulses or shock waves. This emitted energy destroys the underlying microorganism's cellular membranes. In addition the fragmentation of the biofilms outer barrier is then easily absorbed by or flushed out of the host via drainage through the nasal passages. The surrounding healthy cells in the region treated are activated initiating a defense mechanism response to assist in eradication of the unwanted infection.
These shock wave energy transmissions are effective in stimulating a cellular response and can be accomplished without creating the cavitation bubbles in the tissue of the target site when employed in other than high energy focused transmissions. This effectively insures the tissue or organ does not have to experience the sensation of hemorrhaging so common in the higher energy focused wave forms having a focal point at or within the targeted treatment site.
If the target site is subjected to a surgical procedure exposing at least some if not all of the tissue within the nasal cavity the target site may be such that the patient or the generating source must be reoriented relative to the site and a second, third or more treatment dosage can be administered. The fact that some if not all of the dosage can be at a low energy the common problem of localized hemorrhaging is reduced making it more practical to administer multiple dosages of waves from various orientations to further optimize the treatment and cellular stimulation of the target site. Heretofore focused high energy multiple treatments induced pain and discomfort to the patient. The use of low energy focused or un-focused waves at the target site enables multiple sequential treatments.
The present method may need precise site location and can be used in combination with such known devices as ultrasound, cat-scan or x-ray imaging if needed. The physician's general understanding of the anatomy of the patient may be sufficient to locate the target area to be treated. This is particularly true when the exposed tissue or portion of the infected tissue is visually within the surgeon's line of sight and this permits the lens or cover of the emitting shock wave source to impinge on the affected tissue directly or through a transmission enhancing gel, water or fluid medium during the pressure pulse or shock wave treatment. The treated area can withstand a far greater number of shock waves based on the selected energy level being emitted. For example at very low energy levels the stimulation exposure can be provided over prolonged periods as much as 20 minutes if so desired. At higher energy levels the treatment duration can be shortened to less than a minute, less than a second if so desired. The limiting factor in the selected treatment dosage is avoidance or minimization of surrounding cell hemorrhaging and other kinds of damage to the surrounding cells or tissue while still providing a stimulating stem cell activation or a cellular release or activation of VEGF and other growth factors while simultaneously germicidally attacking the infection or biofilm barrier and underlying colony of microorganisms.
Due to the wide range of beneficial treatments available it is believed preferable that the optimal use of one or more wave generators or sources should be selected on the basis of the specific application. Wherein relatively small target sites may involve a single wave generator placed on an adjustable manipulator arm. A key advantage of the present inventive methodology is that it is complimentary to conventional medical procedures. In the case of any operative surgical procedure the surgical area of the patient can be bombarded with these energy waves to stimulate cellular release of healing agents and growth factors. This will dramatically reduce the healing process time. Most preferably such patients may be provided more than one such treatment with an intervening dwell time for cellular relaxation prior to secondary and tertiary post operative treatments.
The underlying principle of these pressure pulse or shock wave therapy methods is to attack the infection or biofilm or the mass in the case of a tumor directly and to stimulate the body's own natural healing capability. This is accomplished by deploying shock waves to stimulate strong cells in the surrounding tissue to activate a variety of responses. The acoustic shock waves transmit or trigger what appears to be a cellular communication throughout the entire anatomical structure, this activates a generalized cellular response at the treatment site, in particular, but more interestingly a systemic response in areas more removed from the wave form pattern. This is believed to be one of the reasons molecular stimulation can be conducted at threshold energies heretofore believed to be well below those commonly accepted as required. Accordingly not only can the energy intensity be reduced in some cases, but also the number of applied shock wave impulses can be lowered from several thousand to as few as one or more pulses and still yield a beneficial stimulating response. The key is to provide at least a sufficient amount of energy to weaken the tumor or mucus laden biofilms protective outer barrier or shield. This weakening can be achieved by any fracture or opening that exposes the underlying colony of microorganisms.
The use of shock waves as described above appears to involve factors such as thermal heating, light emission, electromagnetic field exposure, chemical releases in the cells as well as a microbiological response within the cells. Which combination of these factors plays a role in stimulating healing is not yet resolved. However, there appears to be a commonality in the fact that growth factors are released which applicants find indicative that otherwise dormant cells within the tissue appear to be activated which leads to the remarkable ability of the targeted nasal or sinus tissue to generate new growth or to regenerate weakened vascular networks or blood circulation in for example the sinus tissues. This finding leads to a complimentary use of shock wave therapy in combination with stem cell therapies that effectively activate or trigger stem cells to more rapidly replicate enhancing the ability to harvest and culture more viable cells from the placenta, a nutrient culture of said stem cells, or other sources. The ability to stimulate stem cells can occur within the patients own body activating the naturally occurring stem cells or stem cells that have been introduced to the patient as part of a treatment beneficially utilizing stem cells. This is a significant clinical value in its own right.
In one embodiment, the invention provides for germicidal cleaning of sinusitis diseased or infected areas and for wound cleaning generally after exposure to surgical procedures.
The use of shock wave therapy requires a fundamental understanding of focused and unfocused shock waves, coupled with a more accurate biological or molecular model.
Focused shock waves are focused using ellipsoidal reflectors in electromechanical sources from a cylindrical surface or by the use of concave or convex lenses. Piezoelectric sources often use spherical surfaces to emit acoustic pressure waves which are self focused and have also been used in spherical electromagnetic devices.
The biological model proposed by co-inventor Wolfgang Schaden provides a whole array of clinically significant uses of shock wave therapy.
Accepting the biological model as promoted by W. Schaden, the peak pressure and the energy density of the shock waves can be lowered dramatically. Activation of the body's healing mechanisms will be seen by in growth of new blood vessels and the release of growth factors.
The biological model motivated the design of sources with low pressure amplitudes and energy densities. First: spherical waves generated between two tips of an electrode; and second: nearly even waves generated by generalized parabolic reflectors. Third: divergent shock front characteristics are generated by an ellipsoid behind f2. Unfocused sources are preferably designed for extended two dimensional areas/volumes like skin. The unfocused sources can provide a divergent wave pattern a planar or a nearly planar wave pattern and can be used in isolation or in combination with focused wave patterns yielding to an improved therapeutic treatment capability that is non-invasive with few if any disadvantageous contraindications. Alternatively a focused wave emitting treatment may be used wherein the focal point extends preferably beyond the target treatment site, potentially external to the patient. This results in the reduction of or elimination of a localized intensity zone with associated noticeable pain effect while providing a wide or enlarged treatment volume at a variety of depths more closely associated with high energy focused wave treatment. The utilization of a diffuser type lens or a shifted far-sighted focal point for the ellipsoidal reflector enables the spreading of the wave energy to effectively create a convergent but off target focal point. This insures less tissue trauma while insuring cellular stimulation to enhance the healing process and control the migration or spreading of the infection within the host. More preferably if a resident infection or biofilm location can be isolated and a short, but high energy focused wave pattern can be emitted on the outer barrier of the infection or biofilm causing a fracture or fragmentation in the outer barrier and then a lower unfocused energy transmission can be applied to provide an overall germicidal treatment and surrounding cell stimulation to destroy the biofilm within the infected nasal or sinus site and eradicate the resultant microbial debris which can be flushed out using conventional warm saline irrigation solutions.
This method of treatment has the steps of, locating a biofilm loaded or infected nasal or sinus treatment site, region or location, generating either focused, convergent diffused or far-sighted focused shock waves or unfocused shock waves; directing these shock waves to the treatment site; and applying a sufficient number of these shock waves to induce an outer barrier biofilm or infection weakening while simultaneously activating one or more growth factors in the surrounding tissue cells thereby inducing or accelerating healing.
The unfocused shock waves can be of a divergent wave pattern, planar or near planar pattern preferably convergent diffused or far-sighted wave pattern, of a low peak pressure amplitude and density. Typically the energy density values range as low as 0.000001 mJ/mm2 and having a high end energy density of below 1.0 mJ/mm2, preferably 0.20 mJ/mm2 or less. The peak pressure amplitude of the positive part of the cycle should be above 1.0 and its duration is below 1-3 microseconds.
The treatment depth can vary from the surface to the full depth of the treated organ. The treatment site can be defined by a much larger treatment area than the 0.10-3.0 cm2 commonly produced by focused waves. The above methodology is particularly well suited for surface as well as sub-surface soft tissue organ treatments.
The above methodology is valuable in generation of tissue, vascularization and may be used in combination with stem cell therapies as well as regeneration of tissue and vascularization.
The methodology is useful in (re)vascularization and regeneration of not only nasal or sinus tissue, but also periodontal tissue such as the teeth and gums, the heart, brain, liver, kidney, skin, urological organs, reproductive organs and digestive tract.
The methodology is useful in stimulating enforcement of defense mechanisms in tissue cells to fight infections from bacteria and can be used germicidally to treat or cleanse wounds or other biofilm target sites which is a primary concern in the case of treating human diseases such as sinusitis, native valve endocarditis, cystic fibrosis, periodontal gum disease and urinary or digestive tract infections resulting from such exposures to biofilm type agents.
While the above listed indications cited above are not exhaustive nor intended to be limiting, it is exemplary of the wide range of beneficial uses of high energy focused or low energy and amplitude unfocused divergent, planar or nearly planar shock waves, convergent shock waves, diffused shock waves or a combination of shock wave types in the treatment of humans and other mammals that are exposed to a biofilm type infection or are at high risk to be so exposed as the result of a high potential risk to such biofilm infectious exposure.
A most significant method of preventive medicine can be practiced that is fully enabled by the use of these relatively low amplitude and pressure shock waves. The method includes the steps of identifying high risk patients for a variety of potential risk conditions. Such condition could be by way of example asthma, allergies and related sinus or nasal conditions or cystic fibrosis. After identifying a risk prone candidate providing one or a series of two or more exposure treatments with focused or unfocused, divergent, planar or near planar shock waves or convergent far-sighted focused shock waves or diffused shock waves to the treatment site, in this example the region surrounding or in proximity to an inflammation, infection or a biofilm occurrence risk location. Then after treatments the physician can optionally ultrasound visually or otherwise determine the increase in regeneration or vascularization in the treated tissue after a period of time. Assuming an initial baseline determination of the tissue regeneration or vascularization had been initially conducted an estimate or calculation of dosage requirements can be made. This procedure can be used for any nasal, sinus or respiratory related at risk condition. After a surgical repair procedure the surrounding tissues can be post-operatively shock wave treated as well using low energy waves to stimulate healing.
The implications of using the (re)generative features of this type of shock wave therapy are any weakened sinus or nasal or tissue even adjacent bone can be strengthened to the point of reducing or eliminating the risk of irreparable damage or degenerative failure as a result of microbial, viral or fungal infections.
The stimulation of growth factors and activation of healing acceleration within the cells of the treated tissues is particularly valuable to host patients and other high risk factor subjects wherein conventional antibiotic treatments have been unsuccessful.
Even more striking as mentioned earlier, early prevention therapies can be employed to stimulate tissue or organ modeling to be maintained within acceptable ranges prior to an exposure to nasal or sinus infections. This is extremely valuable in the prevention of spreading the infection for example. The methods would be to identify at risk patients with a known nasal or sinusitis exposure risk, and subjecting that patient to therapeutic shock wave therapy for the purpose of stimulating tissue repair or regeneration effectively remodeling the patient's susceptible olfactory organs to be within accepted functional parameters prior to exposure to an infection. The objective being to preventively stimulate cellular tissue repairs to preemptively avoid a degenerative condition from occurring which may result in the onset of an antibiotic resistant infection which can require invasive surgical procedures.
This preventive therapy is most needed to combat biofilm exposure which left untreated results in cellular destruction or any other degenerative conditions. In the area of sinus or nasal, the use of pressure pulse waves or acoustic shock waves can be administered by a trained ear, nose and throat technician. The acoustic shock wave provides a far more advanced tissue stimulation which activates a germicidal response that continues for many weeks after treatment and thus is a natural defense method of healing that in most cases of nasal or sinus infection or biofilm exposure would not need supplemental antibiotics.
FIG. 1a is a simplified depiction of the a pressure pulse/shock wave (PP/SW) generator, such as a shock wave head, showing focusing characteristics of transmitted acoustic pressure pulses. Numeral 1 indicates the position of a generalized pressure pulse generator, which generates the pressure pulse and, via a focusing element, focuses it outside the housing to treat diseases. The affected tissue or organ is generally located in or near the focal point which is located in or near position 6. At position 17 a water cushion or any other kind of exit window for the acoustical energy is located.
FIG. 1b is a simplified depiction of a pressure pulse/shock wave generator, such as a shock wave head, with plane wave characteristics. Numeral 1 indicates the position of a pressure pulse generator according to the present invention, which generates a pressure pulse which is leaving the housing at the position 17, which may be a water cushion or any other kind of exit window. Somewhat even (also referred to herein as “disturbed”) wave characteristics can be generated, in case a paraboloid is used as a reflecting element, with a point source (e.g. electrode) that is located in the focal point of the paraboloid. The waves will be transmitted into the patient's body via a coupling media such as, e.g., ultrasound gel or oil and their amplitudes will be attenuated with increasing distance from the exit window 17.
FIG. 1c is a simplified depiction of a pressure pulse shock wave generator (shock wave head) with divergent wave characteristics. The divergent wave fronts may be leaving the exit window 17 at point 11 where the amplitude of the wave front is very high. This point 17 could be regarded as the source point for the pressure pulses. In FIG. 1c the pressure pulse source may be a point source, that is, the pressure pulse may be generated by an electrical discharge of an electrode under water between electrode tips. However, the pressure pulse may also be generated, for example, by an explosion, referred to as a ballistic pressure pulse. The divergent characteristics of the wave front may be a consequence of the mechanical setup shown in FIG. 2b. 
FIG. 2a is a simplified depiction of a pressure pulse/shock wave generator (shock wave head) according to the present invention having an adjustable or exchangeable (collectively referred to herein as “movable”) housing around the pressure wave path. The apparatus is shown in a focusing position. FIG. 2a is similar to FIG. 1a but depicts an outer housing (16) in which the acoustical pathway (pressure wave path) is located. In a preferred embodiment, this pathway is defined by especially treated water (for example, temperature controlled, conductivity and gas content adjusted water) and is within a water cushion or within a housing having a permeable membrane, which is acoustically favorable for the transmission of the acoustical pulses. In certain embodiments, a complete outer housing (16) around the pressure pulse/shock wave generator (1) may be adjusted by moving this housing (16) in relation to, e.g., the focusing element in the generator. However, as the person skilled in the art will appreciate, this is only one of many embodiments of the present invention. While the figure shows that the exit window (17) may be adjusted by a movement of the complete housing (16) relative to the focusing element, it is clear that a similar, if not the same, effect can be achieved by only moving the exit window, or, in the case of a water cushion, by filling more water in the volume between the focusing element and the cushion. FIG. 2a shows the situation in which the arrangement transmits focused pressure pulses.
FIG. 2b is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) having an adjustable or exchangeable housing around the pressure wave path with the exit window 17 being in the highest energy divergent position. The configuration shown in FIG. 2b can, for example, be generated by moving the housing (16) including the exit window (17), or only the exit window (17) of a water cushion, towards the right (as shown in the Figure) to the second focus f2 (20) of the acoustic waves. In a preferred embodiment, the energy at the exit window will be maximal. Behind the focal point, the waves may be moving with divergent characteristics (21).
FIG. 2c is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) having an adjustable or exchangeable housing around the pressure wave path in a low energy divergent position. The adjustable housing or water cushion is moved or expanded much beyond f2 position (20) so that highly divergent wave fronts with low energy density values are leaving the exit window (17) and may be coupled to a patient's body. Thus, an appropriate adjustment can change the energy density of a wave front without changing its characteristic.
This apparatus may, in certain embodiments, be adjusted/modified/or the complete shock wave head or part of it may be exchanged so that the desired and/or optimal acoustic profile such as one having wave fronts with focused, planar, nearly plane, convergent or divergent characteristics can be chosen.
A change of the wave front characteristics may, for example, be achieved by changing the distance of the exit acoustic window relative to the reflector, by changing the reflector geometry, by introducing certain lenses or by removing elements such as lenses that modify the waves produced by a pressure pulse/shock wave generating element. Exemplary pressure pulse/shock wave sources that can, for example, be exchanged for each other to allow an apparatus to generate waves having different wave front characteristics are described in detail below.
In certain embodiments, the change of the distance of the exit acoustic window can be accomplished by a sliding movement. However, in other embodiments of the present invention, in particular, if mechanical complex arrangements, the movement can be an exchange of mechanical elements.
In one embodiment, mechanical elements that are exchanged to achieve a change in wave front characteristics include the primary pressure pulse generating element, the focusing element, the reflecting element, the housing and the membrane. In another embodiment, the mechanical elements further include a closed fluid volume within the housing in which the pressure pulse is formed and transmitted through the exit window.
In one embodiment, the apparatus of the present invention is used in combination therapy. Here, the characteristics of waves emitted by the apparatus are switched from, for example, focused to divergent or from divergent with lower energy density to divergent with higher energy density. Thus, effects of a pressure pulse treatment can be optimized by using waves having different characteristics and/or energy densities, respectively.
While the above described universal toolbox of the present invention provides versatility, the person skilled in the art will appreciate that apparatuses that only produce waves having, for example, nearly plane characteristics, are less mechanically demanding and fulfill the requirements of many users.
As the person skilled in the art will also appreciate that embodiments shown in the drawings are independent of the generation principle and thus are valid for not only electro-hydraulic shock wave generation but also for, but not limited to, PP/SW generation based on electromagnetic, piezoceramic and ballistic principles. The pressure pulse generators may, in certain embodiments, be equipped with a water cushion that houses water which defines the path of pressure pulse waves that is, through which those waves are transmitted. In a preferred embodiment, a patient is coupled via ultrasound gel or oil to the acoustic exit window (17), which can, for example, be an acoustic transparent membrane, a water cushion, a plastic plate or a metal plate.
FIG. 3 is a simplified depiction of the pressure pulse/shock wave apparatus having no focusing reflector or other focusing element. The generated waves emanate from the apparatus without coming into contact with any focusing elements. FIG. 3 shows, as an example, an electrode as a pressure pulse generating element producing divergent waves (28) behind the ignition point defined by a spark between the tips of the electrode (23, 24).
FIG. 4a is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) having as focusing element an ellipsoid (30). Thus, the generated waves are focused at (6).
FIG. 4b is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) having as a focusing element an paraboloid (y2=2 px). Thus, the characteristics of the wave fronts generated behind the exit window (33, 34, 35, and 36) are disturbed plane (“parallel”), the disturbance resulting from phenomena ranging from electrode burn down, spark ignition spatial variation to diffraction effects. However, other phenomena might contribute to the disturbance.
FIG. 4c is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) having as a focusing element a generalized paraboloid (yn=2 px, with 1.2<n<2.8 and n≠2). Thus, the characteristics of the wave fronts generated behind the exit window (37, 38, 39, and 40) are, compared to the wave fronts generated by a paraboloid (y2=2 px), less disturbed, that is, nearly plane (or nearly parallel or nearly even (37, 38, 39, 40)). Thus, conformational adjustments of a regular paraboloid (y2=2 px) to produce a generalized paraboloid can compensate for disturbances from, e.g., electrode burn down. Thus, in a generalized paraboloid, the characteristics of the wave front may be nearly plane due to its ability to compensate for phenomena including, but not limited to, burn down of the tips of the electrode and/or for disturbances caused by diffraction at the aperture of the paraboloid. For example, in a regular paraboloid (y2=2 px) with p=1.25, introduction of a new electrode may result in p being about 1.05. If an electrode is used that adjusts itself to maintain the distance between the electrode tips (“adjustable electrode”) and assuming that the electrodes burn down is 4 mm (z=4 mm), p will increase to about 1.45. To compensate for this burn down, and here the change of p, and to generate nearly plane wave fronts over the life span of an electrode, a generalized paraboloid having, for example n=1.66 or n=2.5 may be used. An adjustable electrode is, for example, disclosed in U.S. Pat. No. 6,217,531.
FIG. 4d shows sectional views of a number of paraboloids. Numeral 62 indicates a paraboloid of the shape y2=2 px with p=0.9 as indicated by numeral 64 at the x axis which specifies the p/2 value (focal point of the paraboloid). Two electrode tips of a new electrode 66 (inner tip) and 67 (outer tip) are also shown in the Figure. If the electrodes are fired and the tips are burning down the position of the tips change, for example, to position 68 and 69 when using an electrode which adjusts its position to compensate for the tip burn down. In order to generate pressure pulse/shock waves having nearly plane characteristics, the paraboloid has to be corrected in its p value. The p value for the burned down electrode is indicate by 65 as p/2=1. This value, which constitutes a slight exaggeration, was chosen to allow for an easier interpretation of the Figure. The corresponding paraboloid has the shape indicated by 61, which is wider than paraboloid 62 because the value of p is increased. An average paraboloid is indicated by numeral 60 in which p=1.25 cm. A generalized paraboloid is indicated by dashed line 63 and constitutes a paraboloid having a shape between paraboloids 61 and 62. This particular generalized paraboloid was generated by choosing a value of n≠2 and a p value of about 1.55 cm. The generalized paraboloid compensates for different p values that result from the electrode burn down and/or adjustment of the electrode tips.
FIG. 5 is a simplified depiction of a set-up of the pressure pulse/shock wave generator (43) (shock wave head) and a control and power supply unit (41) for the shock wave head (43) connected via electrical cables (42) which may also include water hoses that can be used in the context of the present invention. However, as the person skilled in the art will appreciate, other set-ups are possible and within the scope of the present invention.
FIG. 6 is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) having an electromagnetic flat coil 50 as the generating element. Because of the plane surface of the accelerated metal membrane of this pressure pulse/shock wave generating element, it emits nearly plane waves which are indicated by lines 51. In shock wave heads, an acoustic lens 52 is generally used to focus these waves. The shape of the lens might vary according to the sound velocity of the material it is made of. At the exit window 17 the focused waves emanate from the housing and converge towards focal point 6.
FIG. 7 is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) having an electromagnetic flat coil 50 as the generating element. Because of the plane surface of the accelerated metal membrane of this generating element, it emits nearly plane waves which are indicated by lines 51. No focusing lens or reflecting lens is used to modify the characteristics of the wave fronts of these waves, thus nearly plane waves having nearly plane characteristics are leaving the housing at exit window 17.
FIG. 8 is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) having an piezoceramic flat surface with piezo crystals 55 as the generating element. Because of the plane surface of this generating element, it emits nearly plane waves which are indicated by lines 51. No focusing lens or reflecting lens is used to modify the characteristics of the wave fronts of these waves, thus nearly plane waves are leaving the housing at exit window 17. Emitting surfaces having other shapes might be used, in particular curved emitting surfaces such as those shown in FIGS. 4a to 4c as well as spherical surfaces. To generate waves having nearly plane or divergent characteristics, additional reflecting elements or lenses might be used. The crystals might, alternatively, be stimulated via an electronic control circuit at different times, so that waves having plane or divergent wave characteristics can be formed even without additional reflecting elements or lenses.
FIG. 9 is a simplified depiction of the pressure pulse/shock wave generator (shock wave head) comprising a cylindrical electromagnet as a generating element 53 and a first reflector having a triangular shape to generate nearly plane waves 54 and 51. Other shapes of the reflector or additional lenses might be used to generate divergent waves as well.
With reference to FIGS. 10, 11 and 12 a schematic view of a shock wave generator or source 1 is shown emitting a shock wave front 200 from an exit window 17. The shock wave front 200 has converging waves 202 extending to a focal point or focal geometric volume 20 at a location spaced a distance X from the generator or source 1. Thereafter the wave front 200 passes from the focal point or geometric volume 20 in a diverging wave pattern as has been discussed in the various other FIGS. 1-9 generally.
With particular reference to FIG. 10 a tissue 100 is shown generally centered on the focal point or volume 20 at a location X0 within the tissue 100. In this orientation the emitted waves are focused and thus are emitting a high intensity acoustic energy at the location X0. This location X0 can be anywhere within or on the organ. Assuming the tissue 100 is a sinus tissue having a biofilm or other infectious tumor or mass 102 at location X0 then the focus is located directly on the tumor or biofilm mass 102. In one method of treating a biofilm infection or mass 102 these focused waves can be directed to destroy or otherwise reduce the tumor or biofilm mass 102 by weakening the outer barrier shield of the tumor or biofilm mass 102.
With reference to FIG. 11, the tissue 100 is shifted a distance X toward the generator or source 1. The tissue 100 at location X0 being positioned a distance X−X1 from the source 1. This insures the tissue 100 is impinged by converging waves 202 but removed from the focal point 20. When the tissue 100 is tissue this bombardment of converging waves 202 stimulates the cells activating the desired healing response as previously discussed.
With reference to FIG. 12, the tissue 100 is shown shifted or located in the diverging wave portion 204 of the wave front 200. As shown X0 is now at a distance X2 from the focal point or geometric volume 20 located at a distance X from the source 1. Accordingly X0 is located a distance X+X2 from the source 1. As in FIG. 10 this region of diverging waves 204 can be used to stimulate the tissue 100 which when the tissue is a cellular tissue stimulates the cells to produce the desired healing effect or response.
Heretofore invasive techniques were not used in combination with shock wave therapy primarily because the shock waves were believed to be able to sufficiently pass through interfering body tissue to achieve the desired result in a non-invasive fashion. While this may be true, in many cases if the degenerative process is such that an operation is required then the combination of an operation in conjunction with shock wave therapy only enhances the therapeutic values and the healing process of the patient and the infected organ such that regenerative conditions can be achieved that would include not only revascularization of nasal tissue, but can also be used on the heart or other organs wherein sufficient or insufficient blood flow is occurring but also to enhance the improvement of ischemic tissue that may be occupying a portion of the infected tissue or organ. This ischemic tissue can then be minimized by the regenerative process of using shock wave therapy in the fashion described above to permit the tissue to rebuild itself in the region that has been afflicted.
As shown in FIGS. 1-12 the use of these various acoustic shock wave forms can be used separately or in combination to achieve the desired therapeutic effect of destroying the infection, tumor or biofilm mass 102 within a paranasal region 300.
Furthermore such acoustic shock wave forms can be used in combination with drugs, chemical treatments, irradiation therapy or even physical therapy and when so combined the stimulated cells will more rapidly assist the body's natural healing response and thus overcomes the otherwise potentially tissue damaging effects of these complimentary procedures.
The present invention provides an apparatus for an effective treatment of indications, which benefit from high or low energy pressure pulse/shock waves having focused or unfocused, nearly plane, convergent or even divergent characteristics. With an unfocused wave having nearly plane, plane, convergent wave characteristic or even divergent wave characteristics, the energy density of the wave may be or may be adjusted to be so low that side effects including pain are very minor or even do not exist at all.
In certain embodiments, the apparatus of the present invention is able to produce waves having energy density values that are below 0.1 mJ/mm2 or even as low as 0.000 001 mJ/mm2. In a preferred embodiment, those low end values range between 0.1-0.001 mJ/mm2. With these low energy densities, side effects are reduced and the dose application is much more uniform. Additionally, the possibility of harming surface tissue is reduced when using an apparatus of the present invention that generates unfocused waves having planar, nearly plane, convergent or divergent characteristics and larger transmission areas compared to apparatuses using a focused shock wave source that need to be moved around to cover the affected area. The apparatus of the present invention also may allow the user to make more precise energy density adjustments than an apparatus generating only focused shock waves, which is generally limited in terms of lowering the energy output. Nevertheless in some cases the first use of a high energy focused shock wave targeting a tumor or a biomass may be the best approach to weaken the outer barrier of the shield of the tumor or biomass followed by a transmission of lower energy unfocused wave patterns, the combination being the most effective in germicidal destruction of the infection, tumor or biofilm mass.
The treatment of the above mentioned nasal or sinus tissue of a patient is believed to be a first time use of acoustic shock wave therapy in the preventive pre-exposure or post-exposure to sinusitis infections or paranasal cancer. None of the work done to date has treated the above mentioned conditions or infections with convergent, divergent, planar or near-planar acoustic unfocused shock waves of low energy or high energy focused shock waves in a germicidal transmission path from the emitting source lens or cover to the infection. Also this is believed to be a first time use of acoustic shock waves for germicidal wound cleaning or preventive medical treatments for such exposures.
It will be appreciated that the apparatuses and processes of the present invention can have a variety of embodiments, only a few of which are disclosed herein. It will be apparent to the artisan that other embodiments exist and do not depart from the spirit of the invention. Thus, the described embodiments are illustrative and should not be construed as restrictive.
The use of acoustic shock waves to patients exposed to sinusitis infections stimulates a cellular response of the treated tissues as well as a cellular response in the surrounding tissue. This response activates otherwise dormant cells to increase the body's own defense mechanisms, allowing the cells to limit the migration of the infection and resultant tissue damage, but also to initiate the healing process. This feature means that the treating physician has the added benefit of a patient whose body will be strengthened to mitigate damage to otherwise healthy tissues and organs.
The nature of infectious disease treatments employing only antibiotics to kill infections is well known to actually make biofilm protected microorganisms mutate making them even harder to kill. The result is the patient is in a greatly weakened state overall. These mutant strains are so severe that the common antibiotic treatments are losing their ability to stop the spread of some infections which is well documented. These symptoms are generally reversible. The more serious complications may not be reversible. In some cases damage and complete destruction of the tissue and bones in the sinus region has been observed as a consequence of such failed treatments. These antibiotic and steroid nasal spray treatments can be cumulative in their adverse reactions and thus the effective treatment of the infections can also permanently damage otherwise healthy tissue and organs. The use of the shock waves as described above stimulates these healthy cells to defend against this spill over intrusion. By way of example, it is believed possible for asthma patients treated for sinusitis to reduce the need for a steroid spray or other inhalant to alleviate respiratory distress. This means a person could lower either the concentration of the drug per dose or the number of doses taken per week. This intuitively means the adverse long term side effects of using such medication such as kidney failure or liver damage can be reduced. This is similarly believed to be applicable to the use of antibiotics which can either be given in lower concentrations or for shorter durations when combined with the use of shock wave treatments on regularly scheduled basis.
This means the physician can use these antibiotic treatments with far less adverse reactions if he combines the treatments with one or more exposures to acoustic shock waves either before introducing chemical antibiotic agents or shortly thereafter or both. This further means that the patient's recovery time should be greatly reduced because the patient treated with shock waves will have initiated a healing response that is much more aggressive than heretofore achieved without the cellular stimulation provided by pressure pulse or shock wave treatments. The current use of medications to stimulate such cellular activity is limited to absorption through the bloodstream via the blood vessels. Acoustic shock waves stimulate all the cells in the region treated activating an almost immediate cellular release of infection fighting and healing agents. Furthermore, as the use of other wise conflicting chemicals is avoided, adverse side effects can be limited to those medicaments used to destroy the infectious cells. In other words the present invention is far more complimentary to such antibiotic treatments in that the stimulation of otherwise healthy cells will greatly limit the adverse and irreversible effects on the surrounding non-infected tissues and organs.
A further benefit of the use of acoustic shock waves is there are no known adverse indications when combined with the use of other medications or drugs. In fact the activation of the cells exposed to shock wave treatments only enhances cellular absorption of such medication making these drugs faster acting than when compared to non stimulated cells. As a result, it is envisioned that the use of one or more medicaments prior to, during or after subjecting the patient to acoustic shock waves will be complimentary to the treatment or pre-conditioning treatment for sinusitis. It is further appreciated that certain drug therapies can be altered or modified to lower risk or adverse side effects when combined with a treatment involving acoustic shock waves as described above.
Variations in the present invention are possible in light of the description of it provided herein. While certain representative embodiments and details have been shown for the purpose of illustrating the subject invention, it will be apparent to those skilled in this art that various changes and modifications can be made therein without departing from the scope of the subject invention. It is, therefore, to be understood that changes can be made in the particular embodiments described which will be within the full intended scope of the invention as defined by the following appended claims.

## Claims

1. A method of treatment for a sinus or nasal tissue exhibiting a sinusitis or rhinosinusitis disease or condition in a diagnosed patient comprises the steps of:
receiving a diagnosed patient;
activating an acoustic shock wave or pressure pulse generator or source to emit low energy unfocused or focused acoustic shock waves or pressure pulses in a path having a low energy density less than 1.0 mJ/mm2 per shock wave or pressure pulse, the pressure pulse being an acoustic pulse which includes several cycles of positive and negative pressure, wherein the pressure pulse has an amplitude of the positive part of such a cycle should be above 0.1 MPa and the time duration of the pressure pulse is from below a microsecond to about a second, rise times of the positive part of the first pressure cycle in the range of nano-seconds (ns) up to some milli-seconds (ms), the acoustic shock waves being very fast pressure pulses having amplitudes above 0.1 MPa and rise times of the amplitude being below 100's of ns, the duration of the shock wave is typically below 1-3 micro-seconds (μs) for the positive part of a cycle and typically above some micro-seconds for the negative part of a cycle; and
subjecting the sinus or nasal tissue, or the entire sinus or nasal region of the patient to converging, diverging, planar or near planar acoustic shock waves or pressure pulses treatment energy density and treatment dosage stimulating said tissue, in the absence of creating cavitation bubbles in the sinus or nasal tissue, wherein the tissue is positioned within a path of the emitted shock waves or pressure pulses, in the absence of any acoustic focal point or if a focal point exists, the sinus or nasal tissue is positioned away from any localized geometric focal volume or point of the emitted shock waves wherein the emitted shock waves or pressure pulses either have no geometric focal volume or point or have a focal volume or point ahead of the tissue or beyond the tissue thereby passing the emitted waves or pulses through the tissue while avoiding having any localized focal point within the tissue wherein the emitted pressure pulses or shock waves are convergent, divergent, planar or near planar and the pressure pulse shock wave generator or source is based on electro-hydraulic, electromagnetic, piezoceramic or ballistic wave generation having an energy density value ranging as low as 0.00001 mJ/mm2 to a high end of below 1.0 mJ/mm2; wherein treatment energy density and treatment dosage are selected to avoid tissue damage within the sinus or nasal tissue as evidenced by the avoidance of cell hemorrhaging, the shock waves or pressure pulses having a low treatment energy density in the range of 0.00001 mJ/mm2 to less than 1.0 mJ/mm2.

2. The method of treatment of claim 1 further comprises the step of:
administering one or more medicaments prior, during or after subjecting the patient to acoustic shock waves or pressure pulses.

3. The method of treatment of claim 1 further comprises the step of:
testing the bacterial count or viability of the treated tissue or region of the diagnosed patient after exposure to one or more acoustic shock wave or pressure pulse treatments.

4. The method of treatment of claim 1 further comprises the step of:
subjecting a tissue to a surgical procedure to remove or repair some or all of any defects or degenerative tissues.

5. The method of treatment of claim 1 wherein the treated sinus or nasal tissue has an indication of one or more pathological conditions.

6. The method of claim 1 wherein the treatment is for prevention of infectious disease.

7. The method of claim 6 further comprises the step of:
debridement.

8. The method of claim 6 wherein the treatment further comprises the step of:
destroying biofilm in or on the treated tissue or region.

9. The method of claim 6 wherein the treatment further comprises the step of:
destroying a tumor in or on the treated tissue or region.

10. The method of claim 6 wherein the treated tissue or region activates or otherwise stimulates stem cells or release of cellular growth factors in the nasal or sinus structure effecting a tissue repair or tissue regeneration.