WO2010113046A1

WO2010113046A1 - Device especially for ventilation of nitric oxide in the paranasal sinuses and the suppression of diseases of the upper respiratory tract

Info

Publication number: WO2010113046A1
Application number: PCT/IB2010/050445
Authority: WO
Inventors: Csaba László PANKUCSI; Róbert Kristóf PÓRSZÁSZ; Zsolt Farkas; Ildikó KISSNÉ HORVÁTH; Attila Zoltán NAGY; Árpád Miklós NAGY
Original assignee: Ventino Kft.
Priority date: 2009-03-28
Filing date: 2010-02-02
Publication date: 2010-10-07
Also published as: EP2416971B1; NZ596027A; HU0900181D0; AU2010230992A1; KR101698222B1; HUP0900181A2; HU227936B1; KR20120038397A; JP2012521791A; CA2793684A1; EA022211B1; JP5619133B2; EA201171183A1; CA2793684C; EP2416971A1; AU2010230992B2

Abstract

Device especially for the ventilation of nitric oxide in the paranasal sinuses and to suppress disorders of the upper respiratory tract, comprising housing (16); vibration generator (11) configured in housing (16); energy supply unit (17) in communication with vibration generator (11); vibration transmitter (19) in mechanical/physical contact with vibration generator (11), partly configured in housing (16). Its vibration transmitter (19) is designed as a unit that prevents the transmission of vibrations below a pre-set bottom value to the human body; the treatment unit of vibration transmitter (19) in engagement with the human body is designed as treatment unit vibrating at a frequency with a pre-set upper threshold limit, and its vibration generator (11) is designed as a unit which produces at least ten vibrations which increase from the bottom value to the ceiling value and decrease from the ceiling value to the bottom value over 30 s. The proposed device is preferably suitable for the treatment and diagnosis of diseases of the lower and the upper respiratory tracts and the pulmonary circulation, respectively, such as, for example, rhinitis, rhinosinusitis, nose congestion, common cold, flu, bronchitis, bronchus contractions, asthma and chronic obstructive pulmonary disease (COPD) of various origins.

Description

Title of Invention: DEVICE ESPECIALLY FOR VENTILATION OF NITRIC OXIDE IN THE PARANASAL SINUSES AND THE SUPPRESSION OF DISEASES OF THE UPPER RESPIRATORY

TRACT

Technical Field

[1] The invention relates to a device for ventilation of nitric oxide in the paranasal sinuses and the suppression of diseases of the upper respiratory tract , especially to wash over the paranasal sinuses to suppress respiratory disorders, said device comprising a housing; a vibration generator arranged in the housing; an energy supply unit connected to the vibration generator; a vibration transfer unit in mechanic/physical contact with the vibration generator, partly configured in the house. The proposed device is preferably suitable for the treatment and examination of diseases of the lower and upper respiratory tracts and of the pulmonary circulation, respectively, such as, for example, rhinitises, rhinosinusitises of various origins, nasal congestion, common cold, flu, bronchitis, bronchus contraction and chronic obstructive pulmonary disease (COPD). Background Art

[2] A skull of a living being, e.g. a human skull contains several air-filled spaces, so- called paranasal sinuses, communicating with the nasal cavity. The biggest of the paranasal sinuses is the so-called maxillary sinus or facial cavity, the volume of which is, in adult humans, 4 cm³ to 35 cm³, on average 12 cm³. Paranasal sinuses are joined to the nasal cavity via small orifices of a diameter of 1 to 3 mm. Since the mucous membrane which lines the sinuses is united with the mucous membrane of the nasal cavity, the diseases of the nasal cavity and of the sinuses usually occur in correlation, as rhinosinusitis.

[3] Rhinosinusitis has several forms. The most frequent one is common cold, meaning inflammation due to a weak infection of the upper respiratory tract. Rhinosinusitis of allergic origin, due to alien substances, mainly vegetable pollens, causing inflammation is also frequent.

[4] The so-called 'rhinitis medicamentosa' develops due to the continuous use in excess of 7-10 days of locally applicable nasal vein-contracting preparations.

[5] The hygienic state of the respiratory tracts, a function mainly of mucociliar transport, is of decisive importance for the development of respiratory diseases. Mucociliar transport is produced by the one-way whip-like motion of the cilia of the mucous membrane. Transport is influenced by the movement of the cilia and the viscoelastic properties of the mucous material.

[6] The ventilation of the sinuses is equally essential in regard of the development of respiratory diseases: blocked or poorly ventilated sinuses will be subject to inflammation.

[7] A well-known method for the examination of the ventilation of the sinuses concerns the observation of the quantity of nitric oxide gas (NO) exhaled through the nose. NO is a substance produced by the human body, which has a protective effect.

[8] The treatment of rhinitis and of diseases of the upper respiratory tract is usually quite simple. The patient needs rest and liquid replacement, and medicines, e.g. pain killers and fever reducers and, furthermore, antihistamines, vitamins, mucus -dissolvents and expectorants may be provided to alleviate the symptoms. As for the treatment of rhinitis provoked by pathogens, there is effectively no adequate medication for viruses. Antibiotics are used to prevent and treat bacterial infections. If the rhinitis fails to improve under the effect of medication, it may spread over to the sinuses.

[9] From among the diseases of the lower respiratory tract, asthma and COPD treatment uses medicaments, but the sudden temporary aggravation of asthma and COPD cannot be prevented effectively with medicinal treatment, because such events are usually due to substances that enter the human body suddenly, with air. Therefore, it is justified to use also a treatment which can enhance the self-clearing mechanism of the lower respiratory system quickly, if need be.

[10] US 2003/0172939 discloses a method and the device whereby it can be realised to eliminate congestion in the internal facial cavities with the help of vibration. The device proposed to that effect comprises a handle part containing a power source and a vibration generator, connected to an external vibration transmitter, and it is this external vibration transmitter that must be pressed against the selected body surface, so as to transmit vibration through the body surface to the hard tissues. It is a particular feature of the method, and the device is designed accordingly, that it is to eliminate congestions mechanically, via the transmitted mechanical vibrations, mainly to reduce or eliminate ear pain, and the vibration transmitter is designed so that the user can grip it between an opposing pair of teeth, in which case the device can relieve tooth-ache according to the document. The device achieves its purposes by applying subsonic frequency, i.e., a frequency below the audibility range of the human ear. The document makes no mention of the possibility to liberate NO via the vibrations and hence it does not contain any specific solution or proposal to that effect either.

[11] US 2008/0195001 describes a device and a method to alleviate pain in the sinuses, where the device is again realised as a device which transmits vibrations to the human body. To make the device applicable also in lying position, it has a specially curved shape, and the vibration transmitter that transfers the vibrations to the body surface is at an angle with the longitudinal axis of the device. This configuration, too, is meant to mechanically loosen and eliminate debris and congestion, but the document makes no mention of the vibration frequency being used. The main drawback of this configuration, the same as of the device mentioned before, is that it tries to eliminate or terminate the deposits and the bad general feeling by producing a mechanical effect.

[12] It is well-known that NO concentration in the sinuses is exceptionally high in healthy humans: it may attain 20-30 ppm (parts per million molecules). Therefore, there is a possibility that high NO concentration in the sinuses may also have some protective function. Efforts to raise NO concentration in the nose exploit this possibility. Since the NO outflow from the sinuses in the direction of the nose is hindered, various technical solutions have been devised to raise the nasal NO concentration.

[13] Lundberg J. and Weitzberg E. realised (cf. patent application WO 03/063703) that oscillating airflow significantly increases the quantity of NO in the nose, because gas exchange between the sinus and the nasal cavity intensifies at the resonance frequency of the sinuses. According to WO 03/063703, it is possible to increase the quantity of NO in the main nasal cavity with the help of an oscillating airflow or by devices which generate such airflow. The oscillating airflow can be generated by humming with closed mouth, i.e. the nasal phonation of the sounds 'm' and 'n', or by external sound source. Such devices can be used in humans for diagnostic purposes.

[14] Strong humming, however, is quite tiring, and the humming of air exhaled through the nose or the inhaling through the nose of air vibrated with the help of an external device cannot be realised if the swollen nasal mucous membrane already prevents the flow of air through the nose. Therefore, in most patients, the ventilation of the sinus by the application of an oscillating airflow cannot be applied clinically.

[15] WO 03/013653 discloses another possibility for the treatment of rhinitis. This is the application of light pointed into the nose, in other words: rhinophototherapy. Similar solutions are described also in e.g. US 2006/0271024. Rhinophototherapy, too, has the disadvantage that it cannot be used with a stuffy nose. Disclosure of Invention Technical Problem

[16] One of the main problems with the treatment of rhinitis or rhinosinusitis is the low co-operation propensity of patients who consider the disease unpleasant, but not dangerous. They stop treatment when the symptoms alleviate and, upon the return of the symptoms, the same treatment is, of course, less efficient or it has no effect at all. Therefore, there is a significant need for such simple and efficient treatment methods as can be applied by the patient in parallel with the routine everyday activities.

[17] The vibration parameters of the maxillary and frontal sinuses, respectively, can be described by a known mathematical formula, the Helmholtz equation, where resonance frequency is the function of the volume of the cavity, the diameter measured at the neck of the cavity and the length of the neck at constant vibration spread velocity.

[18] During our measurements with the methods described in the above-mentioned patent application WO 03/063703, we unexpectedly found that a higher NO level in the nose has a therapeutic effect on diseases of the upper and the lower respiratory tracts. At the same time, the application of oscillating airflow is not advantageous to treat such diseases, since in case of significant or complete nasal congestion the methods concerned are non-applicable and, furthermore, there are significant differences in therapeutic response by individual. Therefore, in order to treat the patients, one needs a method or device suitable to increase the quantity of NO and to trigger therapeutic effects in the upper and lower respiratory tracts, respectively, also in case of nasal stuffiness.

[19] As disclosed in US 2008/0200848, vibrations applied on the face near the paranasal sinuses have a therapeutic effect. However, the vibration generator described in US 2008/0200848 causes a toot-ache in a significant part of humans, since vibrations generated near the maxillary sinus spread over to the roots of the molars of the upper teeth . Although it is possible to reduce the performance of the vibration generator applied on or near the maxillary bone, then the quantity of NO flushed from the maxillary sinus to the main nasal cavity and hence the therapeutic effect exercised on the nasal cavity will decrease as well. Therefore, such a vibration generator device is wanted as will transmit vibration energy exclusively to the upper apex of the maxillary sinus, and the said vibrations do not spread over to the lower wall of the maxillary sinus and/or to the tooth roots lying close to it. Given the complexity of the human skull, the creation of a vibration generator device of this type requires careful experimental analysis, since the actual behaviour of the mechanical vibrations on spatial surfaces of a sophisticated shape and with sutures has parameters that cannot be modelled in advance.

[20] Our experiments surprisingly showed that vibrations transmitted perpendicular to the longitudinal cross-section of the nose, above the zygomatic bone from among the skull bones, can enhance the quantity of NO in the nose without causing a tooth-ache. Vibration generated on the zygomatic bone partly is partly reflected through the three extensions of the zygomatic bone and at the juncture of the zygomatic and the maxillary bones, and it partly penetrates to the maxillary and frontal bones and the mastoid portion of the temporal bone but there it already reverberates with multiple direction changes, dispersed and significantly weakened. The vibration waves divided in three directions are re -united again in the area of the so-called osteomeatal complex on the lateral side of the common nasal cavity. The upper apex of the maxillary sinus is located in the zygomatic bone. Although more than 90 percent of the volume of the maxillary sinus is in the maxillary bone, surprisingly, the vibrations in the zygomatic bone which attain the upper apex of the maxillary sinus are capable also in themselves to wash over to the nasal cavity the total amount of NO stored in the maxillary sinus.

[21] However, no NO increase was experienced in the nose upon touching to the zygomatic bone that part of the device described in US 2008/0200848 which is brought into contact with the human face. Presumably, the frequency of the vibrations generated by the device does not comply with the resonance frequency of the maxillary sinus and hence there is no enhanced gas exchange between the maxillary sinus and the nasal cavity.

[22] It is commonly known that the volume and resonance frequency of the maxillary sinus is, firstly, highly different by individual and, furthermore, it changes continuously with time in each individual. Change with time in a given individual is due to the so-called nasal cycle. During the nasal cycle, the internal cross-section of the nose changes periodically due mainly to the change in the swelling of the mucous membrane. The changes in the thickness of the mucous membrane affect both the cross-section and the length of the ostium of the sinuses. The resonance parameters change continuously under the effect of the resultant of the narrowing of the opening and the simultaneous increase of the length of the ostium due to the swelling of the mucous membrane, and hence they are difficult to calculate. Therefore, we need a vibration generator device the frequency of which can be altered continuously within a pre-set range by manual control over the period of a single treatment cycle, so that the applied vibrations match the actual resonance frequency of the sinuses several times. The mechanical construct according to patent application US 2008/0200848, however, contains several inert masses forced onto a mechanical trajectory that cause strong noise in case of fast frequency change, and the power impulses result in the fast erosion of the suspension points of the moving masses.

[23] Since the Helmholtz resonance frequency of the paranasal sinuses may differ in humans, and since the Helmholtz resonance frequency of the paranasal sinus of a given individual changes continuously with the nasal cycle, it is necessary to develop a vibration generator device for therapeutic purposes which will scan the possible resonance frequencies typical of paranasal sinuses in humans and is suitable for increasing the quantity of NO in the nasal cavity and for the treatment of respiratory diseases in humans, so that the vibrations generated by the device shall not spread on the upper teeth and cause tooth-ache. Technical Solution

[24] We have realised that it is necessary to have a mechanical vibration generator which is capable of fast revolution changes in the desired frequency range, and the parts of which are not exposed to significant attrition. [25] Vibration generator devices known in the art usually comprise a power source, a switch and other sub-units to promote their use, which represent attached vibrating components. The vibration of multi-component systems, however, generates more noise. High-frequency noise can reach the roots of the upper teeth, whereas low- frequency noise can cause eyeball impairment. Therefore, such device is needed as will not transfer any potentially harmful noise to the human body.

[26] It is possible to use for example internal and external vibration damping configurations to reduce the noise. Internal noise damping can be realised through the integration of vibration damping materials or through the tight mechanical fitting of the various vibrating parts. The use of internal vibration damping materials is limited by the growth of the size of the device. The tight integration of the inner sub-units of the device, on the other hand, aggravates the replacement of the power sources.

[27] It was found to our surprise that only those versions of the vibration generator devices produced in various technical forms are suitable for the treatment of diseases of the upper and lower respiratory tracts, respectively, when brought into engagement with the human face as do not transfer to the facial bone vibration in excess of 1500 Hz and, moreover, in intermittent mode of operation, the vibration frequency of which changes from the bottom to the ceiling limit at least ten times in 30 seconds.

[28] These and other objects of the invention have been realized by a device especially for the ventilation of nitric oxide in the paranasal sinuses and the suppression of disorders of the upper respiratory tract, according to Claim 1.

[29] Some further advantageous embodiments of the invention are listed in the dependent claims. Description of Drawings

[30] In what follows, the invention will be described in more detail with reference to the attached drawings which show an exemplary embodiment of the proposed device, whereas

[31] Figure 1 is a detail of the human face where the facial parts affected by the invention are sketched;

[32] Figures 2a, 2b highlight the surroundings of the maxillary sinus upon which the proposed device exerts its effect;

[33] Figure 3 is a possible block diagram of the vibration generator;

[34] Figure 4 is a sketch of a possible embodiment of the device according to the invention;

[35] Figure 5 shows a possible course of the vibration frequency produced by the vibration generator;

[36] Figures 6a, 6b show other possible courses of the vibration frequency produced by the vibration generator; [37] Figures 7 and 8 show the effect of treatment with the device according to the invention at different vibrations;

[38] Figures 9 and 10 show representative acoustic rhynometric study results in adult males and females, respectively;

[39] Figure 11 shows the changes in the resonance frequency of the maxillary sinus due to the nasal cycle in males and females;

[40] Figure 12 shows the vibration frequency of a possible embodiment of the device according to the invention;

[41] Figures 13A and 13B show the vibration spectrum of a possible embodiment of the device according to the invention when the maximum nitric oxide signal typical of men and women, respectively, is triggered, and

[42] Figure 14 sketches a possible method of the operation of the device according to the invention on a block diagram. Best Mode

[43] Figure 1 shows the general overview of a part of the human face, in which areas affected by the invention are indicated. The figure shows frontal sinus 1, maxillary sinus 2 and the line of tear duct 3. Vibrations spreading downward in the maxillary bone, in the line of tear duct 3, reach the upper teeth and cause tooth-ache.

[44] Figure 2a provides a closer view of zygomatic bone 4, where arrow 5 indicates the direction of the applied vibrations. Figure 2b shows maxillary sinus 2, osteomeatal complex 6 (location of the ostium of the nasal cavity), and the position of the upper teeth 7. The direction in which the vibration is to be transmitted to zygomatic bone 4 is again marked by arrow 5.

[45] Figure 3 shows a possible embodiment of the device according to the invention at block diagram level. Note that, on the basis of its function, the concrete structure of each unit will be obvious to a person skilled in the art. The vibration generator known from earlier solutions is associated according to the invention with a novel-type control unit. In the example shown here, a function generator producing the applied wave form is a saw-tooth generator - by the way, it may be something else -, made of microprocessor 8, which can be, for example, of the type Atmel AT tiny 261 operating in the customary connection. The saw-tooth generator is activated by a switch 9, which is realised in the given case as a push-button configured on the housing of the device according to the invention, not indicated separately in the drawing, in a way that provides for easy manual operation. Microprocessor 8 produces pre-set voltage values and through that frequency values, conducted through vibration sensor 10 to motor 11. Motor 11, which essentially constitutes the main part of the vibration generator is, in the given example, a high-revolution vibration motor, such as Penny motor Series 1202 or Faulhaber motor Series 0206, but any motor 11 customary in such devices can be used with appropriate parameter settings.

[46] Furthermore, the saw-tooth generator of microprocessor 8 is connected to a switching and timing stage 12, partly to link power source 13 of the device to the saw-tooth generator, and partly, optionally, to provide for the 30 second treatment cycle which is ideal and necessary according to our measurements. Vibration sensor 10 monitors with the help of one or several electrical transducers the frequency and amplitude of the vibration produced, and provides feedback which influences the production of the envisaged vibration, with a defined nominal frequency and amplitude, by the saw-tooth generator. Stage 12 is connected to spatial position switch 20, the role of which will be described in the document later on.

[47] A preferred embodiment of the device according to the invention contains a microprocessor 8 that can be re-programmed from an external computer in several modes of operation, and the optimum frequency scanning modes of operation can be activated from the memory. Consequently, the device can be used efficiently with several kinds of patient groups. To ensure optimum effect, a preferred embodiment according to the invention makes it possible to build in a revolution or vibration sensor into the part of the device which gets into contact with the human body, which will then in the known way provide feedback to microprocessor 8 and keep the operation parameters within the desired values.

[48] Figure 4 shows a sketch of a possible physical realisation of the device according to the invention which, however, may be altered in line with the area of utilisation, needs and possibilities ever. To provide for hand-holdability, a rod-shaped housing 16 located in the designed mantle 15 contains, one after the other, power source 17, which may be a battery, an accumulator or some other source of electric current, if an electric vibration generator is used. A vibration controller contains switching and timer stage 12, microprocessor 8 with saw-tooth generator and vibration sensor 10. That is followed by the vibration generator, which contains electric motor 11 and eccentric wheel 11 made of the same piece as its axe or wedged onto it, which transmits the vibrations through hammer 19, essentially the vibration transmitter, protruding from the side of housing 16 of the device and indicated symbolically. Spatial position switch 20 guarantees the operation of the device exclusively if held in the right position, and the right position is indicated by sound emitter 21. The total device can be designed as a unit of 50-100 mm length and 15-35 mm width (or diameter, if a cylindrical housing is used), which can be fixed even on a key-ring, ready for application at any time.

[49] According to the invention, in order to avoid tooth-ache, the vibration transmitter of the device according to the invention in contact with the human body is partly provided with vibration damping material (vibration damper component 22) and, on the other hand, due to its design, the device can be held by a natural grip so that vibration generated by the device shall not spread downwards, towards the teeth, but be divided along the three extensions of 4 zygomatic bone 4, and reach the upper teeth only in a significantly weakened form.

[50] As for its technical construction, the device includes a maximum of one vibration generator which consists of no more than two independent mechanical sub-parts (piezo-ceramic, or axe and eccentric wheel 18, or mechanical component moved by electromagnet); furthermore, the device contains at least one flexible or elastic internal vibration damping element (e.g. spring to press down power source 17), and at least one elastic external vibration damping component 22 which gets in contact with the human face, is skin-friendly and easy to clean. Well-known skin-friendly vibration damping materials include polyurethane foam rubbers free of PVC, but these are difficult to clean, since it takes a long time for the humidity entering the inside of the foam to dry. There are also skin-friendly silicon rubber vibration damping materials with a water-tight surface, but these dampen the low sounds to a smaller extent.

[51] The simplest mechanical vibration generator device is an eccentric wheel fitted on a rotating axe, where the rotation of the axe is provided for by a magnetic power field or some mechanical force bearing on the axe. The revolving eccentric wheel results in the vibration of the axe of motor 11, which is transferred to the fixing points of the axe, to housing 16 of electric motor 11, then to casing 15 of electric motor 11, on which a hammer part 19 is designed that transmits the vibrations to the human body. Hammer par 19 is perpendicular to the axe of electric motor 11, and the surface area of hammer part 19 in contact with the human body, that is, vibration damping component 22, is parallel with the axe of motor 11 or it is at an angle of maximum 45° with it. The vibration waves divided into three directions in zygomatic bone 4 re-unite on the lateral wall of the common nasal cavity, in the area of the so-called osteomeatal complex 6, and hence the vibrations produced by the device mainly reach the upper apex of maxillary sinus 2. Vibrations penetrating the maxillary bone will only reach the upper teeth after a distance that is hundreds of times bigger, with significant dispersion and in a weakened form, and therefore, they do not cause tooth-ache.

[52] Figure 5 shows an exemplary frequency course produced by the saw-tooth generator of microprocessor 8. In the case shown here, the saw-tooth generator produces intermittent linear frequency strokes, which appropriately scan the frequency range from 50 Hz to 1500 Hz several times, so that one vibration cycle takes around 1 second. As mentioned already, the duration of the total treatment session does not exceed 30 seconds; this is ensured by switching and timing stage 12.

[53] Figures 6a and 6b show diagrams similar to that in Figure 5, but here the duration of the vibration cycle is much shorter than 1 second. The frequency stroke depicted in Figure 6a is produced by the current of alternating polarity shown in Figure 6b which, in practice, means vibrations realised in opposite rotation directions, so that the amplitudes of the vibrations in opposing directions are equal. The change in polarity checks electric motor 11 producing the vibrations and hence the individual frequency strokes get shorter in time and the total treatment session does not exceed 30 seconds.

[54] Figures 7 and 8 show effects of treatment with the device according to the invention at different vibrations. Figure 7 indicates the level of nasal NO release at various vibration parameters. The highest NO level is produced if the device is applied in scanning mode. As can be observed in Figure 8, NO washed out from the sinuses enhances mucociliar transport in the nose, as indicated by the decreasing mucociliar transport time (saccharin test). The biggest change occurs if the device is used in scanning mode.

[55] Furthermore, as shown in Figures 7 and 8, the extent of effects triggered in males and females, respectively, is different. This is explained by the fact that the nasal cycle influences the resonance frequency of the paranasal sinuses to different extents in males and females.

[56] Figures 9 and 10 show experimental measurement results which demonstrate the continuous and sex-specific change of the inner parameters of the nose during the nasal cycle , which can be examined for example also by acoustic rhynometry. Within the nasal cycle, upon the decrease of the swelling of the mucous membrane of the nose (decongestion), the mouth section (ostium) of the paranasal sinuses at the nasal cavity expands and hence the resonance frequency of the sinuses increases. Figure 9 shows a representative acoustic rhynometry figure for an adult male where the volume increased to 6 cm³. Figure 10 depicts an identical measurement for an adult female, where the change was bigger than usual, and the device could not detect it any more. The records were made at intervals of 1 minute. Point P indicated with an arrow is the ostium of maxillary sinus 2 on the left and the right side, respectively. When the ostium expands during the nasal cycle, the measurement curves above the arrow show a bigger cross-section of the nose, because the ultrasound is refracted also from the sinuses (J. Appl. Physiol. 99:616-623 2005).

[57] Another reason why the changes in resonance frequency due to the nasal cycle differ in men and women is that the average sinus volume value is also different: in women, the sinus volume is smaller and, therefore, with open sinuses, the resonance frequency is higher. In case of closed or partly closed sinuses, the difference between men and women is not significant. This can be seen in Figure 11 which shows the changes due to the nasal cycle in the resonance frequency of maxillary sinus 2 in men (first row) and women (backward row). In men, the resonance frequency changes in the range of 9-164 Hz. Under the effect of treatment with the device according to the invention, the sinus opens and the resonance frequency of the open sinuses is in the range of 132-164 Hz, on average 144 Hz (n=5). In women, the resonance frequency alternates in the range of 9-348 Hz; under the effect of treatment with the device according to the invention the sinus opens and the resonance frequency of the open sinuses is in the range of 111-348 Hz, on average 227 Hz (n=5).

[58] Ventilation of sinuses filled with nitric oxide (NO) and at the same time the quantity of NO measured in the nose will be at its maximum when the vibration devices operate at the actual typical resonance frequency of the paranasal sinus. Therefore, the device to be used to ventilate maxillary sinus 2 and to treat various diseases through the elevation of the nasal NO level should be capable of operation in special frequency scanning modes for men, women, children or other sub-groups (Asian, Afro or Caucasian), respectively. Figure 12 shows the vibration frequency of a possible embodiment of the device according to the invention on a representative sample. The first vibration, 12A, will open and ventilate the maxillary sinus 2 of men of the Caucasian race, whereas the second vibration, 12B, will open and ventilate the maxillary sinus 2 of women of the Caucasian race. In addition to the vibration modalities 12A and 12B shown by way of example only, other vibration patterns can also be produced, for example for children. During the treatment session, the vibration modalities presented here can be repeated and combined at an order chosen at one's discretion, which ensures the efficient use of the device in individuals of different sex, age etc. As will be obvious to persons skilled in the art, the device can also be designed as a device capable of the emission of a single type of vibration only, to be used as therapeutic device with a targeted group.

[59] Although the theoretical resonance frequency of open sinuses can be calculated by a mathematical formula, in reality, the measurability of the anatomical parameters is so inaccurate that the calculated and the effective resonance frequencies differ significantly and, what is more, they are subject to continuous change due to the nasal cycle. From a therapeutic point of view, the effective resonance frequency or resonance frequency band should be the one that results in maximum NO wash-out from the sinuses.

[60] Figures 13A and 13B show the vibration spectrum of a possible embodiment of the device according to the invention when it triggers the maximum nitric oxide signal typical of men and women, respectively. The measured resonance frequency is lower for men than the one calculated on the basis of the formula, whereas in women the resonance frequency defined by measurement is higher than the corresponding calculated value. Nasal NO measurements with 5 ppb definition indicate that, instead of the 144 Hz average resonance frequency calculated for men between the minimum 130 Hz and maximum 164 Hz, in reality, the optimum is 120 Hz vibration, whereas in women, instead of the 227 Hz average resonance frequency calculated between the minimum 111 Hz and maximum 348 Hz, in reality, vibration by 380 Hz provides for maximum NO concentration enhancement in the nose in case of open sinuses. A similar gap is found in regard of the decrease of mucociliar transport time. The reason for these gaps may be that the calculated resonance frequency can, as a matter of fact, be provided only for individual sinuses, e.g. the maxillary sinus that is the biggest in volume terms, whereas in reality, the vibrations spread over to every paranasal sinus and, through the change in NO concentration, we define the real resultant resonance frequency that applies to every paranasal cavity with NO content.

[61] The specification of the protocol of the device according to the invention should also take into consideration that, under the effect of the vibrations, the closed or partly closed large maxillary sinuses 2 with low resonance frequency (9-46 Hz) may open, as a result of which the resultant resonance frequency will increase suddenly and significantly (111-348 Hz), especially in women. Therefore, according to the invention, treatments must always be carried out in a certain frequency range, in scanning mode. The application of low-frequency (0-111 Hz) vibrations is preferable only until the closed sinuses open up under the effect of treatment. After that, the vibrations must be applied for a longer time at the higher resonance frequency of the open sinuses to provoke maximum nasal NO concentration enhancement. To raise the efficiency, the vibration frequency shall preferably be raised for a short time above the expected resonance frequency, to ensure also the ventilation of paranasal sinuses of a lower- than-average volume. At the same time, the noise concurrent with the high vibration frequency must be dampened to prevent any negative effects.

[62] The mode of operation of the device according to the invention outlined above - as a possible example - is described in Figure 14 also as a flow chart, which highlights two more essential features of the device in addition to its so-far unprecedented application in scanning mode, which authorise its use exclusively under physiologically appropriate positions and parameters: control of the vertical position and of the period of use/cycles.

[63] A vibration-free interval (0.1-3.0 ms, cf. Figure 12) must be inserted after each vibration cycle, partly to ensure the partial re-fill of the sinuses with NO and, on the other hand, since the low frequency range of the re-started vibration cycle promotes the opening of the partially closed sinuses that have not opened fully yet during the previous vibration cycle. The total treatment session, of 20-30 s, is made up of vibration cycles reiterated several times.

[64] Breaks of 4-5 minutes have to be held between the treatment sessions, to let the paranasal sinuses get fully refilled with NO gas. Therefore, in a preferred embodiment of the proposed device, the device operates for a definite time only after switch-on, then it automatically stops and cannot be started again in the next 4 minutes, because switching and timer stage 12 blocks that (cf. Figure 3).

[65] The examples listed above demonstrate that a device operating according to the calculated resonance frequency of individual paranasal sinuses is not adequate for the ventilation of the biologically effective NO gas from the paranasal sinuses, because the calculated resonance frequency and the resonance frequency measured with the change in nasal NO concentration are not identical, due to several factors. That is, the appropriate vibration frequency of devices used for therapeutic purposes and suitable to enhance the nasal NO concentration cannot be defined in advance with adequate accuracy and, furthermore, it is quite certain that the application of a constant vibration frequency will not be appropriate for every individual. The chronological courses of the optimum vibration modes may be of several kinds, of which the preferred protocol for a given group of people can only be determined experimentally.

[66] The device is brought into contact with the cheekbone in the area of zygomatic bone

4 in such way that its energy source containing part is on top, as indicated for example by a protruding arrow on the external casing of the device. In one preferred technical embodiment, the device contains an internal spatial position switch 20 that will only let the device be put in operation in the correct, close-to- vertical position. In this close- to- vertical position, vibrations transmitted to the skull bone will mainly spread towards the osteometal complex 6 part of maxillary sinus 2. If an effort is made to direct the vibrations downward, the device held correctly (arrow upward) will either

[67] i) lay against the temporal or frontal bone due to its size, and cannot be turned towards the eye socket (inward and upward), or

[68] ii) the internal spatial position switch 20 will block the operation of the device.

[69] Consequently, the direction of the vibration transmitted by the device to the skull bone cannot be such as would spread directly in the direction of the roots of the upper teeth.

[70] If an individual would use the device on the nasal bone or the forehead, it would again be impossible to tilt the correctly held device so that the vibrations should spread downwards towards teeth 7, since the device held at the wrong angle cannot be started. Therefore, the vibrator device applied according to the guide will cause no tooth-ache, because it can only be operated in the correct direction shown in the figure.

[71] Possible mechanical and, if appropriate, electronic structure of the device according to the invention will be obvious and easy to follow to a person skilled in the art. Possible solutions are described one by one and in various combinations in detail in US 2008/0200848, US 2008/0195001, US 2003/0172939, respectively, the contents of which are considered as reference in full extent in regard of the practical realisation of the device.

Claims

[Claim 1] 1. Device especially for the ventilation of nitric oxide in the paranasal sinuses and the suppression of disorders of the upper respiratory tract, comprising

- a housing (16),

- a vibration generator (11) arranged in the housing,

- an energy supply unit communicating with vibration generator (11),

- a vibration transmitter (19) partly arranged in the housing, in mechanical/physical contact with the vibration generator (11), characterised in that

- its vibration transmitter (19) is designed as a unit that prevents the transmission of vibrations below the threshold value of 50 Hz to the human body,

- the treatment part of vibration transmitter (19) which gets in contact with the human body is designed as treatment component vibrating with maximum 1500 Hz frequency,

- its vibration generator (11) is designed as a unit producing at least 10 vibration periods that increase from the bottom threshold value to the ceiling threshold value and decrease from the latter to the former over 30 s.

[Claim 2] 2. Device according to Claim 1, characterised in that vibration generator (11) is associated with a control unit that influences the vibration frequency.

[Claim 3] 3. Device according to Claim 2, characterised in that vibration generator (11) contains an electric motion means, and the control unit associated to it contains a saw-tooth generator feeding a frequency stroke into the motion means.

[Claim 4] 4. Device according to Claim 3, characterised in that the saw-tooth generator is a saw-tooth generator of alternating polarity.

[Claim 5] 5. Device according to of Claims 3 or 4, characterised in that the sawtooth generator is a saw-tooth generator producing an intermittent output signal.

[Claim 6] 6. Device according to any of Claims 3-5, characterised in that the saw-tooth generator is a saw-tooth generator of asymmetric amplitude and alternating polarity.

[Claim 7] 7. Device according to any of Claims 1-6, characterised in that the control unit contains a timing stage authorising the 30 second operation of the vibration generator (11).

[Claim 8] 8. Device according to any of Claims 1-7, characterised in that it contains at least one flexible external vibration damper component (22) that gets into contact with the human face, is skin-friendly and easy to clean.

[Claim 9] 9. Device according to Claim 8, characterised in that the external vibration damper component (22) is arranged on that surface of vibration transmitter (19) which gets into contact with the human body.

[Claim 10] 10. Device according to any of Claims 1-9, characterised in that it contains at least one flexible internal vibration damper component (17) arranged between the vibration generator component (11) and the housing (16).