Inhaler

FIELD: medicine.

SUBSTANCE: invention relates to medical equipment. An inhaler comprises an inhaler body having a space for accommodating a dry powder container, a vibration element, a flow channel, an electronic circuit for electrical actuation of the vibration element. The container comprises a lower wall, an upper wall and a side wall coupling the upper and lower walls. Besides, the inhaler comprises a drug release outlet on the upper wall of the container. The vibration has a flat surface coupled with a flat floor of the container to ensure the container vibration and to release the drug to be thereafter inhaled by the patient from the container through the drug release outlet into the flow channel. The container has an air inlet opening in its side wall. An area of the release outlet in the upper wall of the container is at least twice greater than that of one air inlet opening or than a total area of the air inlet openings in the side wall of the container.

EFFECT: faster dry powder aerosolisation, ejection and release.

13 cl, 10 dwg

Embodiments of the present invention relate to medical devices, and drug delivery, in particular, to the delivery of aerosol medications for inhalation drugs in the lungs and gastrointestinal tract and to intranasal delivery of drugs.

Device for delivery of aerosolized drug, means, including delivery by inhalation, known in this field, and examples include U.S. patent No. 5694920, 6026809, 6142146, all issued by Abrams and Gumaste, 3948264 by Wilke et al., 6971383 by Hickey et al., 7117867 by Cox et al., 6901929 by Burr et al., 6779520 by Genova et al., 6748944 by Della Vecchia et al., 5590645 by Davies et al. In these patents also presents an overview of the various devices and methods generation of aerosols and inhalations.

Known range of devices for the generation of aerosols and inhalation delivery of medicines, including inhalers metered dose sprays, inhalers dry powder, thermal evaporators, and other devices, with the differences associated with the methods and efficiency of aerosol formation and drug delivery to the patient. In inhalers metered doses typically used under excessive pressure gas for aerosol formation medicinal substance. The disadvantages of these inhalers are difficulties regulating Dostal the emnd dose of medicinal substance and the velocity of aerosol particles, which leads to collision and deposition on various surfaces in the mouth and throat of the patient. Inhalation device delivering medicinal substance in the form of a dry powder, known as dry powder inhalers. Passive dry powder inhalers based on vihalem patient effort to deaggregate and aerosol formation medicinal substance for inhalation, while the active dry powder inhalers usually require the input of additional energy, such as mechanical or electrical energy, to improve the efficiency of deaggregation and education aerosol of powder in order to reduce Diatlovo efforts of the patient and to achieve the best independence Diatlovo flow from the nebulizer. Usually for drug delivery into the lungs of the patient by inhalation an aerosol size particles of the medicinal product should be less than about 10 μm, preferably, less than about 6 microns, and for delivery to the deep lungs is less than about 3.3 μm. Larger pieces will be delivered in the oral cavity and the throat of the patient and the result will be delivered in the gastrointestinal tract of the patient. There is thus a need to increase the quantities of drugs that is able to transform into an aerosol inhalers with the steamboat powder during inhalation by the patient, for example, within one to three or four seconds. There is also a need to increase the speed of deaggregation and education aerosol powder inhalers dry powder.

In the device for inhalation of a dry powder, as described in U.S. patent No. 5694920, 6026809, 6142146, Abrams and Gumaste, used vibrating means for deaggregation and aerosol formation medicines in the form of a dry powder for delivery to the patient in the form of an aerosol. In patent publication U.S. 2005/0183724 Gumaste and Bowers described the method and apparatus of the synthetic jet supply of medicines.

Briefly, one embodiment of the invention includes a device for inhalation drugs in aerosol form, where high-frequency vibrator is connected with the container filled with the medicinal substance in the form of a dry powder. Vibration of the vibrator cause deaggregation, the formation of aerosol and release of drug substance from the container for inhalation by the patient. One or more holes in the container are essentially the opposite of the vibrator and are mainly used to release drugs through synthetic injection jet or other mechanisms of release of powder from the container. At least one other opening in the container is used primarily to enter naru the aqueous gas or air in the container.

As shown in the following examples, unexpected results were obtained when performing experimental tests of embodiments of the present invention for use as a device for inhalation and/or aerosol formation, when observed significantly faster aerosol formation and release of dry powders, as well as the ability of aerosol formation significantly large quantities of dry powders in comparison with the prior art.

Figure 1 is a view in section of a variant of implementation of the present invention, showing the container with the drug, coupled with the vibrator.

Figure 2 is a view in section of a variant of implementation of the present invention, showing the container with the drug, coupled with the vibrator.

Figure 3 is a view in the context of several embodiments of the present invention, showing the container with the medicinal substance, United with vibrators.

Figure 4 is a view in section of a variant of implementation of the present invention, showing the container with the drug, coupled with the vibrator.

Figure 5 is a view in the context of several embodiments of the present invention, showing the container with the drug washes the PTO, United with vibrators.

6 is a view in section of a variant of implementation of the present invention, showing the container with the drug, coupled with the vibrator.

Fig.7 is a view in the context of embodiments of the present invention, showing the inhalation device.

Fig is a view in section of a variant of implementation of the present invention, showing the inhalation device.

Fig.9 is a view in the context of embodiments of the present invention, showing the inhalation device.

Figure 10 is a view in section of a variant of implementation of the present invention, showing the inhalation device.

In the drawings, identical numerals refer to identical parts or signs of several types.

A view in section of a variant of implementation of the present invention is schematically illustrated in figure 1. The vibrator 100 is connected to the blister or container 110, which contains a medicinal substance or substances 120. The vibrator 100 may represent piezodrive or piezoelectric transducer, or a mechanical vibrator, electromagnetic vibrator, a magnetostrictive element or other vibrating mechanism known in this field. In one embodiment, uses piezodrive, usually with the standing of the piezo-ceramic element and a metal housing or Unimarine or bimorph structure. Can be applied to the design of piezoprivod known in this field, including, without limitation, air transducers and piezo-electric sensors. In addition, as vibrators can be used polymer piezomaterial and actuators based on polymer piezomaterials. As is well known in this field, the energy powered vibrators on the basis of piezoprivod is performed by applying electrical energy, usually alternating electric current of appropriate frequency and amplitude, piezocomposite. Can be used piezodrive configured at different resonant frequencies, for example, with resonant frequencies in the range from about 1 kHz to about 100 kHz, typical, in the ultrasonic range from about 30 kHz to about 45 kHz, and the amplitude of mechanical vibrations from about 1 μm to about 50 μm between the peaks. The vibrator 100 can vibrate or at a fixed or variable frequency or several frequencies simultaneously, and transmit vibratory motion to the container 110. The frequency of vibration may be in the range from less than 1 Hz to hundreds of kHz, typical, the oscillation frequency is from about 25 kHz to about 50 kHz. In the embodiment shown in figure 1, the vibrator 100 is in direct contact with the container 110 and, thus, the bar is dstone connected to the container 110.

The container 110 has at least one opening 150 to release the medicinal product is essentially opposite to the vibrator 100, and serves primarily to release of drug substance 120. However, outdoor air or gas may also be supplied to the container through the openings 150. In addition, the container 110 has at least one hole 200 in the side wall which are not located essentially opposite the vibrator 100. The hole 200 in the side wall is not used for release of medicinal substance, but allows admission of air or gas in the container 110 from the outside and, thus, contributes to deaggregate, the formation of aerosol and release of medicinal substance 120 of the container 110 through holes 150 to release the drug.

The medicinal substance or substances 120 provided in the form of dry powder, but other forms of drug substances such as liquid or gas. Can be applied one-component drug substance (pure drug), as well as several drug substances, or drug substance in combination with fillers such as lactose, or combinations thereof. To pharmaceutically active drug substance or substances may also be added other additives, such as pharmaceutically inactive ingredients, de is gregarine agents etc.

The container 110 is made of metal, plastic or composite materials. In one embodiment of the present invention, the container 110 is a blister packaging made from subjected to cold forming or thermal forming film, and the film material is a polymer, a metal foil or polymer film. In one embodiment of the present invention, illustrated in figure 2, the container 110 is a disposable blister pack containing generally conical, pyramidal, hemispherical, elliptical or similar to the top portion 111 and a flat bottom portion 112, where the upper portion 111 and the lower portion 112 is hermetically soldered to each other by methods known in this field, including, without limitation, linking, thermal soldering, brazing, compression, ultrasonic soldering, and the like. The region of connection or soldering 113 is also shown schematically in figure 2 in the contact area between the upper part 111 and the lower part 112. The vibrator 100 is shown in direct contact with the flat bottom part 112 of the container 110.

The number of possible profiles and shapes blister packaging or container 110 is shown schematically in figa-3F, including flat top conical profiles (figa, 3D, 3G), cylindrical (figv and 3E), which is also coated the Zan figure 4, and a hemispherical or conical profiles (figs, 3F, 3H).

The dimensions of the container 110 in one embodiment, comprise in diameter from about 1 mm to about 30 mm and a height of from about 1 mm to about 30 mm, however, in accordance with the present invention can be used in larger or smaller containers 110. In another embodiment, the diameter of the container 110 is from about 3 to about 12 mm, while the height of the container 110 is from about 3 to about 12 mm

The size of the holes 150 for release of drug is from about 10 microns to about 1000 microns, with a preferred size from about 50 microns to about 500 microns. The size of the holes 200 of the side wall is from about 1 μm to about 1000 μm, with a preferred size from about 25 microns to about 500 microns. In one embodiment of the present invention, the total area (section) holes 150 for the discharge of drugs, at least two or more times the total area (section) all holes 200 of the side wall. In another embodiment of the present invention, the total area (section) holes 150 for the discharge of drugs, about at least five times the total area (section) all holes 200 of the side wall.

The number of holes 150 for release lekarstvennoj the money is from 1 to about 10, moreover, the number of holes 150 to release the drug in another embodiment is from about 3 to about 6. The number of holes 200 for the release of the drug in the side wall in another embodiment, ranges from 1 to 2.

In one embodiment of the present invention, the vibrator 100 is directly connected to the container 110 and has essentially the same dimensions as the dimensions of the container 110 on the surfaces of the connection, so the connection pane of the respective surfaces of the vibrator 100 and the container 110 is essentially the same as shown in figure 1, 3B, 3C, 3D, 3E, 3H and figure 4. in another embodiment of the present invention, is shown in figure 2, 3A, 3F and 3G, the size of the vibrator 100 is larger or smaller compared to the dimensions of the container 110 on the surfaces of the connection. Turning now to the cases of implementation of the present invention, is shown in figure 5, the vibrator 100 can also be connected to the container 110 by mechanical strip or integral pin 130, as shown in figa, or through an air gap 140, as shown in figv. The vibrator 100 can also be connected to the container 110 from the side of the container 110 (not shown an implementation option). The vibrator 100 may also be located directly or partially inside the container 110 (not shown vari the NT implementation).

The orientation of the holes 150 for the release of the medicinal product, shown with 1, 2, 3A on fig.3F, 4 and 5, essentially perpendicular to the upper surface of the vibrator 100 or plane connection between the vibrator 100 and the container 110, whereas the orientation of the holes 200 of the side wall essentially parallel to the upper surface of the vibrator 100 or plane connection between the vibrator 100 and the container 110. However, you may have a different orientation of the holes 150 and 200, as shown in fig.3G and 3H where the holes 150 to release drugs perpendicular to the upper surface of the vibrator 100, or the plane of connection between the vibrator 100 and the container 110, and the holes 200 in the side wall is not essentially parallel to the upper surface of the vibrator 100, or the plane of connection between the vibrator 100 and the container 110.

When working variant of implementation of the present invention, after starting the vibrator 100, and to initiate vibration of the vibration energy is transferred to the container 110, while the medicinal substance is expelled from the container 110, at least through one hole 150 to release the drug. In one embodiment of the invention the synthetic jet of fluid, which may be a gas or mixture of gas/medicinal substance, is directed through the opening 150 clavipes medicines. Synthetic jet is characterized by the fact that the fluid flows in both directions through the hole 150 with simultaneous formation of eddies on both sides of the hole. The formation of a synthetic jet of gas or liquid known to experts in this field and is characterized by high-speed jets of gas or other fluid emanating from the hole in the enclosed chamber, and the liquid enters the chamber and out of it many times through the hole, so that the liquid is pushed out of chamber is filled with fluid entering the chamber from the outside. Reference is made to the patent publication U.S. 2005/0183724 Gumaste and Bowers, in which is described a synthetic jet. Because of the gas moving through the hole in both directions, synthetic jets can continue indefinitely. The formation of synthetic jets may require the formation of acoustic waves, which may be formed, for example, pitavastatin, and may require a combination of specific parameters, including frequency, orifice size and shape, and the dimensions of the container for the formation of strong, long-lasting and reproducible synthetic jets.

Figure 6 shows a variant implementation of the present invention, where, after start of the vibrator 100, the hole 200 in the side wall provides the possibility of receiving external air and the gas and the container 110 (as shown schematically by arrow 205) and thus, contributes to the efficient release of medicinal substance 120 of holes 150 for the release of a drug (as schematically shown by the arrow 207), increasing the rate of release and the number of drugs that can be pushed from the container 110.

7 shows a variant implementation of the present invention in the form of a schematic diagram of a dry powder inhaler containing the container 110, the vibrator 100 and the channel 300 for a thread. The channel 300 in the flow shown in figa, refers to the type of cross-flow, whereby the air flows generally perpendicular to the direction of expulsion of the drug substance 120 of the container 110, the specified ejection direction indicated by arrow 207. The channel 300 in the flow shown in figv, refers to the type of parallel flow, whereby the air flows generally parallel to the direction of expulsion of the drug substance 120 of the container 110, when the ejection direction indicated by the arrow 207. The possible range of intermediate constructions channel 300 for the thread and the container 110, whereby the air moves more difficult path, intermediate between parallel flow and cross-flow (not shown an implementation option). After inhalation by the patient of the air flowing through the channel 300 to flow, and the air enters, as shown in the article the trees 310, and out of the device for inhalation, as shown by arrows 320.

After starting the vibrator 100 drug substance 120 deaggregated, agrosolutions and is ejected from the container 110 through the opening 150 to release the drug. The sequence of deaggregation, aerosol formation and release of medicinal substance 120 is optional in the above order, where all three processes can occur simultaneously or sequentially in any order, depending on the process parameters and the final result is the release of medicinal substance 120 of the container 110 through the opening 150 to release drugs available inside the channel 300 for a thread. Aerosol drug substance 120 is then picked up by the air stream 310 from the outside of the container 110, which leads to the delivery of medicinal substance 120 receiving inhalation of the patient, as shown by the arrow 320. The entry of outside air through the opening 200 in the side wall, as shown by the arrow 205, contributes to the process of deaggregation, the formation of aerosol and release of medicinal substance 120 through holes 150 to release the drug.

On Fig variant implementation of the present invention is shown in the form of a schematic diagram of an inhaler dry powder to the housing of the inhaler 480, g is e inside and outside the housing of the inhaler 480 are a few of the components of the inhaler, including the container 110, the channel 300 for a thread, the electronic Board and circuit 462, used for electric starting of the vibrator 100 and the other electronic components of the inhaler. Battery 464 is used to supply components and vibrator, the battery can be any energy source, such as a portable battery pack, which can be a primary or a rechargeable battery or a fuel battery. Other optional components of the inhaler shown in Fig, provide a tool for perforation 400 to pierce holes for release of drug and/or holes in the side wall of the container or blister 110; extra containers of one dose of the medication 450; sensor 420 to register and detect inhalation by the user or the patient, adapted to detect the inhaled air by the user as shown by arrows 310, and mutually connected to the electronic circuit 462 to run the vibrator 100 and process emissions and aerosol formation medicines. The sensor 420 is preferably capable together with the electronic circuit Board and circuit 462 to identify the presence and strength of the air flow in the inhaler and optional, the direction of air flow. Feedback device 460 and 466 with the patient provide sensory feedback to the patient, as well as optional counters, dose and indication the display indicates to the user the status of the delivery of medicines and various options. Arrow 320 indicates the air inhaled by a patient. The channel 220 provides access of external air into the hole 200 in the side wall, so that after the launch of the vibrator 100, the outside air can flow into the container 110, as shown by the arrow 205.

Figure 9 embodiments of the present invention is shown in schematic diagram inhalers dry powder from the container 118 multiple applications, where the medicinal substance 120 is provided in disposable packings 610 and 710 with medicine, located on the ribbon-carrier 620 and 700. The belt direction of travel shown by arrow 650. In the embodiment shown in figa, packaging of the medicinal product 610 disposable covered with the covering tape 630, which is wound on a reel 635, thus providing access to the drug substance 120 for release through holes 150 to release the drug. In another embodiment (not shown) closing the belt 630 is not removed from packaging drug which means 610 disposable, but is perforated before or after admission to mnogorazovyj container 118, thus providing access to the drug substance 120 for discharge through the openings 150. Mnogorazovyj container 118 is in contact with the tape carrier 620 through compressible gasket or seal 600. After inhalation by the patient vibrator 100 is actuated, thereby releasing the drug substance 120 through openings for the discharge of 150. Outside air enters the container 118, as shown by the arrow 205, through the opening 200 in the side wall, while transformed into aerosol drug substance is inhaled by the patient, as shown by the arrow 320, and the air is included in the channel 300 for flow, shown by arrow 310.

Similarly, figv drug substance 120 is provided in the packing of medicine 710 disposable, containing pockets of ribbon, folded it, placed on the tape carrier 700. The direction of movement of the tape 710 under the container multiple applications 118 when the container multiple application 118 in contact with the tape carrier 700, a compressible gasket or seal 600. After inhalation by the patient vibrator 100 is actuated, thereby releasing the drug substance 120 through the opening for the discharge of 150. Outside air enters Conte is ner 118, as shown by the arrow 205, through the opening 200 in the side wall, while transformed into aerosol drug substance is inhaled by the patient, as shown by the arrow 320, and the air is included in the channel 300 for flow sucked in by the inhalation of the patient, indicated by arrow 310.

Puncture holes in the container 110 can be performed directly before giving medicines to the patient. In one embodiment, the invention operates as follows: the inhaler is actuated, the holes in the container for medicines stupidly, simultaneously or sequentially tool to pierce 400, or closing material 630, in the case of the packaging of the medicinal product 610, deleted or moved, or opened pocket 710 tape-based, and then the medicinal substance 120 is converted into an aerosol when the patient produces inhalation through the inhaler. In other embodiments, the implementation of the opening or perforation of individual packages of medicine occurs automatically after inhalation of the patient under the influence of Electromechanical or mechanical means such as a spring or a solenoid actuator, or a thermal blowing agent, all of which are optional are driven detecting inhalation by the sensor 420.

In another embodiment, as the sludge is astronuats figure 10, container for multiple application 118 is used for drug delivery 120, where the hole in the side wall 200 is connected with a source of medicinal substances 900 through conduit 910. Source of medicinal substances 900 has at least two or more doses of a medicinal substance 120. The amount of medicinal substance 120 to be delivered to a patient by altering the start time of the device, or a sensor that detects the actual amount of drug substance 120 and regulating the running of the vibrator 100.

Provides other options for implementation and applications of the invention. The medicinal substance for delivery to the patient may be a vaccine, a DNA fragment or RNA drug for the treatment of pain, asthma, emphysema, chronic bronchitis, scleroderma, chronic obstructive pulmonary disease, diabetes treatment or any medical facility that can prevent or cure disease or alleviate the symptoms of the disease when delivered in the form of an aerosol to a patient, and having a localized and/or systemic effect.

In another embodiment, the present invention is used to deliver drugs in the form of aerosol is not for inhalation, and for intranasal delivery, item is ruralni delivery intraocular delivery or delivery through the skin surface. In another embodiment, the composition of the liquid medicinal product is supplied using the present invention.

Example 1

During the experimental test used model inhaler device, similar to the structures shown in figa able to work or blisters with only holes for the discharge of drugs, or and openings for the discharge of drugs, and openings in the side wall. The device had a built-in electronics and a removable channel for the stream. Piezodrive on the basis of modified air transducer, manufactured by Murata Electronics, Japan, was used as a vibrator. Piezodrive ran at 4 seconds, and he was put in action 90% of the time at a frequency of 33 kHz and 10% of the time when the frequency to 34.4 kHz, switching between the two frequencies at a rate of 10 Hz (duty cycle). An alternating voltage of approximately 160-200 volts generated by the circuit with reverse swing at step form of waves used to run the piezo technology. Blister with approximately hemispherical top and a flat bottom was used as a container disposable model containing dry powder to obtain an aerosol. The height of the blister was approximately 5.5 mm and the diameter of the camera blisters at the base was approximately 11 mm, in the form of blisters, similar to the form shown in figs. The blister was made of aluminum foil coated with a polymer layer. The upper and lower parts of the blisters were thermally welded to each other. Using metal needles with a diameter of 320 μm at the top (hemispherical) part of the blister is pierced 4 holes for the discharge of drugs, similar to that shown in figure 3, which shows only two holes 150 to release the drug. In some experiments in the side wall of the upper part of the blister is pierced, at least one hole 200 of the side wall, similar to those shown in figs. A needle with a diameter of 240 μm was used to puncture holes in the side wall. The air flow through the channel for flow devices were installed at 30 liters per minute (l/min)using a vacuum pump. The blister was filled with varying quantities of the model dry powder, and testing gravimetric removal of the blister performed in the changing experimental conditions.

The results of the experiments are presented in table 1. As can be seen from table 1, were obtained unexpected results, where the presence of one or more openings in the side wall led to a significant increase in the rate of release of drugs, as well as the amount of powder that can eff the objective to throw compared to the conditions without holes in the side wall. Comparison of tests 1 and 2; 2 and 2A, 3 and 3A, 7 and 7a, 9 and 9a indicates that the holes in the side wall led to a very significant increase in the removal of powder from the blister compared with blisters without holes in the side wall in the same conditions. A comparison of tests 4 and 4A, 5 and 5A, 6 and 6A indicates that without piezo technology was found to determine the removal of the powder, even when there were holes in the side wall. Openings in the side wall provided an opportunity for very high gravimetric remove a uniform amount of powder from the blister, i.e. quantities of the order of 3-6 mg, but also very large quantities of powder, for example, of the order of 15-20 mg and even 37 mg, when the ejection powder is practically not observed from blisters in the same conditions without holes in the side wall, as demonstrated by tests 3 and 3A, 7 and 7a; and 9 and 9a. It was visually identified that the removal of the powder from the blister with holes in the side wall occurred quickly, sometimes in less than a second and faster in comparison with blisters without holes in the side wall from which the complete removal of the powder did not occur even after 4 seconds. It was not visible to any detectable quantity of powder ejected from the holes in the side wall during the performed tests.

Example 2

Experimental testing was performed using an experimental Protocol similar to the Protocol described in example 1, but with an integrated piezo technology G9, tuned to the resonant frequency of 34.5 kHz, run 90% of the time with a frequency of 34 kHz and 10% of the time with a frequency of 35 kHz when switching between the two frequencies at a rate of 10 Hz (duty cycle). An alternating voltage of approximately 160-200 volts generated by the circuit with reverse swing at step form wave, used to run the piezo technology. Used powdered insulin, and he showed very good removal from the blister. In the experiment used the amount of powder drugs, considerably more in comparison with the usual quantities of 1-3 mg blister. In the two tests blister containing 5 mg of powder drugs, demonstrated the removal of 94.6% and 95.9% of the powder from the blister during a piezo technology for 4 seconds. It has been observed that the actual time of removal was less than 4 seconds time of piezo technology. Thus, unexpectedly, a much larger amount of powder is removed from the blister having an aperture in the side wall, compared with the number usually seen with the same blisters, but without a hole Bokovoy wall, it culminated with the removal of about 80-95%, only when they were filled with much smaller amounts of insulin, i.e. up to about 2 mg.

Example 3

Using an experimental Protocol similar to the Protocol described in example 2 perform the test with model mixture of powder drugs with very good removal, where 6 mg of the mixture was removed when the gravimetric clearance 97,5% of the blister having an aperture in the side wall. The same blisters, but without a hole in the side wall, showed much lower values of gravimetric clearance.

Example 4

The experiments were performed under a Protocol similar to the experimental Protocol described in example 1, but with not modified air Converter Murata Electronics, serving as a piezo technology, having a resonant frequency of 40 kHz. Can also be used piezodrive with other resonant frequencies, typically in the range from 30 to 45 kHz. The air flow through the device was set at 28 l/min using a vacuum pump. Plastic blisters with the upper part of the conical shape and the blisters conical shape with a flat top flat bottom of the metal foil used as containers disposable model containing powder for aerosol formation, analogion the E. blisters, depicted respectively on fig.3F and 3D. Blisters with the tip of the conical shape had a straight conical tip, whereas the blisters conical shape with a flat top had a conical top, turning into a flat butt with a diameter of approximately 2 mm, the height of the blisters was approximately 4.5 mm, and the diameter of the camera blisters at the base was approximately 8 mm, the tops of the blisters were produced by thermal molding of PVC and modified glycol polietilentereftalatnogo plastic and heat was soldered to the bottom of the blister is made of polymer coated aluminum foil. The top part of the blister is pierced using a metal needle with a diameter of 240 μm, thus forming the 3 holes for the discharge of drugs, similar fig.3D. In some embodiments, the implementation in the side wall of the conical part of the blister is pierced, at least one hole of the side wall, similar figa, 3B, 3C. A needle with a diameter of 240 μm was used to puncture holes in the side wall. The results of these experiments are presented in table 2.

Example 5

Performed the test air flow inside and out of the blister with a few holes for the discharge of drugs, and at least one opening in the side wall. The experimental Protocol was similar to the Protocol described in example 1, but in these experiments the blisters had no powder and no air flow is created using a vacuum pump. In addition, a plastic capillary tube was connected to a hole in the side wall on the outside. In the first test, when conducted intermittent starting blisters piezo technology, it has been observed that light lever indicator is moved in the direction towards the inlet opening of a plastic capillary tube, thus registering a vacuum and/or air flow through the capillary tube and through the opening in the side wall of the blister, while the air was pushed out of the holes for the discharge of pharmaceuticals into the top of the blister.

In the second test the second light lever indicator was placed on the CTE is steamy for the release of the medicinal product, moreover, it was observed that the light lever indicator moves upward, revealing a jet of air emanating from the holes to release the drug. At the same time, it has been observed that the first light sensitive lever indicator is moving in the direction towards the inlet opening of a plastic capillary tube, thus registering a vacuum and/or air flow through the capillary tube and through the opening in the side wall of the blister, and said first lever indicator sassybella to the inlet of a plastic capillary tube and blocked her. In addition, it was observed that when said first lever indicator is manually moved from the site of lock inlet plastic capillary tube, and thus, eliminating blockage of air flow into the opening in the side wall, the second lever indicator pointed to a noticeable increase in air jets coming out of the holes to release drugs on top of blisters. Thus, it appears that the hole in the side wall helped to increase the formation of air jets coming out of the blister, by providing air flow in a blister.

Example 6

The experiments were performed under a Protocol similar to the experimental Protocol described in example 2, but without starting it the AC vacuum pump and suck any air through the channel for flow of the Protocol of the experiment. In this experiment, we used a model of a dry powder of lactose. In blister without a hole in the side wall, filled 6,390 mg of lactose, watched clearance only 28,4%. In the blisters with a side opening, filled USD 5,013 and 6,560 mg of lactose powder, watched clearance respectively 80,8% and 93.4%. Thus, it appears that the hole in the side wall helped to increase the formation of jets of air coming out of the blister, by providing air flow in the blister, and were obtained unexpected results where compared with conditions without holes in the side wall, in the experiment there was a significant increase in the rate of ejection of the powder, and the amount of powder that can be discarded.

Although the present invention has been specifically described in conjunction with specific preferred variant implementation, it is evident that many alternatives, modifications and variations will be obvious to specialists in this field in light of the previous description. Therefore, it is envisaged that the appended claims will embrace any such alternatives, modifications and variations as falling within the valid scope and essence of the present invention.

1. The dry powder inhaler, comprising a housing of the inhaler, containing space for accommodating the container, soteriades the dry powder, vibrating element, a channel for flow, an electronic circuit for electrical actuation of the vibration element, and the specified container has a flat bottom wall, top wall and side wall connecting the upper wall and lower wall, the inhaler further comprises at least one opening for release of pharmaceutical substances on the top wall of the container, and vibrating element has a flat surface that is configured to connect with the flat bottom of the container to provide vibration of the container and to release the specified medicinal substance from the container through at least one opening for release of pharmaceutical substances in the channel to flow for inhalation by a patient, characterized in that the container has at least one hole for air intake in its side wall, and the area of one hole to eject or the total area of the holes to release in the top wall of the container in at least two times larger than the area of one hole for air intake or total area of the openings for air intake in the side wall of the container.

2. The inhaler according to claim 1, characterized in that the medicinal substance is selected from: medicinal powder, the mixture of the medicinal powder filler, a mixture of two or bluefantasies active medicinal powder materials, a mixture of two or more pharmaceutically active drug powder materials with filler, and combinations thereof.

3. The inhaler according to claim 1, wherein the specified at least one hole for air intake is round and has a diameter of from about 25 microns to 400 microns.

4. The inhaler according to claim 1, characterized in that the at least one hole for air intake is round, triangular, square or polygonal.

5. The inhaler according to claim 1, characterized in that the container contains the blister foil, pocket foil, plastic blister, or a combination of both.

6. The inhaler according to claim 1, characterized in that the container is reusable.

7. The inhaler according to claim 1, characterized in that the container is made of metal, metal foil, metal foil, polymer coated, polymer films, polymer films with barrier coating, polymer, polymer laminates, or combinations thereof.

8. The inhaler according to claim 1, characterized in that the vibrating element is piezodrive, piezo or piezogyration.

9. The inhaler according to claim 1, characterized in that it further comprises an actuator for actuating the vibratory element to vibrate at ultrasonic frequencies.

10. The inhaler according to claim 1, characterized in that the container has od what about the hole for air intake and four holes for release of medicinal substance.

11. The inhaler according to claim 1, characterized in that there are at least two holes in the top wall of the container.

12. The inhaler according to claim 1, characterized in that the at least one opening in the top wall of the container is communicated with the air flow in the channel to flow for inhalation by the patient.

13. The inhaler according to claim 1, characterized in that the total area of one hole to eject or the total area of the holes to release in the top wall of the container in at least five times greater than the area of one hole for air intake or total area of the openings for air intake in the side wall of the container.