Nicotine powder inhaler

REPUBLIC OF POLAND (12) TRANSLATION OF THE EUROPEAN PATENT (19) PL (11) PL / EP 3136894

<img file="PL3136894T3_D0001.tif" />

Patent Office of the Republic of Poland (96) Date and number of the European patent application: 23.04.2015 15751065.2 (97) The grant of the European patent was announced:

7/31/2019 European Patent Bulletin 2019/31 EP 3136894 B1 (13) T3 (51) Int.CI.

A24F 47/00 (2006.01)

A61M 15/06 (2006.01)

A61M 15/00 (2006.01) (54) Title of the invention:

NICOTINE POWDER INHALATOR (3 °) o · Priority:

28.04.2014 US 201461984967 P.

28.04.2014 EP 14166205 (43) The application was announced:

08/03/2017 in the European Patent Bulletin No. 2017/10 (45) The filing of the patent translation was announced:

28.02.2020 Patent Office News 2020/02 (73) Patent holder:

Philip Morris Products SA, Neuchatel, CH (72) The inventor (s) of the invention:

£ 2 IHAR NIKOLAEVICH ZINOVIK, Peseux, CH GERARD ZUBER, Froideville, CH σ&gt;

What

JO (74) Representative:

JJ · thing, pat. Sławomir Nowicki_n PATENT AND LEGAL OFFICE INTELLECTPOL iii Podczachy27

99-300 Kutno

Attention:

Within nine months of publication of the information on the grant of the European patent, any person may lodge an objection to the European Patent Office regarding the granted European patent. The objection shall be made in the form of a reasoned statement. It is considered to be filed only when the opposition fee has been paid (Article 99 (1) of the Convention on the Grant of European Patents).

PL / EP3136894

NICOTINE POWDER INHALATOR

This disclosure relates to nicotine powder inhalers in which nicotine powder is delivered at low air flow rates.

Dry powder inhalers (DPIs) are known and are used to treat respiratory diseases by providing a dry powder containing a pharmaceutical agent in the form of an aerosol by inhalation into the patient's respiratory tract. Particles in the range of 1 to 5 micrometers are required for deep lung delivery. In pharmaceutical dry powders, the active pharmaceutical ingredient (API) is agglomerated on the surface of larger carrier particles, e.g. lactose, and therefore DPIs work with complex mechanisms to ensure that such agglomerates disperse, break down or disaggregate before API can be inhaled deeply into the lungs. Pharmaceutical dry powders containing lactose as carrier usually have a range of 20 to 100 microns. Existing DPIs, for example, first "grind" or de-agglomerate dry powder or act on larger dry powder particles to achieve said particle size range.

DPIs rely on the strength of the patient's inhalation to entrain the powder from the device and then break the powder into particles that are small enough to get into the lungs. Sufficiently high inhalation rates are required to establish the correct dosage and complete disaggregation of the powder. Typically, a large amount of API remains attached to the surface of the carrier and settles in the upper respiratory tract due to incomplete disaggregation of the powder. Inhalation rates of existing ones

DPIs are usually in the range of 40-120 liters / min (L / min). Existing DPIs are therefore only suitable for delivering dry powders to users in a way that is different from the inhalation rate associated with smoking articles.

EP 2 399 637 A1 discloses a smokeless cigarette 1 comprising an hollow cylindrical suction handle 2 open at both ends. The hollow cylindrical tobacco insert 20 is placed inside the holder 2 in the distal part of the holder 2. The tobacco insert 20 comprises a cylindrical container 6 open on both sides and a filler 8 placed in the container 6. The air permeable caps 10 are attached to both ends of the container 6. The filter 12 is mounted in the container 6, near the mouthpiece 4 on the container end side 6. The filler 8 and the filter 12 are separated from each other by the filter plug 14. The tobacco cartridge 20 is thus placed inside the holder 2 with the filter 12 on the container end side 6 towards mouthpiece 4. The cap 16 is removed at the distal open end of the handle 2 away from the mouthpiece 4. The cap 16 has an air inlet 18. The handle 2 has an air intake path for air introduced through the air inlet 18 for air flow. The suction path includes a main channel extending from the air inlet 18 to the mouthpiece 4, inside the handle 2. The filler 8 is formed in the container 6 by containing a mixture of tobacco shreds or grains obtained by shredding or granulating tobacco leaves and additives, so that the tobacco cartridge 20 provides predetermined ventilation resistance. By suction by the user through the mouthpiece 4 of the handle 2, air is introduced into the tobacco insert 20 through the air inlet 18 and contacts the filler 8 or tobacco particles. Thus, inside the cartridge 20, air is flavored with tobacco as a result of the flavoring substances released from the tobacco particles. The user can therefore inhale tobacco-flavored air through the main channel and mouthpiece 4 of the handle 2 and enjoy the taste of tobacco.

It would be desirable to provide a nicotine powder inhaler that can deliver nicotine powder to the user upon inhalation or at air flow rates that are close to or within the conventional inhalation pattern or air flow rates during smoking. It would be desirable to provide a nicotine powder inhaler that has a similar size and configuration as a traditional cigarette. It would be desirable to provide a nicotine powder inhaler that can deliver a metered dose of nicotine and optionally can simultaneously provide a second active ingredient.

The nicotine powder inhalers of the invention described herein can be used to deliver nicotine to a user at inhalation or air flow rates that are within the conventional inhalation pattern or air flow rates during smoking. Nicotine powder inhalers can provide a predictable and measured dose of nicotine or other optional active ingredients. The nicotine powder inhalers of the invention described herein have a similar size and configuration to that of a conventional cigarette and have a simple configuration.

As described herein, the nicotine powder inhaler of the invention includes the features of claim 1. It includes a body extending between the mouthpiece part and the distal end part and an air flow channel that extends along the body of the inhaler. A nicotine powder cavity located along the airflow passage receives a capsule containing a dose of nicotine powder, the nicotine powder containing a nicotine salt. The dose of nicotine powder may be inhaled into the user's lungs at an inhalation rate of less than about 5 L / min or preferably less than about 2 L / min. A dose of nicotine powder is contained in a capsule, which can be punctured with an inhaler.

The various aspects of the nicotine powder inhalers described herein may have one or more advantages over standard dry powder inhalers. For example, nicotine powder inhalers provide dry nicotine powder when inhaled or at air flow rates that fall within the conventional inhalation pattern or air flow rates during smoking and the inhalation method. This allows users with even weakened or disturbed breathing conditions to successfully deliver dry nicotine powder and optionally the second active ingredient. The nicotine powder inhalers described herein have a simplified configuration that allows the user to determine in advance the metered dose of dry nicotine powder and optionally the second active ingredient. The dry nicotine powder used in this inhaler and described herein is carrier free and has a constant size during storage until inhaled. Additional advantages of one or more aspects of the flavor delivery system described herein will be apparent to those skilled in the art after reading and understanding this disclosure.

The term "nicotine" refers to nicotine and nicotine derivatives such as nicotine salts.

The present disclosure provides nicotine powder inhalers for inhaling dry nicotine powder. Nicotine powder inhalers include a body extending between the mouthpiece part and the distal end part. The airflow duct extends between the mouthpiece part and the distal end part. The nicotine powder seat is positioned along the air flow channel and receives a capsule containing a dose of nicotine powder, the nicotine powder containing a nicotine salt. Surprisingly, a dose of nicotine powder can be inhaled into the user's lungs at an inhalation rate of less than about 5 L / min or less than about 2 L / min, which mimics the inhalation flow rate used in a conventional smoking regimen. The nicotine powder inhalers described herein are "passive" devices that only use the air flow when inhaled by the user's lungs to create air flow through the body of the nicotine powder inhaler.

The airflow path or airflow duct through the inhaler body is a straight path or duct. In many embodiments, the airflow path or airflow passage through the inhaler body is parallel to the longitudinal axis of the inhaler and is linear along the entire length of the inhaler body. In some embodiments, the inhaler includes two or three concurrent airflow channels. One, two or all three airflow channels may include a capsule seat. In some embodiments, the one or more air flow paths or air flow channels include a swirl generator element that is configured to induce a rotational motion of the flowing air traveling through the inhaler body. The vortex generator element may be discharged into the exhaust duct, which may have a larger volume than one or more individual airflow paths or airflow channels.

The nicotine powder receptacle accepts a nicotine powder capsule. The capsule contains a predetermined amount or dose of nicotine powder. In many embodiments, the capsule may contain enough nicotine powder to provide at least 2 inhalations or "puffs" of nicotine powder or at least about 5 inhalations or "puffs" of nicotine powder or at least about 10 inhalations or "puffs" of nicotine powder. In many embodiments, the capsule may contain enough nicotine powder to deliver about 5 to 50 inhalations or "puffs" of nicotine powder or about 10 to 30 inhalations or "puffs" of nicotine powder. Each inhalation or "puff" of nicotine powder can deliver from about 0.5 mg to about 3 mg of nicotine powder to the user's lungs or from about 1 mg to about 2 mg of nicotine powder to the user's lungs or about 1 mg of nicotine powder to the user's lungs.

In many embodiments, the capsule holds or contains at least about 5 mg of nicotine powder or at least about 10 mg of nicotine powder. In many embodiments, the capsule holds or contains less than about 30 mg nicotine powder or less than about 25 mg nicotine powder or less than 20 mg nicotine powder. In many embodiments, the capsule holds or contains from about 5 mg to about 30 mg of nicotine powder or from about 10 mg to about 20 mg of nicotine powder.

The capsule can be made of an air impermeable material that can be pierced or punctured by the inhaler. The capsule can be made of a metallic or polymeric material that serves to keep contaminants out of the capsule, but may be pierced or punctured by the inhaler during use.

The inhaler may include a piercing member or a pair of opposing piercing members that are configured to pierce the nicotine powder capsule. The piercing element or pair of opposing piercing elements smoothly connect the airflow channel with the dose of nicotine powder. The piercing member or pair of opposing piercing members may engage the nicotine powder capsule after loading the nicotine powder capsule into the nicotine powder cavity or upon request by a servomotor on the inhaler body.

In many embodiments, the nicotine powder is a pharmaceutically acceptable salt of nicotine or a hydrate of nicotine salt. Useful nicotine salts or hydrates of nicotine salts include, for example, nicotine bitartrate, nicotine salicylate, nicotine fumarate, nicotine monopyruvate, nicotine glutamate or nicotine hydrochloride. A compound that combines with nicotine to form a salt or salt hydrate can be selected based on its pharmacological action. For example: nicotine salicylate may be administered to relieve fever as an anti-inflammatory or analgesic; nicotine fumarate may be used to treat multiple sclerosis; and nicotine monopyruvate may be used to treat chronic obstructive pulmonary disease (COPD) or to reduce weight.

The nicotine powder may have any useful size distribution for delivery by inhalation into the lungs of the user. In many embodiments, at least about 90% by weight of the nicotine powder has a particle size of about 10 microns or less, preferably about 7 microns or less. The nicotine powder preferably has an average mean diameter in the range of from about 0.1 to about 10 microns, more preferably from about 1 to about 7 microns, even more preferably from about 2 to 6 microns.

Conventional dry powder inhalation formulations typically contain carrier particles that serve to increase the fluidization of the active particles because the active particles are usually too small to be influenced by the airflow through the inhaler. Carrier particles have therefore been used to improve dose uniformity by acting as a solvent or bulking agent in the formulation. However, the nicotine powder described herein is carrier free. Being carrier-free allows you to inhale nicotine powder and deliver it to the user's lungs with an inhalation or air flow rate that is similar to a typical inhalation pattern or to the air flow rate during smoking. In addition, because the nicotine powder is carrier-free, the inhaler air flow path may have a simple geometry or configuration.

The carrier-free nicotine powder described herein may be a surface-modified nicotine salt, wherein the nicotine salt particle is a coated particle. One preferred coating material is L-leucine. These carrier-free nicotine powders have been described and are available from Teicos Pharma Inc., Espoo, Finland. One particularly useful nicotine powder is L-leucine coated nicotine bitartrate.

A second active agent or ingredient may be provided with the nicotine powder. The second active agent or ingredient may be mixed with nicotine in the capsule or separated from nicotine in its own capsule. The second active agent or component may be fluidized with nicotine powder and inhaled by the user.

The second active agent or ingredient may be any active pharmaceutical material. In many embodiments, the second active agent or component may be combined with the nicotine powder described herein by mixing the two materials upon inhalation. The nicotine powder and second active agent or component may be mixed in the same capsule or may be delivered in series on a single DPI air flow channel or delivered in parallel on separate DPI flow channels. The second active agent or component may have an average average diameter size in the range as the nicotine powder described above.

The nicotine powder inhaler is less complex and has a simplified powder storage and airflow path compared to existing DPIs and does not need a carrier component such as lactose as described above. Therefore, the described nicotine inhaler does not require complex mechanisms for the dissociation / disaggregation of dry pharmaceutical powder, and therefore the described nicotine inhaler operates at low air flow. The inhaler does not require the typical high inhalation rates as in conventional DPIs to deliver the dry nicotine powders described above deep into the lungs.

The nicotine inhaler of this invention operates at a flow rate of less than about 5 L / min or less than about 3 L / min or less than about 2 L / min or about 1.6 L / min. In many embodiments, the flow rate is in the range of from about 1 L min to about 3 L / min, or from about 1.5 L / min to about 2.5 L / min. In preferred embodiments, the inhalation rate or flow rate is similar to the Health Canada scheme when smoking, i.e. about 1.6 L / min. In contrast, conventional DPI operates at a flow rate of about 40-120 L / min and often requires an energy source or propellant to promote airflow to achieve this airflow rate.

The nicotine inhaler described herein can be used by a consumer such as smoking a conventional cigarette or vaporizing an electronic cigarette. Such smoking or evaporation is characterized by two stages: the first stage during which a small volume containing the full amount of nicotine desired by the consumer is drawn into the mouth, and then the second stage during which this small volume containing the aerosol containing the desired amount of nicotine is further diluted fresh air and drawn deeper into the lungs. Both stages are controlled by the consumer. During the first inhalation stage, the consumer can determine the amount of nicotine to be inhaled. During the second stage, the consumer can determine the volume to dilute the first volume to be drawn deeper into the lungs, maximizing the concentration of active agent delivered to the epithelial surface of the airways. This smoking mechanism is sometimes called "inhale-exhale".

All scientific and technical terms are used in the sense commonly used in technology, unless otherwise stated. Definitions are provided to help you understand some of the concepts often used.

The terms "up" and "down" refer to the relative positions of the inhaler components described in relation to the direction of flow of inhaled air when it is drawn through the inhaler body from the distal end to the mouthpiece.

The singular grammatical forms used herein include embodiments having plural equivalents, unless the context otherwise requires.

As used herein, "or generally used in the sense of" and / or, unless the context clearly indicates otherwise. The term and / or means one or all of the listed elements or combinations of two or more of the listed elements.

As used herein, it is intended to include, including, comprising, comprising or the like are used in their open sense and generally mean including in a non-limiting manner. It is understood that substantially comprising, consisting of and the like are pulled up under the containing and the like.

The words preferred and preferably refer to embodiments of the invention that may provide certain benefits under certain circumstances. However, other embodiments may also be beneficial in the same or different circumstances. Furthermore, citing one or more preferred embodiments does not mean that other embodiments are not useful and is not intended to exclude from the disclosure, including claims, other embodiments.

FIG. 1-7 are schematic diagrams of illustrative nicotine powder inhalers 10. FIGS. 3-7 are shown with transparent bodies to facilitate the illustration of flow channels and internal components. Schematic drawings are not necessarily to scale and are provided for illustrative and not restrictive purposes. The drawings will show one or more aspects described in this disclosure. However, it should be understood that other aspects not shown in the drawing fall within the scope of the appended claims.

Referring now to FIGS. 1 and 2, nicotine powder inhalers 10 include a mouthpiece 12 and a distal end portion 14 and a nicotine capsule 20 sandwiched therebetween. The piercing elements 11A and 11B are configured to pierce the capsule 20 and smoothly connect the air flow duct 13 of the mouthpiece 12 to the air flow duct 15 of the distal end 14. The air flow duct extends linearly along the length of the nicotine powder inhaler 10. FIG. 2 further illustrates the capsule 20 in the seat 25 that can be reused.

FIG. 3 and FIG. 4 illustrate nicotine powder inhalers 10 having a single linear air flow channel 13, 15. Piercing members 11A and 11B extend in nicotine powder seat 30 and are configured to pierce a nicotine powder capsule and smoothly connect the air flow channel 13 mouthpiece 12 with distal end airflow channel 15. The airflow duct extends linearly along the length of the nicotine powder inhaler 10 from the proximal end of the mouthpiece 18 to the distal end 19. The mouthpiece 12 can connect to a portion of the distal end 14 via a bayonet type connection. In FIG.3, the mouthpiece 12 is not symmetrical with the distal end portion 14. In FIG.4, the mouthpiece 12 is symmetrical with the distal end portion 14.

FIG.5 and FIG.6 is another illustrative nicotine powder inhaler 10. FIG.6 is a view of FIG.5 taken along line 6-6. This embodiment includes three airflow channels 15 and the first, second and third powder wells 30, 32 and 33, respectively. A nicotine powder capsule can be received in at least one of the powder wells 30, 32 and 33. In some embodiments, the second active agent may be received in at least one of the powder sockets 30, 32 and 33. The three flow channels 15 smoothly connect to the outlet channel 40 via a swirl generator 50 configured to induce rotational movement of the flowing air. The air flow channels 15 extend linearly along the length of the nicotine powder inhaler 10 from the proximal end of the mouthpiece 18 to the distal end 19. Ventilation element 70 may be arranged along air flow channels 15 to provide dilution air as needed.

FIG. 7 is another illustrative nicotine powder inhaler 10. This embodiment includes three air flow channels 15A, 15B and 15C and the first, second and third powder receptacles 30, 32 and 33, respectively. The nicotine powder capsule can be taken into at least one of the powder slots 30, 32 and 33. In some embodiments, the second active agent may be received in at least one of the powder slots 30, 32 and 33. The three flow channels 15 smoothly communicate with the exhaust channel 40 through a swirl generator 50 configured to induce a rotational movement of the flowing air. The air flow channels 15A, 15B extend linearly along the length of the nicotine powder inhaler 10 from the proximal end of the mouthpiece 18 to the distal end 19. In some embodiments, the air flow loop element 60 is located along the air flow channels 15C.