Medical aerosol non-diluting holding chamber

A flexible bag aerosol holding chamber is sealed around the outlet passage of the actuator for a pressurized metered-dose inhaler. An elastic-loaded mouthpiece is sealed around the inlet passage of the actuator so that the user may intermittently break the seal around the inlet passage by withdrawing the mouthpiece, thus allowing inhalation of a portion of the aerosol contents of the chamber. In a preferred embodiment of the invention, the aerosol contains a compound which has traditionally been smoked such as nicotine or a cannabinoid. The user may draw upon the chamber's contents a number of times at a frequency analogous to smoking until the chamber is fully collapsed. One inhaler actuation, and one filled chamber, are comparable to one cigarette. The collapsible bag chamber allows for economy of inhaler actuations relative to user inhalations, without the aerosol being diluted by ambient air.

BACKGROUND OF THE INVENTION

Recent analysis of the public health risks and benefits of replacing cigarettes with a deep nicotine aerosol inhaler (if one were to exist) suggests that such a replacement would have a favourable impact (Sumner II W “Estimating the health consequences of replacing cigarettes with nicotine inhalers” Tobacco Control 2003; 12:124-132). The difficulties arise in developing a device that generates a sufficiently fine aerosol to allow peripheral lung delivery like that of a cigarette in a cost effective and operationally acceptable manner to current smokers, whether or not they intent to quit using nicotine. With currently available nicotine replacement therapy (gum, patch, nasal inhaler, oral vapour inhaler) most attempts at smoking cessation fail, and relapse rates remain over 75%. Many hard core smokers suffer from an underlying psychiatric problem that nicotine may help to ameliorate (Pomerleau CS “Co-factors for smoking and evolutionary psychobiology” Addiction 1997; 92:397-408). None of the available nicotine delivery devices listed above mimic a cigarette in terms of the rapid puff-by-puff delivery of an arterial bolus that reaches the brain within seconds, and this may explain why most individuals relapse to cigarette smoking. While smoking, peak arterial plasma nicotine concentration may be 10 times greater than venous concentrations. It is only by absorption through the lungs that the rapid arterial bolus nicotine delivery of a cigarette can be achieved, as opposed to the relatively slower venous delivery via buccal or nasal mucosa or skin, which is characteristic of current nicotine delivery devices including the oral vapour inhaler. The key to efficient arterial (central nervous system) nicotine delivery is the particle size of the nicotine aerosol. Nicotine vapour entering the mouth condenses onto the mucosal surface of the mouth and throat. Large aerosol droplets affect the upper airway as well. Only nicotine carried by fine droplets or particles is available for absorption into the pulmonary circulation and reaches the brain quickly in high concentration. Cigarette smoke particles have a mass median aerodynamic diameter (MMAD) of 0.4 μm. Such small particles deposit mainly in the alveoli of the lung from which they may be rapidly absorbed into the pulmonary circulation.

Recent improvements in the technology of medicinal inhalers for asthma and chronic lung disease has led to the development of solution formulations for pressurised metered-dose inhalers (pMDI's) that can generate fine droplet aerosols, improving upon that of pMDI's using solid particle suspension formulations and dry powder inhaler technology which are inherently limited in their potential to go into the ultra-fine particle size range. Preliminary tests of a hydrofluoroalkane/ethanol/nicotine solution formulation pMDI has shown an MMAD of 1.5 μm (Andrus PG et. al. “Nicotine microaerosol inhaler” 1999 Canadian Respiratory Journal; Vol 6 No 6:509-512), which is sufficiently small to allow cigarette simulating peripheral lung delivery. The hydrofluoroalkane/ethanol solution has also been developed to replace the marijuana cigarette (Davies, R. J. et al. U.S. Patent Application 20050061314 A1, Mar. 24, 2005; and Peart, J. et al. U.S. Patent Application 20040258622 A1, Dec. 23, 2004) for the same reasons as those which apply to nicotine, and in recognition of the many medicinal benefits of cannabinoids (i.e. tetrahydrocannabinol (THC)) in treating chronic pain and nausea. That is, nicotine and cannabis have been historically and are presently used most efficiently and effectively by deep inhalation, and HFA solution formulations allow the simulation of this where other inhaler technologies fall short.

The parameters of smoking (number of puffs per cigarette, number of cigarettes per day) are not random, but have been refined by user behaviour and preference over the long history of cigarette smoking for therapeutic effect. Simulation of this process by clean deep inhaler is the object of the present invention. A further difficulty however in the simulation of smoking by inhaler, which is addressed by the present invention, is the number of puffs that are typically inhaled in the course of a day. As a result of the high efficiency of pulmonary circulation delivery by a deep inhaler or a cigarette, a unit dose of one cigarette equivalent is best delivered by several puffs over several minutes. If the entire unit dose were delivered in one puff by deep inhalation, this would be less enjoyable and potentially dangerously over stimulating to the user. The entire dose could be delivered to the upper airway in one puff, for example the buccal or nasal mucosa, because it would effectively be delivered more slowly as it is more gradually absorbed into the venous circulation. This of course forgoes the advantages and user preferences for deep inhalation as described above. pMDI's for asthma or emphysema are intended to be discharged 4 to 8 times per day giving the inhaler's 200 puffs a life of about a month. Typically a smoker inhales 10 times per cigarette for 20 cigarettes per day thereby using up one inhaler equivalent per day. This rate of inhaler expenditure is undesirable from both a cost and user acceptability standpoint. The present invention addresses this problem by using a holding chamber to hold a multiple-inhalation concentrated aerosol cloud which can be drawn upon several times from a single actuation of the inhaler. Holding chambers are well known and used to improve efficiency of medicinal aerosol delivery. Typically they have one way valves near the mouthpiece to allow multiple inhalations of the chamber's contents so that the dose is fully received. With each inhalation however, ambient air is drawn into the chamber and mixes freely with the remaining contents. Therefore the concentration of the medicinal aerosol drops off exponentially with successive inhalations. To satisfactorily simulate the cigarette, each inhalation should predictably be of the same concentration. With the present device, the user may draw upon a fraction of the holding chamber's contents at a time, and then deeply inhale ambient air to send the dose to the lungs. With each inhalation the chamber further collapses so that the concentration of the aerosol within the chamber remains constant. In this manner, a single actuation of a concentrated aerosol from the inhaler provides several equal inhalations, thereby greatly extending the life of the inhaler. The gradual emptying of the bag is analogous to the burning down of the cigarette. The user need not coordinate inhaler actuation with inhalation, and need not keep track of number of inhalations to get a unit dose (cigarette equivalent) as the empty bag indicates and regulates the unit dose.

SUMMARY OF THE INVENTION

A pressurised metered-dose inhaler canister contains a solution formulation of nicotine or a cannabinoid in HFA propellant such that a fine microaerosol may be generated. The canister is housed within a standard L-shaped cylindrical actuator. A flexible bag aerosol holding chamber bag is sealed around the outlet passage of the actuator to receive the microaerosol upon actuation of the canister. An elastic-loaded mouthpiece is sealed around the inlet passage of the actuator so that the user may break the seal around the inlet passage by withdrawing the mouthpiece, thus allowing inhalation of a portion of the aerosol contents of the chamber. The inlet passage automatically reseals under the elastic tension as the mouthpiece is released by the user. The user subsequently draws upon the chamber's contents a number of times at a frequency analogous to smoking a cigarette until the chamber is fully collapsed, such that one inhaler actuation and one filled holding chamber are comparable to one cigarette. The holding chamber is folded and stowed within the actuator's outlet passage when not in use.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

A pressurised medical aerosol canister10with valve11contains a solution formulation12of nicotine or a cannabinoid (i.e. THC) in hydrofluoroalkane propellant. Ethanol may also be present as a co-solvent. The canister10is placed in an L-shaped actuator13with valve chamber14. The stem of the valve11sits in the valve chamber14, such that when the valve is actuated by pressure applied to the base15of the canister10, a single metered dose of the nicotine or cannabinoid solution formulation12is sent through a fine bore nozzle16in the valve chamber14causing a fine micoaerosol cloud17to leave the actuator13via it's outlet passage18, to be held in a flexible aerosol holding chamber19which is air-tightly sealed in a fixed manner around the outlet orifice18. The inlet passage20of the actuator13is air-tightly sealed in a sliding manner by an actuator cap21with flange22and baseplate23. The flange22is made of semi-rigid rubber or plastic so that it may slide along the outside of the actuator13during actuation of the canister10. The base plate23is held flatly against the base15of the canister10by an elastic cord24which joins the actuator cap21to the actuator13. A mouthpiece25is connected to the cap baseplate23via a hole26in the center of the baseplate23. The following is the method by which the device is used in the simulation of the smoking of a cigarette: Before use, the holding chamber19is folded in its' stowed position within the outlet passage18of the actuator13. Using the mouthpiece25, the baseplate23is lifted from it's seal with canister base15, such that the user may inflate the holding chamber19by blowing air through the mouthpiece25, into the actuator13around the canister10and then into the holding chamber19. The mouthpiece is then released and the baseplate23is returned to its' sealed position against the canister base15. The baseplate23is then pressed towards the actuator13in the usual manner by which pMDI's are actuated so that a single metered dose leaves the canister10through the valve stem11, into the valve chamber14, through the nozzle16, out through the actuator outlet passage18, and into the pre-inflated holding chamber19. At this point the nicotine or cannabinoid microaerosol cloud17is air tightly held within the holding chamber and adjoining actuator as seen inFIG. 1. The first inhalation may then be taken by the user by using the mouthpiece25to again lift the baseplate23from it's seal with the canister base15allowing passage by inhalation of a portion of the aerosol cloud17into the user's mouth. The mouthpiece25is then released again resealing the actuator13and chamber19. The user may then take a deeper inhalation of ambient air thereby washing the nicotine or THC microaerosol deep into the lungs in the same manner as is usually done during cigarette smoking. At this point the chamber can be put down analogous to the placing of a cigarette in an ashtray as the elastic24maintains the air-tight seal even if a small amount of pressure is applied to the outside of the chamber19. The user then takes 5-10 repeat inhalations from the chamber19, until the aerosol cloud17is depleted and the chamber19fully collapsed, thus completing a cycle equivalent to smoking a single cigarette. The chamber19is again stuffed into the outlet passage18so that the device occupies only the volume of the actuator13for convenient pocket or purse carrying. The chamber19is comprised of a thin plastic bag that can be sealed around the outlet passage18by a circumferential elastic band around the actuator13at its' outlet end. The bag can therefore be replaced frequently for hygienic reasons.