CN101472634A - Inhaler flow channel - Google Patents

Abstract

The present invention provides an inhaler, which separates the drug aerosolization process and the drug delivery process within the inhaler, and controls the inhalation air flow profile in a way, such that transportation of the drug in the inhaler flow channel is enveloped in a laminar air stream presented to the air tract of the user, thereby eliminating drug deposition on the inhaler inside walls. The inhaler invention therefore provides advantages over other inhalers, especially, when a repeatable emitted dose is important and generally, where contamination and hygiene in the flow channel is an issue as is the case with multi-dose inhalers.

Description

Inhaler flow channel

Technical field

The present invention relates generally to pulmonary's medicine and field of drug delivery.The present invention be used in especially conveying through the powdered medicine of metering and packing and medicine being used to suck under the situation of treatment, therefore use to be illustrated in conjunction with this class, although the present invention also can have other application, comprise being used for liquid medicine.

Background technology

As everybody knows, some respiratory tract disease is treated by direct administering therapeutic agent.Exist with powdered because these therapeutic agents are many, it is used therefore to suck the flour most convenient with nose or face.Powdered makes medicine obtain better utilization, because medicine is deposited on the position that needs the hope that it works just; Therefore, the medicine of minimum dosage usually just can play and the heavy dose of identical drug effect of using with other means, thereby the cost of undesirable side effect and medicine descends greatly.Disease outside the also available powdered Drug therapy respiratory system disease.When on the very large tracts of land of drug deposition in pulmonary, its can very rapidly be absorbed in the blood flow; Therefore, this application process can replace injection, tablet or adopt the application process of other traditional means.

Pharmacy industry is thought, bioavailability of medicament the best when the size of the drug particle that flows to respiratory tract is the 1-5 micron.When drug particle need be in this size range, dry powder delivery system need solve some problems:

(1) small-particle can produce static in manufacturing and storing process.This causes particle accumulation or gathers, and causes effective dimensions greater than 5 microns particle group.These big groups reduce its probability that penetrates into deep lung.Thereby the percentage ratio of the absorbable medicine of patient descends.

(2) need flow to patient's the amount of active drug about tens of milligram.Because current dry powder filling apparatus can't be carried the five equilibrium medicine of milligram quantities effectively with acceptable accuracy, so the way of standard is to mix active drug and filler such as lactose.This additive also makes medicine " flow easily ".In some cases, this filler is sometimes referred to as carrier.The size of these carrier particles is usually big than drug particle.The ability that Diskus separates medicine and carrier is an important performance characteristic of design effectiveness aspect.

(3) size can be deposited on face or the throat greater than 5 microns active drug particle.This causes another uncertainty---because the bioavailability of medicine on these positions is different with pulmonary with trap.

Diskus need make the minimal deposition of medicine on these positions, to reduce the uncertainty relevant with bioavailability of medicament.

The Diskus of prior art (DPIs) has the device that is used for medicine (active drug adds carrier) is introduced a high velocity air usually.This high velocity air is used for smashing the microgranule group or the main means of drug particle and carrier separately.The known in the prior art multiple suction apparatus that is used for allotting this powdered drug.For example, at United States Patent(USP) Nos. 3,507,277,3,518,992,3,635,219,3,795,244 and 3,807, in 400, disclosed suction apparatus has the mechanism that is used to pierce through or remove the capsular top that powdered drug is housed, and powdered drug sucks the mouth of user from the capsule that is pierced or is removed the top when air-breathing.In these patents some disclose propeller, and it helps medicine is distributed from capsule when air-breathing, thereby needn't only rely on inspiratory airflow to aspirate powder in the capsule.For example, in U.S. Patent No. 2,517, in 482 disclosed a kind of devices, in a bottom compartment, in this chamber, the user manual depression pierces through the needle-penetration capsule to the capsule that powder is housed in air-breathing anteposition.Begin air-breathingly after piercing through, capsule is inhaled in the upper chambers of this device, and in this upper chambers, it moves along all directions, so that powder distributes through the hole of piercing through, and enters in the inspiratory airflow.U.S. Patent No. 3,831,606 disclosed a kind of suction apparatus have that a plurality of thorns are threaded a needle, propeller and is used for moving angle of rake independent power source via outside manual operation, thereby propeller helps powder dispense in inspiratory airflow when air-breathing.Also referring to U.S. Patent No. 5,458,135.

Another kind of inhaler uses the medicine of liquid-based to patient's medication the time.

An example of this class I liquid I distributor is seen US 2003/0072717, and described device comprises that one is used to store the memorizer of chemical compound/mixture (compound), and described memorizer and generates and links to each other with the system fluid of launching liquid particle.The system that this memorizer and this are used for emitted particle is positioned at a housing.One end of housing is suitable for use as suction nozzle, so that pass through housing also air-breathing in the housing insertion mouth when patient wants to take medicine, thereby generates air-flow around memorizer and particle emission device in housing.Although the air-flow that generates basic nonturbulent flow laminar air flow and do not stopped is declared in housing in this explanation, and is not entirely true from physically seeing this.This particle conveyer device is positioned at the housing middle part, thereby stops the part air-flow by housing, and it is poor air velocity to occur thus on the air-flow section.Air-flow along the housing inboard will be faster than the air-flow in the tight downstream of device of emission drop in the housing.This causes turbulent flow and makes that to be arranged on the droplet distribution that the intravital device of shell launched inhomogeneous, thereby medicine will distribute on the housing section unevenly, and always as was expected therefore to flow to patient's dosage.Obviously, drop emission system in housing and the therefore layout in the air-flow that passes through device that patient inhales causes will influence air-flow and also will cause turbulent flow, thereby will can not get laminar flow on whole section.In addition, this drop discharger is similar to an ink-jet system according to this explanation, needs the chemical compound of energy source and specific type, and reason is that discharger may stop up or be dry and hard, thus because this system jams and the chemical compound dosage of can't reallocating.

Also know a kind of device from US5894841, in this device, for example use a bubble jet device or piezoelectricity discharger dispense liquid shape chemical compound, because patient is air-breathing and generate air-flow in housing on the suction nozzle of this device, the imagination droplet that air-flow surrounded launched and thus their being introduced in user mouth thus.This device comprises the easily worn part of some, simultaneously, because above described same in conjunction with US2003/0072717, air-flow can't cause by the laminar air flow of this device and guarantee that thus the air-flow on the suction nozzle section is constant---may guarantee the dosage of carrying patient desired actually by this.

These one type of prior art syringe exist a plurality of problems and shortcoming.For example, these one type of prior art syringe require the user FI medicated powder is effectively distributed from the capsule that pierces through or be drawn in the inspiratory airflow.Use these one type of prior art syringe, by air-breathing come via the pierced holes suction powder in the capsule generally can't from capsule, aspirate out all or even most of powder, thereby cause drug waste.In addition, this class one type of prior art syringe may cause uncontrolled amounts or agglomerating powdered rubber to be inhaled in the user mouth, rather than sucks the powder of the fine dispersion of controlled quatity consistently.

Mostly from people's such as Wilke U.S. Patent No. 3,948,264, wherein disclosed a kind of device of being convenient to suck powdered drug comprises the body part with first and second air inlet passageway and an exit passageway to the above-mentioned explanation of prior art.Second intake channel provides the capsular capping of medicated powder is housed, and exit passageway forms the suction nozzle that stretches out from body.Be provided with capsule and pierce through structure, it forms one or more holes in capsule when action, thereby when capsule vibrated by electromechanical vibrator, powdered drug can be discharged from capsule.

The disclosed puncturing mechanism of people such as Wilke comprises that three thorns that are installed in radially installing in the trochoidal curve chamber (trochoidalchamber), spring bias voltage thread a needle.When rotating this chamber with hands, described pin radially inwardly moves simultaneously and pierces through capsule.Further rotate this chamber, make these pins to be withdrawn into its initial position, so that these pins withdraw from from capsule owing to its spring installation.Electromechanical vibrator comprises a vibration type piston bar at its inner terminal, and this vibration type piston bar stretches into the crossover location of intake channel and exit passageway.This piston rod is connected with and is used to energy is provided so that the mechanical solenoid buzzer of this bar vibration.This buzzer provides power by high-energy battery, and activates by an outer button switch.

According to people such as Wilke (patent), air-breathing by exit passageway and when pressing switch with actuator electric oscillation device simultaneously, air is inhaled into by intake channel, and the air-flow by second intake channel rises capsule to become against vibration type piston.Thereby capsule vibrates rapidly, and powder is fluidized and the pierced holes from capsule is discharged.Air-flow by intake channel helps powder is extracted out from capsule, and carries this powder and deliver in the user mouth through exit passageway.People such as Wilke (patent) also disclose and can be arranged to the electromechanical vibration device to become a right angle with intake channel, can change Oscillation Amplitude and frequency to regulate the partition characteristic of inhaler.

There are a plurality of shortcomings in one type of prior art syringe, makes them less wish to be used to pulmonary delivery dry powder.Some described shortcomings comprise:

The performance of the inhaler of-prior art is decided by the flow rate that user generates.Lower flow rate does not cause powder all de-aggregated (de-agglomerated), thereby has a strong impact on the dosage that flows to patient.

-owing to being lack of consistency, disaggregation process cause the bioavailability between each dose drug inconsistent.

-because partly being deposited on the inwall of inhaler flow channel, drug dose cause the bioavailability between each dose drug inconsistent.

-being used to drive very macro-energy of electromechanical inhaler needs, this has increased device size, thereby makes them be unsuitable for portable use.

-cause the medicine loss owing to open or remove the capsule at top.

-medicine in the capsule of opening or remove the top is owing to touching oxygen or moisture goes bad.

In the United States Patent(USP) Nos. 6,026,809 and 6,142,146 of prior art, Gumaste provides a kind of inhaler, and this inhaler uses vibrator to promote medicine or pharmaceutical suspension in gas, has overcome the above-mentioned of above-mentioned prior art and other shortcoming.More specifically, the inhaler of above-mentioned patent comprises and is used to make medicine or medicine disaggregation and makes the medicine of disaggregation or the piezoelectric vibrator of pharmaceutical suspension.The U.S. Patent application No.2005/0183724 of Gumaste discloses the method that becomes more meticulous that a kind of dosage discharges, and will synthesize ejector principle (synthetic jet principle) and be applied in this device.

But, the effective means of the unexposed intrinsic problem that is used to solve most of inhalers of above-mentioned one type of prior art syringe---medicine of a certain amount of atomizing will be deposited on the wall of flow channel and suction nozzle---.The amount of sedimentary medicine be decided by patient inspiratory airflow form (flow profile), medicine static characteristic and be derived from moisture in patient's the device of incoming call unintentionally.The sedimentary medicine layer of institute can be along with use thickening, and can As time goes on cause serious dosage control problem, also can cause the danger of health aspect to patient.

Summary of the invention

The invention provides a kind of inhaler design, separate with drug delivery process at this inhaler Chinese medicine atomization process, the inspiratory airflow morphology Control is become: the bull ladle of medicine in inhaler flow channel is rolled in and appears at the user trachea in the laminar air flow, thereby avoided the drug deposition on the inhaler inwall.Therefore the present invention is more superior than previous inhaler, particularly spray repeatedly dosage when very important and usually multi-dose inhaler have the occasion of pollution and hygienic issues.

More specifically, the invention discloses a kind of flow channel design, this flow channel is roughly tubulose, and the one end seals with a wall, and forms the inwall of suction nozzle at the other end.There is the projection that stretches in the flow channel in central authorities at described end wall.In the central authorities of projection, one or more holes make the medicine that is atomized can enter flow channel.Near end wall, an equally distributed air inlet makes air can radially flow to the aerosol outlet opening.By projection, air inlet and the careful design that distributes to the air-flow of air inlet, aerosol will be wrapped in the air-flow and be transported in the user trachea and be not deposited on the wall of flow channel.

The present invention is effective in whole inhalation flow rate scopes relevant with sucking treatment, but the present invention also considers to regulate current limiter, with the deposition the best that makes for certain drug in pulmonary.

Application comprises powdery and liquid based drugs.

The drug packages principle includes but not limited to vesicle (blister), capsule, medicinal cupping (canister), bulk powder and many liquid dosages bag.

Drug aerosolization principles includes but not limited to the combination of ultrasound wave, dynamo-electric shaking machine, nozzle, compressed air, heating and these principles.

The treatment field includes but not limited to respiratory tract disease, diabetes, anaphylaxis and pain relieving.

Those skilled in the art can be obvious, the hat cone piece (cap blocking) that the present invention can discharge with dose counter, dosage, avoid too much the returning of dose counting module mechanism (return blockingmeans), breath actuated dosage discharge, medicine encoder element and patient dependence feedback combine for example explanation among prior art WO04/041334, US2005/0087473 and the WO01/703115.

Description of drawings

Fig. 1 is the cutaway view of flow channel one embodiment,

Fig. 2 illustrates an embodiment of the flow channel of band suction nozzle,

Fig. 3 illustrates an embodiment of outside header designs,

Fig. 4 is the profile of the collector air distributor of band current limiter,

Fig. 5 illustrates the flow channel of band vesicle,

Fig. 6 illustrates the flow channel that nozzle and medicinal cupping will be installed,

Fig. 7 illustrates some modification of projection geometric configuration, and

Fig. 8 illustrates the flow channel simulation for the embodiment of a band vesicle.

The specific embodiment

Usually, be used for powdered drug that pulmonary uses or be packaged in laminated plastic and aluminium foil capsule or vesicle as the agglomerated powder of dosing, pierce through and rock described capsule or vesicle so that powder enters in the inhalation flow passage of inhaler, perhaps selectively, powder is infeeded in the memorizer in bulk (bulk reservoir) in the inhaler, and before sucking or measure in the suction process.

The purpose of flow channel is to make the powder disaggregation become particle size to be preferably the atomized fine particle of 1-5 micron by introduce Turbulence Flow in flow channel, and subsequently this aerosol is transported to the inhaler suction nozzle and enters by inspiratory airflow in the trachea of user.

The medicine that provides with liquid form distributes in being called as the pressure vessel of medicinal cupping usually.Medicinal cupping uses a dosage metering valve, and when discharging a dosage, liquid is atomized through a nozzle and enters in the flow channel, and in flow channel, atomized drop further is atomized and is transported to the inhaler suction nozzle, and is transported to the trachea of user by inspiratory airflow.

Many inhalers on the market, particularly those inhalers based on power formulations medicine (powderformulated drug) depend on the preferred particle size that Turbulence Flow the flow channel from point of drug release to the inhaler suction nozzle comes more or less successfully to make the integrated 1-5 micron of powder particle depolymerization.But the shortcoming of the Turbulence Flow in the described flow channel is that drug particle contacts with suction nozzle with the wall of inhaler, and some particles will be adhered and be deposited on these surfaces, this be a kind of may be As time goes on and the effect of aggravation.Sedimentary degree is decided by the inspiratory airflow form of user, the static characteristic and because the existence of the moisture that breathing and surrounding cause of drug particle.

Consequence is obvious; At first, the effective dose that offers the user trachea will change along with the service life of this device, and this has become a more and more serious problem---since inhaler enter the key treatment of dosage, as in the diabetes; Secondly, sedimentary material is subjected to germ contamination, thereby user is caused the danger of health aspect.

The invention discloses a kind of conventional method that solves the inside deposition problem in the inhaler:

The first step is that atomization process and aerosol course of conveying are separated.This atomization technique is known in the art, that is, the medicinal cupping of the Sprinkle Caps that pierces through of machinery or ultrasonic vibration and vesicle, ultrasonic atomization liquid medicine droplet, heating liquid medicine, band spray nozzle, form by the air-flow in a plurality of holes vesicle and the capsule and the combination of these technology from pressurized-gas source.

Secondly, Fig. 1 flow channel embodiment is connected on the atomizing source on end wall 103 outsides, this flow channel roughly cylindrical 101, the one end is by piercing through the wall base closed thatvesicle 106 constitutes by bottom 103 and (in this embodiment), and the described vesicle that pierces through forms the projection 102 that stretches in the flow channel 101.Piercedholes 104 makes aerosol apparatus to spray into the atomization medicine of disaggregation in the flow channel 101.Near end wall, equally distributed slit orhole 105 make air can radially flow to the hole in the projection 102 in flow channel.The aerosol of injecting will be wrapped in laminar air flow and carry, and be transported to user trachea and not with the wall collision of flow channel.The condition that realizes laminar flow (all gas and drug particle have a positive components of flow with respect to specifying to flow to, and all particle rapidities in any and the concentric barrel surface of flow channel are basic identical) in flow channel is:

The shape of projection 102 arrives between the high taper in the sphere of major diameter, low clearance.All limits inair inlet 105 and the projection 102 and turning answer chamfering to avoid local turbulent flow.

Acceptable inhalation flow rate is limited in per minute 5-100 litre (comprising that the most practical inhalation flow rate is recommended as per minute 15-60 litre usually).

Flow channel should constitute the interior diameter of suction nozzle.For avoiding local turbulent flow, diameter or the shape rapid step that do not have.

The length of preferred flow channel and the aspect ratio of diameter should be at least 1.

Carefully balanced distributionformula air inlet 105 is to avoid the air-flow deflection.

Provide the balance air-flow with acollector 107 withair inlet port 108, distributor chamber 109 and axial current limiter 110.Also can use other embodiment, promptly distributed axial inlet or axial admission port.Under most practical situations, an air inlet port preferably can comprise a breath actuated dose release mechanism, to realize optimum matching between dosage release and user inspiratory airflow form.Selectively,---measuring falling as pressure ondistributed air inlets 105 both sides of maximum---controls dosage release time can to use the differential pressure pick-up of any kind.

Fig. 2 shows the embodiment of theflow channel 101 that has taperedair bladder 203 and the embodiment ofsuction nozzle 201, although this interior shape that illustrates suction nozzle is decided byflow channel 101 basically, but, in fact can simulate any suitablehuman engineering profile 202 of suction nozzle.Shown profile is oval, so that the lip of user can form air tight communication between inhaler and user trachea.

Fig. 3 and 4 illustrates an embodiment offlow channel 101, and whereincollector 107 has the air distributor that is made of a plurality ofaxial rib 110, to realize arriving the uniform air-distribution that flow channel enters slit orhole 105.

Fig. 5 is the profile offlow channel 101, and whereincollector 107 is equipped withhemispherical vesicle 106.

Fig. 6 illustratesband collector 107 and is used for theflow channel 101 of the joint ofball nozzle 601, and thisball nozzle 601 has thepassage 602 thatmedicinal cupping 603 can be mounted in it.This embodiment makes the present invention can be used for the pressurized drug of fluid recipes.

Fig. 7 a-e illustrates the selection of the geometric configuration of projection and aerosol holes.Be stressed that the part of projection can be formed by vesicle:

A. be arranged in the single centre bore 701 of major diameter sphere.

B. be arranged in the single central nozzle 702 that is used for the fluid recipes medicine of major diameter sphere.

C. be arranged in the porous pattern 703 of major diameter sphere.

D. be arranged in the single centre bore 704 of big beveled cone shape.

E. be arranged in the single centre bore 705 of major diameter sphere.This vesicle has the cheese wall of the reverse side that has other hole 706 in addition, and described hole 706 is used to discharge and spray the dosage that is produced by compressed air or user inspiratory airflow.Also can place the elongated shape Sprinkle Caps that pierces through in two dome spaces for atomizing.

Fig. 8 is illustrated in the flow simulating among the embodiment of flow channel, and this flow channel has the spherical vesicle that single radial air inlet collector and a porous pierce through.This flow simulating is clearly shown that the air-flow in the flow channel is a laminar flow after the aerosol decanting point,aerosol 801 remains near the center by flow channel the time.Shown under the geometric configuration, laminar condition exists in per minute 10-90 litre scope at inspiratory airflow, but, regulate for example flow channel aspect ratio, air inlet geometric configuration and parameters such as balance and blister dome geometric configuration, can make optimal flow scope optimum for given application.

Can make multiple change and the protection domain that provides by claims is not provided aforementioned content.

Claims (9)

1. inhaler, comprise drug conveying flow channel and the device that is used to be connected a described drug conveying flow channel and a medicament reservoir, wherein, first end of described flow channel is suitable for inserting in the mouth of user, the opposite end of this flow channel is delimited by an end wall, is provided with a projection in the central part of this end wall, and this projection is provided with one or more holes, near end wall or in the end wall, the end wall of close flow channel is furnished with air inlet.

2. by the described inhaler of claim 1, it is characterized in that described end wall is the lid that is arranged on the drug dose that is packaged in a multiple dose vesicle bag, provides the device that is used to pierce through the described lid on the drug dose.

3. by the described inhaler of claim 1, it is characterized in that, linking to each other with described air inlet is furnished with an inlet manifold, and described collector comprises one or more air inlet ports, a distributor chamber, is provided with one or more axial current limiters to be used for the air-flow air inlet flow channel that leads in this distributor chamber.

4. by claim 1 or 3 described inhalers, it is characterized in that, described air inlet be arranged such that enter flow channel air-flow with respect to the air-flow that carries medicine radially.

5. by claim 1,3 or 4 described inhalers, it is characterized in that described airflow design is per minute 5-100 litre, per minute 15-60 litre more preferably.

6. by the described inhaler of claim 1, it is characterized in that the shape of the described projection in end wall is selected in following shape: convex, concave shape, sphere, all chamferings of all limits and turning.

7. by the described inhaler of claim 1, it is characterized in that, provide the device that is used for medicine is introduced air-flow; Described device can comprise machinery, ultrasonic unit, vibrating device, electromechanical device, spray nozzle device, compressed air, vapourizing unit or its combination.

8. by the described inhaler of arbitrary aforesaid right requirement, it is characterized in that described medicine can be liquid or powdery, wherein, medicine can be packed in any suitable manner, for example vesicle, capsule, medicinal cupping, bulk powder, list or many liquid dosages bag.

9. be used for carrying by an inhaler method of medicine, wherein, described pharmaceutical pack is rolled in the laminar air flow in the drug conveying flow channel, and described passage at one end is communicated with the medicine source of supply, and is communicated with user in the opposite end.

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