Device and method for aerosolized delivery of substance to a natural orifice of the body

Abstract

The present invention provides a device for delivering a predetermined volume of a substance, within at least one body cavity of a subject, comprising a predefined volume for containing the predetermined volume of the at least one substance; a delivery end for placement in proximity to the body cavity; the delivery end comprises at least one orifice of diameter D [mm]; a valve mechanically connectable to the container, characterized by at least two configurations: (i) an active configuration in which the valve enables delivery of predetermined amount M sub of the substance; and, (ii) an inactive configuration, in which the valve prevents delivery of the predetermined amount M sub of the substance from the container to the body cavity; and a fluid tight chamber configured to contain predetermined volume V gas of pressurized gas at a predetermined pressure, P gas .

1 . A unit dose device for delivering a predetermined amount M sub  of at least one substance, within at least one body cavity of a subject, said unit dose device comprising:
 a. at least one predefined volume sized and shaped for containing said predetermined amount M sub  of said at least one substance;   b. a delivery end for placement in proximity to said body cavity, said delivery end being in fluid communication with said container; said delivery end comprises at least one orifice of diameter D;   c. at least one valve mechanically connectable to said container, characterized by at least two configurations: (i) an active configuration in which said valve enables delivery of predetermined amount M sub  of said substance from said container to said body cavity via said delivery end; and, (ii) an inactive configuration, in which said valve prevents delivery of said predetermined amount M sub  of said substance from said container to said body cavity;
 said valve is configurable from said inactive configuration to said active configuration within a predetermined period of time, dT, in response to activation of the same; and 
   d. a fluid tight chamber configured to contain predetermined volume V gas  of pressurized gas at a predetermined pressure, P gas ;   said pressurized gas, once said valve is reconfigured from said inactive configuration to said active configuration, is configured to entrain said substance and deliver the same via said orifice in said delivery end;   wherein said predetermined amount M sub  is no more than 100 μl of a liquid substance per transition to the active configuration and no more than 190 mm 3  of a powder substance per transition to the active configuration.   
     
     
         2 . The unit dose device of  claim 1 , wherein said unit dose device has a configuration selected from a group consisting of configured to deliver a single unit dose or configured to deliver two-unit doses. 
     
     
         3 . The unit dose device of  claim 1 , wherein said inactive configuration, gas that was pressurized beforehand and at a remote location is maintained in its container until activation. 
     
     
         4 . The unit dose device of  claim 2 , wherein said unit dose device configured to deliver a single unit dose delivers no more than 140 mm 3  of a powder substance per transition to the active configuration. 
     
     
         5 . The unit dose device of  claim 1 , wherein said unit dose device is configured to deliver said predetermined amount M sub  of said substance and said predetermined volume V gas  of said pressurized gas through said orifice of diameter D in (a) pressure rate of dP gas /dT; (b) volume rate of dV gas /dT; and (c) amount rate of dM sub /dT;
 at least one of the following being held true:   a. P gas  is in a range of 1 to 10 barg;   b. V gas  is in a range of 1 to 50 ml;   c. D is in a range of 0.2 to 6 mm;   d. said pressure velocity dP gas /dT is greater than 0.001 barg/ms;   e. said amount rate dM sub /dT is greater than 0.0001 ml/ms or greater than 0.0001 mg/ms;   f. said volume rate dV gas /dT is greater than 0.001 ml/ms;   g. plume of said aerosol by a plume angle θ, said plume angle θ subtending the full width of said plume, said plume angle θ subtending an angle of less than about 25 θ;   h. dT is in a range of 0 to 500 millisecond; and   i. any combination thereof.   
     
     
         6 . The unit dose device of  claim 1 , wherein at least one of the following is true:
 a. said body orifice is a nasal cavity, the mouth, the throat, an ear, the vagina, the rectum, the urethra, and any combination thereof   b. viscosity η of said substance is in a range of 1×10 −3  poise to 1 poise;   c. DV50 diameter of particles of said substance, after exit from said unit dose device, is less than 100 μm;   d. DV90 diameter of said particles is less than 1000 μm;   e. a full width of a plume of aerosol comprising said substance and said gas subtends an angle θ of less than 25°;   f. particles in said plume have velocities in a range of 5 m/s to 50 m/s;   g. said pressurized gas comprises air, nitrogen, oxygen, carbon dioxide, helium, neon, xenon and any combination thereof;   h. during dispensing of said at least one substance, a mixture of said predetermined volume V gas  of said pressurized gas with said predetermined amount M sub  of said substance entrained within it forms a plume of aerosol; said aerosol having a predetermined distribution, said distribution being either homogeneous or heterogeneous, said heterogeneous distribution is selected from a group consisting of: an arbitrary distribution, a distribution in which the density of said at least one substance within said mixture follows a predetermined pattern, and any combination thereof; characteristics of said aerosol selected from a group consisting of: particle size, particle shape, particle distribution, and any combination thereof, are determinable from characteristics of said unit dose device selected from a group consisting of: said predetermined volume of said pressurized gas, said predetermined volume of said substance, said predetermined pressure of said pressurized gas, said predetermined orifice size, and any combination thereof;   i. at least one said substance is stored under either an inert atmosphere or under vacuum to prevent reactions during storage;   j. a dose-response curve is substantially linear for brain concentration of said substance when administered nasally via said unit dose device; and   k. a dose-response curve for brain concentration having a fit selected from a group consisting of logarithmic, parabolic, exponential, sigmoid, power-law, and any combination thereof; of said substance when administered nasally via said unit dose device.   
     
     
         7 . The unit dose device of  claim 1 , wherein said volume is stored in a container. 
     
     
         8 . The unit dose device of  claim 5 , wherein said container is a capsule having a main longitudinal axis, said capsule comprising a number n of compartments, said capsule configured to contain said predetermined amount M sub  of said at least one substance, said amount M sub  of said at least one substance containable in at least one of said n compartments; at least one of the following being true:
 a. the number n of said compartments is an integer greater than or equal to 1; at least one said compartment has cross-section with shape selected from a group consisting of: wedge shaped, circular, oval, elliptical, polygonal, annular, and any combination thereof;   b. for said number n of compartments being an integer greater than 1, at least two said compartments have different volumes;   c. for said number n of compartments being an integer greater than 1, at least two said compartments have the same volume;   d. for said number n of compartments being an integer greater than 1, at least two said compartments have different cross-sectional areas;   e. for said number n of compartments being an integer greater than 1, at least two said compartments have the same cross-sectional area;   f. for said number n of compartments being an integer greater than 1, at least two said compartments contain different substances;   g. for said number n of compartments being an integer greater than 1, at least two said compartments contain the same substance;   h. for said number n of compartments being an integer greater than 1, at least two said compartments are disposed coaxially around said main longitudinal axis of said capsule;   i. for said number n of compartments being an integer greater than 1, at least two said compartments are disposed sequentially along said main longitudinal axis of said capsule;   j. for said number n of compartments greater than 1, said plurality of substances mix during said dispensing; and   k. for said number n of compartments greater than 1, said plurality of substances react during said dispensing.   
     
     
         9 . The unit dose device of  claim 1 , wherein said container comprises a port fluidly connectable to the exterior of said unit dose device, said port configured such that said at least one substance is insertable into said chamber via said port. 
     
     
         10 . The unit dose device of  claim 5 , wherein said unit dose device comprises a port cover configured to provide an air-tight closure for said port, said port cover slidable along said unit dose device, rotatable around said unit dose device, rotatable around a hinge on the exterior of said unit dose device and any combination thereof. 
     
     
         11 . A method of delivering a predetermined amount M sub  of at least one substance within at least one body cavity of a subject, comprising:
 a. providing a unit dose device comprising:
 i. at least one predefined volume sized and shaped for containing said predetermined amount M sub  of said at least one substance; 
 ii. a delivery end in fluid communication with said container; said delivery end comprising at least one orifice of diameter D; 
 iii. at least one valve mechanically connected to said container, characterized by at least two configurations: (i) an active configuration in which said valve enables delivery of said predetermined amount M sub  of said substance from said container to said body cavity via said delivery end; and, (ii) an inactive configuration, in which said valve prevents delivery of said predetermined amount M sub  of said substance from said container to said body cavity;
 said valve is reconfigurable from said inactive configuration to said active configuration within a predetermined period of time, dT, in response to activation of the same; and 
 
 iv. a fluid tight chamber configured to contain predetermined volume V gas  of pressurized gas at a predetermined pressure, P gas ; 
   b. emplacing said substance in said predefined volume;   c. setting said valve in said inactive configuration;   d. pressurizing said fluid-tight chamber with said gas to said predetermined pressure;   e. placing said delivery end in proximity to said body cavity;   f. reconfiguring said valve from said inactive configuration to said active configuration thereby entraining said substance in said predetermined volume V gas  of said pressurized gas; thereby   g. delivering said predetermined amount M sub  of said substance and said predetermined volume V gas  of said pressurized gas through said orifice of diameter D in a pressure rate of dP gas /dT;   wherein said predetermined amount M sub  is less than 100 μl of a liquid substance and less than 190 mm 3  of a powder substance.   
     
     
         12 . The method of  claim 11 , additionally comprising a step of selecting a configuration for said unit dose device from a group consisting of configured to deliver a single unit dose or configured to deliver two-unit doses. 
     
     
         13 . The method of  claim 11 , additionally comprising a step of said unit dose device configured to deliver a single unit dose delivering no more than 140 mm 3  of a powder substance per transition to the active configuration. 
     
     
         14 . The method of  claim 11 , additionally comprising at least one of the following steps:
 a. selecting P gas  to be in a range of 1 to 10 barg;   b. selecting V gas  to be in a range of 1 to 50 ml;   c. selecting D to be in a range of 0.2 to 6 mm;   d. selecting said pressure rate to be greater than 0.001 barg/ms;   e. selecting said volume rate dM sub /dT to be greater than 0.0001 ml/ms or greater than 0.0001 mg/ms;   f. selecting said volume rate dV gas /dT to be greater than 0.001 ml/ms;   g. selecting dT to be in a range of 0 to 500 millisecond and   h. any combination thereof.   
     
     
         15 . The method of  claim 11 , additionally comprising at least one of the following steps:
 a. selecting said body orifice from a group consisting of a nasal cavity, the mouth, the throat, an ear, the vagina, the rectum, the urethra, and any combination thereof;   b. selecting viscosity η of said substance to be in a range of 1×10 −3  poise to 1 poise;   c. characterizing particles of said substance in a delivered aerosol, said aerosol a mixture of said at least one substance and said gas, by a DV50 diameter, said DV50 diameter being less than 150 μm;   d. characterizing said particles by a DV90 diameter of less than 1000 μm;   e. characterizing a plume of said aerosol by a plume angle θ, said plume angle θ subtending the full width of said plume, said plume angle θ subtending an angle of less than 25°;   f. characterizing velocities of particles in said plume as being in a range of 5 m/s to 50 m/s;   g. selecting said gas from a group consisting of: air, nitrogen, oxygen, carbon dioxide, helium, neon, xenon and any combination thereof;   h. dispensing said at least one substance, and during said step of dispensing, forming a plume of aerosol with predetermined distribution from a mixture of said predetermined volume V gas  of said pressurized gas and said predetermined amount M sub  entrained within it; selecting said predetermined distribution from a group consisting of: a homogeneous distribution, a heterogeneous distribution; selecting said heterogeneous distribution from a group consisting of: an arbitrary distribution, a distribution in which the density of said at least one substance within said mixture follows a predetermined pattern, and any combination thereof; selecting characteristics of said aerosol from a group consisting of: particle size, particle shape, particle distribution, and any combination thereof, are determinable from characteristics of said unit dose device selected from a group consisting of: said predetermined volume of said pressurized gas, said predetermined volume of said substance, said predetermined pressure of said pressurized gas, said predetermined orifice size, and any combination thereof;   i. storing at least one said substance under either an inert atmosphere or under vacuum, thereby preventing reactions during storage; and   j. characterizing a dose-response curve for brain concentration of said substance to be of substantially linear form; and   k. a dose-response curve for brain concentration having a fit selected from a group consisting of logarithmic, parabolic, exponential, sigmoid, power-law, and any combination thereof; of said substance when administered nasally via said unit dose device.   
     
     
         16 . The method of  claim 11 , wherein said volume is a container. 
     
     
         17 . The method of  claim 16 , additionally comprising steps of providing said container comprising a capsule having a main longitudinal axis, said capsule comprising a number n of compartments, configuring said capsule to contain said predetermined amount M sub  of said at least one substance, containing said amount M sub  of said substance in at least one of said n compartments; additionally comprising at least one of the following steps:
 a. providing said capsule with n compartments; n is an integer greater than or equal to 1;   b. selecting a cross-sectional shape of at least one of said n compartments from a group consisting of: wedge shaped, circular, oval, elliptical, polygonal, annular, and any combination thereof;   c. for said number n of compartments being an integer greater than 1, providing at least two of said plurality of said compartments having different volumes;   d. for said number n of compartments being an integer greater than 1, providing at least two said compartments having the same volume;   e. for said number n of compartments being an integer greater than 1, providing at least two said compartments having different cross-sectional areas;   f. for said number n of compartments being an integer greater than 1, providing at least two said compartments having the same cross-sectional area;   g. for said number n of compartments being an integer greater than 1, providing at least two of said compartments containing different substances;   h. for said number n of compartments being an integer greater than 1, providing at least two of said compartments containing the same substance;   i. for said number n of compartments being an integer greater than 1, disposing said plurality of compartments coaxially around said main longitudinal axis of said capsule;   j. for said number n of compartments being an integer greater than 1, disposing said plurality of compartments sequentially along said main longitudinal axis of said capsule;   k. for said number n of compartments being an integer greater than 1, mixing said plurality of substances during said dispensing; and   l. for said number n of compartments being an integer greater than 1, reacting said plurality of substances during said dispensing.   
     
     
         18 . The method of  claim 11 , additionally comprising a step of inserting said predetermined volume M sub  of said at least one substance into said container via a port fluidly connectable to the exterior of said unit dose device. 
     
     
         19 . The method of  claim 18 , additionally comprising a step of providing an air-tight closure for said port, and of moving said port cover relative to said unit dose device in at least one motion selected from a group consisting of: sliding said port cover along said unit dose device, rotating said port cover around said unit dose device, rotating said port cover around a hinge on the exterior of said unit dose device and any combination thereof.