Methods, devices and systems for pulmonary delivery of active agents

• US 10,118,006 B2
• Filed: 12/11/2016
• Issued: 11/06/2018
• Est. Priority Date: 06/30/2014
• Status: Active Grant

• Current Assignee: Syqe Medical Ltd.
• Original Assignee: Syqe Medical Ltd.
• Inventors: Davidson, Perry, Almog, Shlomo, Kindler, Seth
• Primary Examiner(s): WOODWARD, VALERIE LYNN
• Application Number:
  US15/375,098
• Publication Number:
  US 20170157343A1
• Time in Patent Office: 695 Days
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 36/185 Magnoliopsida (dicotyledons)
• CPC Class Codes: A61K 36/81 Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61M 11/02 operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised sprayers for horticulture A01G, A01H; killing insects A01M; air humidifying by nozzles F24F6/14, F24F6/18; cooling by spraying F28B, F28C
• CPC Class Codes: A61M 11/041 using heaters
• CPC Class Codes: A61M 11/042 electrical
• CPC Class Codes: A61M 15/0001 Details of inhalators; Constructional features thereof
• CPC Class Codes: A61M 15/0003 with means for dispensing more than one drug
• CPC Class Codes: A61M 15/0013 with inhalation check valves
• CPC Class Codes: A61M 15/0015 located upstream of the dispenser, i.e. not traversed by the product
• CPC Class Codes: A61M 15/002 with air flow regulating means
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/005 the dosages being arranged on a cylindrical surface
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0065 : Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• CPC Class Codes: A61M 15/0066 : with means for varying the dose size
• CPC Class Codes: A61M 15/0091 : mechanically breath-triggered
• CPC Class Codes: A61M 15/06 : Inhaling appliances shaped like cigars, cigarettes or pipes
• CPC Class Codes: A61M 16/14 : by mixing different fluids, one of them being in a liquid phase
• CPC Class Codes: A61M 16/20 : Valves specially adapted to medical respiratory devices
• CPC Class Codes: A61M 2016/0039 : in the inspiratory circuit
• CPC Class Codes: A61M 2016/0042 : in the expiratory circuit
• CPC Class Codes: A61M 2205/0216 : Materials providing elastic properties, e.g. for facilitating deformation and avoid breaking
• CPC Class Codes: A61M 2205/276 : preventing unwanted use
• CPC Class Codes: A61M 2205/3303 : Using a biosensor
• CPC Class Codes: A61M 2205/3331 : Pressure; Flow
• CPC Class Codes: A61M 2205/3334 : Measuring or controlling the flow rate
• CPC Class Codes: A61M 2205/3368 : Temperature
• CPC Class Codes: A61M 2205/3553 : remote, e.g. between patient's home and doctor's office
• CPC Class Codes: A61M 2205/3561 : local, e.g. within room or hospital
• CPC Class Codes: A61M 2205/3569 : sublocal, e.g. between console and disposable
• CPC Class Codes: A61M 2205/3592 : using telemetric means, e.g. radio or optical transmission
• CPC Class Codes: A61M 2205/36 : related to heating or cooling
• CPC Class Codes: A61M 2205/502 : User interfaces, e.g. screens or keyboards
• CPC Class Codes: A61M 2205/505 : Touch-screens; Virtual keyboard or keypads; Virtual buttons; Soft keys; Mouse touches
• CPC Class Codes: A61M 2205/52 : with memories providing a history of measured variating parameters of apparatus or patient
• CPC Class Codes: A61M 2205/70 : with testing or calibration facilities
• CPC Class Codes: A61M 2230/005 : Parameter used as control input for the apparatus
• CPC Class Codes: A61M 2230/06 : Heartbeat rate only
• CPC Class Codes: A61M 2230/205 : partial oxygen pressure (P-O2)
• CPC Class Codes: A61M 2230/30 : Blood pressure A61M2230/04 takes precedence
• CPC Class Codes: A61M 2230/42 : Rate
• CPC Class Codes: A61M 2230/50 : Temperature
• CPC Class Codes: A61M 2230/60 : Muscle strain, i.e. measured on the user
• CPC Class Codes: A61M 2230/63 : Motion, e.g. physical activity
• CPC Class Codes: A61M 2230/65 : Impedance, e.g. conductivity, capacity
• CPC Class Codes: A61P 1/00 : Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 : for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/08 : for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/14 : Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 : Antiasthmatics
• CPC Class Codes: A61P 13/10 : of the bladder
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 : Antipruritics
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 25/32 : Alcohol-abuse
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: H05B 1/0227 : Applications
• CPC Class Codes: H05B 1/025 : For medical applications

Abstract

Provided herein is a method of pulmonary delivering to a subject at least one pharmacologically active agent being in a plant material, which is effected by pulmonary delivering the agent to the subject using a metered dose inhaler device that is configured to vaporize at least one pre-determined vaporized amount of the agent upon controllably heating the plant material, wherein the pre-determined vaporized amount is selected so as to achieve at least one pre-determined pharmacokinetic effect and/or at least one pre-determined pharmacodynamic effect induced by the agent in the subject.

Claims

1. A method of delivering to a pulmonary tract of a subject at least one pharmacologically active agent, the method comprising:

vaporizing a first metered amount of at least one pharmacologically active agent;

delivering said first metered amount to the subject from an inhaler device;

wherein a controller associated with said inhaler device is preprogrammed with at least one predetermined effect to be induced in the subject by said at least one pharmacologically active agent;

as a requirement prior to inhalation of a second metered amount of at least one pharmacologically active agent, interrogating the subject via a user interface device to obtain monitoring data indicative of at least one effect induced in the subject by the first metered amount;

receiving said monitoring data at said controller; and

vaporizing, within a treatment regimen including the delivering of the first metered amount, a second metered amount of at least one pharmacologically active agent, wherein a magnitude of the second metered amount is automatically controlled by the controller based at least partially on said monitoring data and on said at least one predetermined effect.

2. The method of claim 1, wherein the vaporizing the second metered amount is during the at least one effect induced in the subject by the first metered amount.

3. The method of claim 1, wherein the first metered amount and the second metered amount are respectively vaporized from substances containing different compositions of pharmacologically active agent.

4. The method of claim 1, wherein the at least one pharmacologically active agent vaporized in the first metered amount and the at least one pharmacologically active agent vaporized in the second metered amount together comprise a plurality of chemically different pharmacologically active agents;

and wherein the first metered amount and the second metered amount comprise different compositions of the plurality of chemically different pharmacologically active agents.

5. The method of claim 1, wherein the vaporizings comprise heating of the at least one agent of the first metered amount and the at least one agent of the second metered amount.

6. The method of claim 5, wherein controlling the magnitude of the first and/or second metered amounts by the controller comprises controlling said heating.

7. The method of claim 1, wherein a magnitude of the first metered amount is controlled by the controller for exhibiting a selected effect of the first metered amount in the subject.

8. The method of claim 7, wherein the magnitude of the second metered amount is controlled by the controller to induce an effect adjusting an induced effect of the first metered amount, the induced effect of the first metered amount differing from the selected effect, upon delivery of the second metered amount.

9. The method of claim 1, wherein the at least one effect comprises at least one of the group consisting of a pharmacokinetic effect and a pharmacodynamic effect.

10. The method of claim 9, wherein said pharmacodynamic effect is selected from the group consisting of a desired effect, an undesired effect, a therapeutic effect, an adverse effect and a level of a biomarker.

11. The method of claim 10, wherein said pharmacodynamic effect is a psychotropic effect and/or a somatic effect.

12. The method of claim 9, wherein the magnitude of the second metered amount is selected to induce a pre-selected profile of the pharmacokinetic and/or pharmacodynamic effect, based on a difference between the pharmacokinetic and/or pharmacodynamic effect indicated by the monitoring data, and the pre-selected profile.

13. The method of claim 1, wherein a timing of the vaporizing of the second metered amount is controlled by the controller based on the monitoring data.

14. The method of claim 1, wherein at least one of the first metered amount and the second metered amount comprises pharmacologically active agent vaporized from a plant material.

15. The method of claim 14, wherein the plant material is of a plant selected from the group consisting of Cannabis sativa, Cannabis indica, Cannabis ruderalis, Nicotiana tabacum, and Nicotiana rustica.

16. The method of claim 1, wherein at least one of the first metered amount and the second metered amount comprises pharmacologically active agent selected from the group consisting of Δ

9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerols (CBG), cannabichromenes (CBC), cannabinol (CBN), cannabinodiol (CBDL), cannabicyclol (CBL), cannabielsoin (CBE), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV) and cannabitriol (CBT).

17. The method of claim 1, wherein at least one pharmacologically active agent is chemically present in both of the first metered amount and the second metered amount.

18. The method of claim 1, comprising defining a personalized therapeutic window for the subject during which an adverse effect is below a threshold, and a symptom is sufficiently alleviated, and selecting said magnitude of said second metered amount so as to maintain said subject within said therapeutic window.

19. The method of claim 18, wherein said adverse effect includes a psychoactive effect.

20. The method of claim 1, wherein said monitoring data comprises one or more of:

data obtained by a sensor of said user interface device;

data inserted by said subject into said user interface device;

data automatically collected or deduced from an interaction of said subject with said user interface device.

21. The method of claim 1, wherein non-invasive biomarker levels are estimated by analyzing the subject'"'"'s input when interacting with the user interface device.

22. The method of claim 1, wherein said interrogating, receiving and vaporizing said second metered amount are performed within 0-30 minutes from said delivering of said first metered amount.

23. The method of claim 1, comprising selecting a dose unit from a plurality of dose units contained in a magazine, said dose unit comprising source material, and wherein said vaporizing comprises vaporizing said source material to release said pharmacologically active agent.

24. The method of claim 1, wherein said monitoring data comprises input from the subject pertaining to at least one of their psychoactive state and their treatment state.

25. The method of claim 1, wherein said interrogating via said user interface is at least partially user-controlled and comprises voluntary data input by said subject.

26. A system for control of pulmonary delivery of pharmacologically active agent, the system comprising:

an inhaler device operable for pulmonary delivery of at least one vaporized, pharmacologically active agent to a subject, the device including;

a repository, configured to hold a substance comprising pharmacologically active agent;

a power source, operable to deliver power to vaporize the pharmacologically active agent from the substance; and

a controller, configured to control delivery of power to the substance, thereby vaporizing metered amounts of the pharmacologically active agent, said controller pre-programmed with at least one predetermined effect to be induced in the subject by said at least one pharmacologically active agent;

and

an interface operable to interact with the subject and obtain monitoring data indicative of at least one effect induced in the subject by a vaporized first metered amount of pharmacologically active agent delivered to the subject from the inhaler device, said interface programmed to interact with the subject as a requirement prior to inhalation of a second metered amount of at least one pharmacologically active agent;

wherein the controller is configured to control delivery of power to the substance to vaporize said second metered amount of pharmacologically active agent for pulmonary delivery to the subject; and

wherein the controller is configured to automatically control a magnitude of the second metered amount of pharmacologically active agent based at least partially on the monitoring data received from the interface and on said at least one predetermined effect.

27. The system of claim 26, wherein the inhaler device includes a heater, and the controlled delivery of power comprises control of the operation of the heater.

28. The system of claim 26, wherein the first metered amount and the second metered amount are vaporized from substances containing different compositions of pharmacologically active agent.

29. The system of claim 26, wherein the magnitude of the second metered amount is controlled by the controller to adjust an induced effect indicated by the monitoring data, the magnitude being selected to re-select a selected effect of the first metered amount.

30. The system of claim 26, wherein said user interface device comprises one or more software applications designed to test the subject'"'"'s cognitive, mental, motoric and/or physical condition, and wherein said monitoring data is collected by analyzing the subject'"'"'s input when interacting with said one or more applications.