Methods, devices and systems for pulmonary delivery of active agents

• US 9,839,241 B2
• Filed: 12/21/2016
• Issued: 12/12/2017
• 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:
  US15/386,182
• Publication Number:
  US 20170127727A1
• Time in Patent Office: 356 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 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• 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 15/003 : using capsules, e.g. 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 2205/3313 : used specific wavelengths
• CPC Class Codes: A61M 2205/332 : Force measuring means
• 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 2205/3375 : Acoustical, e.g. ultrasonic, measuring means
• 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 1/0244 : Heating of fluids H05B1/0247 takes precedence
• CPC Class Codes: H05B 1/025 : For medical applications
• CPC Class Codes: H05B 3/34 : flexible, e.g. heating nets or webs

Abstract

Provided herein is a system that includes a metered dose inhaler device for pulmonary delivering to a subject at least one pre-determined vaporized amount of at least one pharmacologically active agent being in a plant material, wherein vaporization is effected by controllably heating the plant material so as to vaporize a pre-determined vaporized amount of the agent; the system further includes a controller in communication with the inhaler device, configured to control the pre-determined vaporized amount based on data indicative of at least one pharmacodynamic effect induced by the agent in the subject.

Claims

1. An inhaler for use in delivering a series of at least two active agents released from at least first and second substances, said first substance contained in a first cartridge and said second substance contained in a second cartridge, the inhaler comprising:

a vapor chamber configured for being in fluid communication with at least one of said first and second cartridges and in fluid communication with an output of said inhaler for delivery of at least one of said first and second active agents therethrough;

a memory in which dosing data for administering said first and second active agents is stored, said dosing data including defined vaporized amounts of said first and second active agents selected for inducing a predetermined therapeutic effect in said user, said dosing data including provision of said second active agent subsequently to provision of said first active agent, said first and second active agents to be provided at different inhalation events;

a controller in communication with said memory, said controller configured to effect delivery of said first active agent to the user and to sequentially effect delivery of said second active agent to the user according to said dosing data;

said controller configured to automatically adjust at least one of said vaporized amounts from said defined vaporized amount and/or adjust a timing for said delivery of said first and second active agents to provide a combination suitable for inducing said predetermined therapeutic effect in said user.

2. The inhaler according to claim 1, wherein said controller is configured to select a ratio of vaporized amounts of said first and second active agents according to said dosing data.

3. The inhaler according to claim 1, wherein said controller is configured to automatically adjust said vaporized amount from said pre-determined amount during a time period between and including delivery of at least one of said first and second active agents to the user to the dissipation of at least one effect induced in said user by said at least one of said first or second active agents.

4. The inhaler according to claim 1, wherein said controller is configured to select a vaporized amount of at least one of said first and second active agents so as to maintain said user within a therapeutic window calculated per said user and received as input in said inhaler.

5. The inhaler according to claim 4, wherein said vaporized amounts are selected to induce said therapeutic effect in said user while maintaining tolerable psychotropic activity levels.

6. The inhaler according to claim 1, wherein said first and second active agents are selected to induce said therapeutic effect synergistically.

7. The inhaler according to claim 1, wherein said first and second active agents are selected to induce a contradictory effect.

8. The inhaler according to claim 1, wherein said controller is configured to control delivery of said first and second active agents so as to deliver said active agents at a time interval of between 0-30 minutes from each other.

9. The inhaler according to claim 1, wherein said controller is in communication with a user interface, and wherein said controller is configured to adjust said vaporized amount based on feedback received from said user via said user interface.

10. The inhaler according to claim 9, wherein said user interface comprises a smartphone.

11. The inhaler according to claim 9, wherein said controller is configured to iteratively modify, based on said feedback, at least one of said vaporized amounts and a time interval between delivery of said first and second active agents.

12. The inhaler according to claim 9, wherein said user interface is associated with a device which is configured to interact with said user to receive a personal determination of the level of a pharmacodynamic effect induced by at least one of said first and second active agents in said user.

13. The inhaler according to claim 1, wherein said controller is configured to receive feedback data from one or more sensors suitable for measuring one or more biomarkers and to adjust said vaporized amount accordingly.

14. The inhaler according to claim 1, wherein each of said first and second active agents are selected to independently induce at least one of a pharmacokinetic effect and a pharmacodynamic effect in said user.

15. The inhaler according to claim 1, wherein at least one of said first and second active agents are 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).

16. The inhaler according to claim 1, further comprising a feeder for moving said first and second cartridges to said us position.

17. The inhaler according to claim 1, wherein each of said first and second cartridges comprises a dedicated heating element comprising an electrically resistive element.

18. The inhaler according to claim 1, comprising a sensor positioned for measuring an indication of airflow rate through said cartridge, and wherein said controller is configured for adjusting said vaporized amount of at least one of said first and second active agents according to said indication obtained by said sensor.

19. The inhaler according to claim 1, wherein each of said first and second cartridges comprises a predetermined amount of said first and second active agents respectively.

20. The inhaler according to claim 1, wherein at least one of said first and second substances comprises plant material.

21. The inhaler according to claim 20, wherein said plant material comprises cannabis.

22. The inhaler according to claim 20, wherein said plant material comprises tobacco.

23. The inhaler according to claim 1, wherein said controller is configured to automatically adjust the vaporized amount and/or a timing of delivery of said second active agent relative to the vaporized amount and/or relative to a timing of delivery of said first active agent.

24. The inhaler according to claim 18, wherein said controller is configured to detect inhalation of said first active agent based on an indication received from said sensor and to adjust said timing and/or amount of said second active agent accordingly.

25. The inhaler according to claim 1, wherein said controller is configured to effect delivery by controlling movement of each of said first and second cartridges independently into a use position in said vapor chamber.

26. The inhaler according to claim 1, wherein said first and second cartridges are moved into said use position from a magazine in which they are stored, said magazine comprising a plurality of cartridges.

27. The inhaler according to claim 1, wherein said output comprises a mouthpiece shaped and sized to be engaged by a mouth of a user.

28. The inhaler according to claim 1, wherein said output is configured to be in fluid communication with a mouthpiece.

29. The inhaler according to claim 1, wherein said first active agent comprises CBD and said second active agent comprises THC.

30. The inhaler according to claim 1, wherein each of said cartridges comprises apertures therein to permit airflow through the substance.