# US 10,118,006 B2 · Methods, devices and systems for pulmonary delivery of active agents

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- Number: US 10,118,006 B2
- Document ID: US10118006B2
- Status: Granted
- Kind: B2
- Application number: 15/375,098
- Filed: 2016-12-11
- Published: 2017-06-08
- Granted: 2018-11-06
- Earliest claimed: 2014-06-30
- Assignees: Syqe Medical Ltd.
- Applicants: Syqe Medical Ltd.
- Inventors: Perry Davidson; Shlomo Almog; Seth Kindler
- Web page: https://patentgrep.com/patent/US10118006B2

## CPC

- A61M 15/0028: {using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up}
- A61K 9/007: {Pulmonary tract; Aromatherapy}
- 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)}
- A61K 31/465: Nicotine; Derivatives thereof
- A61K 31/658: {o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol}
- A61K 36/185: Magnoliopsida (dicotyledons)
- A61K 36/3482: {Cannabis}
- A61K 36/742: {Coffea, e.g. coffee}
- A61K 36/81: Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
- A61M 11/041: {using heaters}
- A61M 11/042: {electrical}
- A61M 15/0001: {Details of inhalators; Constructional features thereof}
- A61M 15/0003: {with means for dispensing more than one drug}
- A61M 15/0013: {with inhalation check valves}
- A61M 15/0015: {located upstream of the dispenser, i.e. not traversed by the product}
- A61M 15/002: {with air flow regulating means}
- A61M 15/0045: {using multiple prepacked dosages on a same carrier, e.g. blisters}
- A61M 15/005: {the dosages being arranged on a cylindrical surface}
- A61M 15/0051: {the dosages being arranged on a tape, e.g. strips}
- A61M 15/0065: {Inhalators with dosage or measuring devices (A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52)}
- A61M 15/0066: {with means for varying the dose size}
- A61M 15/06: Inhaling appliances shaped like cigars, cigarettes or pipes
- A61M 16/14: by mixing different fluids, one of them being in a liquid phase
- A61M 16/20: Valves specially adapted to medical respiratory devices
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics
- A61P 1/14: Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/10: of the bladder
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/04: Antipruritics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/30: for treating abuse or dependence
- A61P 25/32: Alcohol-abuse
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/14: for RNA viruses
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- H05B 1/0227: {Applications}
- H05B 1/0244: {Heating of fluids (H05B1/0247 takes precedence)}
- H05B 1/025: {For medical applications}
- H05B 3/34: flexible, e.g. heating nets or webs
- 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)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- 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)}
- A61M 15/0021: {Mouthpieces therefor}
- A61M 15/003: {using capsules, e.g. to be perforated or broken-up}
- A61M 15/0091: {mechanically breath-triggered}
- A61M 2016/0039: {in the inspiratory circuit}
- A61M 2016/0042: {in the expiratory circuit}
- A61M 2205/0216: Materials providing elastic properties, e.g. for facilitating deformation and avoid breaking
- A61M 2205/276: preventing unwanted use
- A61M 2205/3303: Using a biosensor
- A61M 2205/3313: used specific wavelengths
- A61M 2205/332: Force measuring means
- A61M 2205/3331: Pressure; Flow
- A61M 2205/3334: Measuring or controlling the flow rate
- A61M 2205/3368: Temperature
- A61M 2205/3375: Acoustical, e.g. ultrasonic, measuring means
- A61M 2205/3553: remote, e.g. between patient's home and doctor's office
- A61M 2205/3561: local, e.g. within room or hospital
- A61M 2205/3569: sublocal, e.g. between console and disposable
- A61M 2205/3592: using telemetric means, e.g. radio or optical transmission
- A61M 2205/36: related to heating or cooling
- A61M 2205/502: User interfaces, e.g. screens or keyboards
- A61M 2205/505: Touch-screens; Virtual keyboard or keypads; Virtual buttons; Soft keys; Mouse touches
- A61M 2205/52: with memories providing a history of measured variating parameters of apparatus or patient
- A61M 2205/70: with testing or calibration facilities
- A61M 2230/06: Heartbeat rate only
- A61M 2230/205: partial oxygen pressure (P-O2)
- A61M 2230/30: Blood pressure (A61M2230/04 takes precedence)
- A61M 2230/42: Rate
- A61M 2230/50: Temperature
- A61M 2230/60: Muscle strain, i.e. measured on the user
- A61M 2230/63: Motion, e.g. physical activity
- A61M 2230/65: Impedance, e.g. conductivity, capacity
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- H05B: ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL

## 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

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 5)

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

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 7)

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.

### Claim 9 (depends on 1)

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.

### Claim 10 (depends on 9)

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.

### Claim 11 (depends on 10)

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

### Claim 12 (depends on 9)

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.

### Claim 13 (depends on 1)

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.

### Claim 14 (depends on 1)

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.

### Claim 15 (depends on 14)

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.

### Claim 16 (depends on 1)

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 Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerols (CBG), cannabichromenes (CBC), cannabinol (CBN), cannabinodiol (CBDL), cannabicyclol (CBL), cannabielsoin (CBE), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV) and cannabitriol (CBT).

### Claim 17 (depends on 1)

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.

### Claim 18 (depends on 1)

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.

### Claim 19 (depends on 18)

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

### Claim 20 (depends on 1)

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.

### Claim 21 (depends on 1)

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.

### Claim 22 (depends on 1)

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.

### Claim 23 (depends on 1)

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.

### Claim 24 (depends on 1)

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.

### Claim 25 (depends on 1)

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.

### Claim 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.

### Claim 27 (depends on 26)

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.

### Claim 28 (depends on 26)

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.

### Claim 29 (depends on 26)

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.

### Claim 30 (depends on 26)

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.