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WO2015009500A1 - Administration d'anatabine sous forme volatilisée pour le traitement d'une toxicomanie - Google Patents

Administration d'anatabine sous forme volatilisée pour le traitement d'une toxicomanie Download PDF

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Publication number
WO2015009500A1
WO2015009500A1 PCT/US2014/045909 US2014045909W WO2015009500A1 WO 2015009500 A1 WO2015009500 A1 WO 2015009500A1 US 2014045909 W US2014045909 W US 2014045909W WO 2015009500 A1 WO2015009500 A1 WO 2015009500A1
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Prior art keywords
anatabine
nicotine
acid
addiction
inhaler
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Ceased
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PCT/US2014/045909
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English (en)
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Jonnie R. Williams
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Individual
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Individual
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Priority claimed from US13/946,201 external-priority patent/US20130298921A1/en
Application filed by Individual filed Critical Individual
Publication of WO2015009500A1 publication Critical patent/WO2015009500A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465—Nicotine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34—Tobacco-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse

Definitions

  • Inhalers have been used as one non-combustion type of device for delivering nicotine for inhalation.
  • Some types of inhalers use a highly pressurized chamber for delivering a powdered medium for inhalation. See, e.g., U.S. Patent 7,461,649 to Gamard et al.
  • Other varieties of inhalers employ a tube in which the active component is volatized into vapor form for inhalation. See, e.g., U.S. Patent 6,769,436 to Horian.
  • Current inhalers of this type generally use nicotine, a toxic and addictive substance, as the sole active component.
  • Embodiments of the present invention are directed to inhalers and similar devices adapted for delivering anatabine in a volatilized form.
  • a volatilized form of anatabine is delivered for treating a substance addiction such as nicotine addiction, cocaine addiction, marijuana addiction, heroin addiction, or alcohol addiction.
  • FIG. 1 is a schematic illustration of an inhaler in accordance with one embodiment.
  • FIG. 2 is a sectional view of the drum of the inhaler shown in FIG. 1 used to hold the alkaloid composition.
  • FIG. 3 is a schematic illustration of an inhaler in accordance with another embodiment.
  • FIG. 4 shows that administration of single doses of anatabine dose-dependently decreased nicotine self-administration.
  • FIG. 5 shows the nicotine dose-effect curve in monkeys under the same conditions as in FIG. 4.
  • FIG. 6 shows the effects of anatabine on nicotine self-administration by rats.
  • Tobacco is among the most chemically complex substances known, with tobacco and tobacco smoke containing more than 8,000 compounds.
  • tobacco contains the minor alkaloids nornicotine, anabasine, and anatabine.
  • nicotine is regarded as the principal addictive component in tobacco, a variety of other factors also are believed to contribute to tobacco addiction.
  • tobacco smoke has been reported to have a monoamine oxidase (MAO) inhibitory effect.
  • MAO is an enzyme involved in the breakdown of dopamine, a pleasure-enhancing neurotransmitter. See J.S. Fowler et al., "Inhibition of Monoamine Oxidase B in the Brain of Smokers," Nature (Lond), 379(6567):733 736 (1996); J. Stephenson, "Clues Found to Tobacco Addiction," Journal of the American Medical Association, 275(16): 1217-1218 (1996). See also Williams et al. U.S. Patent 6,350,479.
  • anatabine is the sole alkaloid present in the composition, e.g., anatabine comprises 100 wt. % of the total alkaloid weight. In other examples, up to about 75 wt. % of one or more other alkaloids, such as nicotine, nornicotine, and/or anabasine, may be present in addition to anatabine.
  • anatabine and nicotine may be combined in a weight ratio (anatabine-to-nicotine) of about 50: 1 to about 1 :3, or from about 25: 1 to about 1 :2, from about 10: 1 to about 3:2, or from about 5: 1 to about 1 : 1.
  • anatabine is the only active component present. In other examples, anatabine may be combined with other active component(s).
  • Anatabine may be prepared synthetically, such as via a benzophenoneimine pathway as described in U.S. Patent 8,207,346 Bl, the disclosure of which is incorporated herein by reference in its entirety.
  • Anatabine may be present in the form of a racemic mixture or as isolated enantiomer, e.g., R-(+)-anatabine or S-(-)-anatabine, and/or as one or more pharmaceutically acceptable (or food grade) salts of anatabine.
  • anatabine refers to racemic mixtures of anatabine, enantiomers of anatabine, salt and non-salt forms of anatabine, as well as salt and non-salt forms of anatabine enantiomers.
  • salts are described in P. H.
  • anatabine may be obtained by extraction from tobacco or other plants, such as members of the Solanaceae family, such as datura, mandrake, belladonna, capsicum, potato, tomato, nicotiana, eggplant, and petunia.
  • a tobacco extract may be prepared from cured tobacco stems, lamina, or both. Flue (bright) varieties of tobacco are often used, i.e., Virginia flue. Other tobacco varieties may be used, such as Burley, dark-fired, and/or other commercial tobacco varieties. Two or more tobacco varieties may be combined to form a blend.
  • cured tobacco material is extracted with a solvent, typically water, ethanol, steam, or carbon dioxide.
  • the resulting solution contains the soluble components of the tobacco, including alkaloids such as anatabine.
  • Anatabine may be purified using known techniques such as liquid chromatography.
  • the amount of anatabine present in the composition may vary depending on factors such as the type of device and/or whether other active components, such as nicotine and/or other alkaloids, are present.
  • the amount of anatabine may range from about 0.1 to about 25 mg, from about 0.5 to about 20 mg, or from about 1 to about 10 mg, per total gram of the composition.
  • anatabine typically is present in an amount ranging from about 1 mg per lOmL to about 40 mg per lOmL of solution, often from about 4 mg per lOmL to about 30 mg per lOmL of solution, and sometimes from about 5 mg per lOmL to about 25 mg per lOmL of solution or from about 6 mg per lOmL to about 20 mg per lOmL of solution.
  • compositions containing anatabine were found to be efficacious for the temporary reduction of tobacco cravings, even without the presence of nicotine.
  • Anatabine and other minor alkaloids also have been reported to bind to nicotinic receptors. See “Receptors for Nicotine in the Central Nervous System: 1 Radioligand Binding Studies,” Group Research & Development Centre, British-American Tobacco Co. Ltd. (1984).
  • the composition may contain up to about 75 wt.% of one or more other alkaloids, such as nicotine, nornicotine, and/or anabasine, based on the total alkaloid weight.
  • alkaloids may be extracted from tobacco or other plant materials and purified using known techniques, and/or prepared synthetically using known synthesis methods.
  • Anatabine and additional alkaloid(s) may be combined in a weight ratio (anatabine -to-total other alkaloids) of about 50: 1 to about 1 :3, or from about 25: 1 to about 1 :2, from about 10: 1 to about 3 :2, or from about 5 : 1 to about 1 : 1.
  • the composition may be provided in a solid, powdered form, or in liquid form, depending on such factors as the structure and operation of the particular device used for volatile delivery.
  • Micronized dry powder used in inhalers typically is produced with an original particle range of about 1-10 microns.
  • An individual dose may include, for example, from about 5 mg to about 20 mg of powder.
  • the active agent(s) may be combined with one or more excipient carriers, non-limiting examples of which include lactose, trehalose, and mannitol.
  • one or more flavorants may be added to the composition, non-limiting examples of which include peppermint, menthol, wintergreen, spearmint, propolis, eucalyptus, cinnamon, natural or artificial tobacco flavors, or the like.
  • the total amount of flavorants and/or other additives typically ranges from about 0.5 to about 15 wt.%, often from about 1 to about 10 wt.%), based on the total weight of the composition.
  • a liquid composition containing both anatabine and nicotine may contain a solvent together with anatabine in an amount of about 1 to about 40 mg per 10 mL of solution, often from about 3 to about 36 mg per 10 mL of solution, and nicotine in an amount of about 1 to about 40 mg per 10 mL of solution, often from about 9 to about 36 mg per 10 mL of solution.
  • Suitable solvents include, but are not limited, to low-molecular-weight grades of polyethylene glycol (PEG), such as PEG 400 which has very low toxicity.
  • the device used for volatile delivery may be of various types of configurations.
  • volatile delivery of anatabine may be carried out by way of atomization, vaporization, use of a compressed gas, or other mechanical or electronic means (e.g., an electronic inhaler) capable of delivering anatabine in gaseous form or in a form otherwise suitable for inhalation.
  • solid forms of anatabine may be dissolved in a suitable solvent or dispersed in a liquid vehicle.
  • the anatabine- containing liquid may be filled into an inhaler or receptacle for a delivery device capable of administering anatabine in a volatilized form as described herein.
  • inhalers may be of a single-use or disposable type, or may be refillable with alkaloid compositions and/or cartridges containing alkaloid compositions to facilitate reuse.
  • FIG. 1 One example of an inhaler is shown in FIG. 1.
  • the inhaler 30 of this embodiment has a high pressure chamber 32 coupled to an equalization chamber 34.
  • the high pressure chamber 32 contains a compressed mixture 52 of helium and oxygen.
  • the chamber 32 has a resealable, refilling opening 31.
  • the high pressure chamber 32 includes a housing 36 defining a third chamber 38.
  • the housing 36 includes an opening 40 on a top portion thereof and a gas passage 42 on a side.
  • the third chamber 38 communicates with both the high pressure chamber 32 and the equalization chamber 34.
  • a consistent volume of gas is produced with the help of a diaphragm plate 56.
  • the equalization chamber 34 includes a housing 58 having a gasket 46 disposed therein.
  • the gasket 46 includes a gas passage 48 on a side thereof for allowing gas disposed in the third chamber 38 to communicate with the second chamber 34.
  • a piston 44 is slidably mounted within the gasket 46 and within the housing 36.
  • the piston 44 includes a communication opening 50.
  • the piston 44 is pushed downwards with a spring 60 located inside chamber 38 to allow gas communication between chambers 32 and 34. When the canister 32 is separated from the inhaler, the spring 60 is pushing the piston 44 sealing the canister by closing the opening 42.
  • the communication opening 50 is designed to selectively allow gas 52 stored in high pressure chamber 32 to communicate with gas stored in the equalization chamber 34.
  • a pressure plate 56 is also disposed within housing 58. One side of pressure plate 56 is coupled to piston 44.
  • inhaler 30 produces a desired gas pressure without requiring an external pump.
  • high-pressure gas 52 from the high pressure chamber 32 fills into equalization chamber 34.
  • a spring 60 and pressure plate 56 are designed to facilitate this operation.
  • the piston 44 has a communication opening 50 which selectively allows high pressure chamber 32 to communicate with equalization chamber 34 through gas passages 42 and 48.
  • the gas 52 applies pressure against a small area defined by the top of piston 44.
  • the net force applied by the high-pressure side of high pressure chamber 32 on the piston 44 works with the biasing force of spring 60 and against the force applied by gas 54 on pressure plate 56.
  • the spring constant of spring 60 and the surface area of pressure plate 56 are chosen so that when equalization chamber 34 has received sufficient pressure to utilize inhaler 30, the force applied by the gas on pressure plate 56 will exceed that of the force produced by the gas 52 on piston 44 on the high- pressure side of the device and the force of the spring 60. At such a time, the force applied by the gas will cause piston 44 to move upward within housings 58 and 36.
  • An activating trigger 94 is disposed on a drum section 64.
  • An inhalation port door 98 coupled to a mouth piece 99 of a spacer 96 closes to inhibit a user from inhaling the gas disposed within spacer 96.
  • the spacer 96 may also have a scented receptacle 110 near to where a patient's nose would be. The air in the spacer 96 is purged through a pressure port 100.
  • vacuum/pressure valve 104 opens, allowing ambient air into the spacer 96. By opening vacuum/pressure valve 104, the user may continue a steady deep inhalation of ambient air following inhalation of the dosage.
  • the drum section 64 includes a housing 65 that contains a rotating drum which includes a plurality of tubes 68 that are substantially cylindrical and extend longitudinally therethrough.
  • the tubes 68 contain the powdered alkaloid composition 76.
  • a disposable multi-dose drum 66 may include hollow tubes 70 which have a diameter that is larger than the diameter of tubes 68.
  • the diameter of each tube 68 is dependent on the volume and weight of dry powder to be delivered. Both tubes 68 and 70 may be packed within the rotating drum 66 so as to maximize the amount of doses available per rotating drum.
  • For each tube 68 there is a corresponding hollow tube 70.
  • One arrangement is for the powder-filled tubes 68 and hollow tubes 70 to be arranged in pairs vertical to each other.
  • the drum 66 may be placed on spindle (not illustrated) which is inserted into a bore 72 such that the drum 66 is coaxial with the spindle.
  • a clear sealed plastic overlay 86 may be disposed on the front and rear surfaces of the drum 66 to cover the tubes 68.
  • a diffuser 112 includes an impact ball 114 at a portion that is proximate to the gas passage.
  • the impact ball 114 is used to reduce the initial high velocity of highly turbulent gas and drug that enters diffuser 112.
  • the diffuser 112 is shaped as an expansion cone to slow down the gas-powder mixture.
  • the spacer 96 may be combined with the diffuser 112 so that the large particles can drop out of particle cloud in the spacer 96.
  • FIG. 3 Another, non- limiting example of an inhaler that may be used is shown in FIG. 3.
  • the inhaler of this embodiment is a one-piece tube 10 of generally uniform wall thickness.
  • the tube 10 may be extruded, molded or fabricated out of flat stock such as a thermoplastic material having suitable gas barrier properties, and then rolled and sealed into a formed tube.
  • the tube should be impermeable to the active agent(s).
  • the tube 10 may have, for example, a wall thickness of about 0.002" to about 0.020".
  • the tube 10 may be formed in a circular (as shown) or noncircular cross-section.
  • the extruded tube may be cut into lengths between about 1" to 5" to resemble the length of conventional cigarettes.
  • a plurality (e.g., 20) of the cut tubes may be provided in a pack (not illustrated) similar to a conventional cigarette pack.
  • the tube 10 is loaded with ingredients comprising the volatile delivery system.
  • An absorbent material 12 compatible with the volatile agent(s) may be inserted into the tube 10 for delivery to the user.
  • the absorbent material 12 can be in the form of a plug, strips, or the like.
  • a liquid alkaloid composition (e.g., anatabine in an organic solvent) may be loaded into the tube 10 via spray or direct injection.
  • the alkaloid composition may be loaded into the tube in a gaseous atmosphere, such as nitrogen or other gas, conducive to preserving the alkaloid(s).
  • the tube 10 then may be pinched closed at the two open ends 16 and heat-sealed according to well known techniques.
  • the inhaler may be used as needed to satisfy cravings, or at intervals such as once daily, twice daily, or three or more times daily, depending on such factors as the concentration of active components and the subject's physiological conditions.
  • Alkaloid compositions for inhalers may be prepared by combining the components listed in Tables 1 and 2 below.
  • Powdered compositions (Table 1) may be prepared by blending the alkaloid(s), excipient carriers, and flavors.
  • Liquid compositions (Table 2) may be prepared by blending the alkaloid(s), solvents, water, and flavors.
  • Anatabine may be prepared synthetically as described in Examples 1-3 of U.S. Patent 8,207,346 Bl . Nicotine, anabasine, and nornicotine may be extracted from tobacco materials and purified using known techniques.
  • a liquid alkaloid composition for an inhaler is prepared by combining polyethylene glycol 400, anatabine (10 mg/ 10 mL) and nicotine to yield a composition containing 10 mg/ 10 mL of anatabine and 18 mg/ 10 mL of nicotine.
  • compositions described in Examples 1-17 may be filled into refilling cartridges for inhalers, or filled into a container that is used as part of a kit for refilling receptacles in inhalers.
  • the compositions alternatively may be filled into a single-use or disposable type of inhaler.
  • This example describes a medication-based treatment of nicotine addiction in a nonhuman primate model of nicotine self-administration.
  • the acute effects of anatabine (0.18-3.2 mg/kg, IM) or saline on nicotine- and food-maintained responding were examined in seven rhesus monkeys. Nicotine (0.01 mg/kg/inj, base) and banana-flavored food pellets (lg) were available under a second-order schedule (FR 2 [VR 16:S]).
  • Anatabine or saline injections were administered 15 min. before the midday food self-administration session began. Saline control treatment was in effect after administration of each anatabine dose.
  • the nicotine dose-effect curve (0.001-0.1 mg/kg/inj) was determined under the same conditions in 7 monkeys (FIG. 5).
  • the peak of the dose effect curve was at 0.0032 mg/kg/inj.
  • Increasing doses of nicotine did not change food-maintained responding.
  • Data for two monkeys suggest that a moderate dose of anatabine (0.32 mg/kg) shifts the peak of the dose-effect curve to the right.
  • a higher dose of anatabine (1.0 mg/kg) flattened the dose-effect curve.
  • Food-maintained responding also decreased at the peak reinforcing doses of nicotine (0.0032 and 0.01 mg/kg/inj) and there was considerable variability across animals.
  • Anatabine was found to dose-dependently reduced nicotine self-administration (P ⁇ 0.005-0.02) with no significant effects on food-maintained responding.
  • Systematic behavioral assessments following each treatment session revealed no evidence of sedation or agitation that could disrupt operant responding.
  • Each monkey returned to baseline levels of nicotine self-administration before administration of the next dose of anatabine, so catheter malfunction could not account for the significant decreases in nicotine self-administration observed.
  • These findings in rhesus monkey are consistent with anatabine's effects on nicotine self-administration in rats (Caine et al., 2013).
  • Anatabine (1.8-5.6 mg/kg) significantly reduced nicotine -maintained responding at doses of 0.003 and 0.01 mg/kg/inj (P ⁇ 0.5-0.001) and flattened the nicotine dose-effect curve.
  • FIG. 6 shows similar effects of anatabine on nicotine self-administration by rats.
  • nAChR human nicotinic acetylcholine receptor
  • FLIPRTETRATM Fluorescence Imaging Plate Reader
  • the maximal response of the channel to nicotine approached that of ACh indicating that nicotine is a full agonist of the ⁇ 3 ⁇ 4 receptor, as expected.
  • the maximal response to anatabine was about 5 -fold lower than that of ACh indicating that anatabine is a partial agonist of this receptor.
  • nicotine and anatabine were both potent agonists, and the EC50's were calculated to be approximately 0.008 ⁇ for each compound.
  • the maximum level of activation for both nicotine and activation was also similar (and similar to ACh), suggesting that anatabine and nicotine are full, potent agonists of the a7 nAChR.
  • anatabine is an agonist of all three nAChR channels tested, but with different characteristics at each subtype, and with some significant differences relative to nicotine.
  • anatabine was a full agonist at the ⁇ 4 ⁇ 2 receptor, it was much less potent than nicotine or ACh.
  • Anatabine showed partial agonist activity towards the ⁇ 3 ⁇ 4 receptor, and was only slightly less potent than nicotine.
  • anatabine showed full agonist activity at the a7 nAChR channel, with similar potency as nicotine.
  • anatabine was shown to be a full and highly potent agonist at the a7 receptor, suggesting that this may be one mechanism by which anatabine exerts anti-inflammatory effects such as those that have been observed in both in vitro and in vivo studies. Although it is not selective for the a7 receptor, the findings from this study suggest that anatabine 's activity toward this particular nAChR subtype is similar to nicotine, and provide evidence that this may be one pathway through which anatabine 's immuno-modulatory effects are mediated.

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Abstract

La présente invention concerne l'anatabine administrée sous forme volatilisée afin de traiter des toxicomanies telles que la dépendance à la nicotine, la dépendance à l'alcool, la dépendance à la marijuana, la dépendance à l'héroïne ou la dépendance à la cocaïne. Des dispositifs tels que des inhalateurs électroniques peuvent être utilisés pour administrer l'anatabine sous forme volatilisée.
PCT/US2014/045909 2013-07-19 2014-07-09 Administration d'anatabine sous forme volatilisée pour le traitement d'une toxicomanie Ceased WO2015009500A1 (fr)

Applications Claiming Priority (2)

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US13/946,201 US20130298921A1 (en) 2011-06-23 2013-07-19 Inhaler for smoking cessation
US13/946,201 2013-07-19

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WO2015009500A1 true WO2015009500A1 (fr) 2015-01-22

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* Cited by examiner, † Cited by third party
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WO2020127225A1 (fr) 2018-12-17 2020-06-25 Philip Morris Products S.A. 3- (1,2,3,6-tétrahydropyridin-2-yl) pyridine glutarate ou un solvate pharmaceutiquement acceptable de celui-ci
WO2021050682A1 (fr) * 2019-09-12 2021-03-18 Cabbacis Llc Articles et formulations pour produits à fumer et vapoteuses
US10973255B2 (en) 2018-07-27 2021-04-13 Cabbacis Llc Articles and formulations for smoking products and vaporizers
US11017689B2 (en) 2018-07-27 2021-05-25 Cabbacis Llc Very low nicotine cigarette blended with very low THC cannabis
CN115697299A (zh) * 2020-06-15 2023-02-03 菲利普莫里斯生产公司 新烟草碱粉末组合物

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US11017689B2 (en) 2018-07-27 2021-05-25 Cabbacis Llc Very low nicotine cigarette blended with very low THC cannabis
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CN115697299A (zh) * 2020-06-15 2023-02-03 菲利普莫里斯生产公司 新烟草碱粉末组合物
US20230233459A1 (en) * 2020-06-15 2023-07-27 Philip Morris Products S.A. Anatabine powder compositions

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