US20140288056A1 - Methods for non-toxic treatment for drug withdrawal - Google Patents
Methods for non-toxic treatment for drug withdrawal Download PDFInfo
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- US20140288056A1 US20140288056A1 US14/214,157 US201414214157A US2014288056A1 US 20140288056 A1 US20140288056 A1 US 20140288056A1 US 201414214157 A US201414214157 A US 201414214157A US 2014288056 A1 US2014288056 A1 US 2014288056A1
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- noribogaine
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Classifications
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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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
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- 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
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- 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
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- 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
- A61P25/32—Alcohol-abuse
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- 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
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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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
Definitions
- the disclosure relates to the treatment of drug withdrawal symptoms.
- Ibogaine has been used as a botanical preparation from the root bark of iboga tabernathe for over 100 years both as a crude preparation and as semisynthetic ibogaine, which was marketed in France until about 1970. Observations in the 1970's suggested that ibogaine in higher doses was useful as a treatment for addiction. The use of ibogaine as a treatment for addiction was controversial because higher doses caused hallucinations and, in spite of many anecdotal reports of striking efficacy, no double-blind, placebo-controlled trials supported the efficacy of ibogaine as a treatment for withdrawal or addiction.
- U.S. Pat. No. 6,348,456 discloses highly purified noribogaine and teaches that it should be provided at dosages from about 0.01 to about 100 mg per kg body weight per day.
- DemeRx, Inc. evaluated the pharmacokinetics and metabolism of ibogaine and noted that the psychotomimetic effects correlated with blood levels of ibogaine, while the anti-addictive effects correlated with blood levels of noribogaine, the only metabolite of ibogaine found in humans, dogs, rats and monkeys. These experiments were followed up with animal studies of noribogaine in various addiction models, which demonstrated that noribogaine significantly reduced drug-seeking behavior and had no activity in an evaluation of psychotomimetic effects in an animal model.
- DemeRx is now developing noribogaine as a treatment for the symptoms of drug addiction and has shown to be effective in animal models of addiction to alcohol, cocaine and opiate dependence.
- noribogaine can cause convulsions and other CNS-related clinical signs, respiratory arrest and death. Given the signs of efficacy that noribogaine has shown, there is a need for a method to administer noribogaine in dosages that provide efficacy without leading to any significant deleterious clinical signs.
- the disclosure provides a method to administer noribogaine to a human patient having drug addiction in dosages that provide efficacy without leading to any significant deleterious clinical signs.
- Such dosages provide maximum serum concentrations (C max ) of noribogaine of less than about 2000 ng/mL, while maintaining efficacious average noribogaine serum levels of between about 100-2000 ng/ml (AUC/T).
- One embodiment of disclosure provides a method for treating withdrawal symptoms in a patient suffering from withdrawal from addiction to a substance comprising administering to the patient a dosage of noribogaine that provides a C max of noribogaine of less than about 1980 ng/mg serum and an average AUC/24 hr of about 1,100 ng/ml.
- the patient is administered a dosage of noribogaine from about 100 mg to about 500 mg at intervals of about 24 hours. In some embodiments, the patient is administered a dosage of noribogaine from about 100 mg to about 400 mg at intervals of about 24 hours. In some embodiments, the patient is administered a dosage of noribogaine from about 100 mg to about 300 mg at intervals of about 24 hours. In some embodiments, the patient is administered a dosage of noribogaine from about 100 mg to about 200 mg at intervals of about 24 hours.
- the patient is administered a dosage of noribogaine from about 200 mg to about 500 mg at intervals of about 24 hours. In some embodiments, the patient is administered a dosage of noribogaine from about 200 mg to about 400 mg at intervals of about 24 hours. In some embodiments, the patient is administered a dosage of noribogaine from about 200 mg to about 300 mg at intervals of about 24 hours.
- the patient is administered a dosage of noribogaine from about 300 mg to about 500 mg at intervals of about 24 hours. In some embodiments, the patient is administered a dosage of noribogaine from about 300 mg to about 400 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 400 mg to about 500 mg at intervals of about 24 hours.
- the disclosure provides a method to administer noribogaine to a human patient having drug addiction in dosages that provide efficacy without leading to any significant deleterious clinical signs.
- Such dosages provide maximum serum concentrations (C max ) of noribogaine of less than about 2000 ng/mL, while maintaining efficacious average noribogaine serum levels of between about 100-1100 ng/ml (AUC/24 hr).
- noribogaine refers to noribogaine as well as its pharmaceutically acceptable salts.
- the methods of the present disclosure entail the administration of a prodrug of noribogaine that provides the desired maximum serum concentrations and efficacious average noribogaine serum levels.
- a prodrug of noribogaine refers to a compound that metabolizes, in vivo, to noribogaine.
- the prodrug is selected to be readily cleavable either by a cleavable linking arm or by cleavage of the prodrug entity that binds to noribogaine such that noribogaine is generated in vivo.
- the prodrug moiety is selected to facilitate binding to the ⁇ and/or ⁇ receptors in the brain either by facilitating passage across the blood brain barrier or by targeting brain receptors other than the ⁇ and/or ⁇ receptors.
- Examples of prodrugs of noribogaine are provided in U.S. patent application Ser. No. 13/165,626, the content of which is incorporated here by reference.
- the dosages administered provide a C max of noribogaine of less than about 1980 ng/mg serum and an average AUC/24 hr of about 1,100 ng/ml. In certain embodiments, the dosages administered provide a C max of noribogaine of less than about 1800 ng/mg serum and an AUC/24 hr of about 1000 ng/ml. In certain embodiments, the dosages administered provide a C max of noribogaine of less than about 1620 ng/mg serum and an AUC/24 hr of about 900 ng/ml.
- the dosages administered provide a C max of noribogaine of less than about 1440 ng/mg serum and an AUC/24 hr of about 800 ng/ml. In certain embodiments, the dosages administered provide a C max of noribogaine of less than about 1260 ng/mg serum and an AUC/24 hr of about 700 ng/ml. In certain embodiments, the dosages administered provide a C max of noribogaine of less than about 1400 ng/mg serum and an AUC/24 hr of from about 600 ng/ml.
- the dosages administered provide a C max of noribogaine of less than about 900 ng/mg serum and an AUC/24 hr of about 500 ng/ml. In certain embodiments, the dosages administered provide a C max of noribogaine of less than about 720 ng/mg serum and an AUC/24 hr of about 400 ng/ml. In certain embodiments, the dosages administered provide a C max of noribogaine of less than about 540 ng/mg serum and an AUC/24 hr of about 300 ng/ml.
- the dosages administered provide a C max of noribogaine of less than about 360 ng/mg serum and an AUC/24 hr of about 200 ng/ml. In certain embodiments, the dosages administered provide a C max of noribogaine of less than about 180 ng/mg serum and an AUC/24 hr of about 100 ng/ml.
- such concentrations are obtained by administering from about 100 to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 200 mg to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 300 mg to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 400 mg to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 500 mg to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 600 mg to about 1,100 mg at intervals of about 24 hours.
- such concentrations are obtained by administering from about 700 mg to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 800 mg to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 900 mg to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 1,000 mg to about 1,100 mg at intervals of about 24 hours.
- such concentrations are obtained by administering from about 100 mg to about 1,100 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 100 mg to about 1,000 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 100 mg to about 900 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 100 mg to about 800 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 100 mg to about 700 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 100 mg to about 600 mg at intervals of about 24 hours.
- such concentrations are obtained by administering from about 100 mg to about 500 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 100 mg to about 400 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 100 mg to about 300 mg at intervals of about 24 hours. In some embodiments such concentrations are obtained by administering from about 100 mg to about 200 mg at intervals of about 24 hours.
- each patient is administered from about 100 mg to about 600 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 100 mg to about 500 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 100 mg to about 400 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 100 mg to about 300 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 100 mg to about 200 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 200 mg to about 600 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 200 mg to about 500 mg at intervals of about 24 hours.
- each patient is administered from about 200 mg to about 400 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 200 mg to about 400 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 200 mg to about 300 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 300 mg to about 400 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 300 mg to about 500 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 300 mg to about 600 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 400 mg to about 500 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 400 mg to about 600 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 500 mg to about 600 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 400 mg to about 600 mg at intervals of about 24 hours. In some embodiments each patient is administered from about 500 mg to about 600 mg at interval
- the patient is administered periodically, such as once, twice, three time, four times or five time daily with noribogaine or its prodrug.
- the administration is once daily, or once every second day, once every third day, three times a week, twice a week, or once a week.
- the dosage and frequency of the administration depends on the route of administration, content of composition, age and body weight of the patient, condition of the patient, without limitation. Determination of dosage and frequency suitable for the present technology can be readily made a qualified clinician.
- noribogaine or its prodrug which may conveniently be provided in tablet, caplet, liquid or capsule form.
- the noribogaine is provided as noribogaine HCl, with dosages reported as the amount of free base noribogaine.
- the noribogaine HCl is provided in hard gelatin capsules containing only noribogaine HCl with no excipients.
- noribogaine provides its anti-withdrawal symptom effects by acting as both an ⁇ 3 ⁇ 4 nicotinic receptor and a serotonin reuptake blocker acting on the 5-HT Transporter.
- the objective of this study was to determine the toxicity and toxicokinetic profile of noribogaine HCl following a single oral (gavage) administration in the Sprague-Dawley rat.
- a single dose of 100, 300 and 800 mg/kg (achieved with doses of 400 mg/kg 3 h +/ ⁇ 30 min apart because of the limitations of maximum dose formulation concentration).
- Five male rats/group were used. Mortality occurred in all male rats in the 800 mg/kg group, approximately 2-3 h after administration of the second dose of 400 mg/kg.
- hypoactivity, vocalization, salivation, stimuli sensitivity, loss of limb function and lying on the cage floor occurred on the day of treatment and persisted until Day 2 in 3/5 rats given 300 mg/kg.
- the low dose rats treated at 100 mg/kg did not show any treatment related signs.
- the NOAEL was determined to be 100 mg/kg.
- the objective of the study was to determine the toxicity and toxicokinetic profile of noribogaine following oral (gavage) administration to the cynomolgus monkey.
- the test article was administered as follows in Table 1:
- MTD maximum tolerated dose
- mice Male and female Sprague-Dawley rats, 10/sex/group, were administered 0, 25, 50 or 100 mg/kg noribogaine HCl daily by single oral gavage for 14 days. An additional 5 rats/sex/group in the 0 (control) and 100 mg/kg groups were retained for a 28 day recovery period during which no drug was administered. Six rats/sex/group (3 rats/sex controls) were similarly dosed and sampled on study days 1 and 14 for analysis of noribogaine-HCl concentrations in the blood.
- Rats were observed for mortality, clinical signs, body weight, food consumption, ophthalmology (pre-dose, during week 2, and at the end of recovery), hematology, coagulation, clinical chemistry, urinalysis, gross necropsy, organ weights and histopathology (full tissue panel, plus immunocytochemistry of 5 sections of the brain and spinal cord by staining for GFAP and Calbindin). There were no test article-related effects on mortality (none occurred), clinical signs, ophthalmoscopy, hematology, coagulation parameters, clinical chemistry, urinalysis, gross necropsy or histopathology.
- NOAEL dose in this study was interpreted to be 100 mg/kg, the highest dose tested in the study.
- Noribogaine HCl was administered to groups of 4 male and 4 female dogs by single oral gavage daily for 14 days at doses of 0, 0.5, 1.0 and 5.0 mg/kg/day.
- An additional group of 4 male and 4 female dogs received either the vehicle control or 5.0 mg/kg/day for 14 days and were held for an additional 28 days after cessation of dosing to assess recovery from any potential drug-induced changes.
- the study was conducted under GLP guidelines and included comprehensive examinations of clinical signs, body weight, clinical pathology parameters, ophthalmologic examinations, ECG recordings and analyses of plasma for bioanalytical measurement of drug levels at appropriate intervals during the study.
- the only target tissue identified in this study was the lacrimal gland of dogs receiving 5 mg/kg/day.
- the lacrimal gland changes were characterized by slight to moderate atrophy and degeneration of the acinar cells accompanied by slight to moderate accumulation of brown/yellow pigment and infiltration of mononuclear cells.
- ophthalmologic examination there was no clear association between these ocular signs and the appearance of the lacrimal gland changes suggesting that these morphologic changes did not result in sufficient functional abnormality of the gland to produce physical changes in exterior structures of the eye.
- the subject mean serum levels over time of noribogaine free base from a single dose of 3 mg noribogaine free base under fasting conditions were plotted.
- the mean C max of 5.2 ng/ml was observed 1.9 hours after administration, while the mean AUC/24 hr of 3.1 ng/ml was obtained.
- the subject mean serum levels over time of noribogaine free base from a single dose of 10 mg noribogaine free base under fasting conditions were plotted.
- the mean C max of 14.5 ng/ml was observed 2.9 hours after administration, while the mean AUC/24 hr of 10.6 ng/ml was obtained.
- the subject mean serum levels over time of noribogaine free base from a single dose of 30 mg noribogaine free base under fasting conditions were plotted.
- the mean C max of 55.9 ng/ml was observed between 1.75 hours after administration, while the mean AUC/24 of 29.2 ng/ml was obtained.
- the subject mean serum levels over time of noribogaine free base from a single dose of 60 mg noribogaine free base under fasting conditions were plotted.
- the mean C max of 116 ng/ml was observed between 1.75 hours after administration, while the mean AUC/24 ng/ml of 61 was obtained.
- the subject mean serum levels over time of noribogaine free base for all 4 cohorts were plotted.
- the extrapolated dosage of noribogaine free base required to provide a C max ranging from about 5.2 ng/ml to about 1980 ng/ml and an AUC/24 hr of about 3.1 ng/ml to about 1100 ng/ml was determined.
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EP (1) | EP2968355A4 (pt) |
JP (1) | JP2016514679A (pt) |
KR (1) | KR20150130461A (pt) |
CN (1) | CN105307658A (pt) |
AR (1) | AR095338A1 (pt) |
AU (1) | AU2014228986A1 (pt) |
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CA (2) | CA2942638A1 (pt) |
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Cited By (11)
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Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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EA201691656A2 (ru) * | 2014-02-18 | 2017-03-31 | Демеркс, Инк. | Терапевтические способы с применением норибогаина и родственных соединений |
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US20220265675A1 (en) * | 2019-07-15 | 2022-08-25 | Demerx, Inc. | Methods for the non-toxic treatment for opioid drug withdrawal combining noribogaine and cannabinoids |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999011250A2 (en) * | 1997-09-04 | 1999-03-11 | Novoneuron, Inc. | Noribogaine in the treatment of pain and drug addiction |
US20130165414A1 (en) * | 2011-12-09 | 2013-06-27 | Demerx, Inc. | Phosphate esters of noribogaine |
US20130165425A1 (en) * | 2011-12-09 | 2013-06-27 | Demerx, Inc. | Sulfate esters of noribogaine |
Family Cites Families (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2817623A (en) | 1956-03-22 | 1957-12-24 | Ciba Pharm Prod Inc | Tabernanthine, ibogaine containing analgesic compositions |
US4626539A (en) | 1984-08-10 | 1986-12-02 | E. I. Dupont De Nemours And Company | Trandermal delivery of opioids |
US4806341A (en) | 1985-02-25 | 1989-02-21 | Rutgers, The State University Of New Jersey | Transdermal absorption dosage unit for narcotic analgesics and antagonists and process for administration |
US5149538A (en) | 1991-06-14 | 1992-09-22 | Warner-Lambert Company | Misuse-resistive transdermal opioid dosage form |
ATE324897T1 (de) * | 1994-07-25 | 2006-06-15 | Nda Int Inc | Verwendung von noribogain derivaten zur behandlung von chemischer abhängigkeit bei säugern |
US5591738A (en) | 1994-10-14 | 1997-01-07 | Nda International, Inc. | Method of treating chemical dependency using β-carboline alkaloids, derivatives and salts thereof |
US5616575A (en) | 1995-12-04 | 1997-04-01 | Regents Of The University Of Minnesota | Bioactive tricyclic ibogaine analogs |
US7220737B1 (en) | 1997-09-04 | 2007-05-22 | Novoneuron, Inc | Noribogaine in the treatment of pain and drug addiction |
US6416793B1 (en) | 2000-07-11 | 2002-07-09 | Bioresponse, L.L.C. | Formulations and use of controlled-release indole alkaloids |
US20030153552A1 (en) | 2002-02-14 | 2003-08-14 | Mash Deborah C. | Method of treating chemical dependency in mammals and a composition therefor |
US6939538B2 (en) * | 2002-04-11 | 2005-09-06 | Biomedical Research Models, Inc. | Extended release analgesic for pain control |
US6933308B2 (en) | 2002-12-20 | 2005-08-23 | Bristol-Myers Squibb Company | Aminoalkyl thiazole derivatives as KCNQ modulators |
US20060229293A1 (en) | 2005-04-06 | 2006-10-12 | Addiction Research Institute, Inc. | Compositions for the treatment of hepatitis C and methods for using compositions for the treatment of hepatitis C |
US8362007B1 (en) | 2010-05-11 | 2013-01-29 | Demerx, Inc. | Substituted noribogaine |
US8765737B1 (en) | 2010-05-11 | 2014-07-01 | Demerx, Inc. | Methods and compositions for preparing and purifying noribogaine |
US9394294B2 (en) | 2010-05-11 | 2016-07-19 | Demerx, Inc. | Methods and compositions for preparing and purifying noribogaine |
US8637648B1 (en) | 2010-06-22 | 2014-01-28 | Demerx, Inc. | Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier |
US8741891B1 (en) | 2010-06-22 | 2014-06-03 | Demerx, Inc. | N-substituted noribogaine prodrugs |
US8802832B2 (en) | 2010-06-22 | 2014-08-12 | Demerx, Inc. | Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier |
US9586954B2 (en) | 2010-06-22 | 2017-03-07 | Demerx, Inc. | N-substituted noribogaine prodrugs |
MX2013000733A (es) | 2010-07-23 | 2013-05-30 | Demerx Inc | Composiciones de noribogaina. |
WO2012024401A2 (en) | 2010-08-17 | 2012-02-23 | University Of Florida Research Foundation, Inc. | Intelligent drug and/or fluid delivery system to optimizing medical treatment or therapy using pharmacodynamic and/or pharmacokinetic data |
US8648198B2 (en) | 2011-01-19 | 2014-02-11 | Cold Spring Harbor Laboratory | Phenylethanolamine-based NMDA receptor antagonists |
EP2481740B1 (en) | 2011-01-26 | 2015-11-04 | DemeRx, Inc. | Methods and compositions for preparing noribogaine from voacangine |
IL296695A (en) | 2011-03-18 | 2022-11-01 | Alkermes Pharma Ireland Ltd | Pharmaceutical preparations containing sorbitan esters |
US8742096B2 (en) | 2011-03-28 | 2014-06-03 | Demerx, Inc. | Methods and compositions for preparing noribogaine from voacangine |
US10702485B2 (en) | 2011-07-09 | 2020-07-07 | Syntrix Biosystems Inc. | Compositions and methods for overcoming resistance to tramadol |
KR102381792B1 (ko) | 2011-09-15 | 2022-04-01 | 데메알엑스, 인크. | 노르이보가인 염 무용매화물 |
CA3122767C (en) | 2011-12-08 | 2023-03-28 | Demerx, Inc. | Stereoselective total synthesis of noribogaine |
WO2013112673A1 (en) | 2012-01-25 | 2013-08-01 | Demerx, Inc. | Synthetic voacangine |
US9150584B2 (en) | 2012-01-25 | 2015-10-06 | Demerx, Inc. | Indole and benzofuran fused isoquinuclidene derivatives and processes for preparing them |
KR20140117380A (ko) | 2012-01-25 | 2014-10-07 | 데메알엑스, 인크. | (1r,4r) 7-옥소-2-아자바이사이클로[2.2.2]옥트-5-엔 및 그의 유도체 |
EP2693223B8 (en) | 2012-08-03 | 2021-09-08 | ABB Schweiz AG | Voltage measurement device with an insulating body |
US8940728B2 (en) | 2012-12-20 | 2015-01-27 | Demerx, Inc. | Substituted noribogaine |
US9045481B2 (en) | 2012-12-20 | 2015-06-02 | Demerx, Inc. | Substituted noribogaine |
WO2014143201A1 (en) | 2013-03-15 | 2014-09-18 | Demerx, Inc. | Method for noribogaine treatment of addiction in patients on methadone |
WO2015126434A1 (en) | 2014-02-18 | 2015-08-27 | Demerx, Inc. | Methods for acute and long-term treatment of drug addiction |
US9561232B2 (en) | 2014-02-18 | 2017-02-07 | Demerx, Inc. | Low dose noribogaine for treating nicotine addiction and preventing relapse of nicotine use |
US9345711B2 (en) | 2014-02-18 | 2016-05-24 | Demerx, Inc. | Methods for acute and long-term treatment of drug addiction |
EA201691656A2 (ru) | 2014-02-18 | 2017-03-31 | Демеркс, Инк. | Терапевтические способы с применением норибогаина и родственных соединений |
US20150246055A1 (en) | 2014-03-03 | 2015-09-03 | Demerx, Inc. | Methods for acute and long-term treatment of opioid and opioid-like drug addiction |
US20150258105A1 (en) | 2014-03-13 | 2015-09-17 | Demerx, Inc. | Methods for acute and long-term treatment of alcohol dependence |
US20150258114A1 (en) | 2014-03-13 | 2015-09-17 | Demerx, Inc. | Methods for acute and long-term treatment of substance abuse using ibogaine |
US20150258111A1 (en) | 2014-03-13 | 2015-09-17 | Demerx, Inc. | Methods and compositions for reducing tolerance to opioid analgesics using ibogaine and derivatives thereof |
US20150258106A1 (en) | 2014-03-13 | 2015-09-17 | Demerx, Inc. | Methods for acute and long-term treatment of substance abuse |
US20150258108A1 (en) | 2014-03-13 | 2015-09-17 | Demerx, Inc. | Methods and compositions for reducing tolerance to opioid analgesics |
US20150258107A1 (en) | 2014-03-13 | 2015-09-17 | Demerx, Inc. | Methods and compositions for treating depression |
US9561233B2 (en) | 2014-03-13 | 2017-02-07 | Demerx, Inc. | Use of ibogaine for the treatment of pain |
US9591978B2 (en) | 2014-03-13 | 2017-03-14 | Demerx, Inc. | Methods and compositions for pre-screening patients for treatment with noribogaine |
EP3164402A1 (en) | 2014-04-21 | 2017-05-10 | DemeRx, Inc. | N-substituted noribogaine prodrugs |
US20150342959A1 (en) | 2014-06-03 | 2015-12-03 | Demerx, Inc. | Methods and compositions for sustained noribogaine treatment |
US9550789B2 (en) | 2014-06-18 | 2017-01-24 | Demerx, Inc. | Halogenated indole and benzofuran derivatives of isoquinuclidene and processes for preparing them |
US9549935B2 (en) | 2014-07-14 | 2017-01-24 | Demerx, Inc. | Methods and compositions for treating migraines using noribogaine |
EP3915639B1 (en) | 2014-11-26 | 2023-06-07 | DemeRx, Inc. | Methods and compostions for potentiating the action of opioid analgesics using iboga alkaloids |
WO2016134019A1 (en) | 2015-02-19 | 2016-08-25 | Demerx, Inc. | Methods for treating disorders associated with undesired activity of neuronal nicotinic acetylcholine receptors |
-
2013
- 2013-11-08 WO PCT/US2013/069235 patent/WO2014143201A1/en active Application Filing
- 2013-11-08 CA CA2942638A patent/CA2942638A1/en active Pending
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2014
- 2014-03-14 TW TW103109815A patent/TW201505634A/zh unknown
- 2014-03-14 US US14/346,655 patent/US20160271139A1/en not_active Abandoned
- 2014-03-14 EA EA201591679A patent/EA201591679A1/ru unknown
- 2014-03-14 KR KR1020157028464A patent/KR20150130461A/ko not_active Application Discontinuation
- 2014-03-14 US US14/214,157 patent/US20140288056A1/en not_active Abandoned
- 2014-03-14 CN CN201480026839.0A patent/CN105307658A/zh active Pending
- 2014-03-14 EP EP14764408.2A patent/EP2968355A4/en not_active Withdrawn
- 2014-03-14 JP JP2016502943A patent/JP2016514679A/ja active Pending
- 2014-03-14 BR BR112015022465A patent/BR112015022465A2/pt not_active IP Right Cessation
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- 2015-10-09 ZA ZA2015/07514A patent/ZA201507514B/en unknown
-
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- 2016-07-19 HK HK16108510.6A patent/HK1220381A1/zh unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999011250A2 (en) * | 1997-09-04 | 1999-03-11 | Novoneuron, Inc. | Noribogaine in the treatment of pain and drug addiction |
US20120083485A1 (en) * | 1997-09-04 | 2012-04-05 | Demerx, Inc. | Noribogaine in the treatment of pain and drug addiction |
US20130165414A1 (en) * | 2011-12-09 | 2013-06-27 | Demerx, Inc. | Phosphate esters of noribogaine |
US20130165425A1 (en) * | 2011-12-09 | 2013-06-27 | Demerx, Inc. | Sulfate esters of noribogaine |
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US9744174B2 (en) | 2013-03-15 | 2017-08-29 | Demerx, Inc. | Method for noribogaine treatment in patients on methadone |
US9561232B2 (en) | 2014-02-18 | 2017-02-07 | Demerx, Inc. | Low dose noribogaine for treating nicotine addiction and preventing relapse of nicotine use |
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US10550087B2 (en) | 2015-11-17 | 2020-02-04 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
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Also Published As
Publication number | Publication date |
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WO2014143201A1 (en) | 2014-09-18 |
BR112015022465A2 (pt) | 2017-07-18 |
JP2016514679A (ja) | 2016-05-23 |
TW201505634A (zh) | 2015-02-16 |
EP2968355A4 (en) | 2016-08-24 |
ZA201507514B (en) | 2018-05-30 |
CA2942511A1 (en) | 2014-09-18 |
CN105307658A (zh) | 2016-02-03 |
KR20150130461A (ko) | 2015-11-23 |
AU2014228986A1 (en) | 2015-10-29 |
US20150045350A1 (en) | 2015-02-12 |
AR095338A1 (es) | 2015-10-07 |
EP2968355A2 (en) | 2016-01-20 |
HK1220381A1 (zh) | 2017-05-05 |
CA2942638A1 (en) | 2014-09-18 |
US9744174B2 (en) | 2017-08-29 |
EA201591679A1 (ru) | 2016-05-31 |
WO2014144508A2 (en) | 2014-09-18 |
US20160271139A1 (en) | 2016-09-22 |
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