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WO2016160542A1 - Compositions et méthodes de traitement de troubles épileptiques - Google Patents

Compositions et méthodes de traitement de troubles épileptiques Download PDF

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Publication number
WO2016160542A1
WO2016160542A1 PCT/US2016/024145 US2016024145W WO2016160542A1 WO 2016160542 A1 WO2016160542 A1 WO 2016160542A1 US 2016024145 W US2016024145 W US 2016024145W WO 2016160542 A1 WO2016160542 A1 WO 2016160542A1
Authority
WO
WIPO (PCT)
Prior art keywords
cbd
composition
naed
lipophilic
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2016/024145
Other languages
English (en)
Inventor
Ramachandra MUKUNDA
Ranga Chelva KRISHNA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
IGC Pharma Inc
Original Assignee
India Globalization Capital Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by India Globalization Capital Inc filed Critical India Globalization Capital Inc
Priority to CA2981285A priority Critical patent/CA2981285A1/fr
Publication of WO2016160542A1 publication Critical patent/WO2016160542A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • 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
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/348—Cannabaceae
    • A61K36/3482—Cannabis
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants

Definitions

  • This invention relates to compositions and methods for treating seizure disorders such as epilepsy in humans and animals (mammals) using a non-barbiturate anti-epileptic drug (NAED), phytocannabinoid cannabidio! (CBD); and a lipophilic fatty acid.
  • NAED non-barbiturate anti-epileptic drug
  • CBD phytocannabinoid cannabidio!
  • the invention provides compositions and methods for treating seizure disorders such as epilepsy in humans and animals using, the combination of a non-barbiturate anti-epileptic drug (NAED), phytocannabinoid cannabidiol (CBD); and a lipophilic fatty acid.
  • NAED non-barbiturate anti-epileptic drug
  • CBD phytocannabinoid cannabidiol
  • NAEDs Non-barbiturate anti-epileptic drugs
  • a preferred group of NAEDs bind to glyprotein SV2A and includes levetriacetam (LEV) and derivatives or analogs thereof with anti- epileptic drug activity such as brivaracetam (BVA) and seletracetam (SEA).
  • LUV levetriacetam
  • BVA brivaracetam
  • SEA seletracetam
  • Preferred drugs such as Leveritacetam and analogs or derivatives thereof bind to glycoprotein SV2A and act by modulating the release of calcium by inhibiting pre-synaptic calcium channels. This results in reducing the release of excitatory neurotransmitters across the synaptic cleft, thereby reducing the excitatory post-synaptic potential discharges,
  • the lipophilic fatty acid component increases the amount of NAED and CBD crossing the blood brain barrier thereby increasing the bioavailability of the NAED and CBD while decreasing or eliminating undesirable side effects.
  • the preferred fatty acid is alpha linolenic acid ("ALA") or a lipophilic mixture high in alpha linolenic acid.
  • hempseed oil extracted from the seed of the hemp plant (Cannabis Sativa).
  • Hempseed oil is essentially free of CBD and tetrahydrocannabinol (THC) and is to be distinguished from hemp oil extracted from the glandular structure of the hemp plant which contains CBD but not THC.
  • CBD can be used in its pure form or as a mixture of compounds that result from extracting cannabis plants.
  • Such mixtures contain CBD, THC or tetrahydrocannabinol (which in turn is a mixture comprising 9-tetrahydrocannabinol (delta-9 THC), 8-tetrahydrocannabinol (delta-8 THC) and 9-THC Acid), Cannabinol (CBN), Cannabichromene (CBC), Cannabigerol (CBG), terpenoids and flavonoids.
  • the preferred CBD mixture is extracted from a Cannabis Indica, the composition of which is known.
  • the use of CBD from Cannabis Indica which can contain up to 50% THC (based on the amount of CBD), is preferred.
  • Preferred mixtures for use in the invention contain at least 50% by weight CBD wherein the weight ratio of CBD to THC is at least 2:1 , preferably at least 3:1 .
  • the preferred CBD mixture is extracted from a Cannabis Indica dominant strain using high pressure and carbon dioxide as a solvent in a 1500-20L subcritical/supercritical C02 system made by Apeks Super Critical Systems, 14381 Biamer Rd., Johnstown, Ohio, 43031 . See http://www.apekssupercritical.com/botanical-extraction-systems/.
  • Apeks Systems use valveless expansion technology with no constrictions or regulating valves to cause clogging in the system between the extraction vessel and the C02 expansion separator. Flow of liquid C02 and dissolved oil travels from the extraction vessel into the separator, and the oil is separated from the C02 in the separator/collection vessel. C02 is recycled during the extraction process and recovered and regenerative heat capture methods are used to increase efficiency.
  • a further process using solvents can be used to remove THC from the mixture leaving either pure CBD or so-called "Organic CBD” containing CBD, CBN, CBC, CBG CBN, terpenoids and fiavonoids.
  • the use of essentially THC-free Organic CBD from Cannabis Indica is more preferred.
  • Another source of CBD essentially free of THC is the CBD mixture obtained by extracting hemp oil from the glandular structure of the hemp plant (Cannabis Sativa). See Leizer et al, J. Nutraceuticals, Functional and Medical Foods, Vol. 2(4) 2000, The Haworth Press, Inc. Hemp oil is to be distinguished from hempseed oil which contains neither CBD nor THC.
  • NAEDs have been used to treat epilepsy and seizure disorders.
  • the addition of CBD creates an additional path to treat epilepsy and or seizures wherein the overall impact of using the combination is higher than those if treaded with each drug individually.
  • a lipophilic fatty acid increases the amount of NAED and CBD crossing the blood brain barrier which in turn increases the bioavailability of the NAED and CBD, lower dosage amounts of NAED can be used to decreasing or eliminating undesirable side effects.
  • Patients being treated for seizure disorders will receive a NAED in an amount to provide from about 14 to about 40 micrograms of said drug per milliliter of blood serum in a patient.
  • the daily dosage of a NAED will be about 4 mg/kg to 60mg/kg of patient weight divided into two doses a day. For adults to neonates, the dosing will be titrated to tolerability and efficacy not to exceed a total adult daily dose of about 6000 mg/day.
  • the daily dosage amount of CBD to be used with a NAED is from about 0.5 to about 1 .0 mg/kg of patient weight.
  • the daily dosage of a fatty acid such as ALA will be about from 1 to 8 grams per day depending on the body mass index of the patient.
  • Candidates to be treated according to the invention will generally present with symptoms or signs associated with seizure disorders such as recurrent loss of consciousness, recurrent seizures and/or a prior diagnoses of medically refractory epilepsy.
  • the invention is especially useful in treating patients who have had recurrent and/or poorly controlled seizures or epilepsy in spite of being treated with one or more know anticonvulsant drugs.
  • the expected response in patients treated according to the invention is a reduction in seizure intensity and/or frequency once a steady state of the active pharmaceutical components is achieved. Up to 14 or more days of treatment may be required before benefits can be achieved.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des compositions et des méthodes de traitement de troubles épileptiques, tels que l'épilepsie chez l'homme et l'animal au moyen de la combinaison d'un médicament anti-épileptique non-barbiturique (NAED), de cannabidiol phytocannabinoïde (CBD); et d'un acide gras lipophile tel qu'un acide alpha-linolénique (ALA)
PCT/US2016/024145 2015-04-01 2016-03-25 Compositions et méthodes de traitement de troubles épileptiques Ceased WO2016160542A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2981285A CA2981285A1 (fr) 2015-04-01 2016-03-25 Compositions et methodes de traitement de troubles epileptiques

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562141438P 2015-04-01 2015-04-01
US62/141,438 2015-04-01

Publications (1)

Publication Number Publication Date
WO2016160542A1 true WO2016160542A1 (fr) 2016-10-06

Family

ID=57007479

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2016/024145 Ceased WO2016160542A1 (fr) 2015-04-01 2016-03-25 Compositions et méthodes de traitement de troubles épileptiques

Country Status (2)

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CA (1) CA2981285A1 (fr)
WO (1) WO2016160542A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017218629A1 (fr) * 2016-06-15 2017-12-21 India Globalization Capital, Inc. Méthode et composition pour traiter des troubles epileptiques
US10117891B2 (en) 2014-09-16 2018-11-06 India Globalization Capital, Inc. Cannabinoid composition for treating pain
US10596159B2 (en) 2015-08-12 2020-03-24 India Globalization Capital, Inc. Method and composition for treating cachexia and eating disorders
US10751300B2 (en) 2015-01-25 2020-08-25 India Globalization Capital, Inc. Composition and method for treating seizure disorders
US11040932B2 (en) 2018-10-10 2021-06-22 Treehouse Biotech, Inc. Synthesis of cannabigerol
US11084770B2 (en) 2016-12-07 2021-08-10 Treehouse Biotech, Inc. Cannabis extracts
US11202771B2 (en) 2018-01-31 2021-12-21 Treehouse Biotech, Inc. Hemp powder
GB2601755A (en) * 2020-12-08 2022-06-15 Gw Res Ltd Use of cannabidiol in the treatment of seizures associated with epilepsy syndromes
US12465589B2 (en) 2018-03-30 2025-11-11 Igc Pharma Ip, Llc Method and composition for treating CNS disorders

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070293440A1 (en) * 2006-05-19 2007-12-20 Smith-Swintosky Virginia L Co-therapy for the treatment of epilepsy and related disorders
US20080254017A1 (en) * 2006-06-19 2008-10-16 Bodybio, Inc. Methods and compositions for treating symptomes of diseases related to imbalance of essential fatty acids
WO2010048423A1 (fr) * 2008-10-24 2010-04-29 Ark Diagnostics, Inc. Immunodosages du lévétiracétam
WO2011063164A2 (fr) * 2009-11-18 2011-05-26 Steady Sleep Rx Co., Inc. Médicaments de cannabinoïde à libération prolongée
US20120165402A1 (en) * 2009-07-03 2012-06-28 Otsuka Pharmaceutical Co., Limited Use of one or a combination of phyto-cannabinoids in the treatment of epilepsy
US20150086494A1 (en) * 2013-09-26 2015-03-26 Ronald D. Sekura Topical treatments incorporating cannabis sp. derived botanical drug product
US20150265637A1 (en) * 2014-03-21 2015-09-24 Bodybio Inc. Methods and compositions for treating symptoms of diseases related to imbalance of essential fatty acids
US20150359756A1 (en) * 2014-06-17 2015-12-17 Gw Pharma Limited Use of cannabinoids in the treatment of epilepsy

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070293440A1 (en) * 2006-05-19 2007-12-20 Smith-Swintosky Virginia L Co-therapy for the treatment of epilepsy and related disorders
US20080254017A1 (en) * 2006-06-19 2008-10-16 Bodybio, Inc. Methods and compositions for treating symptomes of diseases related to imbalance of essential fatty acids
WO2010048423A1 (fr) * 2008-10-24 2010-04-29 Ark Diagnostics, Inc. Immunodosages du lévétiracétam
US20120165402A1 (en) * 2009-07-03 2012-06-28 Otsuka Pharmaceutical Co., Limited Use of one or a combination of phyto-cannabinoids in the treatment of epilepsy
WO2011063164A2 (fr) * 2009-11-18 2011-05-26 Steady Sleep Rx Co., Inc. Médicaments de cannabinoïde à libération prolongée
US20150086494A1 (en) * 2013-09-26 2015-03-26 Ronald D. Sekura Topical treatments incorporating cannabis sp. derived botanical drug product
US20150265637A1 (en) * 2014-03-21 2015-09-24 Bodybio Inc. Methods and compositions for treating symptoms of diseases related to imbalance of essential fatty acids
US20150359756A1 (en) * 2014-06-17 2015-12-17 Gw Pharma Limited Use of cannabinoids in the treatment of epilepsy

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MCMAHAN, K: "Hemp Seed Oil - Why Should We Use It? Monterey Bay Hollistic Alliance.", MONTEREY BAY HOLISTIC ALLIANCE, 23 August 2014 (2014-08-23), pages 1 - 2 , 4, XP055318666, Retrieved from the Internet <URL:https://montereybayholistic.wordpress.com/2014/08123/hemp-seed-oil> *
SCHLANGER, S ET AL.: "Diet Enriched with Omega-3 Fatty Acids Alleviates Convulsion Symptoms in Epilepsy Patients.", EPILEPSIA, vol. 43, no. 1, 2002, pages 103 - 104, XP055318664 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10117891B2 (en) 2014-09-16 2018-11-06 India Globalization Capital, Inc. Cannabinoid composition for treating pain
US10933082B2 (en) 2014-09-16 2021-03-02 India Globalization Capital, Inc. Cannabinoid composition and method for treating pain
US10751300B2 (en) 2015-01-25 2020-08-25 India Globalization Capital, Inc. Composition and method for treating seizure disorders
US10596159B2 (en) 2015-08-12 2020-03-24 India Globalization Capital, Inc. Method and composition for treating cachexia and eating disorders
WO2017218629A1 (fr) * 2016-06-15 2017-12-21 India Globalization Capital, Inc. Méthode et composition pour traiter des troubles epileptiques
US11351152B2 (en) 2016-06-15 2022-06-07 India Globalization Capital, Inc. Method and composition for treating seizure disorders
US11084770B2 (en) 2016-12-07 2021-08-10 Treehouse Biotech, Inc. Cannabis extracts
US11202771B2 (en) 2018-01-31 2021-12-21 Treehouse Biotech, Inc. Hemp powder
US12465589B2 (en) 2018-03-30 2025-11-11 Igc Pharma Ip, Llc Method and composition for treating CNS disorders
US11040932B2 (en) 2018-10-10 2021-06-22 Treehouse Biotech, Inc. Synthesis of cannabigerol
GB2601755A (en) * 2020-12-08 2022-06-15 Gw Res Ltd Use of cannabidiol in the treatment of seizures associated with epilepsy syndromes
WO2022123236A1 (fr) 2020-12-08 2022-06-16 GW Research Limited Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques chez des patients prenant du brivaracétam

Also Published As

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CA2981285A1 (fr) 2016-10-06

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