US20210023053A1 - Method and composition for treating cns disorders - Google Patents
Method and composition for treating cns disorders Download PDFInfo
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- US20210023053A1 US20210023053A1 US17/042,333 US201917042333A US2021023053A1 US 20210023053 A1 US20210023053 A1 US 20210023053A1 US 201917042333 A US201917042333 A US 201917042333A US 2021023053 A1 US2021023053 A1 US 2021023053A1
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Definitions
- This invention relates to compositions and methods for treating a range of Central Nervous System (CNS) disorders and diseases such as amyloidosis, protein folding diseases, tauopathy, and specifically for example Alzheimer's Disease (AD) and Parkinson's Disease (PD), among others, in humans and animals using a formulation comprising of a combination of a cannabis compound, or compounds, melatonin, and turmeric.
- CNS Central Nervous System
- AD Alzheimer's Disease
- PD Parkinson's Disease
- AD Alzheimer's Disease
- the estimated economic burden in 2017 was over $200 billion for AD related services.
- an estimated 11 to 16 million Americans will be living with the disease.
- Several clinical trials had indicated that combination therapy has greater efficacy over monotherapy.
- AD poses an enormous burden on caregivers, as well as the health care system. About 30 percent of the cost of treating AD is the cost of care givers. Currently, there is no cure for AD. (Saxena, Bioenergetics breakdown in Alzheimer's disease: Targets for new therapies. Int J Physiol Pathophysiol Pharmacol. 2011; 3: 133-139; Götz, et al., Modes of A ⁇ toxicity in Alzheimer's disease. Cell Mol Life Sci. 2011; 68: 3359-3375).
- AD pathology can be grouped into two forms, familial inherited AD, and sporadic AD.
- familial inherited AD The pathologies of early onset familial AD and late onset sporadic AD are indistinguishable.
- the two forms of AD are characterized by extracellular amyloid- ⁇ (A ⁇ ) peptide plaque deposits, and by tau-containing neurofibrillary tangles (Götz, et al., Modes of A ⁇ toxicity in Alzheimer's disease. Cell Mol Life Sci. 2011; 68: 3359-3375).
- the misfolded structure of the A ⁇ peptides makes a characteristic tendency for their aggregation around damaged or dead neurons and within cerebral vasculature in the brain. It establishes by memory loss followed by advanced AD. (Chili & Dobson, Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem. 2006; 75: 333-366).
- a ⁇ 1-40 (A ⁇ 40) and A ⁇ 1-42 (A ⁇ 42) aggregates are the constituents of the insoluble plaques that are characteristic of AD. This disease is also accompanied with neuro-inflammation, excitotoxicity, and oxidative stress. (Campbell & Gowran, Alzheimer's disease; taking the edge off with cannabinoids? Br J Pharmacol. 2007; 152: 655-662; Rich, et al., Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology. 1995; 45: 51-55).
- a ⁇ peptides are neurotoxic, as they are reported intermediaries of apoptosis, inflammation, and oxidative stress.
- some of the initial proposed therapeutic strategies involve the prevention or elimination of these A ⁇ peptides and following formation of toxic oligomers.
- a ⁇ peptides are produced via the amyloidogenic pathway of amyloid precursor protein (APP) proteolysis, which involves the combined effort of ⁇ - and ⁇ -secretases.
- APP amyloid precursor protein
- ⁇ -secretase BACE cleaves APP, creating an A ⁇ -containing carboxyl-terminal fragment known as ⁇ -C-terminal fragment ( ⁇ -CTF), or C99 and an amino-terminal, soluble APP- ⁇ (sAPP- ⁇ ) fragment, which is released extracellularly.
- ⁇ -CTF ⁇ -C-terminal fragment
- sAPP- ⁇ amino-terminal, soluble APP- ⁇
- a ⁇ is known to surge: cellular Ca 2+ , mitochondrial progression of the disease condition.
- GSK-3 glycogen synthase kinase 3
- GSK-3 ⁇ induces hyperphosphorylation of tau.
- Lovestone, et al. Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells. Curr Biol. 1994; 4: 1077-1086;
- GSK3alpha exhibits beta-catenin and tau directed kinase activities that are modulated by Wnt In. Eur J Neurosci. 2006; 24: 3387-3392).
- GSK-3 ⁇ plays a role in regulating amyloid- ⁇ protein precursor (A ⁇ PPP) cleavage, resulting in increased A ⁇ production
- a ⁇ PPP amyloid- ⁇ protein precursor
- CB1 cannabinoid 1
- CB2 cannabinoid 2
- CB2 receptor expression is more limited and has been anatomically found in neurons within the brainstem (Van Sickle, et al., Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 2005; 310: 329-332), cerebellum (Ashton, et al., Expression of the cannabinoid CB2 receptor in the rat cerebellum: An immunohistochemical study. Neurosci Lett. 2006; 396: 113-116), and microglia (Nunez, et al., Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: An immunohistochemical study. Synapse. 2004; 53: 208-213).
- the endocannabinoid metabolizing enzyme, fatty acid amide hydrolase is upregulated in the plaque in AD brains (Benito, et al., Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains. J Neurosci. 2003; 23: 11136-11141). There is also an increase in levels of anandamide metabolites, such as arachidonic acid, in the vicinity of the plaque (Benito, et al., Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains. J Neurosci. 2003; 23: 11136-11141). These findings may indirectly suggest that the increase in CB1 and CB2 receptors may be to counterbalance the lack of activity with their ligands due to increased metabolic activity of fatty acid amide hydrolase.
- Endocannabinoid receptors CB1 and CB2 have been confirmed to interact with the endocannabinoid molecules: 2-arachidonoyl glycerol and anandamide. However, it has also been stated that CB1 and CB2 also react interact with ⁇ 9 -tetrahydrocannabinol (THC) an ingredient from the Cannabis sativa plant (Piomelli, The molecular logic of endocannabinoid signaling. Nat Rev Neurosci. 2003; 4: 873-884).
- THC ⁇ 9 -tetrahydrocannabinol
- Dronabinol an oil-based solution of ⁇ 9-THC, improves the disturbed behavior and stimulates appetite in AD patients (Volicer, et al., Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 1997; 12: 913-919).
- THC possesses antioxidant, anti-inflammatory and neuroprotective properties (Jackson, et al., Cannabinoids and neuroprotection in CNS inflammatory disease. J Neurol Sci. 2005; 233: 21-25).
- THC competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE induced amyloid beta-peptide (Abeta) aggregation.
- the concentration of THC used was 50 micromolar at the cellular level (Eubanks L m, Rogers C J, Beuscher A E 4 th , Koob G F, Olson A J, Dickerson T J, Janda K D. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Mol Pharm. 2006 November-December 3(6): 773-7).
- cannabis ingestion causes acute psychotic reactions, anxiety, impaired neuropsychological performance, impaired memory, executive functioning disorder, mitochondrial dysfunction, neuron apoptosis, and severe side effects such as feeling high, anxiety, depression, among others.
- THC Trigger P D 1, Zois V, McKeown D A, Lee T D, Holt D W, Powell J F, Kapur S, Murray R M. Morrison P D 1, Zois V, McKeown D A, Lee T D, Holt D W, Powell J F, Kapur S, Murray R M. Epub 2009 Apr. 1).
- Melatonin N-acetyl-5-methoxytryptamine
- a tryptophan metabolite a tryptophan metabolite and synthesized mainly in the pineal gland and plays an important role in regulation of many physiological functions. This include regulating circadian rhythms, clearing free radicals, improving immunity and generally inhibiting the oxidation of biomolecules.
- Studies have shown decreased levels of melatonin in serum and cerebrospinal fluid (CSF) of AD patients.
- CSF cerebrospinal fluid
- Melatonin supplementation poses low toxicity and may be one of the possible strategies for symptomatic treatment.
- Karasek M. Reiter R. J., Cardinali D. P., Pawlikowski M. Future of melatonin as a therapeutic agent. Neuro Endocrinol. Lett. 2002; 23:118-121.; 23. Singer C., Tractenberg R. E., Kaye J., Schafer K., Gamst A., Grundman M., Thomas R., Thal L. J. Alzheimer's disease cooperative, SA multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. Sleep. 2003; 26:893-901.
- Curcumin is a polyphenolic natural compound derived from the root Curcuma longa or turmeric.
- Curcumin possess a properties of anti-carcinogenic, anti-inflammatory and anti-oxidative properties (Goel A, Kunnumakkara A B, Aggarwal B B. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008 Feb. 15; 75(4):787-809).
- Curcumin has been reported to binds to A ⁇ protein and prevents the aggregation of A ⁇ in-vitro studies (Maiti P and Dunbar G L. Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases Int J Mol Sci. 2018 May 31; 19(6)).
- curcumin has possess an anti-amyloidogenic property by inhibiting formation of amyloid beta oligomers and fibrils, binds plaques in animal models of AD (Koronyo-Hamaoui M, Koronyo Y, Ljubimov A V, Miller C A, Ko M K, Black K L, Schwartz M, Farkas D L. Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage. 2011 January; 54 Suppl 1( ):S204-17; Maiti P, Hall T C, Paladugu L, Kolli N, Learman C, Rossignol J, Dunbar G L.
- Curcumin has been shown to binds to neurofibrillary tangles in AD brain tissue (Mohorko N, Repovs G, Popovi ⁇ M, Kovacs G C, Bresjanac M. Curcumin labeling of neuronal fibrillar tau inclusions in human brain samples. J Neuropathol Exp Neurol. 2010 April; 69(4):405-14; Mutsuga M, Chambers J K, Uchida K, Tei M, Makibuchi T, Mizorogi T, Takashima A, Nakayama H. of curcumin to senile plaques and cerebral amyloid angiopathy in the aged brain of various animals and to neurofibrillary tangles in Alzheimer's brain. J Vet Med Sci. 2012 January; 74(1):51-7)
- curcumin can decrease the level of A ⁇ -induced increases in reactive oxygen species, curcumin can also enhance decreases in mitochondrial membrane potential, and activates or inhibits caspase, a protein that is intimately involved in the regulation of apoptosis activation, as well as defend human neurons from oligomeric A ⁇ induced toxicity (Mishra, et al., 2011) It is also reported that cannabinoids are active against inflammation (Mishra S, Mishra M, Seth P, Sharma S K. Tetrahydrocurcumin confers protection against amyloid ⁇ -induced toxicity. Neuroreport. 2011 Jan. 5; 22(1):23-7).
- AD Alzheimer's disease
- Several hypotheses have been put forward and investigated in AD pathology including beta amyloid pathology, inflammation, neurodegeneration and oxidative stress, hyperphosphorylation of tau, mitochondrial cascade, prion, and so on. Targeting one hypothesis has failed to provide protection against AD.
- monotherapy has limited efficacy as compared to polytherapy.
- Polytherapy involves two or more active ingredients which target key signaling pathways.
- the invention provides methods and compositions for treating central nervous system (CNS) disorders in humans and animals which involves treating a patient with a CNS disorder such as Alzheimer's disease or Parkinson's disease with a composition including (i) tetrahydrocannabinol (THC) in a dose amount per 70 kg patient of from about 14 ⁇ g to about 10.0 mg, preferably in an ultra-low dose per 70 kg patient of from about 14 ⁇ g to about 2.0 mg; (ii) melatonin in a dose amount per 70 kg patient of from about 1.4 mg to about 20.0 mg; and (iii) curcumin in a dose amount per 70 kg patient of about 0.35 mg to about 500 mg.
- CNS central nervous system
- CBD cannabidiol
- a composition for treating central nervous system (CNS) disorders in humans and animals includes: (i) tetrahydrocannabinol (THC) in an ultra-low dose amount per 70 kg patient of from about 14 ⁇ g to about 2.0 mg; and (ii) cannabidiol (CBD) in a dose amount per 70 kg patient of from about 14 ⁇ tilde over ( ) ⁇ g mg to about 200 mg.
- THC tetrahydrocannabinol
- CBD cannabidiol
- compositions for treating central nervous system (CNS) disorders in humans and animals includes: (i) cannabidiol (CBD) in a dose amount per 70 kg patient of from about 14 ⁇ tilde over ( ) ⁇ g mg to about 200 mg; and (ii) melatonin in a dose amount per 70 kg patient of from about 1.4 mg to about 20.0 mg.
- Additional compositions comprise THC or CBD each with curcumin in the dose amounts disclosed herein without melatonin.
- compositions and methods for treating central nervous system (CNS) disorders and diseases such as amyloidosis, protein folding diseases, tauopathy, and specifically for example Alzheimer's Disease and Parkinson's Disease among others, in humans and in veterinary animals are effective to reduce A ⁇ expression; reduce A ⁇ aggregation; maintain APP expression; enhance mitochondrial functioning; decrease phosphorylation of GSK3 ⁇ protein; decrease the expression of GSK3 ⁇ protein; decrease phosphorylation of tau protein; reduce anxiety; reduce agitation; reduce sleep disorder, and/or reduce care giver distress, without severe side effects associated with high doses of THC, CBD melatonin and/or high doses of curcumin.
- CNS central nervous system
- compositions of the invention are administered orally in a liquid carrier which includes a non-ionic emulsifier in an amount sufficient to maintain stability and solubility of the formulation.
- Suitable non-ionic emulsifiers include lecithin from soy or sunflower, polysorbate 80) and vitamin E TPGS (d- ⁇ -tocopheryl polyethylene glycol 1000 succinate).
- Natural anti-fungal agents such as rutin are also preferred to maintain stability.
- the invention provides a method and compositions for treating central nervous system (CNS) disorders in humans and animals which involves treating a patient with a CNS disorder such as Alzheimer's or Parkinson's with a composition including (i) tetrahydrocannabinol (THC) in an ultra-low dose amount per 70 kg patient of from about 14 ⁇ g to about 2.0 mg without severe psychological impairments and side effects associated with higher doses of THC; (ii) melatonin in a dose amount per 70 kg patient of from about 14 ⁇ g to about 77.0 mg; and (iii) curcumin in a dose amount per 70 kg patient of about 7 mg to about 100 mg.
- a CNS disorder such as Alzheimer's or Parkinson's with a composition
- THC tetrahydrocannabinol
- melatonin in a dose amount per 70 kg patient of from about 14 ⁇ g to about 77.0 mg
- curcumin in a dose amount per 70 kg patient of about 7 mg to about 100 mg.
- CBD cannabidiol in a dose amount per 70 kg patient of from about 14 ⁇ g to about 100 mg is administered to a patient along with THC, melatonin and curcumin.
- composition of the invention is administered orally in a liquid carrier which includes a non-ionic emulsifier in an amount sufficient to maintain stability and solubility of the composition components.
- Suitable non-ionic emulsifiers include lecithin from soy or sunflower, Tween 80 (polysorbate 80), and vitamin E TPGS (d- ⁇ -tocopheryl polyethylene glycol 1000 succinate).
- This invention provides a method for treating certain CNS disorders and symptoms, and diseases classified broadly as amyloidosis, protein folding diseases, tauopathy, and specifically for example Alzheimer's Disease (AD), among others, in humans and veterinary animals which includes administering to a subject in need thereof a composition including (i) an effective amount of melatonin, (ii) an effective amount of curcumin and (iii) a cannabis compound containing THC in a micro dosage amount that is sufficient to provide efficacy while not inducing side effects commonly associated with cannabis, melatonin or curcumin.
- a composition including (i) an effective amount of melatonin, (ii) an effective amount of curcumin and (iii) a cannabis compound containing THC in a micro dosage amount that is sufficient to provide efficacy while not inducing side effects commonly associated with cannabis, melatonin or curcumin.
- compositions of the invention for treating Alzheimer's and related CNS diseases in humans and veterinary animals include: (i) an effective amount of melatonin, (ii) an effective amount of curcumin and (iii) a cannabis compound containing THC in an amount that is sufficient to provide efficacy while not inducing side effects commonly associated with cannabis, melatonin or curcumin.
- the composition is administered orally in a suitable carrier.
- compositions of the invention for treating Alzheimer's and related CNS diseases in humans and veterinary animals include: (i) an effective amount of melatonin, (ii) an effective amount of curcumin (iii) a cannabis compound containing THC, and (iv) a cannabis compound containing CBD, in an amount that is sufficient to provide efficacy while not inducing side effects commonly associated with cannabis, melatonin or curcumin.
- the composition is administered orally in a suitable carrier.
- compositions of the invention for treating Alzheimer's and related CNS diseases in humans and veterinary animals include: (i) an effective amount of melatonin, (ii) an effective amount of curcumin and (iii) a cannabis compound containing CBD, in an amount that is sufficient to provide efficacy while not inducing side effects commonly associated with cannabis, melatonin or curcumin.
- the composition is administered orally in a suitable carrier.
- compositions of the invention for treating Alzheimer's and related CNS diseases in humans and veterinary animals include: (i) an effective amount of melatonin, and (ii) an effective amount of curcumin in an amount that is sufficient to provide efficacy while not inducing side effects commonly associated with higher doses of melatonin and curcumin.
- the composition is administered orally in a suitable carrier.
- Cannabis compounds can be synthetic (chemically synthesized) or extracted from cannabis plants such as sativa, indica, hemp or hybrid strains of sativa and indica.
- a preferred source of tetrahydrocannabinol (THC) is so-called organic THC, which is extracted from cannabis and contains minor amounts of other cannabinoids such as CBD.
- THC tetrahydrocannabinol
- full spectrum cannabis oil, full spectrum hemp oil and full spectrum marijuana are extracted from hemp
- This invention provides a method for treating certain disorders, symptoms, and diseases classified broadly as amyloidosis, protein folding diseases, tauopathy, and specifically for example Alzheimer's Disease (AD), among others, in mammals by administering to a subject in need thereof a composition including: (i) an effective amount of melatonin, (ii) an effective amount of curcumin and (iii) a cannabis compound in an amount that is sufficient to provide efficacy while not inducing side effects commonly associated with cannabis.
- a composition including: (i) an effective amount of melatonin, (ii) an effective amount of curcumin and (iii) a cannabis compound in an amount that is sufficient to provide efficacy while not inducing side effects commonly associated with cannabis.
- a preferred 1 ml oral suspension for a 70-kg human is administered once a day, twice a day, thrice a day or four times a day depending on the severity of the symptoms and comprises up to 2.5 mg of THC, up to 1.5 mg of melatonin, and up to 0.5 mg curcumin.
- a preferred 1 ml oral suspension for a 70-kg human is administered once a day, twice a day, thrice a day or four times a day depending on the severity of the symptoms and comprises up to 2.5 mg of THC, up to 1.5 mg of melatonin and up to 200 mg CBD.
- THC is administered with the other inventive components in dose amounts as follows:
- Per kg of patient weight from about 0.2 ⁇ g to about 0.14 mg
- Per 70 kg patient from about 14 ⁇ g to about 10 mg
- Preferred per kg of patient weight from about 0.2 ⁇ g to about 0.03 mg.
- Preferred per 70 kg patient from about 14 ⁇ g to about 2.0 mg.
- Per kg of patient weight from about 0.02 mg to about 0.3 mg.
- Per 70 kg patient from about 1.4 mg to about 20 mg.
- Preferred per kg of patient weight from about 0.01 mg to about 0.15 mg.
- Preferred per 70 kg patient from about 0.7 mg to about 10 mg.
- CBD is administered with the other inventive components in dose amounts as follows:
- Per kg of patient weight from about 0.2 ⁇ g to about 3.0 mg.
- Per 70 kg patient from about 14 ⁇ g to about 200 mg.
- Preferred per kg of patient weight from about 0.03 mg to about 3.0 mg.
- Preferred per 70 kg patient from about 2.0 mg to about 200 mg.
- Also preferred per kg of patient weight from about 0.02 ⁇ g to about 0.036 mg.
- Also preferred per 70 kg patient from about 14 ⁇ g to about 2.5 mg.
- Curcumin is administered with the other inventive components in dose amounts as follows:
- Per kg of patient weight from about 0.005 mg to about 7.0 mg.
- Per 70 kg patient from about 0.35 mg to about 500 mg.
- Preferred per kg of patient weight from about 0.01 mg to about 3.5 mg.
- Preferred per 70 kg patient from about 0.7 mg to about 250 mg.
- the preferred oral dose is in the range of 1 ml of an oral suspension, for a 70-Kg human, once a day, twice a day, thrice a day or four times a day depending on the severity of the symptoms comprising of a cannabis compound with up to 2.5 mg of THC, but less than the amount which causes psychological impairments and side effects associated with higher doses of THC, up to 1.5 mg of melatonin, and up to 0.5 mg curcumin.
- a preferred 1 ml oral suspension, for a 70-Kg human, once a day, twice a day, thrice a day or four times a day depending on the severity of the symptoms comprises THC in the range from about 14 ⁇ g to about 10 mg, melatonin in the range from about 0.02 mg to about 0.3 mg, curcumin in the range from about 0.35 mg to about 500 mg and CBD in the range from about 14 ⁇ g to about 200 mg, but with THC, less than the amount which causes psychological impairments and side effects associated with higher doses of THC, melatonin, curcumin and CBD.
- the preferred oral dose is in the range of 1 ml of an oral suspension, for a 70-Kg human, once a day, twice a day, thrice a day or four times a day depending on the severity of the symptoms comprising of THC in the range shown in Table 1, CBD in the range shown in Table 1 but with THC, less than the amount which causes psychological impairments and side effects associated with higher doses of THC, and CBD.
- melatonin, curcumin, and cannabis is believed to work along several pathways in controlling various end points and the hallmarks of Alzheimer's Disease as well as diseases classified broadly as amyloidosis, protein folding diseases, and/or tauopathy. It is believed that the dosing in the formulation does not cause any of the side effects commonly associated with cannabis, melatonin or turmeric.
- the dosing of cannabis prescribed in the formulation herein is below the 5 mg levels prescribed by the FDA for Dronabinol and well below the 50 micromolar level used in the Eubanks 2006 study (Eubanks L m, Rogers C J, Beuscher A E 4 th , Koob G F, Olson A J, Dickerson T J, Janda K D. A molecular link between the active component of marijuana and Alzheimer's disease pathology, Mol Pharm. 2006 November-December 3(6): 773-7). Using time-release formulations for any of the components, can further enhance bioavailability.
- the combination of lower dose of melatonin, curcumin, cannabis compounds unexpectedly leads to (i) a reduction of side effects, such as transient, acute psychotic reactions, anxiety, impaired neuropsychological performance, memory impairments, executive functioning disorder, mitochondrial dysfunction, and (ii) other side effects like headache, dizziness, nausea, drowsiness, depression, anxiety, tremor, camps, irritability, confusion, hypotension, rash, yellow stool, among others, otherwise present with higher doses of melatonin, curcumin and cannabis compounds, or when each of melatonin, curcumin and or cannabis is used alone.
- side effects such as transient, acute psychotic reactions, anxiety, impaired neuropsychological performance, memory impairments, executive functioning disorder, mitochondrial dysfunction
- other side effects like headache, dizziness, nausea, drowsiness, depression, anxiety, tremor, camps, irritability, confusion, hypotension, rash, yellow stool, among others, otherwise present with higher doses of melatonin, curcumin and cannabis
- Suitable pharmaceutically acceptable cannabis compounds include cannabis extract, which includes phytocannabinoids such as tetrahydrocannabinol “THC” (9-Tetrahydrocannabinol (delta-9 THC), 8-tetrahydrocannabinol (Delta-8 THC) and 9-THC Acid), cannabidiol (CBD), other phytocannabinoids such as cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG) among others, terpenoids and flavonoids.
- Standardized cannabis extract (SCE) consists of mostly THC, CBD and CBN.
- Organic THC consists of solvent extracted THC from cannabis with lesser or trace amounts of other cannabinoids and terpenoids. Synthetic or pure THC is free of CBD and other compounds is a preferred cannabis compound.
- THC and CBD can be extracted from a cannabis indica dominant strain using, for example, high pressure and carbon dioxide or ethanol as a solvent in a 1500-20 L subcritical/supercritical CO2 system made by Apeks Super Critical Systems, 14381 Blamer Rd., Johnstown, Ohio, 43031.
- the cannabis plant in its natural form contains THCA.
- the resin called shatter is extracted from the cannabis flower using any of a variety of methods including CO2 extraction as described herein.
- Shatter is produced using a three-step process: kief separation, extraction, and winterization.
- Cannabis flower is introduced into a steel tumbler over a mesh sieve with dry ice.
- Flower is frozen and broken while tumbled with dry ice chunks allowing fine THCA bearing particles (kief) to fall through the sieve.
- THCA is then extracted from kief using supercritical extraction.
- a solvent such as CO2 and kief are introduced into a chamber. That sealed chamber is pressurized to approximately 2800 psi and heated to 53 degrees C.
- Supercritical CO2 is then allowed to flow out of the pressurized chamber into a vile at room temperature and pressure (while more CO2 is introduced to maintain pressure in the chamber). As the CO2 vaporizes in the collector vile, it deposits shatter.
- the CO2 oil is dissolved in ethanol (3 ⁇ 4 ounce shatter dissolved in 400 ml ethanol). This mixture is then poured through a filter (such as a coffee filter) frozen for 48 hours, then warmed, filtered again, and then spun with heat to evaporate off the ethanol.
- the remaining resin contains a combination of THCA, THC and other cannabis compounds. The resin is heated for 60 minutes at 240° F.
- An HFLC test is run to determine the amount of THC and THCA present in the resin.
- 45 mg of the resin containing 99% THC (as determined by HPLC) is dissolved in 1 ml of ethyl alcohol.
- the dissolved resin is transferred and mixed with the solution of curcumin-honey-ascorbic acid-melatonin solution.
- the solution is filtered and sterilized using a 0.2-micron FES Nalgene filtration unit under constant pressure in a sterilized environment.
- the filtered 30 ml solution is transferred to and stored in an amber glass bottle that is autoclaved in an aseptic condition.
- transitional term “comprising” is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, un-recited elements or method steps.
- the transitional phrase “consisting essentially of” is intended to embrace only specified components or ingredients or steps and those that do not materially affect the basic and novel characteristics of the claimed invention. In other words, elements or ingredients which materially affect the essence of the invention are excluded by the phrase consisting essentially of.
- One dose of the liquid formulation is measured at 1 ml, comprising of 70% of water, 20% honey and 10% ethyl alcohol, 1.5 mg THC, 1.5 mg melatonin, 1 mg turmeric, 1 mg ascorbic acid as an anti-oxidative agent and 0.1% sodium benzoate as an anti-fungal agent.
- Food grade, solvents and carriers include among others DMSO and polyethylene glycol.
- Food grade anti-oxidative agents include among others carotenoids and tocopherols.
- Food grade agents with anti-fungal properties include flavonoids among others.
- a further embodiments of Example 1 comprises of replacing turmeric with any of, or a combination of curcumin, nano-curcumin, and turmeric.
- An Alzheimer's patient exhibiting slight anxiety and/or agitation is given 1 ml of the formulation set out in Example 1, in the morning on an empty stomach, prior to breakfast, and 1 ml prior to dinner in the evening. The patient exhibits reduced anxiety and agitation.
- An advanced stage Alzheimer's patient exhibiting moderate to severe anxiety, sleep disorder and/or agitation is given 1 ml of the formulation three to four times a day, morning afternoon and evening, prior to meals.
- Example 1 The formulation in Example 1, is supplemented with 50 mg of Cannabidiol (CBD) dissolved in 1 ml of ethyl alcohol and added to the overall solution of Example 1.
- CBD Cannabidiol
- a moderate stage Parkinson's patient exhibiting levodopa induced dyskinesia, stammering, anxiety, gait, sleep disorder and/or agitation is given 1 ml of the formulation of Example 4, three to four times a day, morning afternoon and evening, prior to meals. The patient exhibits reduced symptoms.
- CBD Cannabidiol
- Example 4 The formulation of Example 4, without the THC component, is administered three times a day prior to meals to a moderate stage Parkinson's patient exhibiting levodopa induced dyskinesia, stammering, anxiety, gait, sleep disorder and/or agitation. The patient exhibits reduced symptoms.
- Example 4 The formulation and dosing in Example 4, is administered to a patient with moderate incontinence, two times a day, morning and evening, prior to meals. The patient exhibits reduced symptoms.
- Example 1 The formulation and dosing in Example 1, is administered, once a day, twice a day, to an individual exhibiting early signs of Alzheimer's disease, including plaques and tangles, as determined by a PET scan, as a prophylactic. The patient exhibits a slowdown in the buildup of plaques and tangles.
- Example 1 The formulation and dosing in Example 1, without the THC component is administered to a patient with mild symptoms of Alzheimer's disease two times a day, morning and evening, prior to meals as a prophylactic. The patient exhibits reduced symptoms.
- Nonionic emulsifier is preferably added to increase the solubility of THC and other active ingredients in the solution.
- Nonionic emulsifiers include lecithin from soy and sunflower, polysorbate 80 and vitamin E TPGS (d- ⁇ -tocopheryl polyethylene glycol 1000 succinate).
- Polysorbate 80 is a nonionic surfactant and emulsifier derived from polyethoxylated sorbitan and oleic acid.
- Preferred emulsifiers are from 1-3% polysorbate-80, 2-5% vitamin E TPGS and a combination of 1% poltsorbate-80 and 1-2.5% Vitamin TPGS.
- Example 1 Sodium benzoate in Example 1 serves as an antifungal agent and natural antifungal agents such as Rutin are also suitable. Natural antifungal agents with broad spectrum antifungal properties are more potent and less toxic compared to sodium benzoate.
- Rutin also called rutoside, quercetin-3-O-rutinoside and sophorin, is a glycoside combining the flavonol quercetin and the disaccharide rutinose. It is a citrus flavonoid found in a wide variety of plants including citrus fruit.
- a preferred formulation in a 30 ml solution which maintains THC and the other components in a stable solution is as follows:
- CBD 0.25% to 5%
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US11351152B2 (en) | 2016-06-15 | 2022-06-07 | India Globalization Capital, Inc. | Method and composition for treating seizure disorders |
WO2023031961A1 (en) * | 2021-08-30 | 2023-03-09 | Nbi Biosciences Pvt Ltd | Plant-derived neuroprotective composition and a method of manufacturing the same |
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US11622956B1 (en) | 2019-06-26 | 2023-04-11 | RCR BioPharma | Compound and method for treating diseases and disorders |
US20210038558A1 (en) * | 2019-08-07 | 2021-02-11 | Orochem Technologies Inc. | Water-soluble cannabinoids |
CN111150729B (zh) * | 2020-01-16 | 2021-02-12 | 全越 | 一种成膜组合物及其应用 |
WO2022125557A1 (en) * | 2020-12-07 | 2022-06-16 | Orochem Technologies Inc. | Composition comprising a cannabinoid |
WO2023044433A1 (en) | 2021-09-17 | 2023-03-23 | India Globalization Capital, Inc. | Compositions and methods for treating patients with dementia due to alzheimer's disease with a combination of thc and melatonin |
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Habtemariam S. Rutin as a Natural Therapy for Alzheimer's Disease: Insights into its Mechanisms of Action. Curr Med Chem. 2016;23(9):860-73. (Year: 2014) * |
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