38 results about "Endogenous cannabinoid" patented technology

This invention provides compounds that selectively inhibit monoacylglycerol lipase (MAGL). The invention also provides methods of using the MAGL selective inhibitors to stimulate 2-Arachidonoylglycerol (2-AG) mediated endocannabinoid signaling in vivo, and to treat conditions that are associated with or linked to endocannabinoid signaling. The invention additionally provides methods of treating cancer or inhibiting tumor growth by targeting MAGL with MAGL specific inhibitors. The invention further provides methods of screening for MAGL inhibitors with improved biochemical and pharmaceutical properties.

The present invention relates to a compound of the general formula (I) which is a non-hydrolysable analogue of endogenous cannabinoids, which are found to be more potent therapeutic agents as they are more stable, for example, to hydrolytic cleavage in the gastrointestinal tract. The cannabinoid analogues of the invention have a therapeutic value. Therefore, pharmaceutical compositions comprising as active ingredient a therapeutically effective amount of at least one compound of the invention may be prepared. Such compositions may be used as anti-inflammatory, anti-asthmatic, analgetic, hypotensive, antiemetic or anti-spasmodic compositions, and as compositions for treating and / or preventing glaucoma or migraine, or as compositions for relieving symptoms of multiple sclerosis and mood stimulating compositions.

One aspect of this disclosure relates generally to lipid compounds that exert diverse effects in the endocannabinoid system, such as regulating CB1 and CB2 receptor or moderating other bio-macromolecules within the endocannabinoid system. Some of the compounds showed improved receptor binding affinity, and / or improved receptor subtype selectivity, and improved bio-stability. Some of the compounds exhibit activities to regulate the enzymes that moderate the bio-disposal of endogenous cannabinoids, such as the fatty acid amide hydrolase (FAAH). Some of the compounds exhibit activities to inhibit the anandamide transporter. Other aspects of the invention are pharmaceutical preparations employing these ligands and methods of administering therapeutically effective amounts of the preparations to provide a physiological effect.

The invention discloses phytosterol nano-emulsion capable of losing weight and lowering lipid and a preparation method of the phytosterol nano-emulsion. The phytosterol nano-emulsion is prepared fromthe following raw materials in percentage by mass: 0.5 to 4 percent of phytosterol, 5 to 25 percent of nutritional oil, 5 to 15 percent of an emulsifier, 0.1 to 0.6 percent of an antioxidant, 0.1 to 0.5 percent of an inorganic additive and the balance of water which is aaded until the content is 100 percent. According to the phytosterol nano-emulsion disclosed by the invention, the ratio of threetypes of phytosterols are reasonably adjusted, and 4-demethlyate sterol and 4,4'-dimethyl sterol have a sufficient synergetic effect to alleviate the obesity; meanwhile, a cholesterol lowering effectand a mechanism of adjusting an endogenous cannabinoids system are used simultaneously to realize the effect of cooperatively lowering the lipid. The phytosterol nano-emulsion prepared by the invention can be directly applied to functional foods, medicines and the like; the dosage of lipid-lowering Western medicines is reduced and the lipid-lowering effect is remarkable; other complications can beobviously alleviated or eliminated.

A cannabinoid composition having an excipient including α-tocopherol and at least one isolated cannabinoid having a purity of greater than 80%. The α-tocopherol inhibits oxidation, regulates viscosity of the composition, and improves bioavailability of the cannabinoid. The composition includes a carrier oil mixed with the excipient and cannabinoid. In one embodiment, the at least one cannabinoid is an isolated cannabinoid having a greater than 80% purity, and preferably greater than 90% purity. The at least one cannabinoid is selected from the group consisting of phytocannabinoids, endocannabinoids, synthetic cannabinoids, and combinations thereof. The cannabinoid may be derived from plants other than cannabis sativa, or synthesized from fungi, bacteria, yeast or other synthetic method. Preferably the α-tocopherol comprises at least 10% w / w of the composition.

A compound provided by the present invention includes an endocannabinoid, endocannabinoid derivative, or endocannabinoid analog moiety covalently bonded to a biologically active peptide. One example of an inventive compound described is a conjugate of an endocannabinoid, endocannabinoid derivative, or endocannabinoid analog moiety covalently coupled to an opioid peptide, such as an endorphin, enkephalin, dynorphin or endomorphin. Also detailed are processes for making the described conjugates and pharmaceutical compositions including such compounds.

The invention relates to a Cannabis-based pharmaceutical composition for the treatment of hypertensive disorders by submucosal delivery comprising a pharmaceutically acceptable base and an effective amount of at least one cannabinoid or endocannabinoid containing extract of a cloned hybrid of the plant Cannabis sativa, subspecies sativa and Cannabis sativa, subspecies indica of the CTSX-ISS lineage; and methods of treatment of primary and secondary hypertension, the secondary hypertension resulting from pheochromocytoma, primary hyperaldosteronism, adrenal hyperplasia, pulmonary hypertension, portal hypertension, folate deficiency hypertension, arterial hypertension or familial hypertension by administration between one and eight times per day.

An example embodiment may involve (i) receiving, by a server device, deoxyribonucleic acid (DNA) information associated with a user; (ii) parsing, by the server device, the DNA information to identify one or more single nucleotide polymorphisms (SNPs)—(iii) determining, by the server device and based, on the identified SNPs, an endocannabinoid genotype of the user; (iv) determining, based on the endocannabinoid genotype of the user, a recommendation of one or more cannabinoid formulations; (v) transmitting, to a client device associated with the user, a web-based representation of a first graphical user interface; and (vi) receiving, from the client device, an indication to display a detailed representation of a particular cannabinoid formulation of the one or more cannabinoid formulations.

The invention discloses a cannabinoid compound as well as a preparation method, a composition and application thereof. The invention discloses a compound shown as a formula I or a pharmaceutically acceptable salt thereof. The compound disclosed by the invention has medium-to-strong affinity to a cannabinoid receptor 1 or a cannabinoid receptor 2, and can be used as a potential therapeutic drug fortreating diseases and symptoms related to an endogenous cannabinoid system; , including but not limited to anorexia, vomiting, pain, epilepsy, spasm, Parkinson's disease, Alzheimer's disease, anxiety, depression, schizophrenia, or drug addiction.

One aspect of this disclosure relates generally to lipid compounds that exert diverse effects in the endocannabinoid system, such as regulating CB1 and CB2 receptor or moderating other bio-macromolecules within the endocannabinoid system. Some of the compounds showed improved receptor binding affinity, and / or improved receptor subtype selectivity, and improved bio-stability. Some of the compounds exhibit activities to regulate the enzymes that moderate the bio-disposal of endogenous cannabinoids, such as the fatty acid amide hydrolase (FAAH). Some of the compounds exhibit activities to inhibit the anandamide transporter. Other aspects of the invention are pharmaceutical preparations employing these ligands and methods of administering therapeutically effective amounts of the preparations to provide a physiological effect.

An subjects with obsessive compulsive disorder is treated. In one embodiment, the subject is administered a compound down regulates Group I mGluR signaling. In another embodiment, the subject is administered a compound that down regulates endocannabinoid signaling. The subject that has obsessive compulsive disorder can further have at least one condition selected from the group consisting of fragile X syndrome, autism and mental retardation.

The present invention relates to a pharmaceutical composition, a health functional food, and a feed composition for the prevention, improvement, or treatment of non-alcoholic liver disease or insulin resistance comprising ginsenoside F2. The pharmaceutical composition according to the present invention comprising ginsenoside F2 can inhibit the adipogenesis and lipid accumulation in the liver, improve insulin sensitivity, inhibit the expression of inflammatory cytokines such as TNF-alpha, IL-beta, and IL-6 in the Kupffer cell, inhibit the expression of endocannabinoid synthase, thus capable of effectively preventing or treating non-alcoholic liver disease or insulin resistance.

A system and method for treating acute migraine events utilizing multiple sensory / receptive channels (olfactory, audio, visual and other sensory receptors) to both treat and optimize delivery to the afflicted sites in the brain. One of the primary migraine treatment methods includes a composition delivered through the olfactory system. Absorption through the nasal membranes is rapid and avoids delays and dilution inherent in methods using the mouth and gastro-intestinal (GI) processing. Effective, but less preferred methods that avoid GI delays and dilution include delivery as eyedrops or as an intravenous infusion. The effective composition comprises a caffeinic substance to bind and antagonize adenosine receptors in the brain. This immediately blocks continued action of adenosine to dilate the afflicted vessels and inflict pain. The composition also incorporates cannabinolic substances which work simultaneously or in parallel using the body's natural endocannabinoid pathways to rebalance and control blood flow to minimize swelling and pain. Additional features may incorporate additional active components. One available feature may incorporate a recipient / patient control modulus where the patient adjusts treatment using a feedback device such as a stimulation button to increase or adjust delivery. Another additional feature comprises one or more essential oils. Although some essential oil compositions may themselves include one or more compounds that contribute to the desired cannabinolic effects, adding essential oils even those lacking an inherent cannabinolic effect can contribute to effective treatment. Fragrant inclusions in an essential oil additive may provide a calming stimulation to the olfactory system that supports reduced tension and relaxation and thereby removes a tension induced exacerbation of migraine progression.

Mixed inhibitors of aminopeptidase N and of neprilysine are described. Pharmaceutical compositions containing at least one of these compounds, used alone or in combination with morphine and derivatives thereof, endocannabinoids and inhibitors of the metabolism thereof, GABA derivatives such as gabapentin or pregabalin, duloxetine or methadone, can be used as an analgesic, anxiolytic, antidepressant or anti-inflammatory.

The invention discloses a carbamyl uracil derivative and application thereof. The structural formula of the derivative is as shown in the description. The derivative is a novel compound with the endogenous cannabinoid hydrolase inhibiting function, and a new method is provided for inflammation and pain treatment.

Provided is a highly potent and selective endocannabioid cellular reuptake inhibitor represented by formula (I):or a pharmaceutically acceptable solvate or co-crystal thereof as well as to a formulation comprising this inhibitor, and to methods of treatment in which this inhibitor is used.

A compound is provided that has the formula (II):where R1 in each occurrence is independently H, or C1-C4 alkyl; R2 is a nullity or CH—CH3, R3 is a nullity or C(O)—R6—NH; R6 is C2-C6 alkyl, (CH2CH2—O)n, or (CH(OH)CH2)n; n is an integer of between 1 and 4; R4 is a nullity or NH—R6—C(O); and R5 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, endocannabinoids 1 & 2, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosyl ester, lactic acid, leucine, tryptophan, glutamic acid.

The present invention provides, inter alia, compositions and methods for using CB1 cannabinoid receptor agonists, or other compounds capable of increasing endocannabinoids or endocannabinoid signaling, for treating and preventing lysosomal storage disorders in which lipid storage occurs (including, e.g., disorders associated with sphingomyelin accumulation). In particular embodiments, the present invention provides compositions and methods for treating such lysosomal storage disorders with one or more fatty acid amide hydrolase inhibitor alone or in combination with one or more additional agent.

The invention provides a compound as shown by Formula I having an enzyme activity which can inhibit endocannabinoid hydrolases NAAA and / or FAAH, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and a preparation method and a use of the compound. ##STR00001##

The present invention provides a system enabling the oral delivery of therapeutics derived from polyunsaturated fatty acids (PUFAs), their metabolites and derivatives, including, eicosanoids, prostaglandins, prostacyclins, leukotrienes, resolvins, endocannabinoids, thromboxanes, epoxyeicosa-trienoic acids (EETs), hydroxyeicostetraenoic acids (HETEs), and CMX-020. The delivery system includes a vehicle comprising a purified docosahexaenoic acid (DHA) in triglyceride or ester form; a purified eicosapentaenoic acid (EPA) in triglyceride or ester form; a combination of DHA, EPA in either triglyceride or ester forms; or a modified DHA, EPA, or omega-3 fatty acid analog; and optionally, an antioxidant, a surfactant, a solubilizer, a stabilizer, a lubricant, or a pH / tonicity adjustment agent.

The present invention relates to a method for detecting an optimal time for embryo implantation in mammals, particularly humans. In particular, the invention relates to a method for determining the optimal time for implantation of an embryo in a mammalian endometrium comprising detecting the levels of an endocannabinoid in the early, mid and late stage of the menstrual cycle in a subject.

The invention relates to a Cannabis-based pharmaceutical composition for the treatment of hypertensive disorders by submucosal delivery comprising a pharmaceutically acceptable base and an effective amount of at least one cannabinoid or endocannabinoid containing extract of a cloned hybrid of the plant Cannabis sativa, subspecies sativa and Cannabis sativa, subspecies indica of the CTSX-ISS lineage; and methods of treatment of primary and secondary hypertension, the secondary hypertension resulting from pheochromocytoma, primary hyperaldosteronism, adrenal hyperplasia, pulmonary hypertension, portal hypertension, folate deficiency hypertension, arterial hypertension or familial hypertension by administration between one and eight times per day.

The present invention relates to ophthalmic compositions and methods for the treatment of dry eye and other inflammatory ocular conditions. In particular, the present invention relates to a composition comprising an esterified anti-inflammatory lipid mediator, which is an ester of an anti-inflammatory lipid mediator that is a reaction product of the anti-inflammatory lipid mediator and a polyol wherein the majority of the anti-inflammatory lipid mediator is present in an ester form. In this way, the compositions are substantially free of an acid form of the anti-inflammatory lipid mediators. Anti-inflammatory lipid mediators can be selected from the group consisting of polyunsaturated fatty acids (e.g., omega-three and omega-six fatty acids), resolvins or a metabolically stable analog, protectins or a metabolically stable analog, lipoxins or a metabolically stable analog, prostaglandins or a metabolically stable analog, retinoic acids, endocannabinoids, metabolites thereof, and mixtures thereof. This composition can be topically delivered to the ocular surface via a preparation, solution, gel, ointment, and / or strip and / or a contact lens.

A compound is provided that has the formula (II):where R1 in each occurrence is independently H, or C1-C4 alkyl; R2 is a nullity or CH—CH3, R3 is a nullity or C(O)—R6—NH; R6 is C2-C6 alkyl, (CH2CH2—O)n, or (CH(OH)CH2)n; n is an integer of between 1 and 4; R4 is a nullity or NH—R6—C(O); and R5 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, endocannabinoids 1 & 2, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosyl ester, lactic acid, leucine, tryptophan, glutamic acid.

The invention relates to the technical field of novel medicinal application, and particularly relates to novel medicinal application of a CB2 receptor stimulant. An endocannabinoid signal system can be used for maintaining the energy balance and glucose homeostasis in a body; when fat and skeletal muscle cells are subjected to glucose deprivation, the messenger-ribonucleic acid (RNA) expression profile of the signal system changes, and ECS has the effects of mediating insulin resistance and regulating diabetes mellitus, obesity and other metabolic diseases. Animal tests of SER 601 in the CB2 receptor stimulant prove that the CB2 receptor stimulant has a remarkable effect for improving pancreas islet function, improving insulin sensitivity and improving accumulation of whole body fat, especially abdominal fat. The CB2 receptor stimulant can be used for reducing the content of fat in a body while improving the insulin sensitivity, preventing / treating diabetes mellitus patients, especially patients with type 2 diabetes mellitus, and preventing / treating obesity, lipodystrophy, weight and fat reduction and other diseases.

Regulation of striatal indirect pathway endocannabinoid-mediated long-term depression (eCB-LTD) is used to improve motor deficits of striatal-based brain disorders. In such treatment, a dopamine D2 receptor agonist is administered in conjunction with an inhibitor of endocannabinoid degradation. In some embodiments, the inhibitor of endocannabinoid degradation is a fatty acid amine hydrolase inhibitor, or a monoacylglycerol lipase antagonist. The combination provides for a synergistic effect, with improved therapeutic effects. Also provided are kits and systems for practicing the subject methods, as well as methods of use of agents identified in the screening method of the invention.

The present invention relates to high affinity compounds, able to bind CB1 and CB2 endocannabinoid receptors. The compounds of the invention find particular application as agents for pain therapy and / or anti-inflammatory and / or anti-stress and / or anti-oxidising and / or hypotensive and / or immune suppressive therapy and / or anti-spastic activity in multiple sclerosis and / or anti-cancer.

The present invention relates to a pharmaceutical composition, a health functional food, and a feed composition for the prevention, improvement, or treatment of non-alcoholic liver disease or insulin resistance comprising ginsenoside F2. The pharmaceutical composition according to the present invention comprising ginsenoside F2 can inhibit the adipogenesis and lipid accumulation in the liver, improve insulin sensitivity, inhibit the expression of inflammatory cytokines such as TNF-α, IL-β, and IL-6 in the Kupffer cell, inhibit the expression of endocannabinoid synthase, thus capable of effectively preventing or treating non-alcoholic liver disease or insulin resistance.

The inventive method relates to a method for the determination of susceptibility or diagnosis of autism or autism spectrum disorders. Diagnosis or determination of susceptibility determinations are predicated on quantitative analysis of endocannibinoid levels or endocannibinoid receptor expression.