WO2020142692A1

WO2020142692A1 - Topical formulations having cannabinoid

Info

Publication number: WO2020142692A1
Application number: PCT/US2020/012187
Authority: WO
Inventors: Aaron Michael DELY; Shaun BEN-ARI
Original assignee: Columbia Care Llc
Priority date: 2019-01-04
Filing date: 2020-01-03
Publication date: 2020-07-09
Also published as: EP3906025A4; EP3906025A1

Abstract

Disclosed are cannabinoid formulations and methods of use associated therewith. Specifically, disclosed are topical or transdermal formulations having a cannabinoid in combination with a phyto-compound excipient that facilitates absorption and bioavailability of the cannabinoid.

Description

TOPICAL FORMULA TIONSHA VING

CANNABINOID

RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 62/788,494, filed January 4, 2019, the contents of which are incorporated herein by reference in their entirety.

FIELD OF INVENTION

[0002] Disclosed are cannabinoid formulations and methods of use associated therewith.

Specifically, disclosed are topical or transdermal formulations having a cannabinoid in combination with a phyto-compound excipient that facilitates absorption and bioavailability of the cannabinoid.

BACKGROUND OF THE INVENTION

[0003] The medicinal and psychoactive properties of the cannabis plant have been known for centuries. While it has been illegal in many countries, there is a growing population lobbying for legalization of its use, especially for medicinal purposes.

[0004] Cannabis is believed to provide benefits in the treatment of multiple disorders with safer and fewer serious side effects than most prescription drugs currently used as anti emetics, muscle relaxants, hypnotics, and analgesics. A disadvantage in treating patients with cannabis is the psychoactive effect, especially in "naive" cannabis users. Furthermore, there have been reports of unpleasant reactions to cannabis, such as anxiety, panic, or hallucinations. It is believed that the undesirable side effects are most commonly associated with higher doses of cannabis and are related to the difficulty in controlling the dosage when the drug is smoked or eaten in cannabis-enriched

confectionaries.

[0005] Cannabis has also been used to treat the symptoms in patients suffering from serious medical conditions. For example, cannabis has been used to alleviate symptoms associated with cancer, anorexia, AIDS, chronic pain, muscle spasticity, glaucoma, arthritis, migraine, and many other illnesses. Cannabis is recognized as having antiemetic properties and has been successfully used to treat nausea and vomiting in cancer patients undergoing chemotherapy. Cannabis has also been used in treating the weight loss syndrome of AIDS and in treating glaucoma by reducing intraocular pressure. Cannabis is also known for its muscle relaxing and anti-convulsant effects.

[0006] The most prevalent mode of administration of medical cannabis is by smoking. This mode of administration can have adverse effects on the lungs. Cannabis smoke carries more tar and other particulate matter than tobacco and may be a cause of lung diseases including lung cancer. Furthermore, many patients find the act of smoking unappealing, as well as generally unhealthy.

[0007] Accordingly, there is significant interest in developing other means to administer cannabis to patients. There remains an unmet need for topical formulations for

administering cannabis or cannabinoid.

SUMMARY OF THE INVENTION

[0008] In one aspect, provided are formulations comprising: at least one cannabinoid or a derivative thereof and at least one phyto-compound excipient, wherein said at least one phyto-compound excipient is a skin penetration enhancer that facilitates absorption and bioavailability of said at least one cannabinoid or said derivative thereof in a subject. In certain embodiments, the formulation is a topical or a transdermal formulation.

[0009] In some exemplary embodiments, the formulation includes a first cannabinoid (e.g., THC or THCa) and a second cannabinoid (CBD or CBDa). In other exemplary

embodiments, the formulation includes a first polymer (e.g., polyethylene glycol 1450) and a second polymer (e.g., polyethylene glycol 4000).

[0010] In another aspect, provided are methods for treating a disease or disorder in a subject, the methods comprising administering to the subject, for example topically administering, a formulation disclosed herein.

[0011] In yet another aspect, provided are methods for manufacturing a formulation disclosed herein. In certain embodiments, the method comprises the steps of providing one or more cannabinoids; providing one or more phyto-compound excipients; and mixing said one or more cannabinoids with said one or more phyto-compound excipients.

[0012] In a further aspect, provided are metered dose devices having a formulation disclosed herein.

[0013] In a still further aspect, provided herein are devices comprising a formulation described herein. In certain embodiments, the device comprises a regulated pump. In certain embodiments, the device comprises a metered-dosing mechanism. In certain embodiments, the device comprises an air-tight container to store the formulation. In certain embodiments, the device comprises the formulation in a plurality of metered doses. In certain embodiments, the device is an aerosol spray device.

[0014] Other features and advantages of the present disclosure will become apparent from the following detailed description and examples. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

DETAILED DESCRIPTION OF THE INVENTION

[0015] The present subject matter may be understood more readily by reference to the following detailed description which forms a part of this disclosure. It is to be understood that this invention is not limited to the specific products, methods, conditions, or parameters described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed invention.

[0016] Unless otherwise defined herein, scientific and technical terms used in connection with the present application shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0017] As employed above and throughout the disclosure, the following terms and abbreviations, unless otherwise indicated, shall be understood to have the following meanings.

[0018] In the present disclosure the singular forms "a," "an," and "the" include the plural reference, and reference to a particular numerical value includes at least that particular value, unless the context clearly indicates otherwise. Thus, for example, a reference to "a compound" is a reference to one or more of such compounds and equivalents thereof known to those skilled in the art, and so forth. The term "plurality", as used herein, means more than one. When a range of values is expressed, another embodiment includes from the one particular and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it is understood that the particular value forms another embodiment. All ranges are inclusive and combinable.

[0019] As used herein, the terms "treatment" or "therapy" (as well as different forms thereof) include preventative (e.g., prophylactic), curative, or palliative treatment. As used herein, the term "treating" includes alleviating or reducing at least one adverse or negative effect or symptom of a condition, disease, or disorder.

[0020] By "transdermal" drug delivery is meant administration of a drug to the skin surface of an individual so that the drug passes through the skin tissue and into the individual's blood stream.

[0021] The term "topical administration" is used in its conventional sense to mean delivery of an active agent to a body surface such as the skin or mucosa, as in, for example, topical drug administration in the prevention or treatment of various disorders, the application of cosmetics and cosmeceuticals (including moisturizers, masks, sunscreens, etc.), and the like. Topical administration, in contrast to transdermal administration, provides a local rather than a systemic effect.

[0022] Similarly, when the term "transdermal" is used herein, as in "transdermal drug administration" and "transdermal drug delivery systems," it is to be understood that unless explicitly indicated to the contrary, "topical" administration and systems are intended as well.

[0023] The terms "subject," "individual," and "patient" are used interchangeably herein, and refer to an animal, for example a human, to whom treatment, including prophylactic treatment with the pharmaceutical formulation, is provided.

[0024] The inventor of the instant application surprisingly and unexpectedly discovered a formulation which includes, in part, one or more cannabinoids in combination with one or more phyto-compound excipients. The presence of a phyto-compound excipient in the formulation facilitates absorption of a cannabinoid through an epidermis and a dermis. Furthermore, the presence of a phyto-compound excipient improves bioavailability of a cannabinoid.

[0025] In one aspect, provided are formulations comprising: at least one cannabinoid or a derivative thereof and at least one phyto-compound excipient, wherein said at least one phyto-compound excipient is a skin penetration enhancer that facilitates absorption and bioavailability of said at least one cannabinoid or said derivative thereof in a subject. In certain embodiments, the formulation is a topical formulation. In other embodiments, the formulation is a transdermal formulation.

[0026] Certain embodiments of the invention relate to compositions of one or more cannabinoids to provide, for example, a topical or a transdermal delivery of said one or more cannabinoids. The cannabinoids are easily prepared and formulated to provide consistent, therapeutically effective dosage forms from lot to lot.

[0027] In certain embodiments, said formulation facilitates administration via a regulated pump or a metered-dosing device. In certain embodiments, said formulation is a homogeneous formulation.

[0028] In certain embodiments, said cannabinoid is an extract from a cannabis plant.

[0029] In certain embodiments, the formulation has a combination of at least two cannabinoids. In certain embodiments, the formulation comprises a combination of at least two cannabinoids. In certain embodiments, the two cannabinoids are selected from

Tetrahydrocannabinolic acid (THCa), Cannabidiolic acid (CBDa), Cannabinolic acid (CBNa), Cannabichromenic acid (CBCa), Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabigerol (CBG), Cannabigerolic Acid (CBGa), Cannabichromene (CBC), Cannabinol (CBN), Cannabielsoin (CBE), iso-Tetrahydrocannabinol (iso-THC), Cannabicyclol (CBL), Cannabicitran (CBT), Cannabivarin (CBV),

Tetrahydrocannabivarin (THCV), Cannabidivarin (CBDV), Cannabichromevarin (CBCV), Cannabigerovarin (CBGV), Cannabigerol Monomethyl Ether (CBGM), and derivatives thereof. Examples of derivatives include, but are not limited to, esters, amides, and ethers of the compounds disclosed herein.

[0030] In some embodiments, the cannabinoid is a cannabinoid extract that contains a combination of at least two of the following: Tetrahydrocannabinolic acid (THCa), Cannabidiolic acid (CBDa), Cannabinolic acid (CBNa), Cannabichromenic acid (CBCa), Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabigerol (CBG), Cannabigerolic Acid (CBGa), Cannabichromene (CBC), Cannabinol (CBN), Cannabielsoin (CBE), iso- Tetrahydrocannabinol (iso-THC), Cannabicyclol (CBL), Cannabicitran (CBT),

Cannabivarin (CBV), Tetrahydrocannabivarin (THCV), Cannabidivarin (CBDV), Cannabichromevarin (CBCV), Cannabigerovarin (CBGV), Cannabigerol Monomethyl Ether (CBGM) and derivatives thereof. The cannabinoid may be natural or synthetic. [0031] The methods of making cannabinoids extract is well known in the art. The cannabis plants are grown, harvested, and the cannabinoids are extracted through, for example, a CO2 extraction process.

[0032] In certain embodiments, at least two cannabinoids are in a 1 : 1 proportion by weight. In certain embodiments, at least two cannabinoids are in a 10: 1 proportion by weight. In certain embodiments, at least two cannabinoids are in a 20: 1 proportion by weight. In certain embodiments, two cannabinoids are THC and CBD. In certain embodiments, two cannabinoids are THCa and CBDa.

[0033] In certain embodiments, the two cannabinoids are in a 1 : 1 proportion by weight. In certain embodiments, the two cannabinoids are in a 10: 1 proportion by weight. In certain embodiments, the two cannabinoids are in a 20: 1 proportion by weight. In certain embodiments, the two cannabinoids are THC and CBD. In certain embodiments, the two cannabinoids are THCa and CBDa.

[0034] In some embodiments, the formulation includes a first cannabinoid and a second cannabinoid. In certain exemplary embodiments, the first and second cannabinoids are in a ratio ranging from about 1 : 1 to about 20: 1 proportion by weight. In certain

embodiments, the first and second cannabinoids are in a 1 : 1 proportion by weight. In other embodiments, the first and second cannabinoids are in a 10: 1 proportion by weight. In yet other embodiments, the first and second cannabinoids are in a 20: 1 proportion by weight.

[0035] In certain embodiments, the first cannabinoid is THC or THCa and the second cannabinoid is CBD or CBDa.

[0036] In certain embodiments, the first cannabinoid is THC and the second cannabinoid is CBD.

[0037] In certain embodiments, the first cannabinoid is THCa and the second cannabinoid is CBDa.

[0038] In certain embodiments, the at least one cannabinoid is THC or THCa present in an amount ranging from about 0.01 mg to about 200 mg. In certain embodiments, the at least one cannabinoid is CBD or CBDa present in an amount ranging from about 0.01 mg to about 200 mg.

[0039] In certain embodiments, the first cannabinoid can be present in an amount ranging from about 0.01 mg to about 200 mg. The second cannabinoid also can be present in an amount ranging from about 0.01 mg to about 200 mg. [0040] In some embodiments, the cannabinoids are in equal proportion such as, for example, 2.5 mg THC to 2.5 mg CBD. Other embodiments include proportions of

THC/CBD of 0.25 mg THC to 5.0 mg CBD or 5.0 mg THC to 0.25 mg CBD.

[0041] In some embodiments, the cannabinoid of the invention is any member of a group of substances that are structurally related to tetrahydrocannabinol and that bind to a cannabinoid receptor such as CB 1 or CB2 or both (‘THC’). The cannabinoid can be a naturally occurring compound (e.g., present in Cannabis), a compound metabolized by a plant or animal, or a synthetic derivative.

[0042] The cannabinoid may be included in its free form or in the form of a salt; an acid addition salt of an ester; an amide; an enantiomer; an isomer; a tautomer; a prodrug; a derivative of an active agent; different isomeric forms (e.g., enantiomers and

diastereoi somers), both in pure form and in admixture, including racemic mixtures; or enol forms.

[0043] The cannabinoids are further meant to encompass natural cannabinoids, natural cannabinoids that have been purified or modified, and synthetically derived cannabinoids. Methods for purifying cannabinoids from plant material, are well known in the art and fully described in, for example, United States Patent Application Publication 2005/0266108, which is incorporated by reference herein in its entirety.

[0044] The cannabinoids can be any of 9-tetrahydrocannabinol, 8-tetrahydrocannabinol, (+)- 1,1-dimethylheptyl analog of 7-hydroxy-delta-6-tetrahydrocannabinol, 3-(5 '-cyano-1 ',G- dimethylpentyl)- 1 -(4-N-morpholinobutyryloxy)-delta-8-tetrahydrocannabinol hydrochloride, dexanabinol, nabilone, levonantradol, and N-(2-hydroxyethyl)hexadecanoamide. In some embodiments, the cannabinoids can be any of the non-psychotropic cannabinoid 3- dimethylnepty 11 carboxylic acid homologine 8 and delta-8-tetrahydrocannabinol.

[0045] In some embodiments, the cannabinoid extract comprises cannabinoids tincture. The term "tincture", as used herein, refers to an alcoholic extract of plant material.

Methods of tincture preparation are well known in the art and are described, for example, in the U.S. patent application US 9,468,865, hereby incorporated by reference in its entirety. In certain embodiments, the method of tincture preparation according to the present invention comprises the steps of combining medium chain triglycerides and polysorbate in a mixing vessel to form a first combination; mixing the first combination; adding the cannabinoid extract to the first combination to form a second combination; mixing the second combination; adding 200 proof ethanol to the second combination to form a third combination; and mixing the third combination for an extended period of time in order to obtain the cannabinoids tincture. The duration of the final mixing step may vary depending on many factors and can be easily optimized by a skilled artisan. In certain embodiments, the final mixing step ranges from about 5 to about 60 minutes. In other embodiments, the final mixing step ranges from about 10 to about 50 minutes. In other embodiments, the final mixing step ranges from about 15 to about 45 minutes. In other embodiments, the final mixing step ranges from about 20 to about 40 minutes.

[0046] In another aspect, provided are formulations further comprising one or more phyto compound excipients. In certain embodiments, the at least one phyto-compound excipient facilitates absorption of said at least one cannabinoid or said derivative through an epidermis or a dermis of the subject. In certain embodiments, the at least one phyto compound excipient improves bioavailability of said at least one cannabinoid or said derivative in said subject.

[0047] Examples of a phyto-compound excipient include, for example, but are not limited to, a terpene, an essential oil, papain, pipeline, capsaicin, or an extract of Myristica fragrans. In certain embodiments, the at least one phyto-compound excipient is a terpene, an essential oil, papain, pipeline, capsaicin, or an extract of Myristica fragrans.

[0048] Examples of a terpene include, for example, but are not limited to, beta-myrcene, limonene, beta caryophyllene, caryophyllene oxide, terpineol, citronellol, linalool, humulene, beta-amyrin, cycloartenol, famesol, menthol, eucalyptol, eugenol, and borneol.

In certain embodiments, the terpene is selected from beta-myrcene, limonene, beta caryophyllene, caryophyllene oxide, terpineol, citronellol, linalool, humulene, beta-amyrin, cycloartenol, farnesol, menthol, eucalyptol, eugenol, and borneol.

[0049] Examples of an essential oil include, for example, but are not limited to, eucalyptus oil, niaouli oil, fennel oil, cumin oil, almond oil, basil oil, Alpinia oxyphylla oil, turpentine oil, rosemary oil, and cardamom oil. In certain embodiments, the essential oil is selected from eucalyptus oil, niaouli oil, fennel oil, cumin oil, almond oil, basil oil, Alpinia oxyphylla oil, turpentine oil, rosemary oil, and cardamom oil.

[0050] In some embodiments, the minor and major phyto-compounds in the formulation are used in an amount to give a content of from 0.05% to 5% by weight based on 100 parts by weight of the topical formulation. In other embodiments, the minor and major phyto compounds in the formulation are used in an amount to give a content of about 1.1% by weight based on 100 parts by weight of the topical formulation. [0051] In some embodiments, the minor and major phyto-compounds in the formulation are used in an amount to give a content of from 0.05% to 5% by weight based on 100 parts by weight of the formulation. In other embodiments, the minor and major phyto-compounds in the formulation are used in an amount to give a content of about 1.1% by weight based on 100 parts by weight of the formulation.

[0052] In some embodiments, the total cannabinoid content in the formulation is used in an amount to give a content of from 0.05% to 5% by weight based on 100 parts by weight of the topical formulation. In certain embodiments, the total cannabinoid content forms about 0.05% to 5% by weight based on 100 parts by weight of the topical formulation. In certain embodiments, the total cannabinoid content in the formulation is used in an amount to give a content of about 1.1% by weight based on 100 parts by weight of the topical formulation. In certain embodiments, the total cannabinoid content forms about 1.1% by weight based on 100 parts by weight of the topical formulation.

[0053] In some embodiments, the total cannabinoid content in the formulation is used in an amount to give a content of from 0.05% to 5% by weight based on 100 parts by weight of the formulation. In certain embodiments, the total cannabinoid content forms about 0.05% to 5% by weight based on 100 parts by weight of the formulation. In certain embodiments, the total cannabinoid content in the formulation is used in an amount to give a content of about 1.1% by weight based on 100 parts by weight of the formulation. In certain embodiments, the total cannabinoid content forms about 1.1% by weight based on 100 parts by weight of the formulation.

[0054] The formulation of the invention may also include additional ingredients such as solvents, carriers, or excipients.

[0055] In certain embodiments, the formulation further comprises a solvent. In some embodiments, the solvent comprises ethanol, methanol, isopropanol, chloroform, propylene glycol, polyethylene glycol, glycerine, limonene, myrcene, linalool, alpha bisabolol, delta 3 carene, borneol, alpha-pinene, beta-pinene, eucalyptol, terpineol, caryophyllene, camphene, or combinations thereof. In certain embodiments, the solvent is ethanol.

[0056] In certain embodiments, the formulation further comprises a pharmaceutically acceptable carrier. In some embodiments, the carrier comprises cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, starch, pregelatinized starch, dicalcium phosphate, tricalcium phosphate, or mixtures thereof. In other embodiments, the carrier may be comprised of a water-soluble sugar or sugar alcohol. Examples include, but not limited to, lactose, sucrose, dextrose, polydextrose, fructose, maltose, maltodextrin, dextrate, dextrin, lactitol, mannitol, erythritol, maltitol, sorbitol, or xylitol, and mixtures thereof.

[0057] The formulation may further contain an ingredient commonly used in the pharmaceutical field. Examples of the ingredient include, but are not limited to, a diluent, a disintegrant, a binder, a lubricant, a colorant, a pH adjusting agent, a surfactant, a stabilizing agent, a sour agent, a flavor, a glidant, and the like. These ingredients are used in an amount commonly used in the pharmaceutical field unless otherwise specifically stated.

[0058] Examples of the diluent include, but are not limited to, a sugar or a sugar alcohol such as lactose (e.g., lactose monohydrate), fructose, glucose, mannitol or sorbitol; a starch such as com starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch or porous starch; microcrystalline cellulose; anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, and the like.

[0059] In the formulation, the diluent is used in an amount to give a content of from 5% to 95% by weight based on 100 parts by weight of the formulation.

[0060] Examples of a disintegrant include, but are not limited to, carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl starch sodium,

croscarmellose sodium, carmellose calcium, crospovidone, low-substituted

hydroxypropyl cellulose, and hydroxypropyl starch. The amount of the disintegrant can be an amount to give a content of from 0.5 to 25 parts by weight based on 100 parts by weight of the formulation or the topical formulation.

[0061] Examples of a binder include, but are not limited to, hydroxypropyl cellulose (e.g., grade: L, SL, SSL (trade name); Nippon Soda Co., Ltd.), hydroxypropylmethyl cellulose (e.g., hypromello se 2910 (e.g., TC-5 (grade: MW, E, EW, R, RW) (trade name); Shin-Etsu Chemical Co., Ltd.)), polyvinylpyrrolidone (povidone), and gum arabic.

[0062] In the formulation, the binder is used in an amount to give a content of from 1% to 20% by weight based on 100 parts by weight of the formulation or the topical formulation.

[0063] Examples of the lubricant include, but are not limited to, magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, sodium stearyl fumarate and the like. The used amount of the lubricant is an amount to give a content of from about 0.5% to 2% by weight based on 100 parts by weight. [0064] Examples of the colorant include, but are not limited to, a food dye (e.g., food yellow No. 5, food red No. 2, food blue No. 2), a food lake color, iron oxide red, and iron oxide yellow.

[0065] Examples of the pH adjusting agent include, but are not limited to, citrate, phosphate, carbonate, tartrate, fumarate, acetate, and amino acid salt.

[0066] Examples of the surfactant include, but are not limited to, sodium lauryl sulfate, polysorbate 80, and polyoxyethylene (160) polyoxypropylene (30) glycol.

[0067] The formulation may include a stabilizing agent that prevents separation or decomposition upon being transferred to a container or during transit or storage of said container.

[0068] Examples of the stabilizing agent include, but are not limited to, tocopherol, tetrasodium edetate, nicotinamide, and a cyclodextrin.

[0069] Examples of the sour agent include, but are not limited to, ascorbic acid, citric acid, tartaric acid, and malic acid.

[0070] Examples of the flavor include, but are not limited to, menthol, Mentha oil, lemon oil, and vanillin.

[0071] Examples of the glidant include, but are not limited to, colloidal silicon dioxide, aqueous silicon dioxide, and talc.

[0072] The above ingredients may be used by combining two or more members at an appropriate ratio.

[0073] The formulations disclosed herein include a composition for daily administration. In certain embodiments, the therapeutic effect is maintained with one unit, twice daily. In other embodiments, the therapeutic effect is maintained with one unit, three times daily. In certain exemplary embodiments, the duration of each dose's effect is between four (4) to six (6) hours.

[0074] The formulation can be of any suitable form, for example, a cream, a lotion, or a gel. In certain embodiments, the formulation is a cream or lotion.

[0075] In other aspects, provided herein are methods of treating a disease in a subject, the method comprising administering a formulation described herein. In other aspects, provided herein are methods of treating a disease in a subject, the method comprising administering to the subject a formulation described herein.

[0076] In certain embodiments, the formulation is administered topically. In other embodiments, the formulation is administered transdermally. [0077] Examples of a disease or a disorder that can be treated by the invention include, but are not limited to, a skin disease or disorder, pain associated with cancer, neuropathic pain and HIV-associated sensory neuropathy, side effects of chemotherapy including nausea and pain, symptoms of neurological and neurodegenerative diseases such as Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, post-traumatic stress disorder (PTSD), alcohol abuse, bipolar disorder, depression, anorexia nervosa; cancer such as gliomas, leukemia, skin tumors, colorectal cancer; diseases including hepatitis C, methicillin-resistant Staphylococcus aureus (MRSA), pruritus, psoriasis, asthma, sickle-cell disease, sleep apnea, digestive diseases, collagen- induced arthritis, atherosclerosis and dystonia. In certain embodiments, said administration is a topical administration. In other embodiments, said administration is a transdermal administration.

[0078] Examples of a skin disease or disorder include, but are not limited to, itch, pain, and inflammation.

[0079] In another aspect, provided herein are methods for manufacturing a formulation described herein. The methods may include the steps of: providing one or more

cannabinoids; providing one or more phyto-compound excipients; and blending or mixing said one or more cannabinoids with said one or more phyto-compound excipients. These steps are carried out based on the techniques and processes known to one of skill in the art.

[0080] In yet another aspect, provided herein are devices comprising: the formulation described herein. In certain embodiments, the device is an aerosol spray device which can spray the formulation on a skin of a subject. In some embodiments, the device includes a regulated pump. In other embodiments, the device includes a metered-dosing mechanism.

[0081] The device may include an air-tight container to store said formulation. In some embodiments, the formulation is stored in a plurality of metered doses. In certain embodiments, the device comprises the formulation in a plurality of metered doses. In certain embodiments, the device is an aerosol spray device.

[0082] All patents and literature references cited in the present specification are hereby incorporated by reference in their entirety.

[0083] The present invention will be specifically explained by way of examples, but these examples are not intended to limit the present invention. EXAMPLES

[0084] In order that the invention described herein may be more fully understood, the following examples are set forth. The examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting their scope.

Example 1. Topical Formulation Having Cannabinoid

[0085] Formulations described above are shown in Table 1 and are prepared using the methods described herein.

[0086] The formulation is a therapeutic cream for topical or transdermal administration. The formulation includes a mixture of a therapeutic agent (e.g., cannabinoid extract) and a phyto-compound excipient.

[0087] The formulation is suitable for topical or transdermal administration using a metered-dose aerosol spray device.

Table 1. The formulation having CBD and THC cannabinoid extract

[0088] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[0089] Having described embodiments of the present invention with reference to the accompanying drawings, it is to be understood that the present invention is not limited to the above-mentioned embodiments and that various changes and modifications can be affected by one skilled in the art without departing from the spirit or scope of the present invention as defined in the appended claims.

Claims

We claim:

1. A formulation comprising:

at least one cannabinoid or a derivative thereof; and

at least one phyto-compound excipient,

wherein said at least one phyto-compound excipient is a skin penetration enhancer that facilitates absorption and bioavailability of said at least one cannabinoid or said derivative thereof in a subject.

2. The formulation of claim 1, wherein said formulation is a topical formulation.

3. The formulation of claim 1, wherein said formulation is a transdermal formulation.

4. The formulation of any one of claims 1-3, wherein said formulation is a cream or a lotion.

5. The formulation of any one of claims 1-4, wherein said at least one phyto compound excipient facilitates absorption of said at least one cannabinoid or said derivative through an epidermis or a dermis of said subject.

6. The formulation of any one of claims 1-4, wherein said at least one phyto compound excipient improves bioavailability of said at least one cannabinoid or said derivative in said subject.

7. The formulation of any one of claims 1-6, wherein said formulation facilitates administration via a regulated pump or a metered-dosing device.

8. The formulation of any one of claims 1-7, wherein said formulation is a homogenous formulation.

9. The formulation of any one of claims 1-8, wherein said formulation further comprises a stabilizing agent that prevents separation or decomposition upon being transferred to a container or during transit or storage of said container.

10. The formulation of any one of claims 1-9, wherein said cannabinoid is an extract from a cannabis plant.

11. The formulation of any one of claims 1-10, wherein the formulation has a combination of at least two cannabinoids.

12. The formulation of claim 11, wherein the two cannabinoids are selected from Tetrahydrocannabinolic acid (THCa), Cannabidiolic acid (CBDa), Cannabinolic acid (CBNa), Cannabichromenic acid (CBCa), Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabigerol (CBG), Cannabigerolic Acid (CBGa), Cannabichromene (CBC), Cannabinol (CBN), Cannabielsoin (CBE), iso-Tetrahydrocannabinol (iso-THC), Cannabicyclol (CBL), Cannabicitran (CBT), Cannabivarin (CBV),

Tetrahydrocannabivarin (THCV), Cannabidivarin (CBDV), Cannabichromevarin (CBCV), Cannabigerovarin (CBGV), Cannabigerol Monomethyl Ether (CBGM), and derivatives thereof.

13. The formulation of claim 11 or 12, wherein the two cannabinoids are in a 1 : 1 proportion by weight.

14. The formulation of claim 11 or 12, wherein the two cannabinoids are in a 10: 1 proportion by weight.

15. The formulation of claim 11 or 12, wherein the two cannabinoids are in a 20: 1 proportion by weight.

16. The formulation of any one of claims 11-15, wherein the two cannabinoids are THC and CBD.

17. The formulation of any one of claims 11-15, wherein the two cannabinoids are THCa and CBDa.

18. The formulation of any one of claims 1-17, wherein said at least one cannabinoid is THC or THCa present in an amount ranging from about 0.01 mg to about 200 mg.

19. The formulation of any one of claims 1-17, wherein said at least one cannabinoid is CBD or CBDa present in an amount ranging from about 0.01 mg to about 200 mg.

20. The formulation of any one of claims 1-19, wherein the total cannabinoid content forms about 0.05% to 5% by weight based on 100 parts by weight of the topical formulation.

21. The formulation of any one of claims 1-19, wherein the total cannabinoid content forms about 1.1% by weight based on 100 parts by weight of the topical formulation.

22. The formulation of any one of claims 1-21, wherein said at least one phyto compound excipient is a terpene, an essential oil, papain, piperine, capsaicin, or an extract of Myristica fragrans.

23. The formulation of claim 22, wherein said terpene is selected from beta-myrcene, limonene, beta caryophyllene, caryophyllene oxide, terpineol, citronellol, linalool, humulene, beta-amyrin, cycloartenol, farnesol, menthol, eucalyptol, eugenol, and borneol.

24. The formulation of claim 22, wherein said essential oil is selected from eucalyptus oil, niaouli oil, fennel oil, cumin oil, almond oil, basil oil, Alpinia oxyphylla oil, turpentine oil, rosemary oil, and cardamom oil.

25. The formulation of any one of claims 1-24, wherein the formulation further comprises a pharmaceutically acceptable carrier.

26. The formulation of claim 25, wherein the pharmaceutically acceptable carrier is selected from cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, starch, pregelatinized starch, dicalcium phosphate, tricalcium phosphate, and mixtures thereof.

27. The formulation of claim 25, wherein the pharmaceutically acceptable carrier is microcrystalline cellulose.

28. The formulation of any one of claims 1-27, wherein the formulation further comprises a solvent.

29. The formulation of claim 28, wherein the solvent is selected from ethanol, methanol, isopropanol, chloroform, propylene glycol, polyethylene glycol, glycerine, limonene, myrcene, linalool, alpha bisabolol, delta 3 carene, borneol, alpha-pinene, beta- pinene, eucalyptol, terpineol, caryophyllene, camphene, and combinations thereof.

30. The formulation of claim 28, wherein the solvent is ethanol.

31. A method for treating a disease in a subject, the method comprising administering to the subject a formulation according to any one of the claims 1-30.

32. The method of claim 31, wherein the disease is selected from a skin disease or disorder, pain associated with cancer, neuropathic pain and HIV-associated sensory neuropathy, side effects of chemotherapy including nausea and pain, symptoms of neurological and neurodegenerative diseases such as Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, post-traumatic stress disorder (PTSD), alcohol abuse, bipolar disorder, depression, anorexia nervosa; cancer such as gliomas, leukemia, skin tumors, colorectal cancer; diseases including hepatitis C, methicillin-resistant Staphylococcus aureus (MRSA), pruritus, psoriasis, asthma, sickle-cell disease, sleep apnea, digestive diseases, collagen- induced arthritis, atherosclerosis and dystonia.

33. The method of claim 31, wherein said administration is a topical administration.

34. The method of claim 31, wherein said administration is a transdermal

administration.

35. The method of claim 32, wherein said skin disease is an itch, inflammation, or pain.

36. A method for manufacturing a formulation of any one of claims 1-30, the method comprising the steps of:

providing one or more cannabinoids;

providing one or more phyto-compound excipients; and

mixing said one or more cannabinoids with said one or more phyto-compound excipients.

37. A device comprising a formulation according to any one of the claims 1-30.

38. The device of claim 37, wherein said device comprises a regulated pump.

39. The device of claim 37, wherein said device comprises a metered-dosing mechanism.

40. The device of claim 37, wherein said device comprises an air-tight container to store said formulation.

41. The device of claim 37, wherein said device comprises said formulation in a plurality of metered doses.

42. The device of claim 37, wherein said device is an aerosol spray device.