WO2023072954A1

WO2023072954A1 - Topical cannabinoid compositions

Info

Publication number: WO2023072954A1
Application number: PCT/EP2022/079824
Authority: WO
Inventors: Jan HOLMBÄCK; Hadel ONALLAH SAAD; Esmira Naftali
Original assignee: Lipidor Ab
Priority date: 2021-10-25
Filing date: 2022-10-25
Publication date: 2023-05-04

Abstract

Compositions are provided comprising a cannabinoid, in an amount of 5-35 % by weight; a phospholipid, in an amount of 5-25 % by weight; a monoglyceride, in an amount of 2-10 % by weight; and a solvent, wherein the compositions have a water content of 5 % or less. The compositions are suitable for topical administration and have high concentrations of cannabinoids, while maintaining stability and favorable physical and biological characteristics. The compositions are useful for therapeutic or cosmetic treatments.

Description

TOPICAL CANNABINOID COMPOSITIONS

FIELD

Provided herein are compositions for topical administration comprising at least one cannabinoid.

BACKGROUND

Cannabis is a genus of plants comprising the species Cannabis sativa, C. indica, and C. ruderalis. Cannabis plants have been cultivated for a variety of uses including making fibers (hemp), medicinal use and recreational drug use. Cannabis is also commonly known as marijuana.

One of the most common ways that cannabis is used for medicinal use in many countries (also known as medical marijuana) is through smoking. Smoking cannabis is typically performed by using a pipe, by using a water-pipe (also known as a bong) which filters the smoke through water before inhalation or by rolling in paper to form marijuana cigarettes, also known colloquially as "joints." The part of the plant typically used for smoking is the whole flower and budding leaf.

Cannabinoids are compounds active on cannabinoid receptors in humans. Cannabinoids of plant origin, also known as phyto-cannabinoids, are abundant in plants of the Cannabis genus. Two known cannabinoids which are present in relatively high concentrations in Cannabis sativa are tetrahydrocannabinol-acid (THCA) or its decarboxylated product tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) or its decarboxylated product cannabidiol (CBD). Psychoactive and other medical effects of many of the cannabinoids have been studied.

Attempts have been made to prepare compositions comprising CBD for topical administration in the form of roll-on, gel, cream and others. Such products include cbdMD™ available at cbdmd.com, and Joy Organics Premium CBD Salve, available from Joy Organics at https://joyorganics.com/, of Fort Collins, Colorado, USA. However, such compositions typically have low CBD concentrations, at no more than 4% by weight. SUMMARY

Described herein are novel compositions comprising at least one cannabinoid, a phospholipid, and a monoglyceride. These compositions are suitable for topical administration and can include high concentrations of cannabinoids, while maintaining stability and favorable physical and biological characteristics.

Thus, in one aspect, the invention provides a composition comprising a cannabinoid, in an amount of from 5 % to 35 % by weight, such as in an amount of from 7% to 35 % by weight; a phospholipid, in an amount of from 5 % to 25 % by weight; a monoglyceride, in an amount of from 2% to 10 % by weight; and a solvent, wherein the composition has a water content of 5 % or less. In other words, the water content is from 0 % to 5 % by weight of the composition. The composition may be a clear solution. Thus, the composition may be a single-phase homogeneous liquid at room temperature. As used herein, “room temperature” refers to a temperature range of from 18 °C to 25 °C, such as about 20 °C.

The solvent may comprise at least one volatile component, and the solvent may be selected from: C1-C4 alcohol, silicone oil, and mixtures thereof.

The alcohol may be selected from glycerol, ethanol, isopropanol, n-propanol, propylene glycol, and mixtures thereof, or may be selected from glycerol, ethanol, isopropanol, propylene glycol, and mixtures thereof, and may preferably be ethanol.

The silicone oil may be selected from the group consisting of: decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane, and mixtures thereof. The silicone oil may be selected from the group consisting of cyclic or straight chain silicone oils with up to six siloxane units. The silicone oil may be selected from the group consisting of decamethylcyclopentasiloxane and hexamethyldisiloxane.

In embodiments, the solvent may be a mixture of ethanol and silicone oil.

The solvent may be present in the composition an amount of from 10 to 65 %, such as from 20 to 65 %, such as from 30 to 65 %, such as from 40 to 60 % by weight of the composition. The phospholipid may be present in the composition an amount of between 10 and 20 %, such as between 12 and 19 % by weight of the composition. The phospholipid may comprise phosphatidylcholine. Types and origins of phosphatidylcholine is discussed below.

The monoglyceride may be selected from the group consisting of medium chain monoglycerides, such as medium chain monoglycerides containing 40 % by weight or more of Cs-Cio monoacylglycerol, and monoolein, such as monoolein containing 50 % by weight or more of monooleoylglycerol. The monoglyceride may be selected from the group consisting of glycerol monocaprylate, glycerol monocaprate, glycerol monolaurate, glycerol monostearate, glyceryl hydroxystearate and glyceryl monooleate, and may in particular be glyceryl monocaprylate.

In embodiments, the composition may further comprise a fatty acid ester of a Ci- Ci8 monoalcohol, such as of a C1-C3 monoalcohol, in an amount of from 2 to 70 % by weight of the composition. In the case of a fatty acid ester of a C1-C3 monoalcohol, it may preferably be present in an amount of from 2 to 10 % by weight, such as from 2.5 % to 7.5 % by weight, and more preferably about 5 % by weight of the composition. Optionally, the fatty acid ester of a Ci-Cis monoalcohol may be selected from the group consisting of isopropyl myristate, isopropyl palmitate, ethyl oleate, methyl oleate, methyl laurate and coco-caprylate. In one embodiment, the fatty acid ester of a Ci-Cis monoalcohol is isopropyl myristate. When the composition comprises coco-caprylate, coco-caprylate may be present in an amount of from 20 % to 70 %, such as from 30 % to 70 %, such as from 40 % to 65 %, such as from 45 % to 65 %, such as from 50 % to 65 %, such as from 55 % to 65 %; or such as from 40 % to 55 %, by weight of the composition.

The composition may comprise cannabis oil in an amount of from 10 to 50 %, preferably from 20 to 50 %, such as from 25 to 50 %, such as from 30 to 50 %, such as from 33 to 50 %, such as from 35 to 50 %, such as from 40 to 50 %, such as from 45 to 50 % by weight of the composition.

The cannabinoid may comprise at least one of cannabidiol (CBD) and tetrahydracannabinol (THC). In embodiments the cannabinoid may be cannabidiol, tetrahydracannabinol, or a combination thereof. The composition may have at a ratio THC:CBD of from about 1 :20 to about 1: 1, such as from about 1: 19 to about 1: 1, such as from about 1 : 18 to about 1: 1, such as from about 1 : 17 to about 1: 1, such as from about 1 :16 to about 1: 1, such as from about 1 :15 to about 1: 1, such as from about 1: 14 to about 1: 1, such as from about 1 :13 to about 1: 1, such as from about 1: 12 to about 1: 1, such as from about 1: 11 to about 1: 1, such as from about 1: 10 to about 1: 1, such as from about 1:9 to about 1: 1, such as from about 1:8 to about 1: 1, such as from about 1:7 to about 1: 1, such as from about 1 : 6 to about 1: 1, such as from about 1 : 5 to about 1: 1, such as from about 1 : 4 to about 1: 1, such as from about 1 :3 to about 1: 1, such as from about 1 :2 to about 1: 1.

Also described herein are methods of treatment of diseases comprising administering to a patient in need thereof via the topical route, a composition comprising at least one cannabinoid, a phospholipid and a monoglyceride. Thus, for example, the invention provides a composition as described herein for use in treatment of a disease or disorder via topical administration to the skin. The disease or disorder is typically a disease or disorder amenable to topical treatment with a cannabinoid. The disease or disorder may be a skin disorder. The disease or disorder may be selected from the group consisting of psoriasis, dermatitis, wounds or lesions, and local pain. In one embodiment, the disease or disorder is psoriasis. As shown in the appended examples, a composition as disclosed herein is effective in reducing inflammation. In one embodiment, the disease or disorder is dermatitis, such as atopic dermatitis, contact dermatitis, stasis dermatitis and seborrhoeic dermatitis. Dermatitis encompasses conditions caused by inflammation in the skin. Dermatitis may be referred to as “eczema”. The skilled person appreciates that a composition as disclosed herein will be useful in the treatment of various inflammatory skin disorders, such as dermatitis, since the skilled person is aware of the beneficial effects of cannabinoids as inflammation reducing agents. In one embodiment, the disease or disorder is local pain. The skilled person appreciates that a composition as disclosed herein will be useful in the treatment of local pain based on the fact that cannabinoids are known to reduce pain, for example chronic pain.

In a further aspect, there is provided a packaged pharmaceutical composition comprising a composition as defined herein, packaged within a bottle fitted with a spray pump. BRIEF DESCRIPTION OF FIGURES

Fig. 1 is a graph showing average amounts of various cannabinoid compositions permeated through full porcine skins over a 24 hour period in a Franz Cell porcine skin permeability study;

Fig. 2 is a graph showing average amounts of various cannabinoid compositions permeated through stripped porcine skins over a 24 hour period in a Franz Cell porcine skin permeability study; and

Fig. 3 is a bar chart showing maximal ear thickness of mice in a model of imiquimod induced psoriasis after no treatment (2), vehicle (3), or cannabinoid-based composition (4- 6) treatment described herein.

DETAILED DESCRIPTION

Terms

Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise. Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The term “comprises” means “includes.” The abbreviation, “e.g.” is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation “e.g.” is synonymous with the term “for example.”

As used herein, when the term “about” is used in relation to a numerical value, it is to be interpreted as a range of ± 10 %, such as ± 9 %, such as ± 8 %, such as ± 7 %, such as ± 6 %, such as ± 5 %, such as ± 4 %, such as ± 3 %, such as ± 2 %, such as ± 1 %. For example, when the value is stated to be about 10, this means that the value is in fact in the range of from 9 to 11, such as in the range of from 9.9 to 10.9, such as in the range of from 9.8 to 10.8, such as in the range of from 9.7 to 10.7, such as in the range of from 9.6 to 10.6, such as in the range of from 9.5 to 10.5, such as in the range of from 9.4 to 10.4, such as in the range of from 9.3 to 10.3, such as in the range of from 9.2 to 10.2, such as in the range of from 9.1 to 10.1.

The skilled person knows that numerical values relating to measurements are subject to measurement errors which place limits on their accuracy. For this reason, the general convention in the scientific and technical literature is applied: the last decimal place of a numerical value indicates its degree of accuracy. Where no other error margins are given, the maximum margin is ascertained by applying the rounding-off convention to the last decimal place e.g. for a measurement of 3.5 cm, the error margin is 3.45-3.54. When interpreting ranges of values in patent specifications, the skilled person proceeds on the same basis. In case of conflict, the present specification, including explanations of terms, will control. In addition, all the materials, methods, and examples are illustrative and not intended to be limiting.

Cannabinoid: a compound having a cannabinoid structure. Preferably, a phytocannabinoid. A cannabinoid may be produced synthetically, for example, through a chemical synthetic process or by using a biological organism such as a yeast or a bacteria modified to produce the cannabinoid. Alternatively, a cannabinoid may originate from a cannabis plant. A cannabinoid may be isolated, in pure form, or in combination with other cannabinoids.

Cannabis: a plant from the family Cannabaceae, optionally cannabis sativa, indica and ruderalis and fiber-type hemp. Preferably a plant comprising a cannabinoid.

Cannabis oil: A concentrated cannabis plant extract prepared using cannabis inflorescence extracted using a solvent (preferably alcohol, most preferably ethanol). After extraction, the solvent is removed, for example, by evaporation, leaving behind an oil. The cannabis oil is may be used as a source of cannabinoids in the context of the present invention. Preferably, the oil is high in cannabinoids, having 30 % to 90 % cannabinoids, preferably over 50 % cannabinoids, and most preferably between 50 % and 90 %, such as between 60 and 70 %, for example 64 %, and low in residual solvent, preferably lower than 500 ppm. Cannabis oil may further comprise at least one terpene.

CBD: cannabidiol. A cannabinoid having the structure A:

Coco-caprylate: A mixture comprising esters based on coconut oil and caprylic acid, in particular esters formed by a condensation reaction between fatty alcohols derived from coconut and fatty acids comprising caprylic acid. An exemplary coco-caprylate has the CAS Registry number 107525-85-9, and is available from BASF as Cetiol C5.

THC: tetrahydrocannabinol. A cannabinoid having the structure B:

As mentioned above, provided herein are compositions comprising at least one cannabinoid and having enhanced physical and biological characteristics when compared to known cannabinoid compositions.

Preferably, the cannabinoid used is a phyto-cannabinoid. Preferably, it is a phytocannabinoid present in cannabis plant. The cannabinoid may be plant extract. Preferably the cannabinoid is CBD or THC. Thus, preferably the cannabinoid is CBD and/or THC. The THC may be delta9-THC or delta8-THC. Thus, THC may be delta9-THC and/or delta8-THC. Other cannabinoids which can be used in compositions described herein include but are not limited to one or a combination of: cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerol monomethyl ether (CBGM), cannabichromene (CBC), cannabichromanone (CBCN), cannabichromenic acid (CBCA), cannabivarichromene (CBCV), cannabichromevarinic acid (CBCVA), isotetrahydrocannabinol (iso-THC), cannabinol (CBN), cannabinolic acid (CBNA), cannabinol methyl ether (CBNM), cannabinol C4 (CBN-C4), cannabinol C2 (CBN-C2), cannabinol Ci (CBN-Ci), cannabinodiol (CBND), cannabinovarinic acid (CBNVA), cannabinovarin (CBNV), cannabielsoin (CBE), cannabielsoic acid A (CBEA-A), Cannabielsoic acid B (CBEA-B), cannabicyclol (CBL), cannabicycloic acid (CBLA), cannabicyclovarin (CBLV), cannabitriol (CBT), cannabitriolvarin (CBTV), ethoxy-cannabitriolvarin (CBTVE), cannabivarin (CBV), cannabinodivarin (CBVD), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabigerovarin (CBGV), cannabigerovarinic acid (CBGVA), cannabifuran (CBF), dehydrocannabifuran (DCBF), cannabirispol (CBR). The skilled person appreciates that the phyto-cannabinoid(s) present in cannabis plant extract may differ both in amount and type among different plants and plant varieties, thereby providing for different combinations of cannabinoids.

According to an embodiment, the composition comprises an oil prepared by extraction from the cannabis plant. The plant extract may be prepared from extracting dried cannabis inflorescence in an alcohol, preferably ethanol. The plant matter may then be removed, and the alcoholic solvent dried to form a plant extract. The plant extract may comprise between 30 % and 90 %, preferably between 50 % and 90 % by weight of cannabinoids.

Plant inflorescence rich in a specific cannabinoid may be used. For example, inflorescence having high levels of CBD may be used to form extracts with high levels of CBD. Alternatively, plant inflorescence high levels of THC may be used to form extracts with high levels of THC. Various extracts having various ratios of cannabinoids may be used to form compositions described herein. Preferably, the ratio of cannabinoids is THCCBD of 1:20 to 1: 1.

According to an embodiment, compositions described herein comprise high concentrations of cannabis oil. Optionally, the concentration (by weight) of cannabis oil in the compositions is between 10 % and 50 %, such as between 20 % and 50 % of the composition, preferably, 33% or above.

The present composition may comprise at least one cannabinoid, a phospholipid, a monoglyceride, and at least one solvent. The solvent may comprise at least one volatile component, which may form at least 20 % by weight of the total composition. Examples of volatile components include alcohols and volatile silicone oil. In the present context, “volatile” means that the component should evaporate shortly after application of the composition.

The composition is typically free of water, although water may be present in very small amount, e.g. as a minor part of a component described herein. The water content may be 5 % or less by weight of the composition, such as 3 % or less, 2 % or less, or 1 % or less, such about 0 %. Thus, the composition may be essentially free of water. The skilled person appreciates that the term “essentially free of water” does not exclude residual amounts of water, such as residual water originating from the components of the composition. Thus, the composition does not require the components therein to be anhydrous. The composition is essentially not miscible with water and will instead form a two-phase system when water is added in higher amounts, such as when water is added to be present in an amount of over 5 % by weight, such as over 10 % by weight of the composition.

The phospholipid, the monoglyceride and the solvent of the present composition may be referred to as a carrier. The carrier may furthermore comprise additional components that are not pharmaceutically and/or cosmetically active agents. The carrier components may additionally include a fatty acid ester of a Ci-Cis monoalcohol, and optionally other ingredients as outlined below. Useful carrier components are described in WO 2015/072909 Al. For example, the carrier may comprise 20 % by weight of Lipoid S 75, 20 % by weight of methyl laurate, 10 % by weight of MCM, 30 % by weight of ethanol and 20 % by weight of 2-butanol; or the carrier may comprise 20 % by weight of dimyristoylphosphatidylcholine, 20 % by weight of methyl laurate, 10 % by weight of MCM, 30 % by weight of ethanol and 20 % by weight of 2-butanol; or the carrier may comprise 10 % by weight of Lipoid SI 00, 20 % by weight of ethyl oleate, 10 % by weight of monoolein and 60 % by weight of ethanol; or the carrier may comprise 10 % by weight of dioleoylphosphatidylcholine, 20 % by weight of ethyl oleate, 10 % by weight of monoolein and 60 % by weight of ethanol; or the carrier may comprise 20 % by weight of Lipoid SI 00, 10 % by weight of isopropyl palmitate, 10 % by weight of MCM, 20 % by weight of ethanol and 40 % by weight of isopropanol; or the carrier may comprise 20 % by weight of Lipoid S 100, 5 % by weight of isopropyl myristate, 5 % by weight of isopropyl palmitate, 20 % by weight of MCM, 25 % by weight of ethanol and 25 % by weight of isopropanol; or the carrier may comprise 10 % by weight of Lipoid S 100, 10 % by weight of dimyristoylphosphatidylcholine, 5 % by weight of isopropyl myristate, 5 % by weight of isopropyl palmitate, 20 % by weight of MCM, 25 % by weight of ethanol and 25 % by weight of isopropanol; or the carrier may comprise 10 % by weight of Lipoid S 100, 5 % by weight of isopropyl myristate, 5 % by weight of MCM and 80 % by weight of ethanol. Upon addition of a cannabinoid(s), the formulation is referred to as the composition of the invention. The carrier is typically free of water, although water may be present in very small amount, e.g. as a minor part of a component described herein. The water content may be 5 % or less by weight of the composition, such as 3 % or less, 2 % or less, or 1 % or less, such about 0 %. The carrier may be essentially free of water.

Advantageously, the present composition may incorporate a high content of cannabinoid(s), yet forms a clear (transparent) and physically stable solution of low viscosity, which is easily applicable by spraying e.g. to the skin of a subject. The composition is a single-phase, homogeneous liquid that is stable, at room temperature, for an extended period of time, such as for at least 1 day, such as for at least 1 week, such as for at least 1 week, such as for at least 5 week, such as for at least 10 week, such as for at least 15 week, such as for at least 20 week, such as for at least 25 week, such as for at least 30 week, such as for at least 40 week, such as for at least 50 week, such as for at least 1 year, such as for at least 1.5 years, such as for at least 2 years, such as for at least 3 years, such as for at least 4 years, such as for at least 5 years. By “stable” is meant that the composition does not exhibit precipitation, cloudiness, haziness or phase separation.

Upon administration of the composition onto a surface, the volatile component of the solvent evaporates and leaves a thin, coherent lipid layer incorporating the cannabinoid. The lipid layer thus formed is useful for topical delivery of the cannabinoid to the skin and further via diffusion or penetration through the skin into adjacent tissue. The composition comprises a phospholipid, typically in an amount of from 5 % to 25 % by weight of the composition, such as from about 7.5 % to about 20 %, or from 10 % to 20 %, or from 12 % to 19 % by weight of the composition. The phospholipid may be a commercial pharmaceutical or cosmetic grade phospholipid and may be of natural or synthetic origin. Examples of natural origins include lecithin from soybean, sunflower seeds and rapeseed. Preferred is lecithin from soybean or sunflower seeds, or a mixture thereof. Lipoid S 100, Lipoid S 80, Lipoid S 75 and Lipoid H 100, or Lipoid S 100, Lipoid S 75 and Lipoid H lOOare examples of commercial phospholipids supplied by Lipoid AG, Switzerland. Other examples of commercial phospholipids are Leciva S70, Leciva S75, Leciva S80, Leciva S90 and Leciva-S95 supplied by VAV Life Sciences Pvt Ltd, Mumbai, India. Examples of synthetic phospholipids are dioleyolphosphatidylcholine (DOPC), dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLaPC).

The phospholipid typically comprises phosphatidylcholine. Lor example, the phospholipid may contain at least 50 %, such as at least 55 %, such as at least 60 %, such as at least 65 %, such as at least 68 % by weight of phosphatidylcholine. Commercial phospholipid useful in the present composition may also comprise substantial amounts of other polar or non-polar lipids, such as phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and galactolipids, and acylglycerols (mono-, di and triacylglycerols). Lor instance, commercial phospholipid can contain up to about 50 % of mono-, di- and triglycerides.

The monoglyceride of the present composition comprise monoacylglycerol, optionally in mixture with diglycerides (diacylglycerol) and/or triglycerides (triacylglycerol). Lor instance, the monoglyceride may comprise a medium chain monoglyceride, containing 40 % or more of Cs-Cio monoacylglycerol, or monoolein containing 50 % by weight or more of monooleoylglycerol. Examples of monoglycerides useful in the present composition include glycerol monocaprylate, glycerol monocaprate, glycerol monolaurate, glycerol monostearate, glyceryl hydroxystearate and glyceryl monooleate, in particular glycerol monocaprylate, glycerol monocaprate, glycerol monolaurate and glyceryl monooleate. The monoglyceride may be present at a content of from 2 to 20 % by weight of the composition, such as 2 to 10 %, such as from 4 to 6 %, such as about 5 %; or such as from 2 to 3 %, such as about 2.5 %. The solvent of the present composition is a non-aqueous solvent. The solvent may be selected from C1-C4 alcohol, silicone oil, and mixtures thereof. The composition may comprise at least one volatile solvent, also referred to as a volatile component of the solvent. Optionally, the solvent may consist entirely of volatile components as defined herein. For example, the solvent may comprise, or consist of, C1-C4 alcohol and silicone oil, in particular volatile silicone oil.

In this context “volatile” indicates that the component should evaporate shortly after topical administration of the composition onto a subject, typically onto the skin. As used herein, the term “evaporate shortly” refers to the evaporation time after topical administration to the skin and is defined to be 30 minutes or less, such as from 20 minutes or less, such as from 10 minutes or less, such as from 5 minutes or less, such as from 1 minutes or less, such as 30 seconds or less, such as 25 seconds or less, such as 20 seconds or less, such as 15 seconds or less, such as about 7 seconds. The volatile solvent component(s) may have a boiling point of less than 200 °C at atmospheric pressure (1 atm), except for the silicone oil which may have a boiling point of up to 250 °C at 1 atm. Thus in one embodiment, the volatile solvent component(s) has a boiling point of less than 200 °C at atmospheric pressure (1 atm). In one embodiment, wherein the volatile component is silicone oil, the silicone oil has a boiling point of up to 250 °C at 1 atm.

The solvent may form from 10 to 65 % by weight of the composition, such as from 20 to 65 %, such as from 24 to 65 %, such as from 30 to 65 %, such as from 40 to 60 %. The volatile component of the solvent may form from 10 %, such as from 20 % to 65 % by weight of the composition, such as from 24 % to 65 %.

The silicone oil may be a cyclic or linear siloxane. Examples of cyclic siloxanes useful in the present composition include decamethylcyclopentasiloxane (cyclomethicone 5-NF) and dodecamethylcyclohexasiloxane. Preferred examples of linear siloxanes include dimethicones, such as hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, and dodecamethylpentasiloxane. The silicone oil of the present composition may have a boiling point in the range of from 90 to 250 °C, such as 200 °C or less, such as of 150 °C or less, such as of 100 °C or less. The silicone oil may have a heat of vaporization (25 °C) of from 100 to about 300 kJ/kg, such as from 120 kJ/kg to about 200 kJ/kg, such as from 140 kJ/kg to about 180 kJ/kg.

The C1-C4 alcohol may be a monoalcohol, a dialcohol or a trialcohol, such as a C2- C4 monoalcohol. Optionally, the C1-C4 alcohol may be selected from glycerol, ethanol, isopropanol, propylene glycol, and mixtures thereof, and may preferably be ethanol. Advantageously absolute ethanol is used for preparing the present compositions. The Ci- C4 alcohol may be present in the composition at a content of from 10 to 80 %, such as from 10 to 60 %, such as from 10 to 30 %, such as from 12 to 25 % by weight of the composition. In the present context, glycerol is considered a non-volatile solvent.

Optionally, the present composition may additionally contain at least one fatty acid ester of a Ci-Cis monoalcohol, such as of a C1-C3 monoalcohol or of a C12-C18 monoalcohol. The fatty acid ester may be selected from isopropyl myristate, isopropyl palmitate, ethyl oleate, methyl oleate, methyl laurate, coco-caprylate, and mixtures thereof. The fatty acid ester may be present in an amount of from 2 to about 70 % by weight of the composition, such as from 2 to about 60 %, such as from 2 to about 50 %, such as from 2 to about 40 %, such as from 2 to about 30 %, such as from 2 to about 20 %. In particular, a fatty acid ester of a C1-C3 alcohol may be present in an amount of from 2 to 10 % by weight of the composition, such as from 4 to 6 %, e.g. about 5 %. A fatty acid ester of a C12-C18 monoalcohol, such as coco-caprylate, may be present in an amount of from 20 % to 70 % by weight of the composition, such as from 30 % to 70 %, such as from 40 % to 65 %, such as from 45 % to 65 %, such as from 50 % to 65 %, such as from 55 % to 65 %; or such as from 40 % to 55 % , and may be present in addition to a fatty acid ester of a Ci- C3 monoalcohol, such as isopropyl myristate. When present in the composition, coco- caprylate may also be regarded as a non-volatile solvent.

The present composition may optionally contain one or more additional ingredients selected from the group consisting of lactic acid, vitamin E, a triglyceride oil, and an aromatic oil. The aromatic oil may be for instance lavender oil, thyme oil, rosemary oil, eucalyptus oil. An example of a useful triglyceride oil is almond oil. Such additional ingredients may be present in a total amount of up to 5 % by weight of the composition, such as up to 3 %, such as from 0.1 to 3 %. Methods for manufacture:

Compositions described herein may be made using the following method: Preparing a solution comprising a phospholipid and a solvent, and adding a cannabinoid to the solution, preferably preparing a solution comprising a phospholipid, a monoglyceride and a solvent; and adding a cannabinoid or a cannabinoid rich extract to the solution.

Advantages of Compositions Described Herein:

Novel compositions described herein are advantageous relative to other cannabis oil-based compositions in that they are easily sprayed on to the skin, which facilitates administration and accurate dosing. In contrast, conventional creams and ointments are difficult to apply evenly to skin lesions. In addition, the novel compositions facilitate enhanced skin penetration. Furthermore, the present compositions are advantageous in that they can incorporate more than 10 % cannabis oil such as more than 20 % cannabis oil; and/or more than 5% cannabinoid, such as 7% cannabinoid; and can potentially have 20 %, 30 %, 40 % or even 50 % cannabis oil.

In conventional cannabinoid-based topical treatments, which are ointments and creams, cannabinoid active ingredients are not substantially water soluble, and the lipid components are stabilized in a hydrophobic base (ointments) or as lipid-water aggregates or particles (creams), which in both cases complicate interaction with the skin surface. In both cases the initial thick layer needs to be rubbed into the skin before the lipids start to become released from the original ointment/cream system. On the other hand, compositions described herein are preferably free of water and are thereby essentially water free, as discussed above. The compositions described herein comprise preferably lipid soluble components which are dissolved in a volatile, water-free solvent mixture. In the absence of water, lipid soluble components such as phospholipids and monoglycerides, that are less prone to form aggregates in compositions disclosed herein, can therefore move freely in the composition. The low level of aggregation thus results in a low viscous liquid, a low hydrodynamic radius (e.g., as measured by dynamic light scattering) and is also noticeable by a high self-diffusion coefficient for the active component (as measured by NMR diffusion experiments). The low viscosity, low hydrodynamic radius and high self- diffusion coefficient are all signs of a low level of mobility constraints for the active ingredient, thus allowing it to diffuse efficiently into stratum corneum when applied to the skin.

When these compositions are applied onto the skin, the solvent evaporates, and a lipid layer is formed in an immediate interaction with the skin surface. This direct deposition /contact of lipids makes the compositions of the instant application fundamentally different from other cannabinoid dosage forms. The direct deposition of lipids and active compounds leads to highly efficient physicochemical interaction with the skin barrier, resulting in quicker, direct penetration or diffusion into the stratum corneum and potentially a faster onset of action of active compounds. The compositions leave a pleasant feeling on the skin after administration. In particular, the compositions are not greasy and sticky, but rather give a smooth and/or soft feeling on the skin.

Methods for Treatment:

Some embodiments relate to methods for treating a disease comprising administering to a patient in need thereof, a therapeutically effective amount of a composition comprising a cannabinoid, a phospholipid, a solvent and a monoglyceride. The therapeutically effective amount may be an amount, which upon administration to a patient, ameliorates a symptom associated with the disease or modifies the level of a biological marker associated with the disease in the patient. The administration is preferably through the topical route. Optionally, the composition is administered by spraying onto an affected area of the patient’s skin.

According to an embodiment, the disease is psoriasis, dermatitis, wound healing, and/or local pain relief. In one embodiment, the disease or disorder is psoriasis, dermatitis, wounds or lesions, and/or local pain, such as psoriasis, or such as dermatitis, or such as wounds or lesions, or such as local pain. Optionally, the composition is used for cosmetic application to the skin, in particular when CBD is used as the cannabinoid. Exemplary cosmetic applications include: enhancing skin moisture, filling of fine lines, improving skin tone uniformity, skin conditioning, skin soothing and reduction of skin redness.

According to an embodiment, the method of treatment comprises treating a patient in need thereof with the present composition including at least one cannabinoid, for example, THC and/or CBD. The amount of CBD or THC in the composition is optionally in the range of 0.001-20 %, such as 1-20 %, such as 5-35 %, such as 7-35 %, preferably between 7% and 20 %. A dose is preferably between 0.05 ml and 5.0 ml of the composition, preferably between 0.05 ml and 2.0 ml, and may be administered once daily, twice daily, three times daily, or four times daily. Alternatively, the dose may be administered between 1 and 3 times weekly or once every second day. Alternatively, the dose may be administered as needed by the patient.

A problem with topical treatment of skin disorders such as psoriasis, dermatitis and wounds is adequate dosing. While overdosing should be kept at a minimum, underdosing jeopardizes adequate treatment. Conventional creams and ointments are difficult to apply evenly to skin lesions, and thus the risk of wrong dosing is increased with such preparations. Advantageously, the present composition can be applied by spraying and forms an even, homogeneous layer, thus facilitating precise dosing of the cannabinoid.

The following examples are provided to illustrate certain particular features and/or embodiments. These examples should not be construed to limit the disclosure to the particular features or embodiments described.

EXAMPLES

Example 1: Preparation of Cannabis Oil

Cannabis oil was prepared from dried cannabis inflorescence using ethanolic extraction followed by evaporation of the ethanol to achieve a brown sticky extract containing primarily 50 %<cannabinoid <90 % of either THC or CBD, or both, and < 1.5 % of CBN. To clarify, the brown sticky extract comprises more than 50 % to less than 90 % of THC or CBD or a mixture thereof; and less than 1.5 % CBN. Trace amounts of additional cannabinoids can be found at < 5 %.

Example 2A: Preparation of Cannabis Oil-based Compositions for Topical

Administration

The following excipients were used in preparation of cannabis oil- based compositions. The active ingredient used was either cannabis oil manufactured by Cannassure Ltd., Ashdod, Israel as described in Example 1, or Pure Synthetic CBD, purchased from Noramco.

Ethanol Absolute: alcohol which acts as a solvent and a co-solvent. At concentrations around 20 % by weight, alcohol can also act as a preservative.

Cyclomethicone 5 NF: decamethylcyclopentasiloxane, which is a volatile silicone based solvent. Cyclomethicone is used in topical formulations since its low heat of vaporization gives a 'dry' feeling when applied to the skin (no cooling). Cyclomethicone is generally regarded as a relatively nontoxic and non-irritant material.

Three polar lipid materials were used in some of the compositions below:

Lipoid SI 00: soybean phosphatidylcholine. Phosphatidylcholine is a phospholipid which serves as a solubilizing agent. Other phospholipids as described above may also be used. Medium-chain monoglycerides (Capmul MCM C8): Capmul MCM C8 acts as solubilizer and mild penetration enhancer.

Isopropyl myristate (Tegosoft M): a fatty acid ester which functions as emollient, solubilizer, and mild penetration enhancer.

A combination of the polar lipid materials forms a smooth, non-greasy film after evaporation of the volatile ingredients from the skin. The thin film then acts as a carrier for cannabinoids.

Compositions were prepared using the components in the amounts disclosed in Table 1. All values in the table are listed in percentage, as a measure of weight of ingredient relative to total composition weight. Cannabis oil comprised 64% CBD by weight.

Table 1 : amounts are given in % by weight.

The following general process was used for making the seven compositions in Table 1 : When used, Lipoid SI 00 was crushed manually to fine particles when frozen and a Lipoid SI 00 stock solution was prepared by dissolving Lipoid S-100 into absolute ethanol by stirring with a magnetic stirrer for 1 hour at room temperature until fully dissolved and a clear yellow solution was obtained. Cyclomethicone, when used, was added to the clear yellow solution from the previous step and further stirred to achieve homogeneity. Cannabis oil extract or CBD was then added to the solution from step 3 and stirring was carried for additional 30 minutes to 1 hour until Cannabis oil extract / CBD was fully dissolved and the solution color became clear brown. When used, Capmul MCM was added to the clear solution of the previous step and stirring was carried for an additional 30 minutes. When used, isopropyl myristate was added to the solution of the previous step. In those compositions in which isopropyl myristate was not used, a portion of the cyclomethicone was added and further stirred to achieve homogeneity.

Example 2B: Stability of Cannabis Oil Compositions

Compositions described in Example 2A were introduced into 17 mL bag-in-bottle containers made by Gaplast, Germany. Each bottle was equipped with a spray pump configured to give a horizontal dose of 50 mg when the pump button is depressed. The pumps were configured with integrated backflow block to prevent contamination. On the day of preparation, compositions 1, 3, 4, 5, 6 and 7 were all clear, dark brown solutions with no phase separation or precipitation. Composition 2, which only consisted of cyclomethicone and cannabis oil did not show solubility. Compositions 1, 3, 4, 5, 6 and 7 were kept at room temperature in closed containers for 6 months and maintained clear solution without phase separation, precipitation, haziness or color change.

Example 2C: Stability of Cannabis Oil Compositions Under Accelerated Conditions

Composition 4 was prepared as in Example 2A. In addition, a composition 4T was prepared using cannabis oil comprising 64% THC and a composition 4B was prepared using a combination of cannabis oil from various cannabis varietals, the oil comprising 32% THC and 32% CBD.

Cannabinoid concentration was measured using reverse phase HPLC at time of filling (TO) and 1 , 2, 3 and 6 months post filling after being stored at accelerated conditions of 40 °C and 75 % relative humidity. All compositions were found to have acceptable stability and maintained cannabinoid concentrations between 90 % and 110 % relative to TO samples.

Example 3A: Skin Permeability Study.

Cannabinoid-based compositions were prepared in a similar process as described in Example 2A, but for compositions 4 and 6, pure synthetic CBD (purchased from Noramco, Wilmington, Delaware, USA) was used instead of a major portion of the cannabis oil in compositions 4 and 6, and the relative concentration of the cyclomethicone was increased in place of the non-cannabinoid portion of cannabis oil. The amounts of CBD in compositions 4S and 6S are equivalent to the amount of CBD in compositions 4 and 6 respectively. The amounts of ingredients used for compositions 4S and 6S are described in Table 2 below. Table 2: amounts are given in % by weight.

A control composition prepared with 21 % CBD in soybean oil was also prepared by diluting pure synthetic CBD in soybean oil.

In order to determine potential of compositions disclosed herein for dermal/ transdermal delivery system, a model was performed in order to assess percutaneous absorption of molecules. Percutaneous absorption is the penetration of substances into various layers of skin and permeation across the skin into the systemic circulation. Percutaneous absorption of molecules is a stepwise process involving: i. Penetration: The entry of a substance into a particular layer of the skin; ii. Partitioning from the stratum corneum into the aqueous viable epidermis; iii. Diffusion through the viable epidermis and into the upper dermis; iv. Permeation: The penetration of molecules from one layer into another, which is different both functionally and structurally from the first layer; v. Absorption: The uptake of a substance into the systemic circulation.

A surrogate, ex vivo skin model using skin sample from the porcine ear can be used to assess such parameters. The example was intended to determine the Cannabidiol (CBD) 24 hours permeation rate of compositions 4S, 6S and the soybean oil control composition in full and stripped skins. Compositions 4S, 6S and control were tested in 6, 8 and 4 replicates respectively.

Porcine skin samples from ears of animals were prepared as either full skin or stripped ear skin. To prepare stripped ear skin, each piece of the skin was stripped with adhesive tape until the stratum corneum is removed (about 5 times). A Franz cell is a device consists of a small-volume, water-jacketed cell that contains a chamber for drug application, designated the donor chamber, a membrane through which the drug may permeate, and a receptor media chamber from which samples may be extracted and analyzed for drug release. Porcine skin samples were prepared as membranes in Franz cell apparatus and the test drugs were introduced into the donor chamber in amounts of 100 mg in each chamber. The receptor chamber used a cyclodextrin inclusion complex comprising 0.5 % cyclodextrin solution in phosphate buffered saline. Recovered CBD amounts from skins and from receptor chambers were determined using HPLC. A water pump maintained temperature in the receptor chamber at 32 °C.

Cumulative CBD transdermal permeability of the Franz cells represents the average amount of CBD found in the receptor chambers at various time points for various compositions. This data is shown in Figure 1 for full skins and in Figure 2 for stripped skins.

Several conclusions can be drawn from the comparative dermatopharmacokinetic studies. The lowest CBD amount was seen in the control soybean oil-based formulation in both full and stripped skins. The highest CBD amount was found for compositions 6S in both full and stripped skins. About 10 times more CBD diffused through the skin when comparing composition 6S to control in stripped skin and about 7 times through full skins. Composition 4S also showed a much higher permeability through both skin types than the control composition. Both compositions 4S and 6S show similar flux via full skin, however, Composition 6S shows higher flux via stripped skin. Transdermal CBD permeability through stripped porcine skins was increased relative to full skins for all compositions, which is logical due to the fact that the stripped skins, which represent damaged skin, are more permeable. A decrease in CBD amounts after 16 hours was seen in compositions in stripped skin. This decrease may be explained by CBD decomposition after 16 hours.

Example 3B: Psoriasis Study

Psoriasis-like skin inflammation can be induced in mice using a 5 % cream with imiquimod (IMQ) as an active compound. IMQ applied to mouse skin activates inflammatory reactions and induces skin inflammation closely resembling human psoriatic lesions. IMQ-induced skin inflammation enables the assessment of anti-inflammatory potential of novel active ingredients and novel pharmaceutical formulations for the evaluation of new therapies in psoriasis. For this study, IMQ cream, (Aldara 5 %, by 3M Pharmaceuticals UK.) IMQ activates pro inflammatory signaling pathways via the ligation of TLR7/8 upon dermal dendritic cells (DDCs). It is likely that other mechanisms such as NLRP1 inflammasome activation (pyroptosis), direct activation of TRPA1 non-selective cation channels located on immune cells and peripheral nerve endings also contributes to its proinflammatory effects.

In a study, 30 female BALB/C mice, aged 7-8 weeks old and weighing 17-20 grams were acclimated to the study facility for at least 5 days. Animal handling was performed according to guidelines of the National Institute of Health (NIH) and the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC). Animals were provided ad libitum a sterilized, commercial rodent diet, and had free access to acidified autoclaved drinking water obtained from the municipality supply. Animals were housed in air-conditioned animal facility at a temperature from 22±2 °C and RH (Relative Humidity) of 55±15 % and were maintained on alternating 12 hour cycles of light and dark.

Animals were randomly divided into 6 groups of 5 mice in each group. Group 1 was a naive group, which received no IMQ cream. Group 2 was a group which received IMQ cream and no treatment. Group 3 received vehicle only. The vehicle was composition 6 without any cannabinoids. Groups 4-6 received treatment of composition 6 (see Table 1 above), each group receiving a composition with a different ratio of cannabinoids. In group 4, the cannabis oil used for forming the composition was designated C20, and the composition contained 1 % THC and 27.5 % CBD. In group 5, the cannabis oil used for forming the composition was designated Cl 5, and the composition contained 8.9% THC and 20.9% CBD. In group 6, the cannabis oil used for forming the composition was designated CIO, and the composition contained 15.2% THC and 13.8% CBD.

In groups 2-6, skin inflammation was induced as follows. On days 1-6 of the study, mice received a daily topical dose IMQ cream 5 % on the back of 50 mg and on the right ear of 25 mg, equivalent to a daily dose of 3.75 mg of IMQ. Once a day, from day 4 until day 8, treatment or vehicle was administered twice daily in an amount of 50 pl per administration, to the affected area.

Mice were inspected daily for signs of illness. On days 0, 2, 4, 6, 8 and 9 the ear thickness of the right ear was measured using a micrometer. On day 9 the ear thickness was measured after sacrifice. After sacrifice, epidermal thickness in the ear was relatively high in the non-treated and vehicle groups, with respectively 52.4 and 44.2 pm maximal thickness, and relatively lower in Group 4, Group 5 and Group 6 with 35.2, 32.3 and 26.4 pm maximal thickness, respectively. The difference between treated groups 4, 5, 6 in the ear thickness versus the vehicle group was significant and is shown in figure 3 and in Table 3 below.

Table 3: amounts are given in % by weight.

In addition, IL-23 and IL22 cytokine levels were measured in the ear tissue to evaluate the effect of the cannabis compositions on inflammation. The IMQ treatment increased IL-23 and IL22 levels by 1.34 and 19 fold vs. naive animals respectively. The Composition in group 4 reduced the induction to 0.37 and 0.4 fold respectively vs. the no treatment group 2. The composition in group 5 reduced the induction to 0.65 and 0.3 respectively vs. the no treatment group 2. The composition in group 6 reduced the induction to 0.7 and 0.08 respectively vs. the no treatment group.

Composition 6 with a variety of types of cannabis oil was effective in reducing inflammation in the IMQ-induced psoriasis model in mice while not showing any signs of toxicity to the treated mice. This indicates potential of composition 6 and other compositions described herein in treatment of psoriasis and other inflammatory skin conditions. Example 4: Additional Compositions without Silicone

Additional compositions have been prepared with the addition of silicone-free component Cetiol® C5 (coco-caprylate, available from BASF) as an alternative to silicone oil. These compositions have been developed to maintain a high incorporation ability of cannabinoids and polar lipids while maintaining a clear appearance and a low viscosity of the resulting cutaneous solution. In addition, rapid evaporation of a major portion, up to 80 % of the total content, of the cutaneous solution within minutes after application to skin or mucosal membrane should be accomplished. After administration, a polar lipid film containing the active pharmaceutical ingredient after evaporation with ideal cosmetic properties is formed. The compositions are water free.

Novel formulations were prepared with addition of Cetiol® C5 (as alternative to Cyclomethicone) and Glycerol having a concentration of 1-10 % of CBD. Ethanol concentration was 12 to 24%. Cetiol C5 was used at a concentration of 40 to 70 % by weight. Compositions were prepared using the excipients in Table 4. Excipient amounts are expressed in terms of percent weight/weight.

Table 4: amounts are given in % by weight.

The lipid component phospholipid, and Capmul were mixed with absolute ethanol in a suitable clear glass flask. The time required for complete dissolution depends on the amount of lumps in the lipid material and could be as long as 15-20 minutes. Cannabidiol (the required amount to give 1 to 10 %) was weighed in a flask and was dissolved in absolute ethanol. Glycerol was added and mixed.

The two ethanol solutions were combined and mixed well.

Cetiol C5 was then added to the combined ethanol solution. The solution was mixed well by magnetic stirring. Lavender and almond oil were added to the final volume.

The resulting clear yellow solution with a one phase appearance and a low viscosity was filled with 17 mL (15.5 g) in 17 mL Gaplast bag-in-bottle containers. Each container was weighed and capped with the APF+17 pump spray cap. The containers were stored at room temperature, protected from light.

Table 5. Further compositions of the invention; amounts are given in % by weight.

Example 5: NMR Diffusion experiments Proton NMR diffusion measurements are performed on a Bruker 500 MHz

Advance III spectrometer operating at Larmor frequency for protons of 500 MHz and equipped with a dedicated high-field-gradient diffusion setup. A diffusion probe DiffBO with a gradient up to 900 G/cm is used. The 90° pulse width is calibrated to 5 ps. The sample temperature is set to 25 °C. The pulsed-field-gradient (PFG) method based on stimulated echo (STE) is used [Price 1998], In this experiment, the displacements of molecules are monitored via field- gradient-assisted de- and re-phasing of spin coherences. Random molecular translations induce re-phasing errors leading to decreased echo amplitude upon increasing the dephasing efficiency as given by the Stejskal-Tanner relation [Stejskal 1965]:

Equation (1) where g and 3 are the strength and the duration of the applied gradients, respectively; A the diffusion time; D, the self-diffusion coefficient; y the gyromagnetic ratio of the observed nuclei. The signal intensities are recorded on increasing the g and the diffusion coefficient D is calculated by fitting Equation (1) to experimental points. In the measurements 5 is set to 1, A to 20 ms, and g is varied stepwise in the range of 10-640 G/cm.

When measured with the above-described method the cannabinoid in a composition of the invention typically has a diffusion coefficient greater than 0.5 x 10'¹⁰ m²s-¹.

In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as limiting the scope of the invention. Rather, the scope of the invention is defined by the following claims. We therefore claim as our invention all that comes within the scope and spirit of these claims.

REFERENCES

Price, William S., "Pulsed-field gradient nuclear magnetic resonance as a tool for studying translational diffusion: Part II. Experimental aspects." Cone. Magn. Reson. 10 (1998) 197

Stejskal, E. O. and Tanner, J. E., "Spin Diffusion Measurements: Spin Echoes in the Presence of a Time-Dependent Field Gradient" J. Chem. Phys. 42, 288 (1965) ITEMIZED LIST OF EMBODIMENTS

1. A composition comprising a cannabinoid, in an amount of from 5 % to 35 % by weight; a phospholipid, in an amount of from 5 % to 25 % by weight; a monoglyceride, in an amount of from 2% to 10 % by weight; and a solvent, wherein the composition has a water content of 5 % or less.

2. The composition according to item 1, wherein the cannabinoid is present in an amount of from 7% to 35 % by weight.

3. The composition according to item 1 or 2, wherein the composition is a clear solution.

4. The composition according to any one of the preceding items, wherein the solvent comprises at least one volatile component, and wherein the solvent is selected from: Ci- C4 alcohol, silicone oil, and mixtures thereof.

5. The composition according to item 4, wherein the alcohol is selected from glycerol, ethanol, n-propanol, isopropanol, propylene glycol, and mixtures thereof, and is preferably ethanol.

6. The composition according to item 4 or 5, wherein the silicone oil is selected from the group consisting of: decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane, and mixtures thereof, such as selected from list consisting of decamethylcyclopentasiloxane and hexamethyldisiloxane.

7. The composition according to any one of the preceding items, wherein the solvent is a mixture of ethanol and silicone oil. 8. The composition according to any one of the preceding items, wherein the solvent is present in an amount of from 10 to 65 %, such as from 20 to 65 %, such as from 30 to 65 %, such as from 40 to 60 % by weight of the composition.

9. The composition according to any one of the preceding items, wherein the phospholipid is present in an amount of between 10 and 20 %, such as between 12 and 19 % by weight of the composition.

10. The composition according to any one of the previous items, wherein the phospholipid comprises phosphatidylcholine.

11. The composition according to item 10, wherein the phospholipid comprises at least 50 %, such as at least 55 %, such as at least 60 %, such as at least 65 %, such as at least 68 % by weight of phosphatidylcholine.

12. The composition according to any one of the preceding items, wherein the monoglyceride is selected from the group consisting of glycerol monocaprylate, glycerol monocaprate, glycerol monolaurate, glycerol monostearate, glyceryl hydroxystearate and glyceryl monooleate, and preferably is glyceryl monocaprylate.

13. The composition according to any one of the preceding items, further comprising a fatty acid ester of a Ci-Cis monoalcohol, such as of a C1-C3 monoalcohol.

14. The composition according to item 13, wherein the fatty acid ester of a Ci-Cis monoalcohol is present in an amount of from 2 to 70 % by weight or the composition, preferably from 2 to 10 % by weight, such as from 2.5 % to 7.5 % by weight, such as about 5 % by weight of the composition.

15. The composition according to any one of items 13 to 14, wherein the fatty acid ester is selected from the group consisting of isopropyl myristate, isopropyl palmitate, ethyl oleate, methyl oleate, methyl laurate and coco-caprylate, such as from the group consisting of isopropyl myristate.

16. The composition according to any one of the preceding claims, further comprising a fatty acid ester of a Ci-Cis monoalcohol, such as of a C1-C3 monoalcohol, in an amount of from 2 to 70 % by weight or the composition, preferably from 2 to 10 % by weight in the case of a fatty acid ester of a C1-C3 monoalcohol, and more preferably about 5 %, the fatty acid ester optionally being selected from the group consisting of isopropyl myristate, isopropyl palmitate, ethyl oleate, methyl oleate, methyl laurate and coco-caprylate.

17. The composition according to any one of items 12 to 16, comprising coco- caprylate in an amount of from 20 % to 70 %, such as from 30 % to 70 %, such as from 40 % to 65 %, such as from 45 % to 65 %, such as from 50 % to 65 %, such as from 55 % to 65 %; or such as from 40 % to 55 %, by weight of the composition.

18. The composition according to any one of the preceding items, wherein the composition comprises cannabis oil as a source of the cannabinoid, said cannabis oil being present in an amount of from 10 to 50 %, preferably from 20 to 50 %, such as from 25 to 50 %, such as from 30 to 50 %, such as from 33 to 50 %, such as from 35 to 50 %, such as from 40 to 50 %, such as from 45 to 50 % by weight of the composition.

19. The composition according to any one of the preceding items, wherein the cannabinoid is or comprises cannabidiol (CBD) and/or tetrahydrocannabinol (THC).

20. The composition according to item 18, wherein the composition comprises a ratio THC: CBD of from about 1 : 20 to about 1: 1, such as from about 1 : 19 to about 1:1, such as from about 1 : 18 to about 1:1, such as from about 1 : 17 to about 1: 1, such as from about

1 : 16 to about 1: 1, such as from about 1 : 15 to about 1: 1, such as from about 1 : 14 to about 1: 1, such as from about 1 : 13 to about 1: 1, such as from about 1 : 12 to about 1: 1, such as from about 1: 11 to about 1:1, such as from about 1 : 10 to about 1: 1, such as from about 1 : 9 to about 1 :1, such as from about 1 : 8 to about 1:1, such as from about 1 : 7 to about 1: 1, such as from about 1 : 6 to about 1: 1, such as from about 1 : 5 to about 1: 1, such as from about 1 :4 to about 1: 1, such as from about 1 :3 to about 1:1, such as from about 1 :2 to about 1: 1. 21. The composition according to any one of the preceding items, for use in treatment of a disease or disorder via topical administration to the skin.

22. The composition for use according to item 21, wherein the disease or disorder is selected from the group consisting of psoriasis, dermatitis, wounds or lesions, and local pain, such as wherein the disease or disorder is psoriasis.

20. A packaged pharmaceutical composition comprising a composition according to any one of the previous items, packaged within a bottle fitted with a spray pump.

Claims

1. A composition comprising a cannabinoid, in an amount of from 5% to 35 % by weight; a phospholipid, in an amount of from 5 % to 25 % by weight; a monoglyceride, in an amount of from 2% to 10 % by weight; and a solvent, wherein the composition has a water content of from 0 % to 5 % by weight.

2. The composition according to claim 1 , wherein the cannabinoid is present in an amount of from 7% to 35 % by weight.

3. The composition according to claim 1 or 2, wherein the composition is a clear solution.

4. The composition according to any one of the preceding claims, wherein the solvent comprises at least one volatile component, and wherein the solvent is selected from: C1-C4 alcohol, silicone oil, and mixtures thereof.

5. The composition according to claim 4, wherein the alcohol is selected from glycerol, ethanol, isopropanol, propylene glycol, and mixtures thereof, and is preferably ethanol.

6. The composition according to claim 4 or 5, wherein the silicone oil is selected from the group consisting of: decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane, and mixtures thereof.

7. The composition according to any one of the preceding claims, wherein the solvent is a mixture of ethanol and silicone oil.

8. The composition according to any one of the preceding claims, wherein the solvent is present in an amount of from 10 to 65 %, such as from 20 to 65 %, such as from 30 to 65 %, such as from 40 to 60 % by weight of the composition.

9. The composition according to any one of the preceding claims wherein the phospholipid is present in an amount of between 10 and 20 %, such as between 12 and 19 % by weight of the composition.

10. The composition according to any one of the previous claims wherein the phospholipid comprises phosphatidylcholine.

11. The composition according to any one of the preceding claims wherein the monoglyceride is selected from the group consisting of glycerol monocaprylate, glycerol monocaprate, glycerol monolaurate, glycerol monostearate, glyceryl hydroxystearate and glyceryl monooleate, and preferably is glyceryl monocaprylate.

12. The composition according to any one of the preceding claims, further comprising a fatty acid ester of a Ci-Cis monoalcohol, such as of a C1-C3 monoalcohol.

13. The composition according to claim 12, wherein the fatty acid ester of a Ci-Cis monoalcohol is present in an amount of from 2 to 70 % by weight or the composition, preferably from 2 to 10 % by weight, such as from 2.5 % to 7.5 % by weight, such as about 5 % by weight of the composition.

14. The composition according to any one of claims 12 to 13, wherein the fatty acid ester is selected from the group consisting of isopropyl myristate, isopropyl palmitate, ethyl oleate, methyl oleate, methyl laurate and coco-caprylate, such as from the group consisting of isopropyl myristate.

15. The composition according to any one of claims 11 to 14, comprising coco- caprylate in an amount of from 20 % to 70 %, such as from 40 % to 55 %, by weight of the composition.

16. The composition according to any one of the preceding claims wherein the composition comprises cannabis oil in an amount of from 10 to 50 %, preferably from 20 to 50 %, such as from 33 to 50 % by weight of the composition.

17. The composition according to any one of the preceding claims wherein the cannabinoid is or comprises cannabidiol (CBD) and/or tetrahydracannabinol (THC).

18. The composition according to claim 17 wherein the composition comprises a ratio THC: CBD of from 1 : 20 to 1 : 1.

19. The composition according to any one of the preceding claims for use in treatment of a disease or disorder via topical administration to the skin.

20. The composition for use according to claim 19, wherein the disease or disorder is selected from psoriasis, dermatitis, wounds or lesions, and local pain.

21. The composition for use according to claim 20, wherein the disease or disorder is local pain.

22. The composition for use according to claim 20, wherein the disease or disorder is dermatitis.

23. A packaged pharmaceutical composition comprising a composition according to any one of the previous claims, packaged within a bottle fitted with a spray pump.