WO2017193110A1 - Cannabinoid compositions for sublingual spray nebulizer - Google Patents

Abstract

A composition for pulmonary administration includes a cannabis extract, cyclodextrin, ethanol and emulsifiers. The composition is prepared by combining cyclodextrin to propylene glycol, adding ethanol and then slowly adding cannabis extract. The composition is suitable for sublingual or pulmonary administration using a nebulizer.

Description

TITLE OF INVENTION

C ANN AB INOID COMPOSITIONS FOR SUBLINGUAL SPRAY NEBULIZER

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Serial No. 62/333,086 filed on May 6, 2017,the contents of which are hereby incorporated in their entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

NAMES OF PARTIES TO A JOINT RESEARCH AGREEMENT Not Applicable

REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED ON A COMPACT DISC AND INCORPORATION-BY-REFERENCE OF THE MATERIAL

Not Applicable.

COPYRIGHT NOTICE

Not Applicable

BACKGROUND OF THE INVENTION Field of the Invention:

[001] The present invention relates to a systems and methods for formulating a composition having cannabis extracts suitable for sublingual or pulmonary administration by a nebulizer. More particularly, the invention relates to preparation of a composition for sublingual administration including a cannabis extract, cyclodextrin, ethanol and emulsifiers.

Description of the Related Art:

[002] Over the past several years, marijuana or its components have been reported in the scientific literature to counter the symptoms of a broad range of conditions including multiple sclerosis and other forms of muscular spasm, including uterine and bowel cramps; movement disorders; pain, including migraine headache; glaucoma, asthma, inflammation, insomnia, and high blood pressure. There may also be utility for cannabinoids as an oxytoxic, anxiolytic, anti-convulsive, anti-depressant and anti-psychotic agent, or anti-cancer agent, as well as an appetite stimulant.

[003] Over 60 chemically related compounds, collectively classified as cannabinoids, have been isolated from Cannabis sativa L., including tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). The cannabinoids can be isolated from Cannabis sativa L. or they can comprise synthetic analogs of these compounds. With the recent relaxation of marijuana laws, the use of cannabinoids for the treatment of the above explained conditions as well as others has become more common. However, suitable mechanisms for efficiently introducing cannabinoids and other components of cannabis oils or cannabis extracts are still being explored. Historically, marijuana has been incinerated and inhaled. Obviously, this is an undesirable method due to the damage caused to the lungs.

[004] One difficulty encountered in developing methods of ingesting marijuana products is that many of the components exhibit low bioavailability due to its poor dissolution properties and high first-pass metabolism. The bioavailability of orally ingested cannabis products ranges from only 6% to approximately 20% depending on the drug vehicle employed.

[005] Cyclodextrins (CDs) are cyclic oligosaccharides consisting of (a-l,4)-linked a-D-glucopyranose units, with a lipophilic central cavity and a hydrophilic outer surface. CDs are able to form inclusion complexes with many drugs by taking up the whole drug, or more commonly, the lipophilic moiety of the molecule, into the cavity. The most abundant natural CDs are a-cyclodextrin (a-CD), β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD), containing six, seven, and eight glucopyranose units, respectively. Of these three CDs, β-CD appears to be the most useful pharmaceutical complexing agent because of its cavity size, availability, low cost and other properties. There are also a number of CD derivatives available, such as hydroxypropyl-P-CD and methylated CDs. One of the major differences between natural CDs and the CD derivatives above is that natural CDs have been shown to form low solubility complexes with various drugs, as opposed to water-soluble CDs derivatives. Water-soluble CD derivatives form only water-soluble complexes with lipophilic drugs.

[006] In drug formulations, CDs have been used mainly to increase the aqueous solubility, stability and bioavailability of various drugs, food additives and cosmetic ingredients. In addition, CDs can also be used to convert liquid compounds into microcrystalline powders, prevent drug-drug or drug-additive interactions, reduce gastro-intenstinal or ocular irritation, and reduce or eliminate unpleasant taste and smell.

[007] Studies dealing with the use of CDs with cannabinoids have reported that THC forms an inclusion complex with natural β-CD with increasing chemical stability of THC. CDs may also be used to improve the aqueous solubility, membrane permeability and bioavailability of THC. ΗΡ-β-CD increases the aqueous solubility of THC and co-administration of small amounts of a water-soluble polymer. Some studies show that hydroxypropyl methylcellulose (HPMC) enhances the complexation between ΗΡ-β- CD and THC. However, these formulations tended me more suitable for tablet or capsule forms of ingestion.

[008] With the rise in popularity of electronic cigarettes and vaporizers, it has become increasingly common to ingest cannabis oils by vaporizing them which involves heating them to a vaporization point and inhaling the heated gas. While this technology appears to be safer than smoking, the process can damage or destroy many of the components of the cannabis oil while simultaneously creating unhealthy oxidation products.

[009] The above-described deficiencies of today's systems are merely intended to provide an overview of some of the problems of conventional systems, and are not intended to be exhaustive. Other problems with the state of the art and corresponding benefits of some of the various non-limiting embodiments may become further apparent upon review of the following detailed description.

[0010] In view of the foregoing, it is desirable to provide methods and systems for providing rapid and stable bioavailability of cannabis extracts and various components found therein. BRIEF SUMMARY OF THE INVENTION

[0011] Disclosed are compositions having cannabis extracts and suitable for administration with a nebulizer.

[0012] In one embodiment, the composition is prepared by adding cylodextrin to propylene glycol, mixed and heated while stirring for 30 minutes at 30° C. Ethanol is then added. Next, Q-naturale then xanthan gum, are added and the composition is heated for 5 minutes while mixing at 30° C. THC Extract and peppermint are separately mixed and heated to 30° C then slowly add to the PG/ethanol phase while stirring. The composition is then mixed until maximum solubility is reached for 10 minutes a 30° C. Additional ethanol may subsequently be added. This final composition and a propellant are then added to a metered dose nebulizer.

[0013] It is therefore an object of the present invention to provide compositions and formulas suitable for use with inhaler devices for efficiently providing bioavailable components of cannabis extracts.

[0014] These and other objects and advantages of the present invention will become apparent from a reading of the attached specification and appended claims. There has thus been outlined, rather broadly, the more important features of the invention in order that the detailed description thereof that follows may be better understood, and in order that the present contribution to the art may be better appreciated. There are features of the invention that will be described hereinafter and which will form the subject matter of the claims appended hereto.

DETAILED DESCRIPTION

[0015] The disclosed subject matter is described with reference to the drawings, wherein like reference numerals are used to refer to like elements throughout. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the various embodiments of the subject disclosure. It may be evident, however, that the disclosed subject matter may be practiced without these specific details. In other instances, well-known structures and devices are shown in block diagram or other generalized form in order to facilitate describing the various embodiments herein.

[0016] The invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.

[0017] In addition, the term "or" is intended to mean an inclusive "or" rather than an exclusive "or." That is, unless specified otherwise, or clear from context, "X employs A or B" is intended to mean any of the natural inclusive permutations. That is, if X employs A; X employs B; or X employs both A and B, then "X employs A or B" is satisfied under any of the foregoing instances. Moreover, articles "a" and "an" as used in the subject specification and annexed drawings should generally be construed to mean "one or more" unless specified otherwise or clear from context to be directed to a singular form.

[0018] Disclosed are compositions and methods for providing bioavailable cannabis extracts and its components. As used herein, the term "cannabis extracts" refers to extracts formed from natural marijuana plants as well as synthetically formulated components such as THC and other cannabinoids and is used herein interchangeably with "cannabis oil," "oil activated THC," "marijuana," "THC extract" and "cannabis." The compositions and methods described herein in accordance with the principles of the invention include combining cannabis extracts with one or more cyclodextrins, solubilizers such as propylene glycol, emulsifiers, flavoring, preservatives, carriers, adjuvants and other components.

[0019] The formulations described herein in accordance with the principles of the invention may also be for pulmonary or sublingual administration.

[0020] A composition in accordance with the principles of the invention includes one or more of an excipient, a rheology agent, a cannabis derivatives, a disaccharide, an oligosaccharide, a cyclodextrin, sugar alcohols, propylene glycol, ethanol, xanthan gum, carboxymethylcellulose, starch, modified starch, pectin, alginates, guar gum, gelatin, and/or carrageenan.

[0021] Cannabinoid extracts typically include naturally occurring terpenes. In one embodiment of the invention, these natural terpenes are removed and supplanted with synthetic terpenes. The naturally occurring cannabinoid terpenes may also be replaced with other naturally occurring terpenes found in fruits and/or vegetables.

[0022] Formulation Example 1

[0023] Process Example 1

The above described may be prepared using the following formulation procedure:

Add cyclodextrin to propylene glycol, mix on magnetic heated stirrer for 30 minutes at 30° C.

Add the balance of the ethanol not used in prep of CD/PG mixture.

Add Q-Naturale then xanthan gun and heat for 5 minutes while mixing at 30° C.

Heat the THC Extract, peppermint oil to 30° C then slowly add to the PG/ethanol phase while stirring.

Magnetically mix unit maximum solubility is reached for 10 minutes a 30° C. Verify total batch volume. If short due to evaporation, add ethanol to achieve final batch volume. The product is now ready.

[0024] The temperatures in the above described process may be varied within 10°C. Similarly, this method may be practiced under different pressure ranges. In addition to the use of magnetic mixers, other more stringent mixers, macerators and other devices may also be used.

[0025] This formulation may be administered using a unit dose or metered dose nebulizer with a suitable propellant. The composition remains stable at room temperature, as well as slightly elevated or lowered temperatures. THC degradation is minimized. The components of a cannabis extract are at least partially emulsified and capable of misting into fine particles when nebulized.

[0026] The compositions described herein may also be used to make compositions for administration by means other than sublingual nebulizers. Compositions may be utilized to create compositions suitable for mists, atomizers, mucosal compositions, ingestion, application using a dropper including administering drops to the nose, eyes and other locations. Composition may also be suitable for use in a breath strip, gum, a lozenge, confections and beverages. Preferably, the composition is optimized to form and sustain a homogenized mixture in a form that is readily susceptible to measurable dosage. The composition may also be Incorporated into an oil that may be applied to the skin, used in cooking or flavoring.

[0027] Whereas, the present invention has been described in relation to the drawings attached hereto, it should be understood that other and further modifications, apart from those shown or suggested herein, may be made within the spirit and scope of this invention. Descriptions of the embodiments shown in the drawings should not be construed as limiting or defining the ordinary and plain meanings of the terms of the claims unless such is explicitly indicated.

[0028] As such, those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.

Claims

1. A method for preparing a cannabis extract composition for pulmonary administration comprising:

adding cylodextrin to propylene glycol, mix on magnetic heated sitter for 30 minutes at 30° C adding balance of ethanol not used in prep of CD/PG extract;

adding q-naturale then xanthan gun / heat for 5minutes while mixing at 30° C;

heating the THC Extract peppermint or to 30° C then slowly add to the PG/ethanol phase mile stirring;

magnetically mixing until maximum solubility is reached for 10 minutes a 30° C;

verifying total batch volume and if short due to evaporation, add ethanol to achieve final batch volume; and,

adding the composition and a propellant to a metered dose nebulizer.