OILY FORMULATIONS OF CANNABINOIDS

Abstract

The invention relates to cannabinoid solutions in a mixture of sesame oil, amaranth oil and squalene. The invention also relates to pharmaceutical or nutraceutical formulations comprising said solutions.

Claims

1. Cannabinoid solutions in a mixture of sesame oil, amaranth oil and squalene.

2. Solutions according to claim 1 wherein the cannabinoids are selected from cannabidiol and cannabigerol.

3. Solutions according to claim 2 wherein the cannabidiol is in the form of a hydro-ethanolic extract of Cannabis sativa free of delta-9-tetrahydrocannabinol with a cannabidiol titre of 75-85%.

4. Solutions according to claim 1, wherein the ratio by weight of sesame oil, amaranth oil and squalene ranges between 100:100:1 and 100:5:0.1.

5. Solutions according to claim 1, wherein the weight ratio of cannabinoids to the mixture of oils and squalene ranges between 10:1 and 1:10.

6. Nutraceutical, pharmaceutical or cosmetic formulation comprising the solutions of claim 1.

7. Formulations according to claim 6 further comprising antioxidants selected from vitamins, N-acetyl-cysteine, lipoic acid, CoQ10, omega-3 fatty acids, polyphenols.

8. Formulations according to claim 6 in the form of capsules, tablets, sachets, sublingual sprays, gels, emulsions, ointments, transdermal patches for local release, ready-made solutions or solutions to be reconstituted.

Description

DESCRIPTION OF THE INVENTION

[0011] It has now been found that sesame oil, combined with amaranth oil (both in winterized and non-winterized form), added with squalene (between 0.1 and 50% in the final blend) in the formulation of pure cannabidiol (either in amorphous form obtained by extraction or in crystalline form obtained by synthesis) or blended (1 to 99%) with other cannabinoids and cannabis terpenes, allows an important kinetic gain and a substantial improvement in the stability of CBD itself.

[0012] Winterized form means a form that has undergone winterization, i.e. fractional crystallization carried out to achieve separation of various fractions with different melting temperatures.

[0013] The invention, in a first aspect, therefore relates to solutions of cannabinoids, in particular cannabidiol and cannabigerol, in a mixture of sesame oil, amaranth oil and squalene.

[0014] In another aspect, the invention provides nutraceutical, pharmaceutical or cosmetic formulations comprising said solutions.

[0015] Cannabidiol can be used as a substantially pure compound or in the form of a hydro-ethanolic extract of Cannabis sativa free of delta-9-tetrahydrocannabinol with a 75-85% cannabidiol content.

[0016] A preferred extract has the following specifications:

TABLE-US-00001 Colour: Yellow-orange to dark red dark (Visual/Colorimetric) Water activity: <0.6 WA (dual sensor) Transparency: Transparent (Visual/Microscopic) Particles: absent (Visual/microscope) Solubility: Soluble in oils and alcohols Chlorophylls: <1% (Spectrophotometric) Total sesquiterpenes >1% GCMS (sum of Beta-caryophyllene, alpha-humulene, nerolidol, caryophyllene oxide, guaiol, alpha-bisabolol): Total CBD (CBD + CBDA): 75-85% (HPLC) Delta-9-tetrahydrocannabinol: not detected (HPLC/GCMS) CBD/THC ratio: >1000 (HPLC) CBN: <0.2% (HPLC) CBG: 0.8-1% (HPLC) % decarboxylation: >95% (total CBD/CBD)

[0017] The weight ratio of sesame oil, amaranth oil and squalene in the solutions of the invention is not critical, but is in principle between 100:100:1 and 100:5:0.1, while the weight ratio of cannabinoids to the mixture of oils and squalene is between 10:1 and 1:10.

[0018] The formulations comprising the solutions of the invention may further contain antioxidants selected from vitamins, N-acetyl-cysteine, lipoic acid, CoQ10, omega-3 fatty acids, polyphenols.

[0019] Examples of formulations include capsules, tablets, sachets, sublingual sprays, gels, emulsions, ointments, transdermal patches for local release, and ready-made solutions or solutions to be reconstituted.

Pharmacological Experimentation

[0020] Data obtained in mice and rats demonstrated an increase in oral bioavailability for CBD from 5-6%, when administered as an unformulated oil extract, to approximately 50 and 60% (in mice and rats respectively). The use of sesame oil alone produced a kinetic detection of 25-30% in both animal models.

[0021] With regard to stability, the studies underlying the present invention revealed, at room temperature and in the dark, a degradation of CBD at 3 months of 11 and 8% respectively when in pure form (both amorphous and crystalline) or when in products obtained by ethanolic extraction from cannabis. When CBD was solubilised in sesame oil or amaranth oil or in squalene alone, the instability did not show a statistically significant difference. When CBD was formulated in a mixture of sesame oil, amaranth and squalene (with the latter at least 0.1%), the degradation rates under the same conditions dropped to 4 and 3%, respectively.

[0022] The obtained results show that the use of mixtures of sesame oil, amaranth oil and squalene improves both the absorption and stability of CBD.

Formulation Examples

[0023] 1) Soft gelatine capsule

TABLE-US-00002 Ingredient Quantity Cannabis oil extract (50% CBD) 250 mg Sesame oil 100 mg Amaranth oil 10 mg Squalene 1 mg Vitamin E 0.01 mg Other excipients q.s. [0024] 2) Soft gelatine capsule

TABLE-US-00003 Ingredient Quantity Cannabis oil extract (CBD 50%) 400 mg Sesame oil 50 mg Amaranth oil 5 mg Squalene 0.5 mg Omega 3 50 mg Other excipients q.s. [0025] 3) Oily drops for sublingual use:

TABLE-US-00004 Ingredient Quantity Cannabis oil extract (CBD 50%) 100 mg Dietary triglycerides 2.5 mg Sesame oil 25 mg Amaranth oil 2.5 mg Squalene 0.25 mg Vitamin E 3.0 mg Dispersant/emulsifier q.s. [0026] 4) Oily drops for oral/nasal vaporizers and suffumigation:

TABLE-US-00005 Ingredient Quantity Cannabis oil extract (CBD 50%) 200 mg Essential oil of mint 5 mg Essential oil of thyme 0.1 mg Sesame oil 10 mg Amaranth oil 1 mg Squalene 0.10 mg Vitamin E 5.0 mg Dispersant/emulsifier q.s. [0027] 5) Gummy discus for oral use

TABLE-US-00006 Ingredient Quantity Cannabis oil extract (50%) 100 mg Rubber base 100 mg Levilite 20 mg Talc F.U. 20 mg Vegetable magnesium stearate 18 mg Lacquer gum 12 mg Xylitol 250 mg Gum arabic 6 mg Carnauba wax 0.2 mg

[0028] 6) Water-dispersible sachets

TABLE-US-00007 Ingredient Quantity Cannabis oil extract (50%) 250 mg adsorbed with maltodextrins Sucrose 2265 mg Citric acid 50 mg Vitamin C 60 mg Silicon dioxide 20 mg Aroma 150 mg Other excipients q.s. [0029] 7) Effervescent sachets

TABLE-US-00008 Ingredient Quantity Cannabis oil extract (50%) 250 mg adsorbed with maltodextrins Citric acid 500 mg Vitamin C 120 mg Silicon dioxide 400 mg Aroma 150 mg Acesulfame K 15 mg Other excipients q.s. [0030] 8) Gel for skin application:

TABLE-US-00009 Ingredient Quantity Cannabis extract (50%) 2% Sodium hyaluronate 0.5% Vitamin E 0.5% Other excipients q.s.