COMPOSITION CONTAINING CANNABIDIOL/CANNABIS EXTRACT AND CAFFEINE, AND APPLICATION OF COMPOSITION

Abstract

The invention provides a composition comprising cannabidiol or a cannabis extract, and caffein. The mass percentage of the cannabidiol in the cannabis extract is 10%-99%. A mass ratio of the cannabidiol to the caffein in the composition is (1-100):60. The composition can be a food composition or a pharmaceutical composition. The cannabidiol or the cannabis extract can prevent and/or ameliorate adverse reactions induced by the caffeine, and in particular, prevent and/or ameliorate anxiety behaviors induced by the caffeine.

Claims

1-3. (canceled)

4. A pharmaceutical composition, comprising (1) cannabidiol or a cannabis extract, (2) caffeine and (3) a pharmaceutical adjuvant, wherein the cannabis extract contains the cannabidiol, and a mass ratio of the cannabidiol to the caffeine in the pharmaceutical composition is (1-100):60.

5. The pharmaceutical composition according to claim 4, wherein a mass percentage of the cannabidiol in the cannabis extract is 10%-99%.

6. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition comprises 0.1%-1% of the cannabidiol, 0.06%-6% of the caffeine and 93%-99% of the pharmaceutical adjuvant in terms of mass percentage.

7. The pharmaceutical composition according to claim 6, wherein the pharmaceutical adjuvant is one or a combination of two or more selected from a binder, a carrier, a pH regulator, a filler, a disintegrant, a flavoring agent, a stabilizer, a film-forming agent, a plasticizer, a solubilizer, a dispersant, a wetting agent, a solvent, a coating agent, a capsule shell, a colorant, a preservative, an antioxidant, a surfactant.

8. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition is tablets, pulvis, capsules, granules, powders, pills, pigmentum for external use, plasters, films, solutions or injections.

9. A food composition, comprising (1) cannabidiol or a cannabis extract, and (2) caffeine, wherein the cannabis extract contains the cannabidiol, and a mass ratio of the cannabidiol to the caffeine in the food composition is (1-100):60.

10. The food composition according to claim 9, wherein a mass percentage of the cannabidiol in the cannabis extract is 10%-99%.

11. The food composition according to claim 9, wherein the food is selected from a beverage, pasta, rice, edible oil, a dairy product, protein powder, porridge, soup, paste, meat, a soy product, chocolate, a candy or jelly.

12. The food composition according to claim 11, wherein the food is the beverage which further comprises a nutritional supplement substance, and the nutritional supplement substance is one or a combination of two or more selected from a vitamin, a trace element, -carotin, an amino acid, an -aminobutyric acid, taurine and a plant extract.

13. The food composition according to claim 12, wherein the beverage further contains an additive, and the additive is one or a combination of two or more selected from spices, fruit and vegetable juice, scented tea juice, a colorant, an acidity regulator, a preservative, an emulsifier, an antioxidant, a thickener, a chelating agent, a stabilizer, and a sweetener.

14. The food composition according to claim 13, wherein the beverage is a liquid beverage or a solid beverage.

15. The food composition according to claim 13, wherein the beverage is a carbonated beverage or a non-carbonated beverage.

16. An application of cannabidiol or a cannabis extract in the preparation of a product for preventing and/or ameliorating adverse reactions of caffeine.

17. The application of the cannabidiol or cannabis extract according to claim 16 in the preparation of a product for preventing and/or ameliorating adverse reactions of caffeine, wherein the preventing and/or ameliorating the adverse reactions of the caffeine is preventing and/or ameliorating anxiety behaviors induced by the caffeine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0082] The technical solution in the embodiments of the present invention will be illustrated clearly and completely below. It is obvious that the embodiments described are merely some of the embodiments of the present invention, but not all of the embodiments. Based on the embodiments in the present invention, any other embodiments obtained by those ordinarily skilled in the art without making inventive efforts shall fall within the protection scope of the present invention.

Embodiment 1 Preparation of Cannabis Extract

[0083] (1) Cannabis leaves used as raw materials were washed and air-dried.

[0084] (2) The air-dried raw materials described above were crushed and then sieved through a 40-mesh sieve.

[0085] (3) Resulting powder was cold-extracted with 45% ethanol 6 times the amount of the powder 2 times, for 1.5 hours each time;

[0086] (4) Extracting solutions were combined and then adsorbed with 0.5 wt % activated carbon for decolourization.

[0087] (5) At the temperature of 70 C., the concentrating was performed under reduced pressure to reach a relative density of 1.02 to obtain the cannabis extract,

[0088] Among them, the mass content of the cannabidiol contained in the cannabis extract is 50%.

Embodiment 2 Preparation of Cannabis Extract

[0089] (1) Cannabis leaves used as raw materials were washed and air-dried.

[0090] (2) The air-dried cannabis leaves from step (1) was heated for refluxing for 1 hour using 60% ethanol 9 times the amount of the cannabis leaves.

[0091] (3) The residues were removed by filtration and the solvent was removed under vacuum.

[0092] (4) The obtained extractum was heated at the temperature of about 125 C. for about 40 minutes.

[0093] (5) Chromatographic separation was subsequently performed to obtain the cannabis extract, wherein a mobile phase mixture consists of ethanol/water and acetic acid.

[0094] Among them, the mass content of the cannabidiol contained in the cannabis extract is 90%.

Embodiment 3 Preparation of Cannabis Extract

[0095] (1) Cannabis leaves used as raw materials were washed and air-dried.

[0096] (2) The air-dried cannabis leaves from Step (1) was heated for refluxing for 1.5 hour using 80% ethanol 7 times the amount of the cannabis leaves.

[0097] (3) Residues were removed by filtration.

[0098] (4) Liquid-liquid extraction was performed at least twice with 5 wt % of sodium hydroxide aqueous solution. Among them, the sodium hydroxide aqueous solution contains 20 wt % of ethanol.

[0099] (5) A liquid-liquid extracting solution was mixed with 5 wt % of a sulfuric acid solution to regulate the pH value to about 3.

[0100] (6) Then, extraction was performed twice using aliphatic hydrocarbons, and the solvent was removed at low temperature under vacuum.

[0101] (7) Chromatographic separation was subsequently performed to obtain the cannabis extract, wherein a mobile phase mixture consists of ethanol/water and acetic acid.

[0102] Among them, the mass content of the cannabidiol contained in the cannabis extract is 99%.

Embodiment 4 Preparation of Cannabis Extract

[0103] (1) Cannabis leaves used as raw materials were washed and air-dried.

[0104] (2) The air-dried raw materials described above were crushed and then sieved through a 10-mesh sieve.

[0105] (3) Resulting powder was cold-extracted 2 times with 30% ethanol 2 times the amount of the powder, for 1 hours each time;

[0106] (4) Extracting solutions were combined and then adsorbed with 0.5 wt % activated carbon for decolourization.

[0107] (5) At room temperature, the concentration was performed under reduced pressure to reach a relative density of 1.02 to obtain the cannabis extract,

[0108] Among them, the mass content of the cannabidiol contained in the cannabis extract is 10%.

Embodiment 5 Preparation of Pharmaceutical Composition Tablets

[0109] I. Raw Materials (Mass Percentage)

[0110] 0.2% of cannabis extract (obtained in Embodiment 1), 6% of caffeine, 84% of dextrin, 7% of sodium carboxymethyl starch, and 2.8% of magnesium stearate.

[0111] II. Preparation Method

[0112] The cannabis extract and the caffeine were sieved and then mixed with dextrin and sodium carboxymethyl starch till a homogeneous mixture is formed. The mixture is then sieved and then mixed with magnesium stearate. Then, the resulting powder-type mixture is compressed into tablets of desired shape and size to obtain pharmaceutical tablets.

Embodiment 6 Preparation of Pharmaceutical Composition Films

[0113] I. Raw Materials (Mass Percentage)

[0114] 0.66% of a cannabis extract (prepared in Embodiment 2), 0.36% of caffeine, 85% of maltodextrin, 10% of mannitol, 0.08% of sodium benzoate, 1.79% of trichlorosucrose, 0.11% of citric acid and 2% of microcrystalline cellulose.

[0115] II. Preparation Method

[0116] a) The maltodextrin was swelled to obtain colloidal maltodextrin.

[0117] b) The cannabis extract, the caffeine, the sodium benzoate, the trichlorosucrose, the citric acid, the microcrystalline cellulose, and the mannitol were added to the colloidal maltodextrin obtained in Step a) to obtain a colloidal mixture.

[0118] c) The colloidal mixture obtained in Step b) was formed into a thin film by using a scraping method;

[0119] d) The film obtained in Step c) was dried to obtain a pharmaceutical film.

Embodiment 7 Preparation of Pharmaceutical Composition Capsules

[0120] I. Raw Materials (Mass Percentage)

[0121] 2% of cannabis extract (obtained in Embodiment 3), 2% of caffeine, 42% of microcrystalline cellulose, 42% of pregelatinized starch, 10% of croscarmellose and 2% of magnesium stearate.

[0122] II. Preparation Method

[0123] The cannabis extract and the caffeine were sieved and mixed with other adjuvants; and a resulting mixture was filled into glutoid capsules to obtain pharmaceutical capsules.

Embodiment 8 Preparation of Pharmaceutical Composition Capsules

[0124] I. Raw Materials (Mass Percentage)

[0125] 2% of cannabis extract (obtained in Embodiment 4), 0.2% of caffeine, 42.9% of microcrystalline cellulose, 42.9% of pregelatinized starch, 10% of croscarmellose and 2% of magnesium stearate.

[0126] II. Preparation Method

[0127] The cannabis extract and the caffeine were sieved and mixed with other adjuvants; and a resulting mixture was filled into glutoid capsules to obtain pharmaceutical capsules.

Embodiment 9 Preparation of Beverage

[0128] I. Raw Materials (Mass Percentage)

[0129] 0.1% of cannabidiol (purity>99%), 0.06% of caffeine, 0.2% of -aminobutyric acid, 4% of guarana extract, 0.2% of theanine, 60% of L-tyrosine, 0.6% of taurine, 0.1% of vitamin E, 20% of concentrated apple juice, 0.4% of stevioside, 2% of chlorophyll, 0.14% of malic acid, and the balance of water.

[0130] II. Preparation Method

[0131] a) Raw materials were weighed in proportion and placed in a container, and an appropriate amount of water was added to the container.

[0132] b) The container in Step a) was heated, and stirring and mixing was performed to obtain a mixture.

[0133] c) The mixed solution obtained in Step b) was subjected to volume metering to 100 mL, filling, sterilizing at 100 C., and cooling to obtain a beverage.

Embodiment 10 Preparation of Beverage

[0134] I. Raw Materials (Mass Percentage)

[0135] 0.1% of cannabidiol (purity >99%), 6% of caffeine, 0.05% of vitamin C, 0.1% of niacin, 40% of concentrated cherry juice, 3% of sorbitol, 0.4% of chlorophyll, 0.1% of iron oxide, 0.15% of ascorbic acid and the balance of water.

[0136] II. Preparation Method

[0137] a) Raw materials were weighed in proportion and placed in a container, and an appropriate amount of water was added to the container.

[0138] b) The container in Step a) was heated, and stirring and mixing was performed to obtain a mixture.

[0139] c) The mixed solution obtained in Step b) was added with water to reach a constant volume of 100 mL, filled, sterilized at 75 C., and then cooled to room temperature.

[0140] d) Carbon dioxide was filled so that the gas capacity of the product was 2.0 times (at 20 C.) that of the beverage to obtain a beverage.

Embodiment 11 Preparation of Beverage

[0141] I. Raw Materials (Mass Percentage)

[0142] 1% of cannabidiol (purity >99%), 0.6% of caffeine, 0.15% of -carotene, 0.08% of phenethylamine, 4% of aspartame, 0.1% of citric acid, 0.12% of calcium benzoate, and the balance of milk wine.

[0143] II. Preparation Method

[0144] a) Raw materials were weighed in proportion and placed in a container, and an appropriate amount of water was added to the container.

[0145] b) The container in Step a) was heated, and stirring and mixing was performed to obtain a mixture.

[0146] c) The mixed solution obtained in Step b) was added with milk wine to reach a constant volume of 100 mL, filled, sterilized at 130 C., and cooled in sequence to obtain a beverage.

Embodiment 12 Preparation of Beverage

[0147] I. Raw Materials (Mass Percentage)

[0148] 0.1% of cannabis extract (obtained in Embodiment 3), 0.2% of caffeine, 0.1% of vitamin E, 0.05% of inositol, 0.08% of glycine, 50% of L-tyrosine, 25% of grape juice, 0.08% of phenethylamine, 4% of sorbitol, 0.09% of amaranth red, 0.2% of malic acid, 0.1% of heptyl p-hydroxybenzoate, and the balance of water.

[0149] II. Preparation Method

[0150] a) Raw materials were weighed in proportion and placed in a container, and an appropriate amount of water was added to the container.

[0151] b) The container in Step a) was heated, and stirring and mixing was performed to obtain a mixture.

[0152] c) The mixed solution obtained in Step b) was added with water to reach a constant volume of 100 mL, filled, sterilized at 130 C., and cooled in sequence to obtain a beverage.

Embodiment 13 Preparation of Beverage

[0153] I. Raw Materials (Mass Percentage)

[0154] 10% of cannabis extract (obtained in Embodiment 4), 1% of caffeine, 0.15% of -carotene, 0.09% of vitamin C, 0.08% of phenethylamine, 4% of guarana extract, 30% of mango juice, 3% of maltitol, 0.1% of sodium citrate, 0.12% of sodium benzoate, and the balance of water.

[0155] II. Preparation Method

[0156] a) Raw materials were weighed in proportion and placed in a container, and an appropriate amount of water was added to the container.

[0157] b) The container in Step a) was heated, and stirring and mixing was performed to obtain a mixture.

[0158] c) The mixed solution obtained in Step b) was added with water to reach a constant volume of 100 mL, filled, sterilized at 130 C., and cooled in sequence to obtain a beverage.

Embodiment 14 Amelioration of Anxiety Behaviors Induced by Caffeine with Cannabidiol (CBD)

[0159] Test 1

[0160] I. Objective

[0161] To study the effect of different doses of CBD on preventing and treating rat anxiety behavior induced by high-dose intake of caffeine.

[0162] II. Test Animals and Groups

[0163] Test Animals: 50 SPF male wistar rats (180-200 g). Feeding Conditions: SPF animal houses, free feeding, 12 h light/12 h darkness.

[0164] Test Groups: After one week of adaptive feeding, rats were randomly divided into 5 groups as follows according to body weights: a normal control group, a caffeine model group, a CBD-1 mg/kg group, a CBD-10 mg/kg group, and a CBD-100 mg/kg group. Except for the normal control group, animals in other groups were intragastrically administrated with 60 mg/kg caffeine saline solution. Each CBD administration group was also intragastrically administrated with a corresponding dose of a CBD soybean oil solution at the same time, and then an elevated plus-maze test was conducted within 30 minutes after administration.

[0165] III. Test Methodology

[0166] Elevated Plus-maze (EMP) Test: A maze was cross-shaped and consists of 2 open arms (OAs), two closed arms (CAs) and a central platform. The maze was fixed on a support, 50 cm above the ground. A camera was placed above the central platform. The behaviors of rats were recorded and analyzed through a computer. The test was conducted in a quiet shaded condition. Before the test, the rats to be tested were placed in one rat cage. After freely exploring for 5 minutes, the rats were quickly placed on the central platform of the EMP. The observation test was started immediately after release. Each rat was tested for five minutes. After each rat was tested, the maze was thoroughly cleaned with a towel dipped in clean water and low-concentration ethanol. After the ethanol volatilizes and diffuses, the test on the next rat began.

[0167] Test Items:

[0168] (1) Open arm entry (OE): the number of entries into any open arm was based on the fact that four paws of each rat were located within the arms, and when any paw was completely withdrawn from the arms halfway, the current entry event was deemed as being completed.

[0169] (2) Open arm time (OT): it was measured in second.

[0170] (3) Closed arm entry (CE): the number of entries into any closed arm, which was determined based on the same standard as OE.

[0171] (4) Closed arm time (CT): it was measured in second.

[0172] (5) Calculation of the proportion of the number of entries into the open arm (OE %): namely, OE/(OE+CE)100%.

[0173] (6) Proportion of residence time in the open arms (OT %): namely, OT/(OT+CT)100%. OE % and OT % were used as indexes for evaluating the anxiety state of rats.

[0174] Statistical Method:

[0175] The data was expressed with xs. One-way analysis of variance (one way ANOVA) was used to compare multi-sample means, and t test was used for inter-group comparison.

[0176] IV. Results

[0177] The number, time and ratio of the entries into the arms are shown in Table 1.

TABLE-US-00001 TABLE 1 Number, time and ratio of entries into arms OE (times) OT (s) OE % OT % CE (times) CT (s) Normal Control 5.3 0.48 105 4.52 52.94 34.4 4.8 0.68 200 1.24 Caffeine Model 2.1 0.78 42.9 1.89 21.21 14.50 7.8 0.11 253 5.09 CBD-1 mg/kg 3.2 0.45 58.1 3.30 31.37 19.24 7.0 0.92 244 5.14 CBD-10 mg/kg 4.8 0.91 85 2.07 47.52 28.43 5.3 1.07 214 4.01 CBD-100 mg/kg 5.4 0.25 100 1.32 54.00 33.22 4.5 0.91 201 3.05

[0178] From Table 1, it can be seen that CBD shows a significant effect on inhibiting the anxiety behavior of rats. The OE % of the caffeine model group is 21.21%; there is a large slope from CBD-1 mg/kg to CBD-10 mg/kg after the intragastric administration for the rats, exhibiting significant amelioration of the anxiety behavior; but the slope from CBD-10 mg/kg to CBD-100 mg/kg after intragagstric administration is slightly smaller than before, exhibiting certain amelioration of the anxiety behavior.

[0179] Test 2

[0180] I. Test Animals and Groups

[0181] Test Animals: 100 SPF male wistar rats (180-200 g). Feeding Conditions: SPF animal houses, free feeding, 12 h light/12 h darkness.

[0182] Test Groups: After one week of adaptive feeding, rats were randomly divided into 10 groups as follows according to body weight: a normal control group, a group A (prepared in Embodiment 5), a group B (prepared in Embodiment 6), a group C (prepared in Embodiment 7), a group D (prepared in Embodiment 9), a group E (prepared in Embodiment 10), a group F (prepared in Embodiment 11), a group G (prepared in Embodiment 8), a group H (prepared in Embodiment 12) and a group I (prepared in Embodiment 13). Except for the normal control group (intragagstric administration with normal saline), all the administration groups were intragagstrically administrated with the pharmaceutical composition or 50 mL of beverage; an elevated plus-maze test was conducted within 30 min after the administration; and the rats were measured in blood pressure non-invasively after the behavioral test was ended.

[0183] II. Test Methodology and Test Consistency

[0184] III. Test Results

[0185] The number, time and ratio of the entries into the arms are shown in Table 2.

TABLE-US-00002 TABLE 2 Results of the ratios of number of entries into the open arms and the ratios of time thereof Normal Control A B C D E F G H I OE % 52.94 47.17 52.80 50.12 53.14 47.87 51.91 49.14 48.52 49.98 OT % 34.41 30.10 33.19 32.18 34.74 30.73 33.92 31.96 31.00 31.79

[0186] From Table 2, it can be seen that the ratio of the number of entries into the open arms and the ratios of time thereof for the rats administered with the products of Embodiments 5-13 (the groups A-I) are similar to those under normal conditions. That is, the rats basically have no anxiety behaviors compared with the normal control group. Meanwhile, the caffeine model groups show the OE % of 21.21% according to Experiment 1, showing obvious anxiety behaviors. That is to say, the administration of the pharmaceutical composition or beverage prepared in the embodiments of the invention will not induce anxiety behaviors. This partly demonstrates that the cannabis extract or the cannabidiol has a significant effect on inhibiting the anxiety behaviors induced by the caffeine in rats. In particular, the rats in groups B, F and D basically show no excessive anxiety behaviors, and the blood pressure of the rats in groups A-I were within the normal range after the test.

[0187] The preferred embodiments of the invention are described in detail above, but the invention is not limited to the specific details in the above embodiments. Various simple modifications can be made to the technical solutions of the invention within the scope of the technical idea of the invention. All of these simple modifications belong to the protection scope of the invention.

[0188] In addition, it should be noted that the specific technical features described in the above specific embodiments can be combined in any suitable manner without contradictions. To avoid unnecessary repetition, the invention will not make separate explanation for the various possible combinations.