WO2020075170A1

WO2020075170A1 - Compositions comprising dandelion extract and uses thereof

Info

Publication number: WO2020075170A1
Application number: PCT/IL2019/051105
Authority: WO
Inventors: Khaled Khalil
Original assignee: Canaforte Ltd
Current assignee: Canaforte Ltd
Priority date: 2018-10-12
Filing date: 2019-10-10
Publication date: 2020-04-16
Anticipated expiration: 2021-04-12

Abstract

The present invention provides a Taraxacum plant, e.g., Taraxacum Officinale, extract, for use in the treatment of over acidity; as well as combinations of said extract and either a cannabinoid or a Sinapis plant extract, for use in the treatment of cancer or diseases associated with viral infections, respectively.

Description

COMPOSITIONS COMPRISING DANDELION EXTRACT AND USES THEREOF

TECHNICAL FIELD

[0001] The present invention provides a Taraxacum plant extract for use in the treatment of over acidity, as well as combinations of said extract and either a cannabinoid or a Sinapis plant extract, for use in the treatment of cancer or diseases associated with viral infections, respectively.

BACKGROUND ART

[0002] Taraxacum is a large genus of flowering plants in the family Asteraceae, which consists of species commonly known as dandelions.

[0003] The genus is native to Eurasia and North America, but the two commonplace species worldwide, Taraxacum Officinale and Taraxacum Erythrospermum, were introduced from Europe and now propagate as wildflowers. Both species are edible in their entirety. Like other members of the family Asteraceae, they have very small flowers collected together into a composite flower head. Dandelions are one of the most vital early spring nectar sources for a wide host of pollinators. Many Taraxacum species produce seeds asexually, resulting in offspring that are genetically identical to the parent plant.

[0004] Dandelion has been used in folklore medicine and traditional Chinese medicine in the treatment of inflammation and several women’s disease such as breast ant uterine cancers (Choi et al., 2010). In this respect, CN 106729332 discloses a Chinese herbal composition comprising dandelion as well as golden camellia, folium isatidis, purslane, poria cocos, fructus amomi, white paeony root, radix ophiopogonis, ephedra, puerarin, cinnamon, patrinia, rhizoma phragmitis, rehmannia, aloe, semen cuscutae, moutan bark, albumen powder, and saccharomyces cerevisiae, for preventing and treating bovine rumen acidosis; and CN 101214337 discloses a herbal composition comprising dandelion as well as yanhusuo, nutgrass flastedge, mastic gum, alum and liquorice, for curing gastric and duodenal ulcer.

[0005] The dandelion plant is known for its choleretic, diuretic, and anti-rheumatic properties (Newall et al, 1996). As reported, dandelion leaves produce a diuretic effect; while the roots act as an antiviral agent, appetite stimulant, and digestive aid, and may promote gastrointestinal health. Therefore, health care providers clinically use dandelion root to promote liver detoxification and dandelion leaves to support kidney function (Hu and Kitts, 2003). Additional studies revealed that the leaf extract suppressed the production of tumor necrosis factor (TNF)-a by inhibiting interleukin- 1 production from primary cultures of rat astrocytes, and was protective against cholecystokinin octapeptide induced acute pancreatitis by significantly decreasing the pancreatic weight/body weight ratio in rats (Seo et al, 2005). Dandelion flower extract has antioxidant properties, and dandelion leaf extract has stronger hydrogen peroxide scavenging activity compared with the root extract, due to its high polyphenol content (Schiitz et al, 2006).

[0006] The hepatoprotective activity of dandelion aqueous extract was investigated in D- galactosamine-induced hepatitis in rats, and the plant was also found to be therapeutically effective in treating chemically induced or viral hepatitis (Park et al, 2008).

[0007] Dandelion honey, which is rich in 3-methylpentanitrile and phenylacetonitrile, is recommended for strengthening the immune system, and for use in gastric, intestine, liver and kidney diseases.

[0008] The Taxaracum Oficcinale plant contains various terpenoids such as taraxacin, taraxacerin, betaamyrin, taraxasterol, taraxerol; free sterols such as sitosterin, stigmasterin, and phytosterin; large amounts of polysaccharides such as fructosans, inulin, pectin, resin, and mucilage; and various flavonoids such as caffeic acid, chlorogenic acid, luteolin, and luteolin 7-glucoside. The leaves of the plant further contain appreciable amounts of furan fatty acids. The plant is often used as a biomonitor for environmental pollution, due to the fact that its leaves and roots accumulate metals such as cadmium, cobalt, copper, manganese, and lead (Simon et al, 1996; Williams et al, 1996; Sharafzadeh, 2011).

[0009] The plant is a rich source of vitamins and minerals, such as beta carotene, non provitamin A carotenoids, xanthophylls, chlorophyll, vitamins C and D, many of the B- complex vitamins, choline, iron, silicon, magnesium, sodium, potassium, zinc, manganese, copper, and phosphorous (Popescu et al, 2010).

SUMMARY OF INVENTION

[0010] It has been found, in accordance with the present invention, that a Taraxacum plant (dandelion) extract, more specifically a Taraxacum Officinale extract, is highly effective in treating over acidity and may thus be beneficial in treatment of any disease, disorder or indication associated with over acidity.

[0011] In this respect, and surprisingly, it has been further found that combinations of said extract and a particular additional active agent have unexpected therapeutic effects. As specifically found, a combination of a Taraxacum Officinale extract and cannabidiol (CBD) had synergistic cytotoxic effects on various cancer cell lines such as colorectal carcinoma, breast cancer, and pancreatic cancer cell lines, compared to the effects of each one of said extract and CBD alone; and as indicated by a clinical case study, was highly effective in treatment of B-Cell lymphoma. In addition, a combination of a Taraxacum Officinale extract and a Sinapis plant extract, more specifically a Sinapis Arvensis (also known as Charlock, Charlock mustard, or Wild mustard) extract, had synergistic therapeutic effect in treatment of individuals suffering from influenza, compared to the effects shown by each one of the extracts alone; and was dramatically effective in treatment of an individual having active human immunodeficiency virus (HIV) and suffering from all known symptoms of the disease.

[0012] In one aspect, the present invention thus provides a Taraxacum plant (dandelion) extract, e.g., a Taraxacum Officinale extract, for use in the treatment of over acidity.

[0013] In another aspect, the invention relates to a method for treatment of over acidity in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a dandelion extract, e.g., a Taraxacum Officinale extract.

[0014] In still another aspect, the invention relates to use of a dandelion extract, e.g., a Taraxacum Officinale extract, for preparation of a medicament for treating over acidity.

[0015] In another aspect, the present invention provides a combination comprising, or consisting as active agents of, a dandelion extract, e.g., a Taraxacum Officinale extract, and a cannabinoid such as CBD, or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof, for use in the treatment of cancer.

[0016] In yet another aspect, the invention relates to a method for treatment of cancer in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a combination of a dandelion extract, e.g., a Taraxacum Officinale extract, and a cannabinoid such as CBD, or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof.

[0017] In still another aspect, the invention relates to use of a combination comprising a dandelion extract, e.g., a Taraxacum Officinale extract, and a cannabinoid such as CBD, or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof, for preparation of a medicament for treating cancer. [0018] In another aspect, the present invention provides a Sinapis plant extract, e.g., a Sinapis Arvensis extract, for use in the treatment of a disease, disorder or condition associated with a viral infection.

[0019] In yet another aspect, the invention relates to a method for treatment of a disease, disorder or condition associated with a viral infection in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a Sinapis plant extract, e.g., a Sinapis Arvensis extract.

[0020] In still another aspect, the invention relates to use of a Sinapis plant extract, e.g., a Sinapis Arvensis extract, for preparation of a medicament for treatment of a disease, disorder or condition associated with a viral infection.

[0021] In another aspect, the present invention provides a combination comprising, or consisting as active agents of, a dandelion extract, e.g., a Taraxacum Officinale extract, and a Sinapis plant extract, e.g., a Sinapis Arvensis extract, for use in the treatment of a disease, disorder or condition associated with a viral infection.

[0022] In yet another aspect, the invention relates to a method for treatment of a disease, disorder or condition associated with a viral infection in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a combination of a dandelion extract, e.g., a Taraxacum Officinale extract, and a Sinapis plant extract, e.g., a Sinapis Arvensis extract.

[0023] In still another aspect, the invention relates to use of a combination comprising a dandelion extract, e.g., a Taraxacum Officinale extract, and a Sinapis plant extract, e.g., a Sinapis Arvensis extract, for preparation of a medicament for treating a disease, disorder or condition associated with a viral infection.

[0024] In a further aspect, the present invention provides a composition comprising a combination comprising, as active agents, a dandelion plant extract, e.g., a Taraxacum Officinale extract, and either (a) a cannabinoid or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof; or (b) a Sinapis plant extract, e.g., a Sinapis Arvensis extract. The composition of the invention may be either a pharmaceutical composition of a nutraceutical composition. BRIEF DESCRIPTION OF DRAWINGS

[0025] Fig. 1 shows cell viability curves (OD450 after correction with ODeio and reduction of the background of the medium only) for MDA-MB-231, Capan-l and HCT- 116 cell lines, at different cell numbers per well, after 5 h with XTT, in a 96-well plate.

[0026] Fig. 2 shows the cell viability for MDA-MB-231 cells after 24 h incubation with CBD, Taraxacum Officinale extract, or a combination thereof (Triton 0.1% was used as a positive control), and after 5 h with XTT in a 96-well plate (^*p<0.05, /? <0.01 and

/ <0.001 compared to CBD 10 mM; ^m#p< 0.001 compared to the Taraxacum Officinale extract 0.5 mg/mL).

[0027] Fig. 3 shows the cell viability for MDA-MB-231 cells after 48 h incubation with CBD, Taraxacum Officinale extract, or a combination thereof (Triton 0.1% was used as a positive control), and after 5 h with XTT in a 96-well plate ( /^ <0.01 and / <0.001 compared to the cells alone).

[0028] Fig. 4 shows the cell viability for Capan-l cells after 24 h incubation with CBD, Taraxacum Officinale extract, or a combination thereof (Triton 0.1% was used as a positive control), and after 5 h with XTT in a 96-well plate ( /? <0.01 compared to CBD 10 mM; ^m#p< 0.001 compared to Taraxacum Officinale extract 0.5 mg/mL; and ^@p< 0.05 compared to Taraxacum Officinale extract 1 mg/mL).

[0029] Fig. 5 shows the cell viability for Capan-l cells after 48 h incubation with CBD, Taraxacum Officinale extract, or a combination thereof (Triton 0.1% was used as a positive control), and after 5 h with XTT in a 96-well plate (^***p <0.001 compared to CBD 10 pM; ^mp< 0.01 compared to Taraxacum Officinale extract 0.5 mg/mL; and ^@p< 0.05 compared to Taraxacum Officinale extract 1 mg/mL).

[0030] Fig. 6 shows cell viability curve for HCT-116 cells after 24 h incubation with CBD, Taraxacum Officinale extract, or a combination thereof (Triton 0.1% was used as a positive control), and after 5 h with XTT in a 96-well plate (^***p <0.001 compared to CBD 10 pM; ^###p< 0.001 compared to Taraxacum Officinale extract 0.5 mg/mL; and ^{@ @ @}p<0.00l comped to Dandelion plant extract 1 mg/mL).

[0031] Fig. 7 shows the cell viability for HCT-116 cells after 48 h incubation with CBD, Taraxacum Officinale extract, or a combination thereof (Triton 0.1% was used as a positive control), and after 5 h with XTT in a 96-well plate O <0.001 compared to sells alone). DETAILED DESCRIPTION

[0032] In one aspect, the present invention provides a dandelion extract for use in the treatment of over acidity.

[0033] The term“over acidity” as used herein refers to a medical condition commonly known also as acidosis, in which the kidneys and lungs are not keeping the body’s pH in balance, and excess acid is accumulating in the body. According to the American association for clinical chemistry, the normal pH of the blood should be around 7.4. Acidosis is characterized by a pH level of 7.35 or lower (i.e., when the concentration of H⁺ ions in the bloodstream increases), and alkalosis is characterized by a pH level of 7.45 and higher (i.e., when the concentration of H⁺ ions in the bloodstream decreases). Over acidity is very common, especially in individual suffering from various diseases.

[0034] Over acidity may cause problems such as cardiovascular damage including the constriction of blood vessels and the reduction of oxygen; weight gain, obesity and diabetes; bladder and kidney conditions including kidney stones; immune deficiency; acceleration of free radical damage, possibly contributing to cancerous mutations; premature aging; osteoporosis, weak and brittle bones, hip fractures and bone spurs, joint pain, aching muscles and lactic acid build-up; and low energy and chronic fatigue.

[0035] Once the bodily pH shifts outside of the optimal range, a reduction in the molecular movements of white blood cells toward invading pathogens is seen. Therefore, the overall immune response is weakened when an excessive extracellular pH imbalance occurs. Over acidity condition forces the body to borrow minerals, e.g., calcium, sodium, potassium and magnesium, from organs and bones to neutralize the acid and remove it from the body.

[0036] The three main buffer systems in the body are protein buffer system, phosphate buffer system, and bicarbonate buffer system, wherein each one of these buffers has a different mechanism to neutralize the pH level. The protein buffer system includes inter alia hemoglobin that can bind to small amounts of acid in the blood, thereby helping to remove excess acid before the bodily pH is changed. Many other proteins act as buffers as well. Proteins containing the amino acid histidine are particularly useful as buffers. The phosphate buffer system is comprised of hydrogen phosphate ions and dihydrogen phosphate ions. Hydrogen phosphate ions accept all excess H⁺ ions to re-establish the equilibrium between the hydroxide and hydrogen ions in the blood; and dihydrogen phosphate ions release additional H⁺ ions to reinstate the pH level of the blood to its optimal 7.4 value. The bicarbonate buffer maintains the pH level in the blood, plays a major role in the formation of acid in the stomach, and neutralizes the pH of chyme that enters the small intestine from the stomach. The bicarbonate buffer system also manages the release of excess carbon dioxide as a bi product of cellular respiration.

[0037] Treatment with sodium bicarbonate can usually be used for any type of acidosis and may be carried out by either mouth or in an intravenous (IV) drip to raise the pH level of the blood. The treatment for other types of acidosis can involve treating their cause. Treatments for respiratory acidosis are usually designed to help lungs functioning, e.g., giving drugs to dilate airways, or giving oxygen or a continuous positive airway pressure (CPAP) device. The CPAP device may help in breathing if patient has an obstructed airway or muscle weakness. Patients with hyperchloremic acidosis may be given oral sodium bicarbonate. Acidosis from kidney failure may be treated with sodium citrate. Diabetics with ketoacidosis receive IV fluids and insulin to balance out their pH. Lactic acidosis treatment might include bicarbonate supplements, IV fluids, oxygen, or antibiotics, depending on the cause.

[0038] As shown in the experimental section herein, oral administration of Taraxacum Officinale extract to patients having cancer, diabetes type 2, or hypertension, was therapeutically efficient and led, after a three-month treatment period, to a substantial and incremental reduction of over acidity levels. Specifically, while the average pre-treatment salivary pH of the patient group was 6.25, the post-treatment salivary pH was 7.155, suggesting that the extract administered has primarily effect that supports the liver and immune system functioning.

[0039] Based on these findings it is postulated, that at least some of the minerals contained within the plant, e.g., copper and potassium, are actually used by the buffering system to increase pH level in the case of acidic pH. For instance, copper may help tissues getting a sufficient supply of oxygen, and the body incorporating iron into hemoglobin, which in return can bind to small amounts of acid in the blood thereby helping to remove that acid before it changes the blood's pH. It is thus postulated that the plant extract eases the functionality of the buffer systems in cases of over acidity, thereby inter alia improving the functionality of the immune response.

[0040] The dandelion extract used according to the present invention may be obtainable from any dandelion species, e.g., Taraxacum Officinale or Taraxacum Erythrospermum, but it is preferably a Taraxacum Officinale extract. Such an extract may be obtainable from any part of the plant, e.g., the roots, leaves, seeds, or stem.

[0041] In certain embodiments, the dandelion extract used as disclosed herein is obtainable from the root of said dandelion, e.g., from the root of Taraxacum Officinale , either when fresh or after drying, e.g., in the air. Such an extract may be obtainable, e.g., by extracting the root of said dandelion plant with a solvent, preferably while heating to a temperature up to about 70°C, e.g., from about 50°C to about 70°C; filtering; and optionally drying, e.g., by vacuum while stirring, or by lyophilizing (freeze-drying). The solvent used for the extraction process may be an inorganic solvent such as water, an organic solvent such as ethanol, methanol, and acetone, or a mixture thereof, e.g., a mixture of an organic solvent and water. As shown herein, drying of the extract obtained after the filtration step may be carried out while adding an inert, i.e., pharmaceutically or nutraceutically acceptable, carrier.

[0042] The term "inert carrier” as used herein refers to a pharmaceutically or nutraceutically acceptable agent having essentially no therapeutic properties by itself, that is optionally added to a plant extract referred to herein, during the step of drying, so as prevent aggregation and obtain homogeneous and dispersible dried (i.e., solid) product. The amount of carrier optionally comprised within the final dried product obtained can be up to about 95% or more, but it preferably does not exceed about 90%, by weight. In certain embodiments, the amount of carrier added to the plant extract during drying is determined such that its weight percentage in the final dried product is from about 15% to about 85%, from about 20% to about 80%, from about 30% to about 70%, from about 40% to about 60%, from about 45% to about 55%, or about 50%. Examples of inert carrier that may be used in preparing a solid plant extract referred to herein include, without being limited to, mono-, di- or polysaccharides such as lactose, sucrose, mannitol, sorbitol, or maltodextrin; starch-based materials such as maize starch, wheat starch, rice starch, potato starch, and the like; gelatin; gum tragacanth; phosphates such as calcium phosphate, e.g., dicalcium phosphate, and tricalcium phosphate (TCP); and polymers such as polyvinylpyrrolidone (PVP) and cross-linked PVP; or mixtures thereof. Additional components that may be added during the drying process of the plant extract include binders such as acacia, cornstarch, gelatin, carbomer, ethyl cellulose, guar gum, and povidone; disintegrating agents such as corn starch, potato starch, alginic acid, silicon dioxide, crospovidone, guar gum, and sodium starch glycolate; surfactants such as sodium lauryl sulfate; and lubricants such as stearic acid, magnesium stearate, polyethylene glycol, and sodium lauryl sulfate.

[0043] In particular embodiments, the solvent used for extracting the dandelion plant is a mixture of water and ethanol in a ratio of about 1:1 by volume. In more particular embodiments, the dandelion extract is obtainable by extracting the root of said dandelion plant with said solvent, while heating to a temperature of from about 50°C to about 70°C; filtering; and then drying, e.g., by vacuum while stirring, with an inert carrier, e.g., maltodextrin. In specific such embodiments, the amount of carrier added during the drying step is determined such that the weight percentage of the carrier in the final dried product is from about 30% to about 70%, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0044] In another aspect, the present invention relates to a method for treatment of over acidity in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a dandelion extract, e.g., a Taraxacum Officinale extract, according to any one of the embodiments above.

[0045] In still another aspect, the present invention relates to use of a dandelion extract, e.g., a Taraxacum Officinale extract, for preparation of a medicament for treating over acidity.

[0046] According to the literature, CBD has been shown to be effective against various types of tumors. For example, it was found to have cytotoxic effect in human glioma and to inhibit tumor cell migration in vitro (Massi el al., 2006); to induce apoptosis in human leukemia cell lines by activating classical caspase pathway (McKallip el al., 2006); and to inhibit breast cancer growth and downregulate the DNA binding 1 (ID1) inhibitor, which regulates metastasis in breast cancer cell lines (Ligresti et al., 2006; McAllister el al., 2007).

[0047] As shown in the experimental section, a combination of a Taraxacum Officinale extract and CBD was found to be highly cytotoxic for MDA-MB-231, Capan-l and HCT- 116 cells, derived from aggressive breast cancer, pancreatic cancer and colorectal carcinoma, respectively, and had in fact synergistic effect on the various cancer cells tested compared to the cytotoxic effects shown by each one of the active agents (i.e., said extract and CBD) alone. Moreover, as indicated by a clinical case study, such a drug combination was highly effective in treatment of the non-Hodgkin B-Cell lymphoma. [0048] In another aspect, the present invention thus provides a combination comprising, or consisting as active agents of, a dandelion extract according to any one of the embodiments above, and a cannabinoid or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof (herein also referred to as “a dandelion- cannabinoid combination’’), for use in the treatment of cancer.

[0049] In certain embodiments, the dandelion extract used according to the present invention, in combination with said cannabinoid, is obtainable from the root of the plant, e.g., from the root of Taraxacum Officinale , either when fresh or after drying, as described above. In particular embodiments, the solvent used for extracting the dandelion plant is a mixture of water and ethanol in a ratio of about 1: 1 by volume. In more particular embodiments, the dandelion extract is obtainable by extracting the root of said dandelion plant with said solvent, while heating to a temperature of from about 50°C to about 70°C; filtering; and then drying with an inert carrier, e.g., maltodextrin, wherein the amount of carrier added during the drying step is determined such that the weight percentage of the carrier in the final dried product is, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0050] The term“cannabinoid” as used herein refers to a chemical compound acting on cannabinoid receptors, i.e., a cannabinoid type 1 (CB 1) or cannabinoid type 2 (CB2) receptor agonist. Ligands for these receptor proteins include the endocannabinoids produced naturally in the body; the phytocannabinoids found in Cannabis sativa and some other plants; and synthetic cannabinoids.

[0051] The cannabinoid used according to the present invention, in combination with said dandelion extract, may be derived from a Cannabis extract using any suitable extraction and purification procedures known in the art. Alternatively, said cannabinoid may be synthesized following any one of the procedures disclosed in the literature.

[0052] In certain embodiments, the cannabinoid used in combination with said dandelion extract, is selected from cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabidiol monomethyl ether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1), A⁹-tetrahydrocannabinol (A⁹-THC), A⁹-tetrahydrocannabinolic acid (A⁹-THCA), A⁹-tetrahydrocannabivarin (A⁹-THCV), D⁹- THCVA, A⁸-THC, A⁸-THCA, A⁸-THCV, A⁸-THCVA, iso-tetrahydrocannabinol-type (iso- THC), cannabinol (CBN), cannabinolic acid (CBNA), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinol methyl ether (CBNM), cannabinodiol (CBND), cannabigerol (CBG), cannabigerovarin (CBGV), cannabigerolic acid (CBGA), cannabigerovarinic acid (CBGVA), cannabigerol monomethyl ether (CBGM), cannabigerolic acid monomethyl ether (CBGAM), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichromevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabichromanon (CBCN), cannabicyclol (CBL), cannabicyclolic acid (CBLA), cannabicyclovarin (CBLV), cannabivarin (CBV), cannabivarinic acid (CBVA), cannabielsoin (CBE), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabitriol (CBT), cannabitriolvarin (CBTV), ethoxy-cannabitiolvarin (CBTVE), cannabifuran (CBF), dehydrocannabifuran (DCBF), cannabiripsol (CBR), an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof, or a combination thereof.

[0053] In particular embodiments, the cannabinoid used in combination with said dandelion extract is CBD (2-[(lR,6R)-6-isopropenyl-3-methylcyclohex-2-en-l-yl]-5- pentylbenzene-l,3-diol), or an enantiomer, diastereomer, or racemate thereof. CBD has two stereogenic centers, i.e., at positions 3 and 4 of the cyclohexenyl ring, and may accordingly exist as an enantiomer, i.e., an optical isomer (R or S, which may have an optical purity of 90%, 95%, 99% or more), racemate, i.e., an optically inactive mixture having equal amounts of R and S enantiomers, a diastereoisomer, or a mixture thereof. The present invention encompasses the use of all such enantiomers, isomers and mixtures thereof.

[0054] CBD may be synthesized following any one of the procedures known in the art, e.g., by acid condensation of p-mentha-2,8-dien-l-ol with olivetol. Optically active forms of CBD may be prepared using any one of the methods disclosed in the art, e.g., by resolution of the racemic form by recrystallization techniques; chiral synthesis; extraction with chiral solvents; or chromatographic separation using a chiral stationary phase. A non limiting example of a method for obtaining optically active materials is transport across chiral membranes, i.e., a technique whereby a racemate is placed in contact with a thin membrane barrier, the concentration or pressure differential causes preferential transport across the membrane barrier, and separation occurs as a result of the non-racemic chiral nature of the membrane that allows only one enantiomer of the racemate to pass through. Chiral chromatography, including simulated moving bed chromatography, can also be used. A wide variety of chiral stationary phases are commercially available. [0055] In certain embodiments, the dandelion extract used in combination with said cannabinoid, is a Taraxacum Officinale extract or a Taraxacum Erythrospermum extract, preferably a Taraxacum Officinale extract, and said cannabinoid is CBD, or an enantiomer, diastereomer, or racemate thereof. In particular embodiments, said extract is obtainable from the root of said dandelion, either when fresh or after drying, e.g., by extracting the root of said dandelion plant with a solvent as defined above, preferably while heating to a temperature up to about 70°C, e.g., from about 50°C to about 70°C; filtering; and optionally drying, e.g., by vacuum while stirring, or by lyophilizing, optionally with an inert carrier such as maltodextrin or TCP, e.g., in an amount such that the weight percentage of the carrier in the final dried product is from about 30% to about 70%, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0056] In certain embodiments, the dandelion-cannabinoid combination according to any one of the embodiments above is a fixed dose combination, wherein the ratio of said dandelion extract to said cannabinoid in said combination is in a range of about 1:1 to about 1000:1, e.g., about 1:1, 5:1, 10:1, 20:1, 40:1, 50:1, 70:1, 100:1, 200:1, 300:1, 400:1, 500:1, 600:1, 700:1, 800:1, or 1000:1, respectively, by weight.

[0057] The term "fixed dose combination" as used herein refers to a combination of the active agents each in a particular dose, i.e., to a combination of said active agents having a specific weight ratio, which can be formulated in a single dosage form available in certain fixed doses, or may be administered from two separate dosage forms, each comprising a different one of said active agents, so as to improve medication compliance by patients.

[0058] In certain embodiments, the daily dosage of the dandelion extract in the dandelion-cannabinoid combination, according to any one of the embodiments above, is in a range of from about 0.5 g to about 3 g, e.g., from about 0.8 g to about 2.5 g, from about 1 g to about 2.2 g, from about 1.4 g to about 2 g, or about 1.8 g; and the daily dosage of the cannabinoid in said combination is in a range of from about 5 mg to about 10 mg, e.g., about 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, or 10 mg, per kg weight.

[0059] The cancer treatable with the dandelion-cannabinoid combination may be a solid cancer of any type as well as a blood cancer. Examples of cancer include, without being limited to, skin cancer (both melanoma and non-melanoma skin cancer), lung cancer, prostate cancer, breast cancer, pancreatic cancer, gastric cancer, colorectal cancer such as colorectal carcinoma, kidney (renal) cancer such as renal carcinoma, bladder cancer, gallbladder cancer, liver cancer, brain cancer such as glioblastoma, multiple myeloma, leukemia, and lymphoma (both Hodgkin’s and non Hodgkin's lymphoma). In particular embodiments, the cancer treatable according to the present invention is breast cancer, pancreatic cancer, colorectal carcinoma, or lymphoma such as B-Cell lymphoma.

[0060] In certain embodiments, the dandelion-cannabinoid combination, according to any one of the embodiments above, is administered from two separate compositions each containing a different one of the active agents, either concurrently or sequentially at any order. In other embodiments, said combination is administered from a sole composition. According to the present invention, each one of the compositions may independently be a nutraceutical composition formulated for oral administration, e.g., as a food supplement or comprised within a drink or beverage, or a pharmaceutical composition formulated for any suitable route of administration, e.g., for oral, sublingual, buccal, or rectal administration, or for inhalation.

[0061] In yet another aspect, the invention relates to a method for treatment of cancer in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a dandelion-cannabinoid combination according to any one of the embodiments above.

[0062] In certain embodiments, the dandelion-cannabinoid combination administered according to the method of the invention comprises a Taraxacum Officinale or Taraxacum Erythrospermum extract, preferably a Taraxacum Officinale extract, and CBD, or an enantiomer, diastereomer, or racemate thereof. In particular embodiments, said extract is obtainable from the root of said dandelion, either when fresh or after drying. Such an extract may be obtainable, e.g., by extracting the root of said dandelion plant with a solvent as defined above, preferably while heating to a temperature up to about 70°C, e.g., from about 50°C to about 70°C; filtering; and optionally drying, e.g., by vacuum while stirring, or by lyophilizing, optionally with an inert carrier such as maltodextrin or TCP, e.g., in an amount such that the weight percentage of the carrier in the final dried product is from about 30% to about 70%, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0063] According to the method of the present invention, the dandelion-cannabinoid combination administered may be formulated as two separate compositions each containing a different one of the active agents, for administration either concurrently or sequentially at any order, or as a sole composition. Each one of those compositions may independently be a nutraceutical composition formulated for oral administration, e.g., as a food supplement or comprised within a drink or beverage, or a pharmaceutical composition formulated for any suitable route of administration, e.g., for oral, sublingual, buccal, or rectal administration, or for inhalation.

[0064] Examples of cancer treatable according to the method disclosed herein are listed above and include breast cancer, pancreatic cancer, colorectal carcinoma, and lymphoma such as B-Cell lymphoma.

[0065] In a particular embodiment, the invention relates to a method for treatment of cancer as defined above, e.g., lymphoma, wherein each one of the active agents is formulated as separate composition; the dandelion extract is administered orally at a daily dosage of from about 0.5 g to about 3 g; and the cannabinoid is administered by inhalation at a daily dosage of from about 5 mg to about 10 mg, per kg weight. In a more particular such embodiment, the dandelion extract is a Taraxacum Officinale extract, preferably obtainable from the root of said dandelion as described above, and the cannabinoid is CBD, or an enantiomer, diastereomer, or racemate thereof.

[0066] According to the method of the present invention, the dandelion-cannabinoid combination can be administered to the subject treated over a time period of, e.g., days, weeks, months, years, or more.

[0067] As well-known to any person skilled in the art, in a multi drug-based treatment, both the exact ratio between the drugs administered as well as the timing, dosing and pharmacokinetic aspects, play an extremely important role. In other words, in order to determine the optimal ratio between the drugs administered, not only the combined/synergistic efficacy and potency are of importance, but also the relative pharmacokinetics of each drug and the optimal formulation. Thus, in certain embodiments, the weight ratio of the two drugs administered is precisely calibrated and the two drugs are preferably formulated, each independently, for optimal pharmacokinetic performance and efficacy and for patient’s compliance. Moreover, the synergistic effects between the drugs in the combination may depend on the time they have to act together in the body, i.e., on the relative release profile of the drugs determined by the formulation of each one of the drugs in the combination.

[0068] In still another aspect, the invention relates to use of a dandelion-cannabinoid combination according to any one of the embodiments above for preparation of a medicament for treating cancer. [0069] Sinapis Arvensis is an annual or winter annual plant of the genus Sinapis in the family Brassicaceae, found in North Africa, Asia and Europe. Sinapis Arvensis reaches on average 20-80 cm of height, but under optimal conditions can exceed one meter. The stems are erect, branched and striated, with coarse spreading hairs especially near the base. The leaves are petiolate with a length of 1-4 cm. The basal leaves are 4-18 cm long, and 2-5 cm wide. The inflorescence is a raceme made up of yellow flowers having four petals. The fruit is a silique 3-5 cm long with a beak 1-2 cm long that is flattened-quadrangular. The valves of the silique are glabrous or rarely bristly, three to five nerved. The seeds are dark red or brown, smooth 1-1.5 mm in diameter.

[0070] The seeds of the plant contain inter alia glucosinolates, mainly sinalbin; gibberellic acid (gibberellin A3), which is a plant hormone affecting the seed dormancy; and fatty acids such as linoleic acid, oleic acid, and erucic acid (Daun et al., 2003). The seeds can be grounded into a powder and used as a food flavoring.

[0071] Sinapis Arvensis plant is used as part of the Bach flower remedies for reliving symptoms associated with depression. Sinapis is used as an emetic and diuretic, as well as a topical treatment for inflammatory conditions such as arthritis and rheumatism. According to the literature, Sinapis may also be pharmacologically effective in cardiovascular disease, cancer, and diabetes; however, there are limited clinical data supporting these statements.

[0072] As shown in the experimental section, an extract obtained from Sinapis Arvensis was effective in treatment of individuals suffering from influenza. Surprisingly, a combination of a Taraxacum Officinale extract and said Sinapis Arvensis extract had synergistic effect in treatment of such individuals compared to the effects of each one of the extracts alone, and said drug combination was highly effective in treatment of HIV as well.

[0073] In another aspect, the present invention thus provides a Sinapis plant extract, e.g., a Sinapis Arvensis extract, for use in the treatment of a disease, disorder or condition associated with a viral infection.

[0074] In yet another aspect, the present invention relates to a method for treatment of a disease, disorder or condition associated with a viral infection in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a Sinapis plant extract, e.g., a Sinapis Arvensis extract. [0075] In still another aspect, the invention relates to use of a Sinapis plant extract, e.g., a Sinapis Arvensis extract, for preparation of a medicament for treatment of a disease, disorder or condition associated with a viral infection.

[0076] In another aspect, the present invention provides a combination comprising, or consisting as active agents of, a dandelion extract according to any one of the embodiments above, and a Sinapis plant extract (herein also referred to as “a dandelion- Sinapis combination’’), for use in the treatment of a disease, disorder or condition associated with a viral infection.

[0077] In certain embodiments, the dandelion extract used according to the present invention in combination with said Sinapis plant extract is obtainable from the root of the plant, e.g., from the root of Taraxacum Officinale , either when fresh or after drying, as described above. In more particular embodiments, the solvent used for extracting the dandelion plant is a mixture of water and ethanol in a ratio of about 1:1 by volume. In more particular embodiments, the dandelion extract is obtainable by extracting the root of said dandelion plant with said solvent, while heating to a temperature of from about 50°C to about 70°C; filtering; and then drying with an inert carrier, e.g., maltodextrin, wherein the amount of carrier added during the drying step is determined such that the weight percentage of the carrier in the final dried product is, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0078] The Sinapis plant extract used according to the present invention, either alone or in combination with said dandelion extract, may be obtainable from any Sinapis species, but is preferably a Sinapis Arvensis extract. Such an extract may be obtainable from any part of the plant, e.g., the roots, leaves, seeds, or stem.

[0079] In certain embodiment, the Sinapis plant extract used as disclosed herein is obtainable from the seeds of said Sinapis plant, e.g., from the seeds of Sinapis Arvensis. Such an extract may be obtainable, e.g., by extracting the seeds of said Sinapis plant with a solvent as defined above, e.g., a mixture of water and ethanol in a ratio of 1:1 by volume, preferably while heating to a temperature up to about 70°C, e.g., from about 50°C to about 70°C; filtering; and optionally drying, e.g., by vacuum while stirring, or by lyophilizing (freeze-drying). As shown herein, drying of the extract obtained after the filtration step may be carried out while adding an inert, i.e., pharmaceutically or nutraceutically acceptable, carrier. In particular such embodiments, said Sinapis plant extract is obtainable by extracting the seeds of said Sinapis plant with said solvent, while heating to a temperature of from about 50°C to about 70°C; filtering; and then drying, e.g., vacuum drying while stirring, with an inert carrier, e.g., TCP, in an amount such that the weight percentage of the carrier in the final dried product is, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0080] In certain embodiments, the dandelion extract used in combination with said Sinapis plant extract, is a Taraxacum Officinale extract or a Taraxacum Erythrospermum extract, preferably a Taraxacum Officinale extract, and said Sinapis plant extract is Sinapis Arvensis extract. In particular embodiments, said Taraxacum plant extract is obtainable from the root of said dandelion, e.g., by extracting the root of said dandelion plant with a solvent as defined above, preferably while heating to a temperature up to about 70°C, e.g., from about 50°C to about 70°C; filtering; and optionally drying, e.g., by vacuum while stirring, or by lyophilizing, optionally with an inert carrier such as maltodextrin or TCP, in an amount such that the weight percentage of the carrier in the final dried product is from about 30% to about 70%, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%; and said Sinapis plant extract is obtainable by extracting the seeds of said Sinapis plant with a solvent as defined above, preferably while heating to a temperature up to about 70°C, e.g., from about 50°C to about 70°C; filtering; and optionally drying, e.g., by vacuum while stirring, or by lyophilizing, optionally with an inert carrier such as maltodextrin or TCP, in an amount such that the weight percentage of the carrier in the final dried product is from about 30% to about 70%, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0081] In certain embodiments, the Dandelion -Sinapis combination according to any one of the embodiments above is a fixed dose combination, wherein the ratio of said dandelion extract to said Sinapis plant extract in said combination is in a range of about 100:1 to about 1:100 by weight. In certain particular such fixed dose combinations, the ratio of said dandelion extract to said Sinapis plant extract in the combination is about 100:1, 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, or 2:1, respectively, by weight. In other particular such combinations, the ratio of said dandelion extract and said Sinapis plant extract in the combination is about 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, or 1:100, respectively, by weight. In further particular such combinations, the ratio of said dandelion extract and said Sinapis plant extract in said combination is about 1:1 by weight. [0082] In certain embodiments, the daily dosage of the dandelion extract in the dandclion-S/H^/Vs combination according to any one of the embodiments above is in a range of from about 0.5 g to about 3 g, e.g., from about 0.8 g to about 2.5 g, from about 1 g to about 2.2 g, from about 1.4 g to about 2 g, or about 1.8 g; and the daily dosage of the Sinapis plant extract in said combination is in a range of from about 0.5 g to about 5 g, e.g., from about 0.8 to about 4 g, from about 1 g to about 3 g, from about 1.5 g to about 2.5 g, or about 2.4 g.

[0083] The Sinapis plant extract and dandelion -Sinapis combination disclosed herein are useful for treatment of a disease, disorder or condition associated with a viral infection. Examples of viral infections include, without limiting, infections caused by an influenza virus, HIV virus, a herpes virus, e.g., herpes virus simplex-l (HVS-l), herpes virus simplex-2 (HSV-2), varicella zoster virus (VZV/HHV-3), Epstein-Barr virus (EBV/HHV- 4), cytomegalovirus (CMV/HHV-5), human herpesvirus type 6 (HBLV/HHV-6), human herpesvirus type 7 (HHV-7), and human herpesvirus type 8 (KSHV/HHV-8). In particular embodiments, the disease, disorder or condition treated by the Sinapis plant extract or dandelion -Sinapis combination is associated with influenza virus infection, a herpes virus, e.g., HVS-l and HSV-2, infection, or HIV infection.

[0084] In certain embodiments, the dandelion -Sinapis combination, according to any one of the embodiments above, is administered from two separate compositions each containing a different one of the active agents, either concurrently or sequentially at any order. In other embodiments, said combination is administered from a sole composition. According to the present invention, each one of those compositions may independently be a nutraceutical composition formulated for oral administration, e.g., as a food supplement or comprised within a drink or beverage, or a pharmaceutical composition formulated for any suitable route of administration, e.g., for oral, sublingual, buccal, or rectal administration.

[0085] In yet another aspect, the present invention relates to a method for treatment of a disease, disorder or condition associated with a viral infection in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a dandelion- Sinapis combination according to any one of the embodiments above.

[0086] In certain embodiments, the dandelion -Sinapis combination administered according to the method of the invention comprises a Taraxacum Officinale or Taraxacum Erythrospermum extract, preferably a Taraxacum Officinale extract, and a Sinapis plant extract, preferably a Sinapis Arvensis extract.

[0087] In particular embodiments, said dandelion extract is obtainable from the root of the plant, either when fresh or after drying, and said Sinapis plant extract is obtainable from the seeds of the plant. The dandelion extract can be obtained, e.g., by extracting the root of said dandelion plant with a solvent as defined above, e.g., a mixture of water and ethanol in a ratio of about 1 : 1 by volume, preferably while heating to a temperature up to about 70°C, e.g., from about 50°C to about 70°C; filtering; and optionally drying, e.g., by vacuum while stirring, or by lyophilizing, optionally with an inert carrier such as maltodextrin or TCP, in an amount such that the weight percentage of the carrier in the final dried product is, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%. The Sinapis plant extract can be obtained, e.g., by extracting the seeds of said Sinapis plant with a solvent as defined above, e.g., a mixture of water and ethanol in a ratio of about 1:1 by volume, while heating to a temperature up to 70°C, e.g., from about 50°C to about 70°C; filtering; and optionally drying, e.g., by vacuum drying while stirring, or by lyophilization, optionally with an inert carrier such as maltodextrin or TCP, in an amount such that the weight percentage of the carrier in the final dried product is, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0088] According to the method of the present invention, the dandelion -Sinapis combination administered may be formulated as two pharmaceutical compositions each containing a different one of the active agents, for administration either concurrently or sequentially at any order, or as a sole composition. Each one of those compositions may independently be a nutraceutical composition formulated for oral administration, e.g., as a food supplement or comprised within a drink or beverage, or a pharmaceutical composition formulated for any suitable route of administration, e.g., for oral, sublingual, buccal, or rectal administration.

[0089] Examples of viral infections treatable according to the methods disclosed herein are listed above and include, e.g., influenza virus infection, a herpes virus, e.g., HVS-l and HSV-2, infection, or HIV infection.

[0090] In a particular embodiment, the invention relates to a method for treatment of HIV infection, wherein each one of the active agents is formulated as separate composition for oral administration, or both active agents are formulated as a sole composition for oral administration; the dandelion extract is administered at a daily dosage of from about 0.5 g to about 3 g, preferably about 1.8 g; and the Sinapis plant extract is administered at a daily dosage of from about 0.5 g to about 5 g, preferably about 2.4 g. In a more particular such embodiment, the dandelion extract is a Taraxacum Officinale extract, preferably obtainable from the root of said dandelion as described above, and the Sinapis plant extract is a Sinapis Arvensis extract, preferably obtainable from the seeds of said Sinapis plant as described above.

[0091] In still another aspect, the invention relates to use of a dandelion -Sinapis combination according to any one of the embodiments above for preparation of a medicament for treating a disease, disorder or condition associated with a viral infection.

[0092] The term "subject" as used herein refers to any mammal, e.g., a human, non human primate, horse, ferret, dog, cat, cow, and goat. In a preferred embodiment, the term "subject" denotes a human, i.e., an individual.

[0093] The term "treatment" as used herein refers to the administering of a therapeutic amount of a drug (i.e., active agent) or drug combination as defined in any one of the aspects of the present invention (i.e., dandelion-cannabinoid combination or dandelion- Sinapis combination), which is effective to ameliorate undesired symptoms associated with the medical condition treated; prevent the manifestation of such symptoms before they occur; slow down the progression of said medical condition; slow down the deterioration of symptoms; enhance the onset of remission period; slow down the irreversible damage caused in the progressive chronic stage of said medical condition; delay the onset of said progressive stage; lessen the severity or cure said medical condition; improve survival rate or more rapid recovery; and/or prevent said medical condition form occurring.

[0094] The term "therapeutically effective amount" as used herein means an amount of said drug or drug combination that will elicit the biological or medical response of a tissue, system, animal or human that is being sought. The amount must be effective to achieve the desired therapeutic effect as described above, depending inter alia on the type and severity of the condition to be treated and the treatment regime. The effective amount is typically determined in appropriately designed clinical trials (dose range studies) and the person versed in the art will know how to properly conduct such trials to determine the effective amount. As generally known, an effective amount depends on a variety of factors including the affinity of the ligand to the receptor, its distribution profile within the body, pharmacological parameters such as half-life in the body, undesired side effects, if any, factors such as age and gender, etc. [0095] The phrase“consisting as active agents of’ as used herein with respect to the drug combinations disclosed (i.e., dandelion-cannabinoid combination or dandelion -Sinapis combination) means that the drugs composing each one of said combinations are essentially the only active agents comprised within said combination, and that no further agent other than, e.g., carriers, solvents, dispersion media, preservatives, antioxidants, coatings, isotonic and absorption delaying agents, is included in said drug combination.

[0096] In a further aspect, the present invention provides a composition comprising a combination comprising, as active agents, a dandelion-cannabinoid combination according to any one of the embodiments above, or a dandelion -Sinapis combination according to any one of the embodiments above. The composition disclosed may be either a nutraceutical composition formulated for oral administration, e.g., as a food supplement or comprised within a drink or beverage, or a pharmaceutical composition formulated for any suitable route of administration.

[0097] In certain embodiments, the dandelion extract comprised within the composition of the present invention is obtainable from the root of the plant, e.g., from the root of Taraxacum Officinale , either when fresh or after drying, as described above. In particular embodiments, the solvent used for extracting the dandelion plant is a mixture of water and ethanol in a ratio of about 1:1 by volume. In more particular embodiments, the dandelion extract is obtainable by extracting the root of said dandelion plant with said solvent, while heating to a temperature of from about 50°C to about 70°C; filtering; and then drying with an inert carrier, e.g., maltodextrin, wherein the amount of carrier added during the drying step is determined such that the weight percentage of the carrier in the final dried product is, e.g., from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[0098] In certain embodiments, the composition disclosed herein comprises a dandelion- cannabinoid combination, i.e., a dandelion extract according to any one of the embodiments above, and a cannabinoid or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof. In particular such embodiments, said cannabinoid is CBD, or an enantiomer, diastereomer, or racemate thereof.

[0099] In other embodiments, the composition disclosed herein comprises a dandelion- Sinapis combination, i.e., a dandelion extract according to any one of the embodiments above, and a Sinapis plant extract. In particular such embodiments, said Sinapis plant extract is Sinapis Arvensis extract. [00100] In certain embodiments, the Sinapis plant extract comprised within the composition of the present invention is obtainable from the seeds of said Sinapis plant, e.g., from the seeds of Sinapis Arvensis. In particular embodiments, the solvent used for extracting the Sinapis plant is a mixture of water and ethanol in a ratio of about 1:1 by volume. In more particular embodiments, the Sinapis plant extract is obtainable by extracting the seeds of said Sinapis plant with said solvent, while heating to a temperature of from about 50°C to about 70°C; filtering; and then drying with an inert carrier, e.g., TCP, wherein the amount of carrier added during the drying step is determined such that the weight percentage of the carrier in the final dried product is from about 40% to about 60%, from about 45% to about 55%, or about 50%.

[00101] The nutraceutical composition disclosed herein is a "Dietary Supplement" as established by the F.D.A. in the Dietary Supplement Act of 1994, according to which a dietary supplement includes vitamins, minerals, herbs or other botanicals, antioxidants, amino acids, or other dietary substances used to supplement the diet by increasing the total daily intake.

[00102] As with pharmaceutical compositions, the amount of active agent(s) in the nutraceutical composition will depend on several factors, but will generally comprise a concentration that is sufficient to provide a consumer with an effective amount of the active agent upon consumption of a regular (e.g., daily) portion of the composition.

[00103] The pharmaceutical composition disclosed herein may be prepared by conventional techniques, e.g., as described in Remington: The Science and Practice of Pharmacy, 19* Ed., 1995. The compositions can be prepared, e.g., by uniformly and intimately bringing the active agents into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product into the desired formulation. The compositions may be in the form of a liquid (e.g., solution, emulsion, or suspension), gel, cream, solid, semisolid, film, lyophilisate, or aerosol, and may further include pharmaceutically acceptable fillers, carriers, diluents or adjuvants, and other inert ingredients and excipients. In one embodiment, the pharmaceutical composition of the present invention is formulated as nanoparticles.

[00104] The pharmaceutical composition of the present invention may be formulated for any suitable route of administration, but it is preferably formulated for oral, sublingual, buccal, or rectal administration, or for inhalation. [00105] The pharmaceutical compositions of the invention, when formulated for oral administration, may be in any suitable form, e.g., tablets, troches, lozenges, aqueous, or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. In certain embodiments, said tablets are in the form of matrix tablets in which the release of a soluble active is controlled by having the active diffuse through a gel formed after the swelling of a hydrophilic polymer brought into contact with dissolving liquid {in vitro ) or gastro-intestinal fluid {in vivo). Many polymers have been described as capable of forming such gel, e.g., derivatives of cellulose, in particular the cellulose ethers such as hydroxypropyl cellulose, hydroxymethyl cellulose, methylcellulose or methyl hydroxypropyl cellulose, and among the different commercial grades of these ethers are those showing fairly high viscosity. In other embodiments, the tablets are formulated as bi- or multi-layer tablets, made up of two or more distinct layers of granulation compressed together with the individual layers lying one on top of another, with each separate layer containing a different active agent. Bilayer tablets have the appearance of a sandwich since the edge of each layer or zone is exposed.

[00106] Pharmaceutical compositions for oral administration might be formulated so as to inhibit the release of one or both of the active agents in the stomach, i.e., delay the release of one or both of the active agents until at least a portion of the dosage form has traversed the stomach, in order to avoid the acidity of the gastric contents from hydrolyzing the active agent. Particular such compositions are those wherein the active agent is coated by a pH-dependent enteric-coating polymer. Examples of pH-dependent enteric-coating polymer include, without being limited to, Eudragit^® S (poly(methacrylicacid, methylmethacrylate), 1:2), Eudragit^® L 55 (poly (methacrylicacid, ethylacrylate), 1:1), Kollicoat^® (poly(methacrylicacid, ethylacrylate), 1:1), hydroxypropyl methylcellulose phthalate (HPMCP), alginates, carboxymethylcellulose, and combinations thereof. The pH- dependent enteric-coating polymer may be present in the composition in an amount from about 10% to about 95% by weight of the entire composition.

[00107] In certain embodiments, the invention provides a pharmaceutical composition for oral administration, which is solid and may be in the form of granulate, granules, grains, beads or pellets, mixed and filled into capsules or sachets, or compressed to tablets by conventional methods. In some particular embodiments, the pharmaceutical composition is in the form of a bi- or multilayer tablet, in which each one of the layers comprise one of the two active agents, and the layers are optionally separated by an intermediate, inactive layer, e.g., a layer comprising one or more disintegrants.

[00108] Another contemplated formulation is depot systems, based on biodegradable polymers. As the polymer degrades, the active agent(s) is slowly released. The most common class of biodegradable polymers is the hydrolytically labile polyesters prepared from lactic acid, glycolic acid, or combinations of these two molecules. Polymers prepared from these individual monomers include poly (D,L-lactide) (PLA), poly (glycolide) (PGA), and the copolymer poly (D,L-lactide-co-glycolide) (PLG).

[00109] Pharmaceutical compositions for oral administration may be prepared according to any method known to the art and may further comprise one or more agents selected from sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active agents in admixture with non-toxic pharmaceutically acceptable excipients, which are suitable for the manufacture of tablets. These excipients may be, e.g., inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate, or sodium phosphate; granulating and disintegrating agents, e.g., corn starch or alginic acid; binding agents, e.g., starch, gelatin or acacia; and lubricating agents, e.g., magnesium stearate, stearic acid, or talc. The tablets may be either uncoated or coated utilizing known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated using the techniques described in the US Patent Nos. 4,256,108, 4,166,452 and 4,265,874 to form osmotic therapeutic tablets for control release. The pharmaceutical composition of the invention may also be in the form of oil-in-water emulsion.

[00110] Useful dosage forms of the pharmaceutical compositions include orally disintegrating systems including, but not limited to, solid, semi-solid and liquid systems including disintegrating or dissolving tablets, soft or hard capsules, gels, fast dispersing dosage forms, controlled dispersing dosage forms, caplets, films, wafers, ovules, granules, buccal/mucoadhesive patches, powders, freeze dried (lyophilized) wafers, chewable tablets which disintegrate with saliva in the buccal/mouth cavity and combinations thereof. Useful films include, but are not limited to, single layer stand-alone films and dry multiple layer stand-alone films. [00111] The pharmaceutical composition of the invention may comprise one or more pharmaceutically acceptable excipients. For example, a tablet may comprise at least one filler, e.g., lactose, ethylcellulose, microcrystalline cellulose, silicified microcrystalline cellulose; at least one disintegrant, e.g., cross-linked polyvinylpyrrolidinone; at least one binder, e.g., polyvinylpyridone, hydroxypropylmethyl cellulose; at least one surfactant, e.g., sodium laurylsulfate; at least one glidant, e.g., colloidal silicon dioxide; and at least one lubricant, e.g., magnesium stearate.

[00112] Pharmaceutical compositions according to the invention, when formulated for inhalation, may be in any suitable form, e.g., liquid or fine powder, and may be administered utilizing any suitable device known in the art, such as pressurized metered dose inhalers, liquid nebulizers, dry powder inhalers, sprayers, thermal vaporizers, electrohydrodynamic aerosolizers, and the like.

[00113] The pharmaceutical composition of the invention may be formulated for controlled release of one or both of the active agents. Such compositions may be formulated as controlled-release matrix, e.g., as controlled-release matrix tablets in which the release of a soluble active agent is controlled by having the active diffuse through a gel formed after the swelling of a hydrophilic polymer brought into contact with dissolving liquid {in vitro ) or gastro-intestinal fluid {in vivo). Many polymers have been described as capable of forming such gel, e.g., derivatives of cellulose, in particular the cellulose ethers such as hydroxypropyl cellulose, hydroxymethyl cellulose, methylcellulose or methyl hydroxypropyl cellulose, and among the different commercial grades of these ethers are those showing fairly high viscosity. In other configurations, the compositions comprise the active agent formulated for controlled release in microencapsulated dosage form, in which small droplets of the active agent are surrounded by a coating or a membrane to form particles in the range of a few micrometers to a few millimeters.

[00114] Unless otherwise indicated, all numbers expressing, e.g., weight or volume ratios of the active agents, or temperature, used in this specification, are to be understood as being modified in all instances by the term "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification are approximations that may vary by up to plus or minus 10% depending upon the desired properties to be obtained by the present invention.

[00115] The invention will now be illustrated by the following non-limiting Examples. EXAMPLES

Materials and Methods

[00116] Taraxacum Officinale plant extract was prepared by Changsha JDS Bro-Products Co., Ltd (China), following the procedure described herein. CBD 99.6% was manufactured (synthesized) by Pharma Hemp d.o.o., Slovenia (Cat. 20116). Triton^®X-l00 was purchased from Sigma (USA). Ethanol was purchased from Gadot Chemical Terminals Ltd., Israel. Kolliphor^® EL (CAS 61791-12-6) was purchased from Sigma, USA. Saline was purchased from Baxter International Inc., USA.

Example 1: Taxaracum Officinale extract preparation and toxicity

[00117] Extraction with 99% ethanol. 50 kg of milled plant was extracted with 130 kg of 99% ethanol for 2.5 hours at a temperature of 70°C, then filtered through a fine filter. The residue was again extracted using another 130 kg of 99% ethanol and filtered. The filtrates from the first and second extractions were mixed and evaporated. 240 kg of the filtrate at a starting total dissolved solids (TDS) percentage of 0.81% was evaporated up to 30% TDS at a temperature lower than 60°C with a final weight of 8 Kg. The product can be supplied in a liquid form or dried with an inert carrier, e.g., maltodextrin or tricalcium phosphate (TCP).

[00118] Extraction with a mixture of 50% ethanol and 50% water. 50 kg of milled plant was extracted with 233 kg mixture of 50% ethanol and 50% water for 2.5 hours at a temperature of 70°C, then filtered through a fine filter. The residue was again extracted using another 50 kg mixture of 50% ethanol and 50% water and filtered. The filtrates from the first and second extractions were mixed and evaporated, providing a dried extract. 350 kg of the filtrate with a starting TDS of 1.7% was evaporated up to 30% TDS at a temperature lower than 60°C with a final weight of 5.95 kg. The product can be supplied in a liquid form or dried with an inert carrier, e.g., maltodextrin or TCP.

[00119] Extraction with water. 15 kg of milled plant was extracted with 70 kg water for 2.5 hours at a temperature of 70°C, then filtered through a fine filter. The residue was again extracted using another 50 kg water and filtered. The filtrates from both extractions were mixed and evaporated. 100 kg of the filtrate at a starting TDS of 2.1% was evaporated up to 30% TDS at a temperature lower than 60°C with a final weight of 7 kg. The product can be supplied in a liquid form or dried with an inert carrier, e.g., maltodextrin or TCP. [00120] The plant extracts prepared were analyzed by HPLC and UV-VIS spectroscopy, using acetonitrile:water 70:30 (all reagents used are HPLC grade).

[00121] The Taxaracum Officinale extract used in the Examples herein were prepared as described herein, by extraction of the plant root with a mixture of ethanol and water in a ratio of about 1:1 by volume. The concentrated extract obtained was then dried with maltodextrin (added during the drying process) as an inert carrier, such that the weight percentage of the carrier in the final dried product was about 50%. Vacuum drying was used; however, other drying methods such as freeze drying (i.e., lyophilization) and spray drying might be used.

[00122] The material safety data sheet of said extract have shown high level of safety. For example, the extract contained <10 ppm of total heavy metals, <0.5 ppm of arsenic, <2 ppm of lead, <1 ppm of cadmium, and <0.5 ppm of mercury; zero amount of sulfate, organic phosphate, organic residues or pesticide residues; and no E. coli, Salmonella and Staphylococcus.

Example 2. Oral capsules containing Taxaracum Officinale extract

[00123] Oral capsules, each containing 450 mg dried product prepared as described in Example 1 (more specifically, 230 mg Taxaracum Officinale concentrated extract and 220 mg maltodextrin), were prepared (referred herein as Acidlevel capsules).

Example 3: Taxaracum Officinale extract is effective in treating over acidity

[00124] Patient selection and clinical protocol. Patients were selected based on routine visits to Biomed clinic in Shefa-‘Amr, an Arab city in the northern district of Israel (exclusion factors were smoking and alcohol drinking), and were motivated to take herbal therapy to maintain a healthy acids level in the body. In particular, they were asked to continue their daily activities and food habits unchanged, and to take 2 Acidlevel capsules (see Example 2) twice daily, before breakfast and after dinner. All other usual medications were kept unchanged during the study period of 3 months (90 days). Each patient had to give an oral consent and was given a free-of-charge box containing 360 Acidlevel capsules.

[00125] A total of 20 patients (12 women and 8 men, ranging from 19 to 56 years) were eligible to participate in the study. Five of the patients had cancer (CA), seven had diabetes type 2 (DT2), and eight had hypertension (HT). The participants had two total spontaneous saliva samples collected in the morning after a l2-hour fasting period, one in the pre treatment phase and another in the post treatment (2 days after medication interruption). The patients were instructed not to use toothpaste on the harvesting day.

[00126] Salivary pH was digitally measured through a digital pH sensor. The sensor was first calibrated using buffered solutions with pH 4.0 and pH 7.0, and was then dipped in the saliva filled Falcon tube for 30 seconds, to yield automatic pH reading.

[00127] Results. The average pre-treatment salivary pH of the patient group was 6.25 and the post-treatment salivary pH was 7.155, indicating a statistically significant difference (p< 0.05). The results were statistically analyzed and are summarized in Table 1.

Table 1. Salivary pH data from the participants in the study

[00128] Discussion. As shown, Acidlevel capsules were therapeutically efficient, as substantial and incremental reductions of over acidity levels were observed before and after 3 months. At 3 months, baseline acid levels in the patients participating in the study were significantly changed and became normal. These results suggest that the Taxaracum Officinale extract has primarily effect that supports the liver and immune system functioning. Example 4: A combination of Taxaracum Officinale extract and CBD is cytotoxic to human cancer cell lines

[00129] The objective of this study was to evaluate the cytotoxicity of the Taxaracum Officinale extract and its combination with cannabidiol (CBD) on various cancer cell lines. For this purpose, MDA-MB-231 (breast cancer), Capan-l (pancreatic cancer) and HCT 116 (colorectal carcinoma) cell lines were incubated with said extract at two concentrations (0.5 or 1 mg/mL), with or without CBD (10 mM). Cell viability was evaluated by Cell Proliferation Kit (XTT based).

Formulations

[00130] Vehicle solution was prepared by mixing ethanol: Kolliphor^® EL:saline at 1:1:18, respectively. Vehicle was further diluted 1:50 in assay medium to a final concentration of 0.1% ethanol and 0.1% Kolliphor^® EL in the well.

[00131] The plant extract was dissolved in the above vehicle solution to reach stock concentrations of 50 mg/mL and 25 mg/mL. Stock solutions were filtered via 40 pm strainer. Each of the stock solutions was further diluted 1:50 in assay medium to final concentrations of 0.5 mg/mL and 1 mg/mL in the well.

[00132] CBD was dissolved in the same vehicle solution to reach a stock concentration of 1 mM (314.5 mg/L, 0.31 mg/mL). CBD stock solutions were further diluted 1:100 in assay medium to a final concentration of 10 pM for CBD (3.1 pg/mL) in the well.

Cell lines

[00133] Breast cancer (Triple neg; MDA-MB-231 ) assay medium. Dulbecco's Modified Eagle Medium (DMEM; High Glucose) supplemented with 1% fetal bovine serum (FBS; heat inactivated), 2 mM L-glutamine, and 1% of penicillin- streptomycin (Pen/Strep) solution.

[00134] Pancreatic cancer ( Capan-l ) culture medium. Iscove's Modified Dulbecco's Medium (IMDM) supplemented with 20% FBS (heat inactivated), and 1% of Pen/Strep solution.

[00135] Pancreatic cancer ( Capan-l ) assay medium. IMDM supplemented with 2% FBS (heat inactivated), and 1% of Pen/Strep solution.

[00136] Colorectal carcinoma ( HCT 116) culture medium. McCoy’s medium supplemented with 10% FBS (heat inactivated), 2 mM L-glutamine, and 1% of Pen/Strep solution. [00137] Colorectal carcinoma (HCT 116) assay medium. McCoy’s medium supplemented with 1% FBS (heat inactivated), 2 mM L-glutamine, and 1% of Pen/Strep solution.

Cell proliferation kit

[00138] Cell Proliferation Kit (XTT based) (Biological industries, Cat. 20-300-1000): XTT reagent solution and the activation solution were defrosted immediately prior to use at 37°C. The solutions were swirled gently until clear solutions were obtained. To prepare a reaction solution sufficient for one plate (96 wells), 0.1 mL activation solution were added to 5 mL XTT reagent.

Experimental design

[00139] Part 1 - cell number calibration. MDA-MB-231 (passage 9), Capan-l (passage 5) and HCT 116 (passage 13) cell lines were plated each in a 96 well plate, in their culture medium, at various cell concentrations per well (at 100 pL/well), in triplicates, as illustrated in Scheme 1. Cells were allowed to attach for 24 hours, at 37°C in 5% C0₂. Thereafter, culture medium was discarded, 100 pL assay medium were added, and the cells were incubated for additional 48 hours, at 37 °C in 5% C0₂. Finally, assay medium was discarded and 100 pL fresh culture medium were added to the cells along with 50 pL XTT reagent. The cells were incubated at 37 °C in 5% C0₂. The optical density (OD) was measured every one or two hours (depending on the OD elevation rate during measurements, until the mean OD of control wells was around 0.8-1): Plates were shaken to evenly distribute the dye in the wells and the absorbance of the samples was measured with a spectrophotometer (ELISA reader) at a wavelength of 450 nm. In order to correct for non-specific readings, measurements at wavelength of 620 nm were subtracted from the 450 nm readings. The highest cell concentration within the linear curve was used in part 2 of the study.

[00140] Cells incubation with test items. MDA-MB-231 (passage 13), Capan-l (passage 9) and HCT 116 (passage 17) cell lines were plated each in a separate 96 well plate, in their culture medium, at the optimal cell concentration (at 100 pL/well) according to the results from the previous section. Cells were allowed to attach to the plate for 24 hours, at 37°C in 5% C0₂. Thereafter, culture medium was discarded and 100 pL assay medium were added to the cells, supplemented with test item concentrations, in quadruplicates, according to Scheme 2. Triton^®X-l00 0.1% was used as positive control for cell death. Cells in vehicle were used as negative control. The cells were incubated for additional 24 and 48 hours (each time point using a different plate), at 37°C in 5% C0₂. Finally, assay medium was discarded and 100 pL fresh culture medium were added to the cells along with 50 pL XTT reagent. The cells were incubated at 37 °C in 5% C0_2, and the OD was measured at the optimal time point according to the results in the previous section: Plates were shaken to evenly distribute the dye in the wells and the absorbance of the samples was measured with a spectrophotometer (ELISA reader) at a wavelength of 450 nm. In order to correct for non-specific readings, measurements at wavelength of 620 nm were subtracted from the 450 nm readings.

Scheme 1: Cell number and XTT calibration (plate design)

Scheme 2: Incubation with test items (plate design: one plate/cell line/time point)

Results

[00141] Part 1 - cell number calibration. As shown in Fig. 1, after 5 hours of incubation with XTT, the linear cell growth of MDA-MB-231 cells was from 1,000 to 20,000 cells/well; the linear cell growth of Capan-l cells was from 1,000 to 15,000 cells/well; and the linear cell growth of HCT-116 cells was from 1,000 to 7,500 cells/well. The highest cell-number/well was chosen for part 2. Raw data of OD readings are shown in Table 2 (referring to the plate design illustrated in Scheme 1).

[00142] Part 2 - cells incubation with test items. Optimal incubation time points with XTT were determined according to the control OD (cells only), which was between 0.5-1 hour in 450 nm wavelength. The OD readings after 24 and 48 hours incubation with the test items, after 6 hours of incubation with XTT, are shown in Tables 3 and 4 (referring to the plate design illustrated in Scheme 2).

Table 2: OD readings of cell number and XTT calibration after 5 hours with XTT

Table 3: OD readings of 24 hours incubation with test items after 6 hours with XTT

Conclusions

[00143] The main objective of this study was to determine whether the Taxaracum Officinale extract by itself can exhibit comparable or better effects compared to CBD and whether the combination of the two can exhibit a synergistic effect. As shown, there were small differences between the response of the three cell-lines, but generally in all of them, the Taxaracum Officinale extract (mostly at the high dose) was superior to CBD, and the combination thereof exhibited a synergistic effect against CBD alone.

[00144] At 48 hours incubation, all treatments almost completely demolished colorectal and breast cancer cells (Figs. 2-3 and Figs. 6-7), and the comparison between them was therefore not effective. However, the results showed highly statistical difference between all treatments and cells only. For pancreatic cancer cells, both the superiority of the Taxaracum Officinale extract over CBD and the synergistic effect of the combination were very pronounced (Figs. 4-5).

[00145] Similarly, after 24 hours of incubation these effects were apparent. For colorectal and breast cancer cell-lines, only the higher concentration of Taraxacum Officinale extract had statistically significant better results than CBD at 10 mM.

Table 4: OD readings of 48 hours incubation with test items after 6 hours with XTT

* This result was excluded since it seems to be an experimental error

Example 5: A combination of Taxor acum Officinale extract and CBD is effective in treatment of BCL lymphoma - clinical study

[00146] The case study described herein indicates that a Taxaracum Officinale plant extract, when taken in combination with CBD, is highly effective in treatment of cancer. The subject treated was a 53-year old patient, diagnosed on December 2017 with high grade B-Cell lymphoma (a non-Hodgkin lymphoma) and having a lO-cm size tumor in the kidney. The subject was treated with the Acidlevel capsules (see Example 2; 4 capsules daily; daily dosage 1800 mg) for 3 months, and at the same time smoked marijuana cigarette on a daily base. The treatment with the Acidlevel capsules started together with, and was carried out in parallel to, a chemotherapeutic treatment. [00147] Positron emission tomography -computed tomography (PET-CT) test conducted in the Rambam Health Care Campus, Israel, at the end of the treatment period (March 14, 2018), and compared to a previous PET-CT test conducted on November 24, 2017, showed complete disappearance of all the pathological absorptions identified in the first PET-CT test both above and below the diaphragm, with no indication of lymphoma, indicating that the patient was cured from the disease. Further PET-CT tests conducted after March 2018, including the last one conducted on August 2019, were consistent and showed no indication of lymphoma.

Example 6: Sinapis Arvensis extract preparation and toxicity

[00148] Extraction with 99% ethanol. 15 kg of milled plant was extracted with 40 kg of 99% ethanol for 2.5 hours at a temperature of 70°C, then filtered through a fine filter. The residue was again extracted using another 40 kg of ethanol 99% and filtered. The filtrates from the first and second extractions were mixed and evaporated. 69 kg of the filtrate at a starting TDS percentage of 0.81% was evaporated up to 30% TDS at a temperature lower than 60°C with a final weight of 2.3 Kg. The product can be supplied in a liquid form or dried with an inert carrier, e.g., maltodextrin or TCP.

[00149] Extraction with a mixture of 50% ethanol and 50% water. 15 kg of milled plant was extracted with 70 kg mixture of 50% ethanol and 50% water for 2.5 hours at a temperature of 70°C, then filtered through a fine filter. The residue was again extracted using another 50 kg mixture of 50% ethanol and 50% water and filtered. The filtrates from the first and second extractions were mixed and evaporated, providing a dried extract, which was used for the preparation of the compositions of this invention. 105 kg of the filtrate with a starting TDS of 1.7% was evaporated up to 30% TDS at a temperature lower than 60°C with a final weight of 5.95 kg. The product can be supplied in a liquid form or dried with an inert carrier, e.g., maltodextrin or TCP.

[00150] Extraction with water. 15 kg of milled plant was extracted with 70 kg water for 2.5 hours at a temperature of 70°C, then filtered through a fine filter. The residue was extracted again using another 50 kg water and filtered. The filtrates from the first and second extractions were mixed and evaporated. 100 kg of the filtrate at a starting TDS of 2.1% was evaporated up to 30% TDS at a temperature less than 60°C with a final weight of 7 kg. The product can be supplied in a liquid form or dried with an inert carrier, e.g., maltodextrin or TCP. [00151] The plant extracts prepared were analyzed by HPLC and UV-VIS spectroscopy, using acetonitrile:water 70:30 (all reagents used are HPLC grade).

[00152] The Sinapis Arvensis extract used in the Examples herein were prepared as described herein, by extraction of the plant seeds with a mixture of ethanol and water in a ratio of 1:1 by volume. The concentrated extract obtained was then dried with TCP (added during the drying process) as an inert carrier, such that the weight percentage of the carrier in the final dried product was about 50%. Vacuum drying was used; however, other drying methods such as freeze drying (i.e., lyophilization) and spray drying might be used.

[00153] Oral capsules, each containing 450 mg dried product prepared as described herein (more specifically, 230 mg Sinapis Arvensis concentrated extract and 220 mg TCP), were prepared (referred herein as Sinapis capsules).

Example 7: Sinapis Arvensis extract is effective in treating influenza

[00154] 58 human volunteers (aged 18-65), suffering from either the common cold or influenza, were recruited for this study from two general physician clinics in the Galilee in the north of Israel. The volunteers were not taking any pharmaceutical agents and were willing to take an herbal therapy. The subjects were asked to continue their normal daily activities and habits and to take one Sinapis capsule (see Example 6) three times a day, for a week. They were also asked to refrain from using any other medications during the one- week study period. Each subject had to give an oral consent and was given a free-of-charge box containing 21 Sinapis capsules.

[00155] 54 of the patients treated with the Sinapis Arvensis extract experienced reduced fever from the third day of using the capsules and started to feel well and revitalized on the fourth day, without suffering from pain or any other influenza symptoms. All patients took the capsules for three more days as a preventative measure. Four patients did not react.

Example 8: A combination of a Taxaracum Officinale extract and a Sinapis Arvensis extract is effective in treatment of influenza

[00156] 22 human volunteers (aged 18-65), suffering from either the common cold or influenza, were recruited for this study from two general physician clinics in the Galilee in the north of Israel. The volunteers were not taking any pharmaceutical agents and were willing to take an herbal therapy. The subjects were asked to continue their normal daily activities and habits and to take two Acidlevel capsules (see Example 2) and two Sinapis capsules (see Example 6), twice a day for a week. They were also asked to refrain from using any other medications during the one-week study period. Each subject had to give an oral consent and was given free-of-charge a box containing 14 Acidlevel capsules and a box of containing 14 Sinapis capsules.

[00157] 19 of the patients experienced reduced fever from the first or second day of treatment and started to feel well and revitalized on the third day, without suffering from pain or any other influenza symptoms. All patients took the capsules for three more days as a preventative measure. Three patients did not react. These results suggest that the combination of the two plant extracts have a synergistic effect in treating influenza. More specifically, while the effect of the Sinapis Arvensis extract alone started on the third day of the treatment (see Example 7), the combination of the two plant extracts showed an effect starting already from the first or second day.

Example 9: A combination of a Taxaracum Officinale extract and a Sinapis Arvensis extract is effective in treatment of HIV - clinical study

[00158] The present case study indicates that a Taxaracum Officinale extract, when taken in combination with a Sinapis Arvensis extract, is highly effective in treatment of the human immunodeficiency virus (HIV). The subject treated in this study was a 27-year old patient, diagnosed on February 2019 with active HIV and suffering from all known symptoms of the disease. The subject was treated with 4 Acidlevel capsules per day (2 at morning and 2 at evening; 450 mg each capsule; 1800 mg per day), and 4 Sinapis capsules per day (2 at morning and 2 at evening; 600 mg each capsule (containing Sinapis Arvensis concentrated extract and TCP at a ratio of about 1:1 by weight); 2400 mg per day). The patient started the treatment with the combination of the extracts 2 months after starting a chemical therapy.

[00159] In a blood test conducted after 25 days of treatment with the extract combination, no HIV was diagnosed. In an additional blood test conducted 3 months later, no HIV was diagnosed as well. REFERENCES

Choi, U.K.; Lee, O.H.; Yim, J.H.; Cho, C.W.; Rhee, Y.K.; Lim, S.L; Kira, Y.C., International journal of molecular sciences , 2010, 11, 67-78

Daun, J.K.; Barthet, V.J.; Scarth, R., Proceeding of die llⁱⁿ International Rapeseed Congress, Copenhagen, Denmark, 610, 2003

Hu, C.; Kits, D.D., Journal of agricultural and food chemistry , 2003, 51, 301-310 Ligresti, A.; Moriello, A.S.; Starowicz, K.; Matias, ].; Pisanti, S.; De Pelroeellis, L.; Laezza, C.; Portella, G.; Bifulco, M.; Di Marzo, V., Journal of Pharmacology and Experimental Therapeutics, 2006, 318, 1375-1387

Massi, P.; Yaccani, A.; Bianchessi, S.; Costa, B ; Macchi, P.; Parolaro, D., Cellular and Molecular Life Sciences CMLS , 2006, 63, 2057-2066

McAllister, S.D.; Christian, R.T.; Horowitz, M.P.; Garcia, A.; Desprez, P.Y., Molecular cancer therapeutic , 2007, 6, 2921-2927

McKallip, R.J.; Jia, W ; Schlomer, L; Warren, J.W.; Nagarkatti, P.S.; Nagarkatti, M , Molecular Pharmacology, 2006, 70, 897-908

Newa!i, C.A.; Anderson, L.A.; Phillipson, J.D., The pharmaceutical press, 1996 Park, J.Y.; Park, C.M.; Kim, J.J.; Song, Y.S Journal of the Korean Society of Food Science and Nutrition, 2008, 37, 177-183

Popescu, M.L.; Dinu, M.; Ursache, D.D., F armada, 2010, 58, 646-653

Schiitz, K.; Carle, R.; Schieber, A., Journal of ethnopharrnacology , 2006, 107, 3 LB- 323

Seo, S.W.; Koo, H.N.; An, H.J.; Kwon, K.B.; Lira, B.C.; Seo, E.A.; Ryu, D.G.; Moon, G.; Kim, H.Y.; Kim, H.M.; Hong, S.H., World journal of Gastroenterology, 2005, 11, 597-599

Sharafzadeh, S., Australian Journal of Basic and Applied Sciences, 2011, 5, 1787 -

1791

Simon, L.; Martin, H.W.; Adriano, D.C., Water, Air, and Soil Pollution, 1996, 91, 351-362

Williams, C.A.; Goldstone, F.; Greenham, J., Phytochemistry, 1996, 42, 121-127

Claims

1. A combination comprising a Taraxacum plant extract and a cannabinoid or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof, for use in the treatment of cancer.

2. The combination for use of claim 1, wherein said Taraxacum plant is Taraxacum Officinale or Taraxacum Erythrospermum.

3. The combination for use of claim 1 or 2, wherein said extract is obtainable by extracting the root of said Taraxacum plant with a solvent, preferably while heating to a temperature up to about 70°C; filtering; and optionally drying.

4. The combination for use of claim 3, wherein said drying is carried out while adding an inert carrier such as maltodextrin or tricalcium phosphate.

5. The combination for use of claim 4, wherein said extract is obtainable by extracting the root of said Taraxacum plant with a solvent comprising water and ethanol in a ratio of about 1: 1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with maltodextrin as a carrier.

6. The combination for use of claim 1, wherein said cannabinoid is selected from cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabidiol monomethyl ether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1), A⁹-tetrahydrocannabinol (A⁹-THC), A⁹-tetrahydrocannabinolic acid (A⁹-THCA), A⁹-tetrahydrocannabivarin (A⁹-THCV), A⁹-THCVA, A⁸-THC, A⁸-THCA, A⁸-THCV, A⁸-THCVA, iso-tetrahydrocannabinol-type (iso-THC), cannabinol (CBN), cannabinolic acid (CBNA), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinol methyl ether (CBNM), cannabinodiol (CBND), cannabigerol (CBG), cannabigerovarin (CBGV), cannabigerolic acid (CBGA), cannabigerovarinic acid (CBGVA), cannabigerol monomethyl ether (CBGM), cannabigerolic acid monomethyl ether (CBGAM), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichromevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabichromanon (CBCN), cannabicyclol (CBL), cannabicyclolic acid (CBLA), cannabicyclovarin (CBLV), cannabivarin (CBV), cannabivarinic acid (CBVA), cannabielsoin (CBE), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabitriol (CBT), cannabitriolvarin (CBTV), ethoxy-cannabitiolvarin (CBTVE), cannabifuran (CBF), dehydrocannabifuran (DCBF), cannabiripsol (CBR), an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof, or a combination thereof.

7. The combination for use of claim 6, wherein said cannabinoid is CBD, or an enantiomer, diastereomer, or racemate thereof.

8. The combination for use of claim 1, wherein said Taraxacum plant is Taraxacum Officinale or Taraxacum Erythrospermum, and said cannabinoid is CBD, or an enantiomer, diastereomer, or racemate thereof.

9. The combination for use of claim 8, wherein said extract is obtainable by extracting the root of said Taraxacum plant with a solvent comprising water and ethanol in a ratio of about 1:1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with maltodextrin as a carrier.

10. The combination for use of claim 1, wherein the ratio of said Taraxacum plant extract to said cannabinoid in said combination is in a range of about 1:1 to about 1000:1 by weight.

11. The combination for use of claim 1, wherein the daily dosage of the extract in said combination is in a range of from about 0.5 g to about 3 g; and the daily dosage of said cannabinoid in said combination is in a range of from about 5 mg to about 10 mg, per kg weight.

12. The combination for use of claim 1, wherein said cancer is selected from skin cancer (both melanoma and non-melanoma skin cancer), lung cancer, prostate cancer, breast cancer, pancreatic cancer, gastric cancer, colorectal cancer such as colorectal carcinoma, kidney (renal) cancer such as renal carcinoma, bladder cancer, gallbladder cancer, liver cancer, brain cancer such as glioblastoma, multiple myeloma, keukemia, and lymphoma (both Hodgkin’s and non-Hodgkin's lymphoma).

13. The combination for use of any one of claims 1 to 12, wherein (i) said extract and said cannabinoid are administered from two separate compositions, either concurrently or sequentially at any order; or (ii) said extract and said cannabinoid are administered from a sole composition.

14. The combination for use of claim 13, wherein each one of said compositions is independently a nutraceutical composition, or a pharmaceutical composition formulated for oral or sublingual administration, or for inhalation.

15. A method for treatment of cancer in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a combination of a Taraxacum plant extract and a cannabinoid or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof.

16. The method of claim 15, wherein said Taraxacum plant is Taraxacum Officinale or Taraxacum Erythrospermum, and said cannabinoid is CBD, or an enantiomer, diastereomer, or racemate thereof.

17. The method of claim 16, wherein said extract is obtainable by extracting the root of said Taraxacum plant with a solvent comprising water and ethanol in a ratio of about 1:1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with maltodextrin as a carrier.

18. The method of claim 17, wherein said cancer is selected from skin cancer (both melanoma and non-melanoma skin cancer), lung cancer, prostate cancer, breast cancer, pancreatic cancer, gastric cancer, colorectal cancer such as colorectal carcinoma, kidney (renal) cancer such as renal carcinoma, bladder cancer, gallbladder cancer, liver cancer, brain cancer such as glioblastoma, multiple myeloma, keukemia, and lymphoma (both Hodgkin’s and non-Hodgkin's lymphoma).

19. The method of claim 17, wherein said cancer is lymphoma; said extract is administered from a composition formulated for oral administration at a daily dosage of from about 0.5 g to about 3 g; and said cannabinoid is administered from a composition formulated for inhalation at a daily dosage of from about 5 mg to about 10 mg, per kg weight.

20. A combination comprising a Taraxacum plant extract and a Sinapis plant extract for use in the treatment of a disease, disorder or condition associated with a viral infection.

21. The combination for use of claim 20, wherein said Taraxacum plant is Taraxacum Officinale or Taraxacum Erythrospermum.

22. The combination for use of claim 20 or 21, wherein said Taraxacum plant extract is obtainable by extracting the root of said Taraxacum plant with a solvent, preferably while heating to a temperature up to about 70°C; filtering; and optionally drying.

23. The combination for use of claim 22, wherein said drying is carried out while adding an inert carrier such as maltodextrin or tricalcium phosphate (TCP).

24. The combination for use of claim 23, wherein said Taraxacum plant extract is obtainable by extracting the root of said Taraxacum plant with a solvent comprising water and ethanol in a ratio of about 1 : 1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with maltodextrin as a carrier.

25. The combination for use of claim 20, wherein said Sinapis plant is Sinapis Arvensis.

26. The combination for use of claim 25, wherein said Sinapis plant extract is obtainable by extracting the seeds of said Sinapis plant with a solvent, preferably while heating to a temperature up to about 70°C; filtering; and optionally drying.

27. The combination for use of claim 26, wherein said drying is carried out while adding an inert carrier such as maltodextrin or TCP.

28. The combination for use of claim 27, wherein said Sinapis plant extract is obtainable by extracting the seeds of said Sinapis plant with a solvent comprising water and ethanol in a ratio of about 1:1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with TCP as a carrier.

29. The combination for use of claim 20, wherein said Taraxacum plant is Taraxacum Officinale or Taraxacum Erythrospermum, and Sinapis plant is Sinapis Arvensis.

30. The combination for use of claim 29, wherein said Taraxacum plant extract is obtainable by extracting the root of said Taraxacum plant with a solvent comprising water and ethanol in a ratio of about 1 : 1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with maltodextrin as a carrier; and said Sinapis plant extract is obtainable by extracting the seeds of said Sinapis plant with a solvent comprising water and ethanol in a ratio of about 1:1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with TCP as a carrier.

31. The combination for use of claim 20, wherein the ratio of said Taraxacum plant extract to said Sinapis plant extract in said combination is in a range of about 100:1 to about 1:100 by weight.

32. The combination for use of claim 20, wherein the daily dosage of the Taraxacum plant extract in said combination is in a range of from about 0.5 g to about 3 g; and the daily dosage of the Sinapis plant extract in said combination is in a range of from about 0.5 g to about 5 g.

33. The combination for use of claim 20, wherein said viral infection is caused by an influenza virus, a herpes virus, or HIV virus.

34. The combination for use of any one of claims 20 to 33, wherein (i) said Taraxacum plant extract and said Sinapis plant extract are administered from two separate compositions, either concurrently or sequentially at any order; or (ii) said Taraxacum plant extract and said Sinapis plant extract are administered from a sole composition.

35. The combination for use of claim 34, wherein each one of said compositions is independently a nutraceutical composition, or a pharmaceutical composition formulated for oral or sublingual administration.

36. A method for treatment of a disease, disorder or condition associated with a viral infection in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a combination of a Taraxacum plant extract and a Sinapis plant extract.

37. The method of claim 36, wherein said Taraxacum plant is Taraxacum Officinale or Taraxacum Erythrospermum, and said Sinapis plant is Sinapis Arvensis .

38. The method of claim 37, wherein (i) said Taraxacum plant extract is obtainable by extracting the root of said Taraxacum plant with a solvent comprising water and ethanol in a ratio of about 1:1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with maltodextrin as a carrier; and (ii) said Sinapis plant extract is obtainable by extracting the seeds of said Sinapis plant with a solvent comprising water and ethanol in a ratio of about 1 : 1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with tricalcium phosphate as a carrier.

39. The method of claim 36, wherein said viral infection is caused by an influenza virus, HIV virus, or a herpes virus.

40. The method of claim 36, wherein said viral infection is caused by HIV; said Taraxacum plant extract is administered from a composition formulated for oral administration at a daily dosage of from about 0.5 g to about 3 g; and said Sinapis plant extract is administered from a composition formulated for oral administration at a daily dosage of from about 0.5 g to about 5 g.

41. A composition comprising a combination comprising, as active agents, a Taraxacum plant extract and either (a) a cannabinoid or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof; or (b) a Sinapis plant extract.

42. The composition of claim 41, wherein said Taraxacum plant extract is obtainable from the root of said Taraxacum plant.

43. The composition of claim 42, wherein said Taraxacum plant extract is obtainable by extracting the root of said Taraxacum plant with a solvent comprising water and ethanol in a ratio of about 1 : 1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with maltodextrin as a carrier.

44. The composition of any one of claims 41 to 43, comprising said Taraxacum plant extract, and said cannabinoid, or an enantiomer, diastereomer, racemate, or pharmaceutically acceptable salt thereof.

45. The composition of claim 44, wherein said cannabinoid is CBD, or an enantiomer, diastereomer, or racemate thereof.

46. The composition of any one of claims 41 to 43, comprising said Taraxacum plant extract and said Sinapis plant extract.

47. The composition of claim 46, wherein said Sinapis plant extract is obtainable by extracting the seeds of said Sinapis plant with a solvent comprising water and ethanol in a ratio of about 1:1 by volume, while heating to a temperature of from about 50°C to about 70°C; filtering; and drying with tricalcium phosphate as a carrier.

48. A Taraxacum plant extract for use in the treatment of over acidity.

49. A method for treatment of over acidity in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a Taraxacum plant extract.

50. A Sinapis plant extract for use in the treatment of a disease, disorder or condition associated with a viral infection.

51. A method for treatment of a disease, disorder or condition associated with a viral infection in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a Sinapis plant extract.