WO2019244160A1

WO2019244160A1 - Cannabidiol-containing antimicrobial non-irritating hyperosmotic compositions

Info

Publication number: WO2019244160A1
Application number: PCT/IL2019/050697
Authority: WO
Inventors: Ruben Tel-Ari; Yorav KRIEF
Original assignee: Tel Ari Ruben; Krief Yorav
Priority date: 2018-06-20
Filing date: 2019-06-20
Publication date: 2019-12-26

Abstract

The present invention discloses antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 5.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent. The invention also discloses a process of preparing the same; and therapeutic compositions for treating a subject from topical microbial contamination and/or for treating a subject from internal microbial contamination. The invention further discloses synergic method for treating clinical indications characterized by step(s) of providing an antimicrobial non-irritating hyperosmotic composition with both an active cannabinoid ranging from about 0.1 to about 5.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent.

Description

CANNABIDIOL-CONTAINING ANTIMICROBIAL NON-IRRITATING HYPEROSMOTIC

COMPOSITIONS

FIELD OF THE INVENTION

The present invention generally pertains to cannabidiol-containing antimicrobial non-irritating hyperosmotic compositions, decontaminating methods and medical devices comprising the same.

BACKGROUND OF THE INVENTION

Many of the commonly used antimicrobial agents are synthetic compounds. In recent years, there has been an increased interest in avoiding or eliminating the use of synthetic compounds and in developing and promoting the use of natural materials. Consumers generally consider plant materials less toxic and a more suitable natural alternative to synthetic compounds, see US8449926 which is incorporated herein as a reference. Cannabinoids are found as components in cannabis plants. It is estimated that the resin of the cannabis plant contains over 70 different cannabinoids, some of which, such as THC, have psychotropic effects. The target structures of the cannabinoids upon consumption in the human organism are the cannabinoid receptors CB-l and CB-2 of the endocannabinoid system. The physiological ligand of these receptors is the arachidonic acid derivative anandamide. Currently, the cannabinoid THC is known as a medical drug above all. Thus, for example, semisynthetic THC, dronabinol, is usable in Germany and other countries as a prescription narcotic for anorexia and cachexia in HIV and AIDS patients, and as an antiemetic for nausea and vomiting under cytostatic or radiation therapy in the context of a cancer therapy. The completely synthetic THC derivative nabilon has a similar indication. In addition, THC is in the clinical testing phase for the treatment of glaucoma and autoimmune diseases, such as multiple sclerosis, Crohn's disease, or ulcerative colitis. A further known, but non-psychoactive cannabinoid from female hemp plants of Cannabis sativa is cannabidiol (CBD). Medicinally, it relieves cramps and anxiety, is anti-inflammatory, is an anti-nauseant, and reduces internal eye pressure, see US8337908. Moreover, an effective medication, which is free of side effects, for the treatment of diseases, preferably for the treatment of diseases of the allergically and immunologically related spectrum disorder, based on plants, which is not only cost-effective and simple to produce, but rather also achieves very high compliance with the patients because of its rapid and convincing initial effect and lack of side effects. The object of the present invention is achieved in a first aspect by a plant extract made of the flowers and flower-proximal leaves and/or stems and/or roots and/or seeds, preferably the flowers and flower-proximal leaves of a low- tetrahydrocannabinol (THC) variety of Cannabis sativasub species sativa for the treatment of diseases, see US patent application No. 20150044315 which is incorporated herein as a reference.

The inventor has recently disclosed a non-irritating tea tree oil (TTO)-based topical therapeutic composition useful for both veterinary and human dermatology. The composition comprises a homogeneous mixture of TTO, 0.05 to 1.0% (wt/wt); at least one hypertonic composition providing the TTO-based composition to 1700 to 2500 mOsm/L, 10 to 60% (wt/wt); and inorganic salts, 0.01% to 0.50% (wt/wt) and it is characterized by an effective, rapid & wide spectrum of action while being non-irritant to patient skin, see US patent No. 9161961 which is incorporated herein as a reference. A cannabidiol-containing antimicrobial non -irritating hyperosmotic compositions is hence still an unmet need.

SUMMARY OF THE INVENTION

It is hence an object of the present invention to provide an antimicrobial non-irritating hyperosmotic composition, inter alia characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent. Addition of various cannabinoids, hyperosmotic agents, including inorganic salts and/or sugars and polysaccharides thereof, mud and mud-like substances, terpene and terpene-like substances was also demonstrated synergistic therapeutic results.

It is another object of the present invention to provide an antimicrobial non-irritating hyperosmotic composition characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent.

It is another object of the present invention to provide an antimicrobial non-irritating hyperosmotic composition wherein the composition further comprising about 2 to about 20 w/w percent mud, especially green mud ( Argile Verde). It is another object of the present invention to provide an antimicrobial non-irritating hyperosmotic compositions wherein said composition further comprising at least one member of a group consisting of Beta-Bisabolene, Caryophyllene oxide, Citronellol, Geraniol, Sabinene, Pulegone, Humulene, Carene, Myrcene: Myrcene, b-myrcene; Pinene: a-pinene and b-pinene; Limonene; Caryophyllene: b-caryophyllene; Linalool; Terpinolene; Camphene; Terpineol: a-Terpineol, terpinen-4-ol, and 4-terpineol, Phellandrene; Carene: Delta-3 -carene; Humulene: also known as a- humulene and a-caryophyllene; Pulegone; Sabinene: Sabinene exists as (+)- and (-)-enantiomers; Geraniol; Phytol; Citronellol ; Caryophyllene oxide; Beta Bisabolene, Phellandrene, Terpineol, Camphene, Terpinolene, Linalool, Caryophyllene, Limonene, Pinene, Myrcene; and extracts of Lavender, rosemary, Thyme, Citrus, Cymbopogon, Bay leaf, Mangifera indica, Pinus, Sinensis, Origanum syriacum, Mango, Anise, Bergamot and any composition, mixture and derivative thereof.

It is another object of the present invention to provide an antimicrobial non-irritating hyperosmotic compositions wherein the composition comprising, as active ingredients, comprising a cannabidiol ranging from about 0.1 to about 1.5 w/w percent, and an hyperosmotic agent ranging from about 2 to about 75 w/w percent wherein the cannabidiol and the hyperosmotic agent act in synergy.

It is another object of the present invention to provide an antimicrobial non-irritating hyperosmotic compositions wherein the composition comprises both at least one first member of Group A, ranging from about 0.1 to about 1.5 w/w percent, and at least one second member of Group B, ranging from about 2 to about 75 w/w percent; the Group A is one or more cannabinoids selected from a group consisting of active cannabinoids, including THC (Tetrahydrocannabinol), THCA (Tetrahydrocannabinolic acid), BDA (Cannabidiolic Acid), CBN (Cannabinol), CBG (Cannabigerol), CBC (Cannabichromene), CBD (referring to Cannabidiol and/or CBDA), CBL (Cannabicyclol), CBV (Cannabivarin), THCV (Tetrahydrocannabivarin), CBDV (Cannabidivarin), CBCV (Cannabichromevarin), CBGV (Cannabigerovarin), CBGM (Cannabigerol Monomethyl Ether), CBE (Cannabielsoin), CBT (Cannabicitran), hemp oil, cannabis oil, cannabis-seed oilderivatives, and any derivatives, extracts and mixtures thereof; the Group B is one or more hyperosmotic agents selected from Subgroup B 1 , B2 and B3 ; the Subgroup Bl consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof; the Subgroup B2 consists inorganic salts, including zinc salts, ferric and ferrous salts, cupper salts, argentum salts, barium salts, sodium salts, potassium salts, barium salts, bismuth salts, calcium salts and calamine, magnesium salts, manganese salts, gold, silver, and further consisting bivalent metals sulfates, sulfites, nitrates, nitrates, amines, chlorides, bromides, iodines, phosphates, oxides; Dead Sea salts, sea salts, derivatives, salts, powders including nano powders, and mixtures thereof; the Subgroup B2 consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof; the Subgroup B3 consists clay, Medical Clay, Kaolin, Kaolinite, Kaopectate, Attapulgite-active ingredient in kaolin with/or without added Aluminum, Palygorskite, Terr am in [California red clay], temnian clay [Terra Sigillata], Terra Chia, Terra Cymolia, Cimolean earth, Cimolite, Argentiera, Semian earth, Colyrium, Egyptian earth, Chios earth, Bentonite clay, Montmorillonite, Green Clay, Argile Verte [French green clay], Illite, Montmorillonite, Kaolinite, Red clay, White clay and any mixture and derivatives thereof.

It is another object of the present invention to provide a process of preparing the composition defined above, the process comprising admixing at least one first active cannabinoid and at least one second hyperosmotic agent thereby obtaining the antimicrobial non-irritating hyperosmotic composition.

It is another object of the present invention to provide an antimicrobial non-irritating hyperosmotic composition wherein the composition for treating a subject from topical microbial contamination.

It is another object of the present invention to provide an antimicrobial non-irritating hyperosmotic composition wherein the composition for treating a subject from internal microbial contamination.

It is another object of the present invention a method of decontaminating treating topical microbial contamination in a subject, comprising applying an effective amount of a composition as defined in any of the above on top of at least a portion of the subject.

It is another object of the present invention to provide a method of decontaminating treating internal microbial contamination in a subject, comprising introducing an effective amount of a composition as defined in any of the above to the subject. It is another object of the present invention to provide a medical pad comprising the composition of the above, useful for treating a subject from topical microbial contamination.

It is another object of the present invention to provide an antimicrobial non-irritating hyperosmotic compositions for treating a subject from an indication selected form diabetic ulcers; psoriasis; edema; varicose veins; topical and internal ulcers; inflammation and tumor in the gastroenterological trucks including IBD-related indications; fissures and fistulas, burns, skin indications, including skin irritations; Periodontal inflammations; and corneal ulcers.

It is another object of the present invention to provide a synergic method for treating clinical indications characterized by step(s) of providing an antimicrobial non-irritating hyperosmotic composition with both an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent.

It is another object of the present invention to provide a synergic method as defined above, the method further comprising step of admixing within the composition about 2 to about 20 w/w percent mud, especially green mud ( Argile Verde).

It is another object of the present invention to provide a synergic method as defined above, the method further comprising step of providing within the composition at least one member of a group consisting of Beta-Bisabolene, Caryophyllene oxide, Citronellol, Geraniol, Sabinene, Pulegone, Humulene, Carene, Myrcene: Myrcene, b-myrcene; Pinene: a-pinene and b-pinene; Limonene; Caryophyllene: b-caryophyllene; Linalool; Terpinolene; Camphene; Terpineol: a- Terpineol, terpinen-4-ol, and 4-terpineol, Phellandrene; Carene: Delta-3-carene; Humulene: also known as a-humulene and a-caryophyllene; Pulegone; Sabinene: Sabinene exists as (+)- and (-)- enantiomers; Geraniol; Phytol; Citronellol ; Caryophyllene oxide; Beta Bisabolene, Phellandrene, Terpineol, Camphene, Terpinolene, Linalool, Caryophyllene, Limonene, Pinene, Myrcene; and extracts of Lavender, rosemary, Thyme, Citrus, Cymbopogon, Bay leaf, Mangifera indica, Pinus, Sinensis, Origanum syriacum, Mango, Anise, Bergamot and any composition, mixture and derivative thereof.

It is another object of the present invention to provide a synergic method as defined above, the method comprising step of providing within the composition as active ingredients, comprising a cannabidiol ranging from about 0.1 to about 1.5 w/w percent, and an hyperosmotic agent ranging from about 2 to about 75 w/w percent wherein the cannabidiol and the hyperosmotic agent act in synergy.

It is another object of the present invention to provide a synergic method as defined above, the method further comprising step of providing an antimicrobial non-irritating hyperosmotic compositions characterized by providing both at least one first member of Group A, ranging from about 0.1 to about 1.5 w/w percent, and at least one second member of Group B, ranging from about 2 to about 75 w/w percent; the Group A is one or more cannabinoids selected from a group consisting of active cannabinoids, including THC (Tetrahydrocannabinol), THCA (Tetrahydrocannabinolic acid), BDA (Cannabidiolic Acid), CBN (Cannabinol), CBG (Cannabigerol), CBC (Cannabichromene), CBD (referring to Cannabidiol and/or CBDA) CBL (Cannabicyclol), CBV (Cannabivarin), THCV (Tetrahydrocannabivarin), CBDV (Cannabidivarin), CBCV (Cannabichromevarin), CBGV (Cannabigerovarin), CBGM (Cannabigerol Monomethyl Ether), CBE (Cannabielsoin), CBT (Cannabicitran), hemp oil, cannabis oil, cannabis-seed oilderivatives, and any derivatives, extracts and mixtures thereof; the Group B is one or more hyperosmotic agents selected from Subgroup B 1 , B2 and B3 ; the Subgroup Bl consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof; the Subgroup B2 consists inorganic salts, including zinc salts, ferric and ferrous salts, cupper salts, argentum salts, barium salts, sodium salts, potassium salts, barium salts, bismuth salts, calcium salts and calamine, magnesium salts, manganese salts, gold, silver, and further consisting bivalent metals sulfates, sulfites, nitrates, nitrates, amines, chlorides, bromides, iodines, phosphates, oxides; Dead Sea salts, sea salts, derivatives, salts, powders including nano powders, and mixtures thereof; the Subgroup B2 consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof; the Subgroup B3 consists clay, Medical Clay, Kaolin, Kaolinite, Kaopectate, Attapulgite-active ingredient in kaolin with/or without added Aluminum, Palygorskite, Terr am in [California red clay], temnian clay [Terra Sigillata], Terra Chia, Terra Cymolia, Cimolean earth, Cimolite, Argentiera, Semian earth, Colyrium, Egyptian earth, Chios earth, Bentonite clay, Montmorillonite, Green Clay, Argile Verte [French green clay], Illite, Montmorillonite, Kaolinite, Red clay, White clay and any mixture and derivatives thereof. It is another object of the present invention to disclose the non-irritating hyperosmotic compositions as defined in any of the above wherein the active cannabinoid is ranging from about 0.1 to about 1.5 w/w percent.

It is another object of the present invention to disclose the non-irritating hyperosmotic compositions as defined in any of the above wherein the active cannabinoid is ranging from about

1.5 to about 3.5 w/w percent.

3.5 to about 5.5 w/w percent.

It is another object of the present invention to disclose the synergic method as defined in any of the above wherein the active cannabinoid is ranging from about 0.1 to about 1.5 w/w percent.

It is another object of the present invention to disclose the synergic method as defined in any of the above wherein the active cannabinoid is ranging from about 1.5 to about 3.5 w/w percent.

It is another object of the present invention to disclose the synergic method as defined in any of the above wherein the active cannabinoid is ranging from about 3.5 to about 5.5 w/w percent.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following description is provided, alongside all chapters of the present invention, so as to enable any person skilled in the art to make use of the invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, will remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide antimicrobial non-irritating hyperosmotic compositions.

The present invention discloses antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent. Synergistic therapeutic effect is shown when both aforesaid different family members of at least one cannabinoid and at least one hyperosmotic agent is in the formula. The term‘about’ refers hereinafter to ±20% of the defined measure. The term‘cosmetics’ refers hereinafter in a non-limiting manner to various skin-care creams, lotions, powders, perfumes, lipsticks, fingernail and toe nail polish, eye and facial makeup, towelettes, permanent waves, colored contact lenses, hair colors, hair sprays and gels, deodorants, hand sanitizer, baby products, bath oils, bubble baths, bath salts, butters and many other types of products.

It is in the scope of the invention wherein the compositions defined and claimed are useful for treating dermatological conditions, such as pathological conditions, chronic dermal problems and age related dermal conditions which may include in a non-limiting manner acne, pyoderma, chronic skin irritation, atopic dermatitis or dermatitis as general bites, skin related inflammatory conditions and Gl-related IBD, autoimmune diseases, hyper keratosis, psoriasis, burns caused by chemical, radiation, or physical reasons, hemorrhoid and fissure, dry skin condition, old age dermal condition, or wrinkles age related conditions. The compositions defined and claimed are also useful for treating herpes virus including herpes zoster, infectious mononucleosis, pox virus, foot-and-mouth disease, foot-hand-and-mouth disease. This list in provided herein as an example and in a non-limiting manner.

The terms‘hypertonic’ and‘hyperosmotic’ interchangeably refer to any topical cosmetics and medications which has a higher concentration of solutes than the cells with which it is in contact, so that water is drawn out of the cells and into the solution by osmosis. The terms are especially useful to hypertonic compositions characterized by about 1700 to about 2,500 mOsm/L.

The term ‘additives’ refers hereinafter to either organic (natural occurring or synthesized materials) or inorganic compositions, in a fluid, gas or solid state, selected in a non-limiting manner form a group consisting, inter alia, of biocides, medicaments, narcotics, pain-relieving agents, oils and oils as described above, heparin and heparin-like agents, anticoagulants or coagulation factors, pharmaceuticals, binders, pigments, emulsifiers or soaps, de-emulsifiers, solvents, oils, plant extracts, essential oils, perfumes, sustain released drugs, markers, biomarkers, electrolytes, inorganic salts and compositions thereof, such as calamine, enzymes, hormones, proteins, vitamins, nutrients, hash oil, or any combination thereof.

The term‘carrier’ refers to any fluid that is characterized by being able to withdraw water from living cells, the fluid being in any appropriate form, including but not limited to liquids, solutions (whether water-miscible or water-immiscible), organic solvents, suspensions, dispersions, emulsions, fluid polymers, finely divided solids, nano-particles, micro-particles, powders, fine powders, gases, gels, aerosols, supercritical fluids, ionic liquids, surfactants, liposomes or any combination thereof. According an embodiment of the invention, the term‘salts’ refers, in a non limiting manner, to one or more compositions that are selected in a non-limiting manner from one or more compositions selected from a group consisting, inter alia, of one or more cations and elements, such as sodium, potassium, boron, silica, magnesium, calcium, zinc, copper, ferrous silver pt gold; and one or more anions, such as chlorides, hydroxides, phosphates or ammonium; or any combination thereof.

The term ‘sugars’ refers to one or more of four chemical groupings of carbohydrates: monosaccharide, disaccharide, oligosaccharide, and polysaccharide. The term‘honey’ refers to any natural occurring honey, or honey-like synthesized compositions, such as compositions comprise ingredients as follows e.g., fmctose: about 38.0%, glucose: about 31.0%, sucrose: about 1.0%, water: about 17.0%, other sugars: about 9.0% (maltose, melezitose), ash: about 0.17% and additives: about 3.38% (weight percent). The term‘hydrogels’ refers to any composition adapted to comprise more than 98% water. It is one embodiment of the invention wherein cationic polymers are utilized, such as copolymers of vinylpyrrolidone, methacrylamide, and N-vinylimidazole. It is another embodiment of the invention wherein Poly ethylene glycol (PEGs) familyare utilized. The family comprises, inter alia, PEG, polyethylene oxides (PEOs) or polyoxyethylenes (POEs) etc.

The present invention also discloses antimicrobial non-irritating hyperosmotic compositions as defined above, where the composition further comprising about 2 to about 20 w/w percent mud or a mud-like substance, e.g., green mud ( Argile Verde). Synergistic therapeutic effect is shown when the three aforesaid different family members of at least one cannabinoid, at least one hyperosmotic agent and at least one portion of mud are in the formula.

The present invention further discloses antimicrobial non-irritating hyperosmotic compositions as defined in any of the above, where the composition further comprising at least one terpene or terpene-like substances, being member of a group consisting, inter alia, of Beta-Bisabolene, Caryophyllene oxide, Citronellol, Geraniol, Sabinene, Pulegone, Humulene, Carene, Myrcene: Myrcene, b-myrcene; Pinene: a-pinene and b-pinene; Limonene; Caryophyllene: b- caryophyllene; Linalool; Terpinolene; Camphene; Terpineol: a-Terpineol, terpinen-4-ol, and 4- terpineol, Phellandrene; Carene: Delta-3-carene; Humulene: also known as a-humulene and a- caryophyllene; Pulegone; Sabinene: Sabinene exists as (+)- and (-)-enantiomers; Geraniol; Phytol; Citronellol ; Caryophyllene oxide; Beta Bisabolene, Phellandrene, Terpineol, Camphene, Terpinolene, Linalool, Caryophyllene, Limonene, Pinene, Myrcene; and extracts of Lavender, rosemary, Thyme, Citrus, Cymbopogon, Bay leaf, Mangifera indica, Pinus, Sinensis, Origanum syriacum, Mango, Anise, Bergamot and any composition, mixture and derivative thereof. Synergistic therapeutic effect is shown twice, i.e., (a) when three aforesaid different family members of at least one cannabinoid, at least one hyperosmotic agent and at least one terpene or terpene-like agent, are contained in the formula; and (b) when four aforesaid different family members of at least one cannabinoid, at least one hyperosmotic agent, at least one mud or mud like portions, and at least one terpene or terpene-like agent are contained in the formula

In one embodiment of the invention, the present invention discloses an antimicrobial non-irritating hyperosmotic compositions as defined in any of the above, wherein the composition comprises, as active ingredients, one or more cannabidiols ranging from about 0.1 to about 5.5 w/w percent, and one or more hyperosmotic agents ranging from about 2 to about 75 w/w percent.

The present invention further discloses antimicrobial non-irritating hyperosmotic compositions as defined in any of the above, where the composition further comprising both (a) at least one first member of Group A, ranging from about 0.1 to about 5.5 w/w percent, and (b) at least one second member of Group B, ranging from about 2 to about 75 w/w percent; or alternatively, ranging from about 2 to about 75 w/w percent; or alternatively, ranging from about 2 to about 20 w/w percent; or alternatively, ranging from about 15 to about 45 w/w percent; or alternatively, ranging from about 40 to about 75 w/w percent;

Group A one or more cannabinoids selected from a group consisting of active cannabinoids, including inter alia, THC (Tetrahydrocannabinol), THCA (Tetrahydrocannabinolic acid), BDA (Cannabidiolic Acid), CBN (Cannabinol), CBG (Cannabigerol), CBC (Cannabichromene), CBD (Cannabidiol and/or CBDA) CBL (Cannabicyclol), CBV (Cannabivarin), THCV (Tetrahydrocannabivarin), CBDV (Cannabidivarin), CBCV (Cannabichromevarin), CBGV (Cannabigerovarin), CBGM (Cannabigerol Monomethyl Ether), CBE (Cannabielsoin), CBT (Cannabicitran), hemp oil, cannabis oil, cannabis-seed oilderivatives, and any derivatives, extracts and mixtures thereof. Group B is one or more hyperosmotic agents selected from Subgroup Bl, B2 and B3. Subgroup Bl consists sugars and polysaccharides thereof, including inter alia, monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof.

Subgroup B2 consists inorganic salts, including inter alia, zinc salts, ferric and ferrous salts, cupper salts, argentum salts, barium salts, sodium salts, potassium salts, barium salts, bismuth salts, calcium salts and calamine, magnesium salts, manganese salts, gold, silver, and further consisting bivalent metals sulfates, sulfites, nitrates, nitrates, amines, chlorides, bromides, iodines, phosphates, oxides; Dead Sea salts, sea salts, derivatives, salts, powders including nano-powders, and mixtures thereof; the Subgroup B2 consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof. Subgroup B3 consists clay, Medical Clay, Kaolin, Kaolinite, Kaopectate, Attapulgite-active ingredient in kaolin with/or without added Aluminum, Palygorskite, Terramin [California red clay], temnian clay [Terra Sigillata], Terra Chia, Terra Cymolia, Cimolean earth, Cimolite, Argentiera, Semian earth, Colyrium, Egyptian earth, Chios earth, Bentonite clay, Montmorillonite, Green Clay, Argile Verte [French green clay], Illite, Montmorillonite, Kaolinite, Red clay, White clay and any mixture and derivatives thereof.

The present invention further discloses a process of preparing the composition as defined in any of the above. This process comprising step(s) of admixing at least one first active cannabinoid and at least one second hyperosmotic agent thereby obtaining the antimicrobial non -irritating hyperosmotic composition.

The present invention further discloses a therapeutic composition carrier and/or cosmetic, as defined in any of the above. This composition is provided useful for treating a subject from topical microbial contamination.

The present invention further discloses a therapeutic composition carrier and/or cosmetics, as defined in any of the above. This composition is provided useful for treating a subject from internal microbial contamination. The present invention further discloses a method of decontaminating treating topical microbial contamination in a subject. This method comprising step(s) of applying an effective amount of a composition as defined in any of the above on top of at least a portion of the subject.

The present invention further discloses a therapeutic composition carrier and/or cosmetics, as defined in any of the above. This composition is provided useful for decontaminating treating internal microbial contamination in a subject, comprising step(s) of introducing an effective amount of a composition as defined in any of the above.

The present invention further discloses a medical pad comprising the composition as defined in any of the above, provided useful for treating a subject from topical microbial contamination.

The present invention further discloses a cosmetic substance comprising the composition as defined in any of the above, provided useful for treating the skin of a subject.

The present invention further discloses a composition contained in a carrier comprising the composition as defined in any of the above.

The present invention further discloses a therapeutic composition as defined in any of the above, provided useful for treating a subject from an indication selected form diabetic ulcers; psoriasis; edema; varicose veins; topical and internal ulcers; inflammation and tumor in the gastroenterological trucks including IBD-related indications; fissures, hemorrhoids and fistulas, burns, skin indications, including skin irritations; periodontal inflammations; and corneal ulcers.

The technology of the present invention is provided useful for synergistic therapeutic of various clinical indications as defined, in a non-limiting manner, along the following 22 examples.

EXAMPLE IA

Synergistic therapeutic effect in treating diabetic ulcers and infections has been characterized by an antimicrobial non-irritating hyperosmotic composition characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and a hyperosmotic agent comprising both or either nano-powders of silver and/or nano-powders of zinc.

EXAMPLE IB

Synergistic therapeutic effect in treating diabetic ulcers and infections has been characterized by an antimicrobial non-irritating hyperosmotic composition characterized by an active cannabinoid ranging from about 1.5 to about 3.5 w/w percent, and a hyperosmotic agent comprising both or either nano-powders of silver and/or nano-powders of zinc.

EXAMPLE IC

Synergistic therapeutic effect in treating diabetic ulcers and infections has been characterized by an antimicrobial non-irritating hyperosmotic composition characterized by an active cannabinoid ranging from about 3.5 to about 5.5 w/w percent, and a hyperosmotic agent comprising both or either nano-powders of silver and/or nano-powders of zinc.

EXAMPLE IIA

Synergistic therapeutic effect in treating varicose veins and edema has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and an hyperosmotic agent comprising at least one type of inorganic salt, where the salt concentration is ranging from about 3 to about 9 percent (w/w).

EXAMPLE IIB

Synergistic therapeutic effect in treating varicose veins and edema has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 1.5 to about 3.5 w/w percent, and an hyperosmotic agent comprising at least one type of inorganic salt, where the salt concentration is ranging from about 3 to about 9 percent (w/w).

EXAMPLE IIC

Synergistic therapeutic effect in treating varicose veins and edema has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 3.5 to about 5.5 w/w percent, and an hyperosmotic agent comprising at least one type of inorganic salt, where the salt concentration is ranging from about 3 to about 9 percent (w/w).

EXAMPLE IIIA

Synergistic therapeutic effect in treating varicose veins and edema has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and an hyperosmotic agent comprising both (a) at least one type of inorganic salt, where the salt concentration is ranging from about 2 to about

7.5 percent (w/w), and (b) at least about 1 mud or mud-like substances.

EXAMPLE IIIB

Synergistic therapeutic effect in treating varicose veins and edema has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 1.5 to about 3.5 w/w percent, and an hyperosmotic agent comprising both (a) at least one type of inorganic salt, where the salt concentration is ranging from about 2 to about

7.5 percent (w/w), and (b) at least about 1 mud or mud-like substances.

EXAMPLE IIIB

Synergistic therapeutic effect in treating varicose veins and edema has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 3.5 to about 5.5 w/w percent, and an hyperosmotic agent comprising both (a) at least one type of inorganic salt, where the salt concentration is ranging from about 2 to about

7.5 percent (w/w), and (b) at least about 1 mud or mud-like substances.

EXAMPLE IV

A synergistic therapeutic effect in treating ulcers, tumors and infections has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and an hyperosmotic agent comprising both (a) at least one type of sugar or polysaccharides thereof, where sugar concentration is ranging from about 20 to about 40 percent, e.g., 30% (w/w), and (b) at least about 1 mud or mud-like substances.

This composition can be administrated orally (e.g., as is or by means of capsule/enteric coating administration) or topically.

EXAMPLE VA

Synergistic therapeutic effect in treating fissures, hemorrhoids and fistulas has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 2.5 w/w percent, and an hyperosmotic agent ranging from about 2 to about 70 w/w percent, and further comprising, inter alia, terpene and terpene-like substances, ranging from about 0.05 to about 2.5 w/w percent. The composition is administrated topically or by other applicable rectal-administrating means.

EXAMPLE VB

Synergistic therapeutic effect in treating fissures, hemorrhoids and fistulas has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 2.5 to about 5.5 w/w percent, and an hyperosmotic agent ranging from about 2 to about 70 w/w percent, and further comprising, inter alia, terpene and terpene-like substances, ranging from about 0.05 to about 2.5 w/w percent. The composition is administrated topically or by other applicable rectal-administrating means.

EXAMPLE VIA

Synergistic therapeutic effect in treating burns and complications thereof has been characterized by an antimicrobial non-irritating hyperosmotic composition characterized by an active cannabinoid ranging from about 0.1 to about 2.5 w/w percent, and a hyperosmotic agent ranging from about 50 to about 85 w/w percent, e.g., 70%.

EXAMPLE VIB

Synergistic therapeutic effect in treating burns and complications thereof has been characterized by an antimicrobial non-irritating hyperosmotic composition characterized by an active cannabinoid ranging from about 2.5 to about 5.5 w/w percent, and a hyperosmotic agent ranging from about 50 to about 85 w/w percent, e.g., 70%.

EXAMPLE VIIA

Synergistic therapeutic effect in treating skin allergies has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 2.5 w/w percent, and an hyperosmotic agent comprising both (a) in organic salts and (b) sugar or polysaccharides thereof, ranging all together from about 20 to about 75 w/w percent.

EXAMPLE VIIB

Synergistic therapeutic effect in treating skin allergies has been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 2.5 to about 5.5 w/w percent, and an hyperosmotic agent comprising both (a) in organic salts and (b) sugar or polysaccharides thereof, ranging all together from about 20 to about 75 w/w percent.

EXAMPLE VIIIA

Synergistic therapeutic effect in treating inflammations in gums, gingiva has and other dental or oral indications been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and an hyperosmotic agent comprising both (a) in organic salts and (b) sugar or polysaccharides thereof, ranging all together from about 20 to about 75 w/w percent.

EXAMPLE VIIIB

Synergistic therapeutic effect in treating inflammations in gums, gingiva has and other dental or oral indications been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 1.5 to about 3.5 w/w percent, and an hyperosmotic agent comprising both (a) in organic salts and (b) sugar or polysaccharides thereof, ranging all together from about 20 to about 75 w/w percent.

EXAMPLE VIIIC

Synergistic therapeutic effect in treating inflammations in gums, gingiva has and other dental or oral indications been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 3.5 to about 5.5 w/w percent, and an hyperosmotic agent comprising both (a) in organic salts and (b) sugar or polysaccharides thereof, ranging all together from about 20 to about 75 w/w percent.

EXAMPLE IXA

Synergistic therapeutic effect in treating conjunctivitis inflammation and other eye indications been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and an hyperosmotic agent comprising both (a) in organic salts and (b) sugar or polysaccharides thereof, ranging all together from about 20 to about 75 w/w percent.

EXAMPLE IXB

Synergistic therapeutic effect in treating conjunctivitis inflammation and other eye indications been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 1.5 to about 3.5 w/w percent, and an hyperosmotic agent comprising both (a) in organic salts and (b) sugar or polysaccharides thereof, ranging all together from about 20 to about 75 w/w percent.

EXAMPLE IXC

Synergistic therapeutic effect in treating conjunctivitis inflammation and other eye indications been characterized by an antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 3.5 to about 5.5 w/w percent, and an hyperosmotic agent comprising both (a) in organic salts and (b) sugar or polysaccharides thereof, ranging all together from about 20 to about 75 w/w percent

EXAMPLE X

Synergistic therapeutic effect is provided useful by an antimicrobial non-irritating hyperosmotic composition characterized by an active cannabinoid composition comprising CBD 90%, ranging from about 0 to about 5.5 w/w percent, and a hyperosmotic agent containing dextrose, ranging from about 0 to about 50w/w percent, see Table 1 below.

Table 1 Mixtures of CBD, green mud and dextrose [wt/wt percent] provided herein as an antimicrobial non-irritating hyperosmotic composition:

Using compositions as defined above, and applying methods adapted from Connell, Sean, et al. "Nonderma! irritating hyperosmotic nanoemulsions reduce treatment times in a contamination model of wound healing." Wound Repair and Regeneration 24.4 (2016): 669-678, which is incorporated herein as a reference, bacteria was successfully decontaminated (e.g., CFU decreases from 5.7 to 2.7 after 24h treatment; wound healing time was shortening from 9.2 to 7.5 days; and wound dimeter was reduced significantly after 7 days from 76% in the treatment group as compared to 95.5% in control group.

EXAMPLE XIA

Synergistic therapeutic effect is provided useful in treating Athlete Foot. A thick gel configured to be applied in small areas.

Table 2 Mixtures of Cannabidiol and dextrose provided herein as a composition treating athlete foot:

EXAMPLE XIB

EXAMPLE XII

Synergistic therapeutic effect is provided useful in treating Urticaria. Light cream to be applied on skin surface is configured to be applied in small areas.

Table 3 Mixtures of Cannabidiol and dextrose provided herein as a composition Urticaria (pH 5.5):

EXAMPLE XIII

Synergistic therapeutic effect is provided useful in treating Psoriasis. Light cream to be applied on skin surface is configured to be applied in small areas.

Table 4 Mixtures of Cannabidiol and dextrose provided herein as a composition Psoriasis (pH

5.5):

EXAMPLE XIV

Synergistic therapeutic effect is provided useful in treating Herpes. Thick Gel to be applied on skin surface is configured to be applied in small areas.

Table 5 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XV

Synergistic therapeutic effect is provided useful in treating Acne. Face gel to be applied on facial surface.

Table 6 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XVIA

Synergistic therapeutic effect is provided useful in treating Acne. Face cream or Acne face mask to be applied on facial surface.

Table 7 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XVI

Table 7 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XVII

Synergistic therapeutic effect is provided useful in treating Hemorrhoids. Thick Gel to local application.

Table 8 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XVIII

Synergistic therapeutic effect is provided useful in treating Dandruff. A water base shampoo to local application.

Table 9 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XIX

Synergistic therapeutic effect is provided useful in treating Seborrhea. A water base shampoo For a local application.

Table 10 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XXA

Synergistic therapeutic effect is provided useful in treating Urticaria. A lotion for a local application.

Table 11 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XXB

Table 11 Mixtures of Cannabidiol and dextrose provided herein as a composition:

EXAMPLE XXIA

Synergistic therapeutic effect is provided useful in treating IBD. An IBD Capsule characterized by Double layer capsule arrangement utilizes for treating intestinal inflammation. Capsule consists of at least one internal layer

Table 12 Synergistic therapeutic effect is provided useful in treating IBD.

NAME MG CAS

EXAMPLE XXIB

Table 12 Synergistic therapeutic effect is provided useful in treating IBD.

EXAMPLE XXIIA

Synergistic therapeutic effect is provided useful in treating IBD. An IBD Gelatin Capsule characterized by Double layer capsule arrangement utilizes for treating intestinal inflammation. Capsule consists of at least one internal layer

Table 13 Synergistic therapeutic effect is provided useful in treating IBD.

Synergistic therapeutic effect is provided useful in treating IBD. An 1BD Gelatin Capsule characterized by Double layer capsule arrangement utilizes for treating intestinal inflammation. Capsule consists of at least one internal layer

Table 13 Synergistic therapeutic effect is provided useful in treating IBD.

Claims

1. Antimicrobial non-irritating hyperosmotic compositions characterized by an active cannabinoid ranging from about 0.1 to about 5.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent.

2. The composition of claim 1, further comprising about 2 to about 20 w/w percent mud, especially green mud (Argile Verde).

3. The composition of claim 1, further comprising at least one member of a group consisting of Beta-Bisabolene, Caryophyllene oxide, Citronellol, Geraniol, Sabinene, Pulegone, Humulene, Carene, Myrcene: Myrcene, b-myrcene; Pinene: a-pinene and b-pinene; Limonene; Caryophyllene: b-caryophyllene; Linalool; Terpinolene; Camphene; Terpineol: a-Terpineol, terpinen-4-ol, and 4-terpineol, Phellandrene; Carene: Delta-3-carene; Humulene: also known as a-humulene and a-caryophyllene; Pulegone; Sabinene: Sabinene exists as (+)- and (-)-enantiomers; Geraniol; Phytol; Citronellol ; Caryophyllene oxide; Beta Bisabolene, Phellandrene, Terpineol, Camphene, Terpinolene, Linalool, Caryophyllene, Limonene, Pinene, Myrcene; and extracts of Lavender, rosemary, Thyme, Citrus, Cymbopogon, Bay leaf, Mangifera indica, Pinus, Sinensis, Origanum syriacum, Mango, Anise, Bergamot and any composition, mixture and derivative thereof.

4. The composition of claim 1, comprising, as active ingredients, comprising a cannabidiol ranging from about 0.1 to about 1.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent wherein said cannabidiol and said hyperosmotic agent act in synergy.

5. The composition of claim 1, characterized by both at least one first member of Group A, ranging from about 0.1 to about 1.5 w/w percent, and at least one second member of Group B, ranging from about 2 to about 75 w/w percent; said Group A is one or more cannabinoids selected from a group consisting of active cannabinoids, including THC (Tetrahydrocannabinol), THCA (Tetrahydrocannabinolic acid), BDA (Cannabidiolic Acid), CBN (Cannabinol), CBG (Cannabigerol), CBC (Cannabichromene), CBD (Cannabidiol) CBL (Cannabicyclol), CBV (Cannabivarin), THCV (Tetrahydrocannabivarin), CBDV (Cannabidivarin), CBCV (Cannabichromevarin), CBGV (Cannabigerovarin), CBGM (Cannabigerol Monomethyl Ether), CBE (Cannabielsoin), CBT (Cannabicitran), hemp oil, cannabis oil, cannabis-seed oilderivatives, and any derivatives, extracts and mixtures thereof; said Group B is one or more hyperosmotic agents selected from Subgroup Bl, B2 and B3; said Subgroup Bl consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof; said Subgroup B2 consists inorganic salts, including zinc salts, ferric and ferrous salts, cupper salts, argentum salts, barium salts, sodium salts, potassium salts, barium salts, bismuth salts, calcium salts and calamine, magnesium salts, manganese salts, gold, silver, and further consisting bivalent metals sulfates, sulfites, nitrates, nitrates, amines, chlorides, bromides, iodines, phosphates, oxides; Dead Sea salts, sea salts, derivatives, salts, powders including nano-powders, and mixtures thereof; said Subgroup B2 consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof; said Subgroup B3 consists clay, Medical Clay, Kaolin, Kaolinite, Kaopectate, Attapulgite-active ingredient in kaolin with/or without added Aluminum, Palygorskite, Terramin [California red clay], temnian clay [Terra Sigillata], Terra Chia, Terra Cymolia, Cimolean earth, Cimolite, Argentiera, Semian earth, Colyrium, Egyptian earth, Chios earth, Bentonite clay, Montmorillonite, Green Clay, Argile Verte [French green clay], Illite, Montmorillonite, Kaolinite, Red clay, White clay and any mixture and derivatives thereof.

6. A process of preparing the composition of claim 1 , the process comprising admixing at least one first active cannabinoid and at least one second hyperosmotic agent thereby obtaining the antimicrobial non-irritating hyperosmotic composition.

7. A therapeutic composition according to claim 1, useful for treating a subject from topical microbial contamination.

8. A therapeutic composition according to claim 1, useful for treating a subject from internal microbial contamination.

9. A method of decontaminating treating topical microbial contamination in a subject, comprising applying an effective amount of a composition as defined in claim 1 on top of at least a portion of said subject.

10. A method of decontaminating treating internal microbial contamination in a subject, comprising introducing an effective amount of a composition as defined in claim 1 to said subject.

11. A medical pad comprising the composition of claim 1, useful for treating a subject from topical microbial contamination.

12. A therapeutic composition according to claim 1, useful for treating a subject from an indication selected form diabetic ulcers; psoriasis; edema; varicose veins; topical and internal ulcers; inflammation and tumor in the gastroenterological trucks including IBD- related indications; fissures and fistulas, burns, skin indications, including skin irritations; Periodontal inflammations; and corneal ulcers.

13. A synergic method for treating clinical indications characterized by step(s) of providing an antimicrobial non-irritating hyperosmotic composition with both an active cannabinoid ranging from about 0.1 to about 1.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent.

14. The synergic method of claim 13, wherein said method comprising step(s) of providing further comprising step of admixing within said composition about 2 to about 20 w/w percent mud, especially green mud ( Argile Verde).

15. The synergic method of claim 13, wherein said method comprising step of providing within said composition at least one member of a group consisting of Beta-Bisabolene, Caryophyllene oxide, Citronellol, Geraniol, Sabinene, Pulegone, Humulene, Carene, Myrcene: Myrcene, b-myrcene; Pinene: a-pinene and b-pinene; Limonene; Caryophyllene: b-caryophyllene; Linalool; Terpinolene; Camphene; Terpineol: a-Terpineol, terpinen-4-ol, and 4-terpineol, Phellandrene; Carene: Delta-3-carene; Humulene: also known as a- humulene and a-caryophyllene; Pulegone; Sabinene: Sabinene exists as (+)- and (-)- enantiomers; Geraniol; Phytol; Citronellol ; Caryophyllene oxide; Beta Bisabolene, Phellandrene, Terpineol, Camphene, Terpinolene, Linalool, Caryophyllene, Limonene, Pinene, Myrcene; and extracts of Lavender, rosemary, Thyme, Citrus, Cymbopogon, Bay leaf, Mangifera indica, Pinus, Sinensis, Origanum syriacum, Mango, Anise, Bergamot and any composition, mixture and derivative thereof.

16. The synergic method of claim 13, wherein said method comprising step of providing within said composition as active ingredients, comprising a cannabidiol ranging from about 0.1 to about 1.5 w/w percent, and a hyperosmotic agent ranging from about 2 to about 75 w/w percent wherein said cannabidiol and said hyperosmotic agent act in synergy.

17. A synergic method for treating clinical indications characterized by step(s) of providing an antimicrobial non-irritating hyperosmotic compositions characterized by providing both at least one first member of Group A, ranging from about 0.1 to about 1.5 w/w percent, and at least one second member of Group B, ranging from about 2 to about 75 w/w percent; said Group A is one or more cannabinoids selected from a group consisting of active cannabinoids, including THC (Tetrahydrocannabinol), THCA (Tetrahydrocannabinolic acid), BDA (Cannabidiolic Acid), CBN (Cannabinol), CBG (Cannabigerol), CBC (Cannabichromene), CBD (Cannabidiol) CBL (Cannabic yclol), CBV (Cannabivarin), THCV (Tetrahydrocannabivarin), CBDV (Cannabidivarin), CBCV (Cannabichromevarin), CBGV (Cannabigerovarin), CBGM (Cannabigerol Monomethyl Ether), CBE (Cannabielsoin), CBT (Cannabicitran), hemp oil, cannabis oil, cannabis-seed oilderivatives, and any derivatives, extracts and mixtures thereof; said Group B is one or more hyperosmotic agents selected from Subgroup Bl, B2 and B3; said Subgroup Bl consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof; said Subgroup B2 consists inorganic salts, including zinc salts, ferric and ferrous salts, cupper salts, argentum salts, barium salts, sodium salts, potassium salts, barium salts, bismuth salts, calcium salts and calamine, magnesium salts, manganese salts, gold, silver, and further consisting bivalent metals sulfates, sulfites, nitrates, nitrates, amines, chlorides, bromides, iodines, phosphates, oxides; Dead Sea salts, sea salts, derivatives, salts, powders including nano-powders, and mixtures thereof; said Subgroup B2 consists monosaccharides, disaccharides, oligosaccharides and polysaccharides, including dextrose, maltose, sucrose, glucose, fructose, honey, molasses, starch, amylum, derivatives and mixtures thereof; said Subgroup B3 consists clay, Medical Clay, Kaolin, Kaolinite, Kaopectate, Attapulgite-active ingredient in kaolin with/or without added Aluminum, Palygorskite, Terr am in [California red clay], temnian clay [Terra Sigillata], Terra Chia, Terra Cymolia, Cimolean earth, Cimolite, Argentiera, Semian earth, Colyrium, Egyptian earth, Chios earth, Bentonite clay, Montmorillonite, Green Clay, Argile Verte [French green clay], Illite, Montmorillonite, Kaolinite, Red clay, White clay and any mixture and derivatives thereof.

18. The non-irritating hyperosmotic compositions of claim 1, wherein said active cannabinoid is ranging from about 0.1 to about 1.5 w/w percent.

19. The non-irritating hyperosmotic compositions of claim 1, wherein said active cannabinoid is ranging from about 1.5 to about 3.5 w/w percent.

20. The non-irritating hyperosmotic compositions of claim 1 , wherein said active cannabinoid is ranging from about 3.5 to about 5.5 w/w percent.

21. The synergic method of claim 13, wherein said active cannabinoid is ranging from about 0.1 to about 1.5 w/w percent.

22. The synergic method of claim 13, wherein said active cannabinoid is ranging from about 1.5 to about 3.5 w/w percent.

23. The synergic method of claim 13, wherein said active cannabinoid is ranging from about 3.5 to about 5.5 w/w percent.