WO2020255133A1 - Nouvelles préparations thérapeutiques comprenant du scutellaria barbata - Google Patents

Nouvelles préparations thérapeutiques comprenant du scutellaria barbata Download PDF

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WO2020255133A1
WO2020255133A1 PCT/IL2020/050675 IL2020050675W WO2020255133A1 WO 2020255133 A1 WO2020255133 A1 WO 2020255133A1 IL 2020050675 W IL2020050675 W IL 2020050675W WO 2020255133 A1 WO2020255133 A1 WO 2020255133A1
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composition
cells
effect
composition according
fraction
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PCT/IL2020/050675
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English (en)
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Tomer ZIMMERMAN
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The Cures Ltd.
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Publication of WO2020255133A1 publication Critical patent/WO2020255133A1/fr
Priority to IL289031A priority Critical patent/IL289031A/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/539—Scutellaria (skullcap)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present disclosure relates to preparations comprising herbal plant extract conferring therapeutic effects. More particularly, the current invention pertains to preparations comprising Scutellaria barbata extract and optionally one or more organic compounds for treating medical conditions.
  • Scutellaria barbata is a species of flowering plant in the mint family, Lamiaceae. It is a perennial herb generally reaching up to 35 centimeters tall. The flowers are borne on pedicels that have tiny, sharp bracteoles. The purple-blue, lightly hairy flower corolla is roughly a centimeter long. The plant grows in moist and wet habitat, such as paddy fields. It is known as being native to Asia.
  • Ban Zhi Lian As an herb used in traditional Chinese medicine it is known as Ban Zhi Lian. It has been tested in clinical trials for the treatment of metastatic breast cancer. It has been further reported that extracts induced apoptosis in prostate cancer cells in laboratory studies. The plant is known as an herbal remedy for inflammation and traumatic injury.
  • Scutellaria barbata Some selected chemical constituents of Scutellaria barbata include: Scutellarein (6- hydroxyapigenin), Catalpol, Limonene, (+)-a-Terpineol, b-Cadinene and b-Caryophyllene.
  • Cannabis is a genus of flowering plants in the family Cannabaceae. Three species may be recognized within the genus: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. The genus is widely accepted as being indigenous to and originating from Asia. Cannabis has long been used for hemp fiber, hemp seeds and their oils, hemp leaves for use as vegetables and as juice, medicinal purposes, and as a recreational drug.
  • a cannabinoid is one of a class of diverse chemical compounds that acts on cannabinoid receptors, AKA the Endocannabinoid system in cells that alter neurotransmitter release in the brain.
  • Ligands for these receptor proteins include the endocannabinoids produced naturally in the body by animals; phytocannabinoids (Phyto-plant based), found in Cannabis and some other plants; and synthetic cannabinoids, manufactured artificially.
  • the most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC), the primary psychoactive compound in Cannabis.
  • Cannabidiol (CBD) is another major constituent of the plant.
  • THC phytocannabinoid tetrahydrocannabinol
  • CBD Cannabidiol
  • Synthetic cannabinoids encompass a variety of distinct chemical classes: the classical cannabinoids structurally related to THC, the nonclassical cannabinoids (cannabimimetics) including the aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides as well as eicosanoids related to endocannabinoids.
  • Cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce the entourage effect of Cannabis. Knowledge of the individual medicinal properties of the cannabinoids, terpenes, and flavonoids is necessary to obtain optimal standardized synergistic compositions. This will enable targeting individual symptoms and/or diseases.
  • Terpenes are a large and diverse class of organic compounds, produced by a variety of plants. They are mostly hydro-carbons. Terpenoids (or isoprenoids) are modified terpenes as they contain additional functional groups.
  • Terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers.
  • Essential oils are used widely as fragrances in perfumery and traditional medicine, such as aromatherapy.
  • Synthetic variations and derivatives of natural terpenes and terpenoids also greatly expand the variety of aromas used in perfumery and flavors used in food additives
  • compositions comprising (a) Scutellaria barbata extract or a fraction thereof, and (b) a compound selected from the group consisting of: at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof, and a combination thereof, wherein said composition confers an activating or inhibiting effect on at least one of hematopoietic stem cells (HSC) or blood cells.
  • HSC hematopoietic stem cells
  • terpene compound or a derivative thereof is selected from the group consisting of Hemiterpene, Monoterpene, Sesquiterpenes, Diterpenes, Sesterterpenes, Triterpenes, Sesquarterpenes, Tetraterpenes, Polyterpenes, Norisoprenoids, terpinenes, phellandrenes, terpinolene, terpenoids and any mixture thereof.
  • compositions as defined in any of the above wherein said terpene compound or a derivative thereof is selected from the group consisting of myrcene, limonene, D-limonene, a-pinene, b- pinene, b-caryophyllene and any mixture thereof.
  • composition as defined in any of the above, wherein said cannabinoid compound or a derivative thereof is selected from the group consisting of an endocannabinoid, a phytocannabinoid, a synthetic cannabinoid and any combination thereof.
  • composition as defined in any of the above, wherein said cannabinoid compound or a derivative thereof is a Cannabis plant extract or a fraction thereof.
  • compositions as defined in any of the above wherein said cannabinoid compound or a derivative thereof is derived from a Cannabis plant extract or a fraction thereof.
  • CBD cannabinoid compound
  • white blood cells include immune system cells selected from the group consisting of Human Peripheral Blood Mononuclear Cells (HPBMC) including phagocytes such as neutrophils, monocytes, macrophages and mast cells, lymphocytes such as B lymphocytes, T lymphocytes and NK cells and any combination thereof.
  • HPBMC Human Peripheral Blood Mononuclear Cells
  • compositions as defined in any of the above, wherein said composition comprises therapeutically effective amount of said Scutellaria barbata extract or a fraction thereof and said compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and a combination thereof.
  • compositions as defined in any of the above, wherein said composition comprises predefined ratios of said Scutellaria barbata extract or a fraction thereof and said compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and a combination thereof.
  • compositions as defined in any of the above, wherein the concentration of said Scutellaria barbata extract or a fraction thereof is in the range of about 10% (wt.) to about 40%(wt.).
  • compositions as defined in any of the above, wherein said composition confers at least one effect to said blood cells, said effect is selected from the group consisting of reduced cancerous cells viability, cytotoxic effect, anti inflammatory effect, immune response activation, enhancement of hematopoietic cells, enhanced platelets count or recovery or rehabilitation, inhibition of immune system cells and any combination thereof.
  • compositions as defined in any of the above wherein said effect is additive or synergistic relative to the effect conferred by said Scutellaria barbata extract or a fraction thereof, or said compound, administered separately in a similar concentration.
  • composition as defined in any of the above, wherein said Scutellaria barbata extract or a fraction thereof and said compound have a combination index (Cl) value lower than 1 indicating synergism.
  • composition as defined in any of the above, wherein said Scutellaria barbata extract or a fraction thereof, and said compound have a combination index (Cl) value of 1 indicating an additive effect.
  • compositions as defined in any of the above, wherein said composition comprises Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of: limonene, D-limonene, a-pinene, b- pinene, b-caryophyllene and any mixture thereof.
  • compositions as defined in any of the above wherein said composition confers an anti-inflammatory effect on immune system cells such as on human Peripheral Blood Mononuclear Cells (PBMC).
  • PBMC Peripheral Blood Mononuclear Cells
  • anti-inflammatory effect on immune- system cells comprises enhanced cytokine secretion relative to control.
  • compositions as defined in any of the above wherein said cytokine is selected from the group consisting of TNF, TNFa, INFg, interleukins IL-1b, IL-4, IL-6, IL-10, IL-12, IL-18, CCL4/RANTES, TGFb and any combination thereof.
  • compositions as defined in any of the above, wherein said composition is useful for providing an immune response activation effect and/or an anti-inflammatory effect.
  • compositions as defined in any of the above, wherein said composition provides an immune response activation effect via a mechanism selected from the group consisting of alternative complement pathway, phagocytosis NK cell activation, cytokine secretion and any combination thereof.
  • compositions as defined in any of the above, wherein said composition provides an additive or more than additive effect or a synergistic effect with respect to activation of immune system cells or with respect to an anti-inflammatory effect as compared to the effect provided by said Scutellaria barbata extract or a fraction thereof, or said terpene compound or a derivative thereof, or said cannabinoid compound or a derivative thereof, administered separately in a similar concentration.
  • composition as defined in any of the above, wherein said Scutellaria barbata extract or a fraction thereof and said compound have a combination index (Cl) value lower than 1 indicating synergism.
  • composition as defined in any of the above, wherein said Scutellaria barbata extract or a fraction thereof, and said compound have a combination index (Cl) value of 1 indicating an additive effect.
  • compositions as defined in any of the above wherein said composition confers a cytotoxic effect on cancerous cells such as breast cancer cells. It is another object of the present invention to disclose the composition as defined in any of the above, wherein said composition is conferring an additive or synergistic effect with respect to inhibition or cytotoxicity of cancerous cells, relative to said Scutellaria barbata extract or a fraction thereof or said compound, administered separately in a similar concentration.
  • compositions as defined in any of the above, wherein said composition comprises Scutellaria barbata extract or a fraction thereof, or a combination of Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof, and said composition confers enhanced hematopoietic recovery and/or enhanced platelet or lymphocyte count relative to said count when a control treatment, particularly comprising a vehicle only is administered.
  • compositions as defined in any of the above, wherein said composition confers enhanced hematopoietic recovery or enhanced platelet or lymphocyte rehabilitation following irradiation treatment, as compared to said control treatment.
  • compositions as defined in any of the above, wherein said composition comprises Scutellaria barbata extract and said composition confers enhanced lymphocyte recovery relative to said recovery when a control treatment, particularly comprising a vehicle only is administered.
  • compositions as defined in any of the above, wherein said composition is useful for treatment of at least one of thrombocytopenia, severe acute respiratory syndrome (SARS), COVID-19, lymphopenia, autoimmune diseases, treatment- related lymphopenia (TRL) and other treatments or conditions associated with bone marrow dysfunction or disorders, for example chemotherapy drugs, biological therapies or other drugs, radiation therapy to the pelvis or to a large amount of bone marrow tissues.
  • compositions as defined in any of the above, wherein said composition comprises alcohol based Scutellaria barbata extract or a fraction thereof and CBD, or a combination of alcohol based Scutellaria barbata extract or a fraction thereof, CBD and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof and said composition has an anti- inflammatory effect or inhibitory effect on immune system cells activity.
  • compositions as defined in any of the above wherein said anti inflammatory or inhibitory effect is at least two fold higher relative to a control treatment comprising a vehicle only or treatment with a composition comprising said at least one terpene and CBD and absent of said Scutellaria barbata extract.
  • compositions as defined in any of the above, wherein said composition comprises water based Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof and said composition has an activating effect on immune system cells.
  • compositions as defined in any of the above, wherein said composition provides an additive or more than additive effect or a synergistic effect with respect to activation of immune system cells or with respect to an anti-inflammatory effect as compared to the effect provided by said Scutellaria barbata extract or a fraction thereof or said at least one terpene, or said CBD, administered alone in a similar concentration.
  • compositions as defined in any of the above, wherein said composition comprises water, Scutellaria barbata extract, flavor, sweetener, Gum arabic, Estergum, vegetable oil, D-limonene, Alpha Pinene, Beta Pinene and potassium sorbate.
  • compositions as defined in any of the above wherein said composition comprises at least one excipient selected from the group consisting of: a solvent, absorbent, a disintegrant, a thickener, a binder, a lubricant, a glidant, an antiadherant, a coating agent, sweetener, flavours, colours, sorbents, preservatives and any combination thereof. It is another object of the present invention to disclose the composition as defined in any of the above, wherein said composition is formulated for an administration route selected from the group consisting of: transdermal, intravenous, vaginal, sublingual, buccal, oral, and any combination thereof.
  • compositions as defined in any of the above, wherein said composition is formulated for rapid release or for controlled release.
  • It is another object of the present invention to disclose a synergistically effective composition wherein said composition comprising (a) a therapeutically effective amount of Scutellaria barbata extract or a fraction thereof and (b) a therapeutically effective amount of a compound selected from the group consisting of: at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof, and a combination thereof, in a predefined ratio conferring a synergistic effect with respect to stimulation or inhibition of blood cells relative to the effect of said Scutellaria barbata extract or a fraction thereof and said compound administered separately in a similar concentration.
  • It is another object of the present invention to disclose a composition comprising Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of: limonene, D-limonene, a-pinene, b- pinene, b-caryophyllene and any mixture thereof, wherein said composition confers an anti-inflammatory effect or activation of immune- system cells.
  • compositions as defined in any of the above wherein said effect comprises enhanced cytokine secretion and/or enhanced NO secretion relative to control.
  • compositions as defined in any of the above wherein said cytokine is selected from the group consisting of TNF, TNFa, INFg, interleukins IL-1b, IL-4, IL-6, IL-10, IL-12, IL-18, CCL4/RANTES, TGFb and any combination thereof.
  • compositions as defined in any of the above, wherein said composition provides an additive or more than additive effect or a synergistic effect with respect to activation of immune system cells or with respect to an anti-inflammatory effect as compared to the effect provided by said Scutellaria barbata extract or a fraction thereof or said at least one terpene, administered separately in a similar concentration.
  • It is another object of the present invention to disclose a composition comprising Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of: limonene, D-limonene, a-pinene, b- pinene, b-caryophyllene, myrcene and any mixture thereof, wherein said composition confers a cytotoxic effect on cancerous cells such as breast cancer cells.
  • compositions as defined in any of the above, wherein said composition confers an additive or synergistic cytotoxic effect relative to said Scutellaria barbata extract or a fraction thereof or said at least one terpene, administered separately in a similar concentration.
  • It is another object of the present invention to disclose a composition comprising Scutellaria barbata extract or a fraction thereof, or a combination of Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof, wherein said composition confers enhanced hematopoietic recovery or enhanced platelet or lymphocyte count relative to said count when a control treatment, particularly comprising a vehicle only is administered.
  • compositions as defined in any of the above, wherein said composition comprises Scutellaria barbata extract and said composition confers enhanced lymphocyte recovery relative to said recovery when a control treatment, particularly comprising a vehicle only is administered.
  • compositions as defined in any of the above, wherein said composition is useful for treatment of at least one of thrombocytopenia, severe acute respiratory syndrome (SARS), COVID-19, lymphopenia, autoimmune diseases, treatment- related lymphopenia (TRL) and other treatments or conditions associated with bone marrow dysfunction or disorders, for example chemotherapy drugs, biological therapies or other drugs, radiation therapy to the pelvis or to a large amount of bone marrow tissues.
  • compositions as defined in any of the above, wherein said composition provides an additive or more than additive effect or a synergistic effect with respect to enhanced platelet or lymphocyte count as compared to the effect provided by said Scutellaria barbata extract or a fraction thereof or said at least one terpene, administered separately in a similar concentration.
  • It is another object of the present invention to disclose a composition comprising alcohol based Scutellaria barbata extract or a fraction thereof and CBD or a combination of alcohol based Scutellaria barbata extract or a fraction thereof, CBD and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof wherein said composition has an anti- inflammatory effect or inhibitory effect on immune system cells activity.
  • compositions as defined in any of the above wherein said anti inflammatory or inhibitory effect is at least two fold higher relative to a control treatment, particularly comprising a vehicle only or to a treatment with a composition comprising said at least one terpene and CBD in similar concentrations.
  • compositions as defined in any of the above, wherein said composition provides an additive or more than additive effect or a synergistic effect with respect to an anti- inflammatory effect or inhibitory effect on immune system cells activity as compared to the effect provided by said Scutellaria barbata extract or a fraction thereof, said at least one terpene and said CBD administered separately or in partial combinations, in a similar concentration.
  • It is another object of the present invention to disclose a composition comprising water based Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof wherein said composition has an activating effect on immune system cells.
  • compositions as defined in any of the above, wherein said composition provides an additive or more than additive effect or a synergistic effect with respect to activation of immune system cells or with respect to an anti-inflammatory effect as compared to the effect provided by said Scutellaria barbata extract or a fraction thereof or said at least one terpene, administered alone in a similar concentration.
  • It is another object of the present invention to disclose a cytotoxic composition comprising a therapeutically effective amount of (a) a Scutellaria barbata extract or a fraction thereof, and (b) a therapeutic agent selected from the group consisting of: at least one terpene compound or a derivative thereof, a Cannabis extract or a fraction thereof, and a combination thereof, wherein said composition confers inhibition or cytotoxicity of cancerous cells.
  • Cannabis extract comprises CBD, THC or a combination thereof. It is another object of the present invention to disclose the cytotoxic composition as defined in any of the above, wherein said composition decreases significantly the viability of MCF-7 cells in comparison with said Scutellaria barbata extract or a fraction thereof or said therapeutic agent, alone.
  • white blood cells include immune system cells selected from the group consisting of Human Peripheral Blood Mononuclear Cells (HPBMC) including phagocytes such as neutrophils, monocytes, macrophages and mast cells, lymphocytes such as B lymphocytes, T lymphocytes and NK cells) and any combination thereof.
  • HPBMC Human Peripheral Blood Mononuclear Cells
  • said immune- system related disorder is selected from the group consisting of auto immune disorder, infectious disease, hematological malignancy, vaccine related disease, transplant immunology, inflammation, thrombocytopenia, severe acute respiratory syndrome (SARS), COVID-19, lymphopenia, treatment-related lymphopenia (TRL) and other treatments or conditions associated with bone marrow dysfunction or disorders, for example chemotherapy drugs, biological therapies or other drugs, radiation therapy to the pelvis
  • It is another object of the present invention to disclose a method for conferring cytotoxic effect on cancerous cells comprising (a) providing a composition according to claim 47; and (b) administering said composition to said cells in a therapeutically effective dosage to confer said effect.
  • It is another object of the present invention to disclose a method for conferring enhanced hematopoietic recovery or enhanced platelet or lymphocyte cell count comprising (a) providing a composition according to claim 49; and (b) administering said composition to said cells in a therapeutically effective dosage to confer said effect.
  • It is another object of the present invention to disclose a method for conferring an activating or stimulating effect on immune system cells comprising (a) providing a composition according to claim 56; and (b) administering said composition to said cells in a therapeutically effective dosage to confer said effect.
  • terpene compound or a derivative thereof is selected from the group consisting of Hemiterpene, Monoterpene, Sesquiterpenes, Diterpenes, Sesterterpenes, Triterpenes, Sesquarterpenes, Tetraterpenes, Polyterpenes, Norisoprenoids, terpinenes, phellandrenes, terpinolene, terpenoids and any mixture thereof.
  • CBD cannabinoid compound
  • composition comprises therapeutically effective amounts of said Scutellaria barbata extract or a fraction thereof and said compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and a combination thereof.
  • composition comprises predefined ratios of said Scutellaria barbata extract or a fraction thereof and said compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and a combination thereof. It is another object of the present invention to disclose the method as defined in any of the above, wherein the concentration of said Scutellaria barbata extract or a fraction thereof is in the range of about 10% (wt.) to about 40% (wt.) ⁇
  • composition is formulated for an administration route selected from the group consisting of: transdermal, intravenous, vaginal, sublingual, buccal, oral, and any combination thereof.
  • composition is useful for providing an effect selected from the group consisting of reduced cancerous cells viability, cytotoxic effect, anti-inflammatory effect, immune response activation, enhancement of hematopoietic cells, enhanced platelets recovery or rehabilitation, inhibition of immune system cells and any combination thereof.
  • said immune- system related disorder is selected from the group consisting of auto immune disorder, infectious disease, hematological malignancy, vaccine related disease, transplant immunology, inflammation, thrombocytopenia, severe acute respiratory syndrome (SARS), COVID-19, lymphopenia, treatment-related lymphopenia (TRL) and other treatments or conditions associated with bone marrow dysfunction or disorders, for example chemotherapy drugs, biological therapies or other drugs, radiation therapy to the pelvis or to a large amount of bone marrow tissues and any combination thereof.
  • said immune- system related disorder is selected from the group consisting of auto immune disorder, infectious disease, hematological malignancy, vaccine related disease, transplant immunology, inflammation, thrombocytopenia, severe acute respiratory syndrome (SARS), COVID-19, lymphopenia, treatment-related lymphopenia (TRL) and other treatments or conditions associated with bone marrow dysfunction or disorders, for example chemotherapy drugs, biological therapies or other drugs, radiation therapy to the pelvis or to a large amount of bone marrow tissues and any combination thereof.
  • compositions as defined in any of the above for use in the treatment of immune system or inflammation related disorders.
  • compositions as defined in any of the above wherein said immune- system related disorder is selected from the group consisting of auto- immune disorder, infectious disease, hematological malignancy, vaccine related disease, transplant immunology, inflammation, thrombocytopenia, severe acute respiratory syndrome (SARS), COVID-19, lymphopenia, treatment-related lymphopenia (TRL) and other treatments or conditions associated with bone marrow dysfunction or disorders, for example chemotherapy drugs, biological therapies or other drugs, radiation therapy to the pelvis or to a large amount of bone marrow tissues and any combination thereof.
  • said immune- system related disorder is selected from the group consisting of auto- immune disorder, infectious disease, hematological malignancy, vaccine related disease, transplant immunology, inflammation, thrombocytopenia, severe acute respiratory syndrome (SARS), COVID-19, lymphopenia, treatment-related lymphopenia (TRL) and other treatments or conditions associated with bone marrow dysfunction or disorders, for example chemotherapy drugs, biological therapies or other drugs, radiation therapy to the pelvis or to a large amount of bone
  • compositions as defined in any of the above for use in stimulating or inhibiting hematopoietic stem cells or blood cells.
  • composition comprises about 0.1% w/w of said emulsion.
  • FIG. 1 is a graphic illustration presenting viability (%) of MCF-7 cells treated with Scutellaria barabata extract or with Cannabis extract in dose dependent manner;
  • FIG. 2 is a graphic illustration presenting viability (%) of MCF-7 cells treated with different terpene compounds in dose dependent manner
  • FIG. 3 is a graphic illustration presenting viability (%) of MCF-7 cells treated with different Scutellaria barabata extract, Cannabis extract and terpene compounds combinations in dose dependent manner;
  • FIG. 4 is a schematic illustrating of the experimental design of the study for evaluating the effect of S. barbata + terpenes treatment on hematopoietic recovery post irradiation;
  • FIG. 5 is a graphic illustration presenting safety evaluation of the mice treatment groups
  • FIG. 6A is graphically presenting platelets recovery one week following irradiation in response to oral administration of S. barbata only (Treatment A) as compared to oral administration of the formula including S. barbata + Terpenes (Treatment B);
  • FIG. 6B is graphically presenting time dependent platelets recovery following irradiation in response to oral administration of the formula including S. barbata + Terpenes (Treatment B);
  • FIG. 7 is graphically presenting lymphocytes recovery following irradiation, in response to oral (Fig. 7A) or IP (Fig.7B) administration of S. barbata extract with or without terpenes (Treatment B, or Treatment A, respectively);
  • FIG. 8A is graphically presenting NO secretion (mM) by RAW cells exposed to different S. barbata (WSB101) treatments;
  • FIG. 8B is graphically presenting viability evaluation of the tested immune system cells exposure to the various treatments described in Fig. 8A;
  • FIG. 8C is graphically presenting NO secretion results as % of vehicle.
  • Fig. 8D is graphically presenting NO secretion results of Fig. 8A as (% from vehicle)/normalized to the viability.
  • the present invention provides a composition
  • a composition comprising (a) Scutellaria barbata extract or a fraction thereof, and (b) a compound selected from the group consisting of: at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof, and a combination thereof.
  • the aforementioned composition confers an activating or inhibiting effect on at least one of hematopoietic stem cells (HSC) or blood cells.
  • HSC hematopoietic stem cells
  • the present invention provides a composition comprising (a) Scutellaria barbata extract or a fraction thereof, and (b) at least one terpene compound or a derivative thereof, wherein said composition confers an activating effect on immune- system cells.
  • compositions comprising Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of: limonene, D-limonene, a-pinene, b- pinene, b-caryophyllene and any mixture thereof, wherein said composition confers an anti-inflammatory or activating effect on immune- system cells.
  • compositions comprising Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of: limonene, D-limonene, a-pinene, b- pinene, b-caryophyllene, myrcene and any mixture thereof, wherein said composition confers a cytotoxic effect on cancerous cells such as breast cancer cells.
  • compositions comprising Scutellaria barbata extract or a fraction thereof, or a combination of Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof, wherein said composition confers enhanced hematopoietic recovery or enhanced platelet or lymphocyte count relative to said count when a control treatment comprising a vehicle only is administered.
  • compositions comprising alcohol based Scutellaria barbata extract or a fraction thereof and CBD or a combination of alcohol based Scutellaria barbata extract or a fraction thereof, CBD and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof wherein said composition has an anti- inflammatory effect or inhibitory effect on immune system cells activity.
  • composition comprising water based Scutellaria barbata extract or a fraction thereof and at least one terpene selected from the group consisting of D-limonene, Alpha Pinene, Beta Pinene and any combination thereof wherein said composition has an activating effect on immune system cells.
  • Non limiting examples of terpene compounds within the scope of the present invention include Hemiterpene, Monoterpene, Sesquiterpenes, Diterpenes, Sesterterpenes, Triterpenes, Sesquarterpenes, Tetraterpenes, Polyterpenes, Norisoprenoids, terpinenes, phellandrenes, terpinolene, terpenoids and any mixture thereof.
  • the terpene compound or a derivative thereof is selected from the group consisting of myrcene, limonene, a-pinene, b- pinene, b- caryophyllene and any mixture thereof.
  • the present invention provides a composition comprising (a) Scutellaria barbata extract or a fraction thereof, and (b) at least one cannabinoid compound or a derivative thereof, wherein said composition confers an activating effect on immune- system cells.
  • the cannabinoid compound or a derivative thereof is selected from the group consisting of an endocannabinoid, a phytocannabinoid, a synthetic cannabinoid and any combination thereof.
  • composition of the present invention provides a more than additive effect or a synergistic effect with respect to activation of immune system cells as compared to the effect provided by the Scutellaria barbata extract or a fraction thereof or the terpene compound or a derivative thereof, or the cannabinoid compound or a derivative thereof, administered separately in a similar concentration.
  • plant refers to any plant at any stage of development, particularly a seed plant.
  • plant includes the whole plant or any parts or derivatives thereof, such as plant cells, seeds, plant protoplasts, plant cell tissue culture from which tomato plants can be regenerated, plant callus or calli, meristematic cells, microspores, embryos, immature embryos, pollen, ovules, anthers, fruit, flowers, leaves, cotyledons, pistil, seeds, seed coat, roots, root tips and the like.
  • plant cell refers to a structural and physiological unit of a plant, comprising a protoplast and a cell wall.
  • the plant cell may be in a form of an isolated single cell or a cultured cell, or as a part of higher organized unit such as, for example, plant tissue, a plant organ, or a whole plant.
  • plant cell culture means cultures of plant units such as, for example, protoplasts, regenerable cells, cell culture, cells, cells in plant tissues, pollen, pollen tubes, ovules, embryo sacs, zygotes and embryos at various stages of development, leaves, roots, root tips, anthers, meristematic cells, microspores, flowers, cotyledons, pistil, fruit, seeds, seed coat or any combination thereof.
  • plant material or “plant part” used herein refers to leaves, stems, roots, root tips, flowers or flower parts, fruits, pollen, egg cells, zygotes, seeds, seed coat, cuttings, cell or tissue cultures, or any other part or product of a plant or a combination thereof.
  • a "plant organ” as used herein means a distinct and visibly structured and differentiated part of a plant such as a root, stem, leaf, flower, flower bud, or embryo.
  • Plant tissue as used herein means a group of plant cells organized into a structural and functional unit. Any tissue of a plant in planta or in culture is included. This term includes, but is not limited to, whole plants, plant organs, plant seeds, tissue culture, protoplasts, meristematic cells, calli and any group of plant cells organized into structural and/or functional units. The use of this term in conjunction with, or in the absence of, any specific type of plant tissue as listed above or otherwise embraced by this definition is not intended to be exclusive of any other type of plant tissue.
  • the present invention provides preparations and compositions comprising Scutellaria barbata extract in combination with a compound, preferably an organic compound comprising (i) a terpene compound or a derivative thereof, (ii) a cannabinoid compound or a derivative thereof and (iii) a combination thereof.
  • plant or “cultivar” used herein means a group of similar plants that by structural features and performance can be identified from other varieties within the same species.
  • germplasm refers to the totality of the genotypes of a population or other group of individuals (e.g., a species).
  • the term “germplasm” can also refer to plant material; e.g., a group of plants that act as a repository for various alleles.
  • Such germplasm genotypes or populations include plant materials of proven genetic superiority; e.g., for a given environment or geographical area, and plant materials of unknown or unproven genetic value; that are not part of an established breeding population and that do not have a known relationship to a member of the established breeding population.
  • Scutellaria barbata also used as 'barbed skullcap' or 'Ban Zhi Lian' refers hereinafter to a species of flowering plant in the mint family, Lamiaceae, which is native to Asia. It is herein acknowledged that it is a perennial herb generally reaching up to 35 centimeters height or more.
  • Scutellaria barbata extracts or fractions thereof are used for stimulation of immune system cells.
  • constituents within Scutellaria barbata extract include Scutellarein (6-hydroxyapigenin), Catalpol, Limonene, D-limonene, (+)-a-Terpineol, b- Cadinene and b-Caryophyllene.
  • Scutellaria barbata extracts or fractions thereof are useful for treatment of metastatic breast cancer, apoptosis of prostate cancer cells and as an herbal remedy for inflammation and traumatic injury.
  • the present invention surprisingly shows that Scutellaria barbata extract is effective in activating immune system cells and treatment of immune- response associated disorders.
  • Terpene refers to a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers, and by some insects. Terpenes are hydrocarbons. Terpenes are the major components of rosin and of turpentine produced from resin. Terpenes are also major biosynthetic building blocks. Steroids, for example, are derivatives of the triterpene squalene.
  • Terpenes may be classified by the number of isoprene units in the molecule. Examples of terpenes within the scope of the present invention include:
  • Hemi terpenes consist of a single isoprene unit. Isoprene itself is considered the only hemiterpene, but oxygen-containing derivatives such as prenol and isovaleric acid are hemiterpenoids.
  • Monoterpenes consist of two isoprene units and have the molecular formula C10H16.
  • Examples of monoterpenes and monoterpenoids include geraniol, terpineol (present in lilacs), limonene (present in citrus fruits), D-limonene, myrcene (present in hops), linalool (present in lavender) or pinene (present in pine trees). Iridoids derive from monoterpenes.
  • Sesquiterpenes consist of three isoprene units and have the molecular formula C15H24.
  • Examples of sesquiterpenes and sesquiterpenoids include humulene, farnesenes, farnesol.
  • Diterpenes composed of four isoprene units and have the molecular formula C20H32. They derive from geranylgeranyl pyrophosphate. Examples of diterpenes and diterpenoids are cafestol, kahweol, cembrene and taxadiene (precursor of taxol). Diterpenes also form the basis for biologically important compounds such as retinol, retinal, and phytol.
  • Sesterterpenes are terpenes having 25 carbons and five isoprene units.
  • An example of a sesterterpenoid is geranylfarnesol.
  • Triterpenes consist of six isoprene units and have the molecular formula C30H48.
  • the linear triterpene squalene the major constituent of shark liver oil, is derived from the reductive coupling of two molecules of farnesyl pyrophosphate. Squalene is then processed biosynthetically to generate either lanosterol or cycloartol, the structural precursors to all the steroids.
  • Sesquarterpenes are composed of seven isoprene units and have the molecular formula C35H56. Sesquarterpenes are typically microbial in their origin. Examples of sesquarterpenoids are ferrugicadiol and tetraprenylcurcumene.
  • Tetraterpenes contain eight isoprene units and have the molecular formula C40H64.
  • Examples of tetraterpenoids include the acyclic lycopene, the monocyclic gamma-carotene, and the bicyclic alpha- and beta-carotenes.
  • Polyterpenes consist of long chains of many isoprene units. Some plants produce a polyisoprene with trans double bonds, known as gutta-percha.
  • Norisoprenoids such as the C13-norisoprenoids 3-oxo-a-ionol present in Muscat of Alexandria leaves and 7,8-dihydroionone derivatives, such as megastigmane-3,9-diol and 3-oxo-7,8-dihydro- a-ionol found in Shiraz leaves (both grapes in the species Vitis vinifera) or wine (responsible for some of the spice notes in Chardonnay), can be produced by fungal peroxidases [14] or glycosidases.
  • terpenoids refers to modified terpenes that contain additional functional groups, usually oxygen-containing.
  • terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers. Synthetic variations and derivatives of natural terpenes and terpenoids are also within the scope of the present invention.
  • terpenes and derivatives thereof are used in combination with Scutellaria barbata extracts or fractions thereof to enhance or preferably synergistically enhance immune system cells.
  • Cannabisbis refers hereinafter to a genus of flowering plants in the family Cannabaceae.
  • Cannabis is an annual, dioecious, flowering herb that includes, but is not limited to three different species, Cannabis sativa, Cannabis indica and Cannabis ruderalis.
  • the term also refers to hemp.
  • Cannabis plants produce a group of chemicals called cannabinoids. Cannabinoids, terpenoids, and other compounds are secreted by glandular trichomes that occur most abundantly on the floral calyxes and bracts of female Cannabis plants.
  • cannabinoid receptor refers hereinafter to a class of cell membrane receptors under the G protein-coupled receptor superfamily.
  • CB1 and CB2 There are currently two known subtypes of cannabinoid receptors, termed CB1 and CB2.
  • the CB1 receptor is expressed mainly in the brain, but also in the lungs, liver and kidneys.
  • the CB2 receptor is expressed mainly in the immune system and in hematopoietic cells.
  • Cannabinoid receptor type 1 refers hereinafter to a G protein -coupled cannabinoid receptor located primarily in the central and peripheral nervous system. It is activated by the endocannabinoid neurotransmitters anandamide and 2-arachidonoyl glyceride (2- AG); by plant cannabinoids, such as the compound THC, an active ingredient of the psychoactive drug Cannabis; and by synthetic analogues of THC.
  • Cannabinoid receptor type 2 refers hereinafter to a G protein -coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene. It is closely related to the cannabinoid receptor type 1, which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic-inhibition, the psychoactive properties of Tetrahydrocannabinol, the active agent in marijuana, and other phytocannabinoids (natural cannabinoids).
  • the principal endogenous ligand for the CB2 receptor is 2-arachidonoylglycerol (2-AG).
  • nonpsychoactive refers hereinafter to products or compositions or elements or components of Cannabis not significantly affecting the mind or mental processes.
  • cannabinoid refers hereinafter to a class of diverse chemical compounds that act on cannabinoid receptors on cells that repress neurotransmitter release in the brain. These receptor proteins include the endocannabinoids (produced naturally in the body by humans and animals), the phytocannabinoids (found in Cannabis and some other plants), and synthetic cannabinoids.
  • the main cannabinoids are concentrated in a viscous resin produced in structures known as glandular trichomes. Up until now, at least 113 different cannabinoids have been isolated from the Cannabis plant.
  • the main classes of cannabinoids from Cannabis are THC (tetrahydrocannabinol), THCA (tetrahydrocannabinolic acid), CBD (cannabidiol), CBDA (cannabidiolic acid), CBN (cannabinol), CBG (cannabigerol), CBC (cannabichromene), CBL (cannabicyclol), CBV (cannabivarin), THCV (tetrahydrocannabivarin), CBDV (cannabidivarin), CBCV (cannabichromevarin), CBGV (cannabigerovarin), CBGM (cannabigerol monomethyl ether), CBE (cannabielsoin), CBT (cannabicitran) and any combination thereof.
  • cannabinoids include tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN).
  • CBC Cannabichromene
  • CBCA Cannabichromenic acid
  • CBCV Cannabichromevarin
  • CBCVA Cannabichromevarinic acid
  • CBL Cannabicyclol
  • CBLA Cannabicyclolic acid
  • CBD Cannabidiol
  • CBD Cannabidiol monomethylether
  • CBDA Cannabidiolic acid
  • CBDV Cannabidivarin
  • CBDVA Cannabidivarinic acid
  • Cannabielsoic acid B (CBEA-B)
  • Cannabielsoin acid A (CBEA-A)
  • CBG Cannabigerol
  • Cannabigerol monomethylether CBGM
  • Cannabigerolic acid CBG A
  • CBGAM Cannabigerolic acid monomethylether
  • CBGV Cannabigerovarin
  • CBGVA Cannabigerovarinic acid
  • Cannabinol methylether (CBNM)
  • CBNA Cannabinolic acid
  • CBV Cannabivarin
  • THC-C4 Delta-9-tetrahydrocannabinol-C4
  • THCA-A Delta-9-tetrahydrocannabinolic acid A
  • THCA-B Delta-9-tetrahydrocannabinolic acid-C4
  • THCVA Delta-9-tetrahydrocannabivarinic acid
  • CBR Cannabiripsol
  • CBT Cannbicitran
  • DCBF Dehydrocannabifuran
  • Tetrahydrocannabinol the primary psychoactive component of the Cannabis plant.
  • Delta-9-tetrahydrocannabinol A9-THC, THC
  • delta-8- tetrahydrocannabinol A8-THC
  • THC Delta-9-tetrahydrocannabinol
  • A8-THC delta-8- tetrahydrocannabinol
  • cannabinoids produce the effects associated with Cannabis by binding to the CB 1 cannabinoid receptors in the brain.
  • Cannabidiol which is considered as non-psychotropic.
  • Cannabidiol has little affinity for CB1 and CB2 receptors but acts as an indirect antagonist of cannabinoid agonists. It is further acknowledged herein that it is an antagonist at the putative cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen.
  • Cannabidiol has also been shown to act as a 5-HT1A receptor agonist.
  • CBD shares a precursor with THC and is the main cannabinoid in CBD-dominant Cannabis strains.
  • CBD is combined with Scutellaria barbata extract and optionally with a terpene compound to enhance or preferably, synergistically enehance immune system response.
  • hematopoietic stem cells refers to an immature cells that can develop into all types of blood cells, including white blood cells, red blood cells, and platelets. Hematopoietic stem cells are found in the peripheral blood and the bone marrow. They are also called blood stem cell.
  • HSCs hematopoietic stem cells
  • a hematopoietic stem cell is a cell isolated from the blood or bone marrow that can renew itself, can differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosis— a process by which cells that are detrimental or unneeded self-destruct.
  • IR ionizing radiation
  • HSC hematopoietic stem cell
  • Recovering or rehabilitating HSCs from IR is a primary goal in the development of novel medical countermeasures against radiation.
  • the mechanisms by which IR causes HSC damage include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche.
  • Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury.
  • BM bone marrow
  • Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. It is included within the scope that the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system.
  • the present invention provides a composition comprising S. barbata extract with or without terpenes that significantly enhance hematopoietic cells rehabilitation post irradiation treatment. It is shown that treatment with the composition comprising S. barbata extract improved platelet and/or lymphocyte recovery as compared to control treatment.
  • blood cells generally refers to white blood cells, red blood cells, and platelets and further includes hematopoietic stem cells.
  • anti-inflammatory refers herein after to a property of a substance or treatment that reduces inflammation or swelling. It is within the context of the present invention that the nutraceutical composition of the present invention comprising S. barnata extract and preferably at least one terpene confers an anti-inflammatory effect with respect to immune system cells in a subject. It is noted that the composition of the present invention may be administered together with one or more anti-inflammatory drugs, analgesic compounds, remedying pain by reducing inflammation or with opioids, which affect the central nervous system to block pain signaling to the brain.
  • inhibitortion of cancerous cells or “inhibition of breast cancer cells” or “inhibition of MCF-7 cells” as used herein refers to an anti-cancer or tumor effect including decrease in survival rate of cancerous cells, cytotoxic effect on cancerous cells, tumor size reduction, reduced viability of cancerous cells, apoptosis, cell cycle arrest, cell signaling arrest, mitochondrial trans membrane potential arrest and ROS production arrest.
  • terapéuticaally effective amount or “therapeutically effective dose or dosage” refers hereinafter to the amount of an agent or agents present at a sufficient concentration to produce a therapeutic effect on a patient, cells, or any combination thereof.
  • vehicle generally refers hereinafter to pharmaceutical vehicles or placebo or control group or control treatment which for example include carrier or inert medium used as a solvent (or diluent) in which the medicinally active agent is formulated and or administered.
  • a control or control treatment may include a vehicle only or a combination of ingredients which is used as a control or reference to an experimental group or treatment.
  • XTT refers hereinafter to a colorimetric assay for analyzing the number of viable cells or cell proliferation.
  • the assay is based on the cleavage of the tetrazolium salt XTT in the presence of an electron-coupling reagent, producing a soluble formazan salt. This conversion only occurs in viable cells.
  • Cells grown in a 96-well tissue culture plate are incubated with the XTT labeling mixture for 2-20 hours. After this incubation period, the formazan dye formed is quantitated using a scanning multi-well spectrophotometer (ELISA reader). The measured absorbance directly correlates to the number of viable cells.
  • ELISA reader scanning multi-well spectrophotometer
  • cytotoxic composition refers hereinafter to a combination of compounds which have an inhibitory or cytotoxic effect on cancer or tumor cells, for example breast cancer cells, e.g. MCF-7 cells.
  • similar concentration refers hereinafter to a concentration which is +/- 25% of the defined concentration value, preferably +/- 10% of the defined concentration value, more preferably +/- 5% of the defined concentration value.
  • Crobis extract or “Scutellaria barabata extract” refers hereinafter to any extract or concentrate derived from the Cannabis or Scutellaria barabata plant.
  • the Cannabis extract may contain at least one cannabinoid.
  • the cannabinoids may be extracted from the Cannabis plant using any one of the many known extraction methods, such as non-hydrocarbons extraction methods and hydrocarbons extraction methods.
  • chemical constituents of Scutellaria barabata extract may include Scutellarein (6-hydroxyapigenin), Catalpol, Limonene, (+)-a- Terpineol, b-Cadinene and b-Caryophyllene.
  • fraction thereof refers to a plant extract, preferably a Cannabis or Scutellaria extract treated by separation or purification or fractionation processes. More particularly it refers to purified or partially purified plant extract containing chemical compounds or constituents or portions or the extract or elements.
  • Cannabis extract contains cannabinoid- type portions or elements.
  • Cannabis or cannabinoid fraction may contain synthetic cannabinoids.
  • the Cannabis extract or Scutellaria barabata extract or a fraction thereof may comprise noncannabinoid-type constituents selected from the group consisting of: terpenes, terpenoids, hydrocarbons, essential oil derived from Cannabis or Scutellaria, nitrogen-containing compounds, carbohydrates, flavonoids, fatty acids, noncannabinoid phenols, simple alcohols, aldehydes, ketones, acids, esters, lactones, phytosterols such as campesterol, ergosterol, E-sitosterol, and stigmasterol, vitamin K, pigments such as carotene and xanthophylls, elements such as Na, K, Ca, Mg, Fe, Cu, Mn, Zn and Hg and any combination thereof.
  • Cannabis and/or Scutellaria plant are distinct and specific classes of compounds that are only known to exist in the Cannabis plant.
  • Other constituents of the Cannabis and/or Scutellaria plant are: nitrogenous compounds, amino acids, proteins, glycoproteins, enzymes, sugars and related compounds, hydrocarbons, simple alcohols, aldehydes, ketones, simple acids, fatty acids, simple esters, lactones, steroids, terpenes, non-cannabinoid phenols, flavonoids, vitamins (such as Vitamin A, pigments, and elements.
  • the measurable effect on cells is selected from the group consisting of: anti proliferative, regenerative, anti-inflammatory, anti-mitotic, differentiative, anti-metastatic, anti-angiogenic, apoptotic, cytotoxic, cytopathic and any combination thereof.
  • sustained release dosage form refers hereinafter to the release of a therapeutic compound at a predetermined rate or controlled rate in order to maintain a constant concentration of the compound for a specific period of time with minimum side effects. This can be achieved through a variety of formulations, including liposomes and drug-polymer conjugates. Sustained release in the present invention also includes within its scope “modified”, “controlled”, “sustained”, “prolonged”, “extended” or “delayed” release of a compound and/or extract.
  • immediate release dosage form refers to a drug or active ingredient or a composition or formulation, which disintegrates rapidly and gets dissolved to release the medicaments. Immediate release may be provided for by way of an appropriate pharmaceutically acceptable diluent or carrier, which diluent or carrier does not prolong, to an appreciable extent, the rate of drug or active compound release and/or absorption.
  • synergistic refers hereinafter to an effect arising between two or more agents, compounds, entities, factors, or substances that produces an effect greater than the sum of their individual effects. It is opposite of antagonism.
  • synergy is the creation of a whole that is greater than the simple sum of its parts. A synergistic effect can be beneficial or harmful. It is within the scope of the present invention that the combination index (Cl) analysis provides quantitative estimation of the extent of synergy.
  • Cl value lower than 1 indicates synergism between the constituents of the composition of the present invention with respect to stimulation of the immune response.
  • a combination index (Cl) value of 1 indicates an additive effect between the constituents of the composition of the present invention with respect to stimulation of the immune response.
  • the present invention provides a composition comprising therapeutically effective amount of, or an extract consisting essentially therapeutically effective amount of Scutellaria barbata extract or a fraction thereof, and a compound selected from the group consisting of: at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof, and a combination thereof, for use in conferring an activating effect on immune- system cells.
  • the present invention provides a synergistically effective pharmaceutical composition, wherein said composition comprising a therapeutically effective amount of Scutellaria barbata extract or a fraction thereof, and a compound selected from the group consisting of: at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof, and a combination thereof, in a predefined ratio conferring a synergistic effect with respect to immune- system cells' stimulation, relative to the effect of said Scutellaria barbata extract or a fraction thereof, and said compound administered separately in a similar concentration.
  • immune system cells or immune cells generally refers to white blood cells, also called leukocytes. There are two main types of leukocyte:
  • Phagocytes including, neutrophils, monocytes, macrophages and mast cells
  • Lymphocytes including, B lymphocytes (B cells) and T lymphocytes (T cells).
  • the response to pathogens is orchestrated by the complex interactions and activities of the large number of diverse cell types involved in the immune response.
  • the innate immune response is the first line of defense and occurs soon after pathogen exposure. It is carried out by phagocytic cells such as neutrophils and macrophages, cytotoxic natural killer (NK) cells, and granulocytes.
  • the subsequent adaptive immune response includes antigen-specific defense mechanisms and may take days to develop.
  • Cell types with critical roles in adaptive immunity are antigen-presenting cells including macrophages and dendritic cells.
  • Antigen-dependent stimulation of various cell types including T cell subsets, B cells, and macrophages play critical roles in host defense.
  • activating effect on immune- system cells or “stimulating effect on immune system cells” refers to an effect that stimulate the immune system by inducing activation or increasing activity of any of its components.
  • immunostimulants There are two main categories of immunostimulants:
  • Specific immunostimulants that provide antigenic specificity in immune response, such as vaccines or any antigen.
  • Non-specific immunostimulants that act irrespective of antigenic specificity to augment immune response of other antigen or stimulate components of the immune system without antigenic specificity.
  • the herein disclosed composition comprising Scutellaria barbata extract has properties of a non-specific immunostimulant.
  • activation of immune responses evokes the release of cytokines, such as IL-1, TNF-a, and IL-6, which initiate the acute -phase response of inflammation, aimed at fighting infection.
  • cytokines such as IL-1, TNF-a, and IL-6
  • the acute -phase response facilitate or enhances immune responsiveness and also inhibit the ability of some pathogens to multiply and inhibit or limit or reduce the spread of infection
  • cytokine refers hereinafter to a category of small proteins (-5-20 kDa) that are important in cell signaling. Cytokines are peptides, and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines are signaling molecules involved in autocrine signaling, paracrine signaling and endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors, but generally not hormones or growth factors (despite some overlap in the terminology).
  • Cytokines are produced by a broad range of cells, including immune cells such as macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells. It is noted that a given cytokine may be produced by more than one type of cell. It is further within the scope of the present invention that cytokines act through receptors, and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the function of other cytokines through complex pathways. Cytokines are important in health and disease, specifically in host responses to infection, immune responses, inflammation, trauma, sepsis, cancer, and reproduction.
  • inflammatory cytokine which is a type of cytokine that is secreted from immune cells and other cell types that promotes inflammation. Inflammatory cytokines are predominantly produced by T helper cells (Th) and macrophages and involved in the upregulation of inflammatory reactions.
  • Th T helper cells
  • inflammatory cytokines play a role in initiating the inflammatory response and to regulate the host defense against pathogens mediating the innate immune response.
  • Some inflammatory cytokines have additional roles such as acting as growth factors.
  • pro-inflammatory cytokines include IL-1b, IL-6, and TNF-a.
  • Excessive chronic production of inflammatory cytokines contribute to inflammatory diseases such as atherosclerosis and cancer.
  • Dysregulation of proinflammatory cytokines have also been linked to depression and other neurological diseases. A balance between proinflammatory and anti inflammatory cytokines is necessary to maintain health.
  • inflammatory cytokines include interleukin- 1 (IL-1), IL-12, and IL-18, tumor necrosis factor alpha (TNF-a), interferon gamma (INFg), and granulocyte-macrophage colony stimulating factor (GM-CSF).
  • IL-1 interleukin- 1
  • IL-12 IL-12
  • IL-18 tumor necrosis factor alpha
  • INFg interferon gamma
  • GM-CSF granulocyte-macrophage colony stimulating factor
  • the present invention thus provides a composition
  • a composition comprising (a) Scutellaria barbata extract or a fraction thereof, and (b) a compound selected from the group consisting of: at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof, and a combination thereof.
  • the composition confers an activating effect on immune- system cells.
  • terpene compound or a derivative thereof is selected from the group consisting of Hemiterpene, Monoterpene, Sesquiterpenes, Diterpenes, Sesterterpenes, Triterpenes, Sesquarterpenes, Tetraterpenes, Polyterpenes, Norisoprenoids, terpinenes, phellandrenes, terpinolene, terpenoids and any mixture thereof.
  • composition as defined in any of the above, wherein the cannabinoid compound or a derivative thereof is selected from the group consisting of an endocannabinoid, a phytocannabinoid, a synthetic cannabinoid and any combination thereof.
  • composition as defined in any of the above, wherein the cannabinoid compound or a derivative thereof is a Cannabis plant extract or a fraction thereof.
  • composition as defined in any of the above, wherein the cannabinoid compound or a derivative thereof is derived from a Cannabis plant extract or a fraction thereof.
  • the cannabinoid compound or a derivative thereof is selected from the group consisting of THC (tetrahydrocannabinol), THCA (tetrahydrocannabinolic acid), CBD (cannabidiol), CBDA (cannabidiolic acid), CBN (cannabinol), CBG (cannabigerol), CBC (cannabichromene), CBL (cannabicyclol), CBV (cannabivarin), THCV (tetrahydrocannabivarin), CBDV (cannabidivarin), CBCV (cannabichromevarin), CBGV (cannabigerovarin), CBGM (cannabigerol monomethyl ether), CBE (cannabielsoin), CBT (cannabicitran) and any combination thereof.
  • CBD cannabinoid compound
  • compositions as defined in any of the above wherein the immune system cells are selected from the group consisting of Human Peripheral Blood Mononuclear Cells (HPBMC) including lymphocytes (T cells, B cells, NK cells) and monocytes. It is a further embodiment of the present invention, to disclose the composition as defined in any of the above, wherein the composition comprises therapeutically effective amounts of the Scutellaria barbata extract or a fraction thereof and the compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and a combination thereof.
  • HPBMC Human Peripheral Blood Mononuclear Cells
  • T cells T cells, B cells, NK cells
  • monocytes monocytes
  • the composition comprises therapeutically effective amounts of the Scutellaria barbata extract or a fraction thereof and the compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and
  • composition as defined in any of the above, wherein the composition comprises predefined ratios of the Scutellaria barbata extract or a fraction thereof and the compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and a combination thereof.
  • composition as defined in any of the above, wherein the activating effect on immune- system cells comprises enhanced cytokine secretion relative to negative control.
  • cytokine is selected from the group consisting of TNF, TNFa, INFg, interleukins IL-1b, IL-4, IL-6, IL-10, IL-12, IL-18, CCL4/RANTES, TGFb and any combination thereof.
  • composition as defined in any of the above, wherein the composition is useful for providing an immune response activation effect.
  • composition as defined in any of the above, wherein the composition provides an immune response activation effect via a mechanism selected from the group consisting of alternative complement pathway, phagocytosis NK cell activation, cytokine secretion and any combination thereof.
  • composition as defined in any of the above, wherein the composition provides a more than additive effect or a synergistic effect with respect to activation of immune system cells as compared to the effect provided by the Scutellaria barbata extract or a fraction thereof or the terpene compound or a derivative thereof, or the cannabinoid compound or a derivative thereof, administered separately in a similar concentration.
  • composition as defined in any of the above, wherein the Scutellaria barbata extract or a fraction thereof and the compound have a combination index (Cl) value lower than 1 indicating synergism.
  • composition as defined in any of the above, wherein the Scutellaria barbata extract or a fraction thereof, and the compound have a combination index (Cl) value of 1 indicating an additive effect.
  • composition as defined in any of the above, wherein the concentration of the Scutellaria barbata extract or a fraction thereof is in the range of about 10% (wt.).
  • composition as defined in any of the above, wherein the composition comprises at least one excipient selected from the group consisting of: a solvent, absorbent, a disintegrant, a thickener, a binder, a lubricant, a glidant, an antiadherant, a coating agent, flavours, colours, sorbents, preservatives and any combination thereof.
  • excipient selected from the group consisting of: a solvent, absorbent, a disintegrant, a thickener, a binder, a lubricant, a glidant, an antiadherant, a coating agent, flavours, colours, sorbents, preservatives and any combination thereof.
  • compositions as defined in any of the above wherein the composition is formulated for an administration route selected from the group consisting of: transdermal, intravenous, vaginal, sublingual, buccal, oral, and any combination thereof.
  • composition as defined in any of the above, wherein the composition is formulated for rapid release or for controlled release.
  • composition as defined in any of the above, wherein the composition is useful for providing a cytotoxic effect on cells.
  • composition as defined in any of the above, wherein the cells are cancerous cells, preferably breast cancer cells.
  • composition as defined in any of the above, wherein the composition is conferring a synergistic effect with respect to inhibition or cytotoxicity of cancerous cells, relative to the Scutellaria barbata extract or a fraction thereof or the compound, administered separately in a similar concentration.
  • composition comprising (a) a therapeutically effective amount of Scutellaria barbata extract or a fraction thereof and (b) a therapeutically effective amount of a compound selected from the group consisting of: at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof, and a combination thereof, in a predefined ratio conferring a synergistic effect with respect to stimulation of immune- system cells relative to the effect of the Scutellaria barbata extract or a fraction thereof and the compound administered separately in a similar concentration.
  • composition as defined in any of the above, wherein the effect is enhanced cytokine secretion relative to negative control.
  • cytokine is selected from the group consisting of TNF, TNFa, INFg, interleukins IL-1b, IL-4, IL-6, IL-10, IL-12, IL-18, CCL4/RANTES, TGFb and any combination thereof.
  • composition as defined in any of the above, wherein the composition provides an immune response activation effect via a mechanism selected from the group consisting of alternative complement pathway, phagocytosis NK cell activation, cytokine secretion and any combination thereof.
  • a method for stimulating immune- system cells comprises steps of (a) providing a composition as defined in any of the above; and (b) administering a therapeutic dose of the composition to human immune- system cells.
  • the immune- system cells are selected from the group consisting of: in vitro, ex vivo and in situ cells. It is a further embodiment of the present invention, to disclose the method as defined in any of the above, wherein the immune- system cells comprising Human Peripheral Blood Mononuclear Cells (HPBMC) including lymphocytes (T cells, B cells, NK cells) and/or monocytes.
  • HPBMC Human Peripheral Blood Mononuclear Cells
  • the immune- system related disorder is selected from the group consisting of auto immune disorder, infectious disease, hematological malignancy, vaccine related disease, transplant immunology and any combination thereof.
  • terpene compound or a derivative thereof is selected from the group consisting of Hemiterpene, Monoterpene, Sesquiterpenes, Diterpenes, Sesterterpenes, Triterpenes, Sesquarterpenes, Tetraterpenes, Polyterpenes, Norisoprenoids, terpinenes, phellandrenes, terpinolene, terpenoids and any mixture thereof.
  • terpene compound or a derivative thereof is selected from the group consisting of myrcene, limonene, a-pinene, b- pinene, b-caryophyllene and any mixture thereof.
  • the cannabinoid compound or a derivative thereof is selected from the group consisting of an endocannabinoid, a phytocannabinoid, a synthetic cannabinoid and any combination thereof. It is a further embodiment of the present invention, to disclose the method as defined in any of the above, wherein the cannabinoid compound or a derivative thereof is a Cannabis plant extract or a fraction thereof.
  • the cannabinoid compound or a derivative thereof is selected from the group consisting of THC (tetrahydrocannabinol), THCA (tetrahydrocannabinolic acid), CBD (cannabidiol), CBDA (cannabidiolic acid), CBN (cannabinol), CBG (cannabigerol), CBC (cannabichromene), CBL (cannabicyclol), CBV (cannabivarin), THCV (tetrahydrocannabivarin), CBDV (cannabidivarin), CBCV (cannabichromevarin), CBGV (cannabigerovarin), CBGM (cannabigerol monomethyl ether), CBE (cannabielsoin), CBT (cannabicitran) and any combination thereof.
  • CBD cannabinoid compound
  • the immune system cells are selected from the group consisting of Human Peripheral Blood Mononuclear Cells (HPBMC) including lymphocytes (T cells, B cells, NK cells) and monocytes.
  • HPBMC Human Peripheral Blood Mononuclear Cells
  • composition comprises therapeutically effective amounts of the Scutellaria barbata extract or a fraction thereof and the compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and a combination thereof.
  • composition comprises predefined ratios of the Scutellaria barbata extract or a fraction thereof and the compound selected from the group consisting of at least one terpene compound or a derivative thereof, at least one cannabinoid compound or a derivative thereof and a combination thereof.
  • cytokine is selected from the group consisting of TNF, TNFa, INFg, interleukins IL-1b, IL-4, IL-6, IL-10, IL-12, IL-18, CCL4/RANTES, TGFb and any combination thereof.
  • composition provides an immune response activation effect via a mechanism selected from the group consisting of alternative complement pathway, phagocytosis NK cell activation, cytokine secretion and any combination thereof.
  • composition provides a more than additive effect or a synergistic effect with respect to activation of immune system cells as compared to the effect provided by the Scutellaria barbata extract or a fraction thereof or the terpene compound or a derivative thereof, or the cannabinoid compound or a derivative thereof, administered separately in a similar concentration.
  • the concentration of the Scutellaria barbata extract or a fraction thereof is in the range of about 10% (wt.). It is a further embodiment of the present invention, to disclose the method as defined in any of the above, wherein the composition comprises at least one excipient selected from the group consisting of: a solvent, absorbent, a disintegrant, a thickener, a binder, a lubricant, a glidant, an antiadherant, a coating agent, flavours, colours, sorbents, preservatives and any combination thereof.
  • composition is formulated for an administration route selected from the group consisting of: transdermal, intravenous, vaginal, sublingual, buccal, oral, and any combination thereof.
  • composition is formulated for rapid release or for controlled release.
  • the cells are cancerous cells, preferably breast cancer cells.
  • composition is conferring a synergistic effect with respect to inhibition or cytotoxicity of cancerous cells, relative to the Scutellaria barbata extract or a fraction thereof or the compound, administered separately in a similar concentration.
  • compositions as defined in any of the above in the manufacture of a medicament for treating immune system related disorder of a subject.
  • composition as defined in any of the above, for use in the treatment of immune system related disorders.
  • composition as defined in any of the above, for use in stimulating immune system cells.
  • This protocol is designed to evaluate the effect of the combination of Scutellaria barbata extract and terpenes and/or at least one Cannabis extract or cannabinoid compound on enhancing the immune system. More specifically, the exemplified protocol examines the anti-inflammatory effect of the composition of the present invention on human Peripheral Blood Mononuclear Cells (PBMC).
  • PBMC Peripheral Blood Mononuclear Cells
  • Study duration 1-2 weeks, including cell culture and cytokine analysis.
  • Model Quantitation of cytokine secretion from stimulated human PBMC in the presence or absence of a test item.
  • Test Item will be added to the culture medium of PBMC derived from 2 different donors before the addition of LPS (or similar stimulation). Cytokine secretion will be quantitated in supernatants by multiplex and viability will be evaluated by XTT following microscopic observation.
  • TI denotes Test Item
  • WSB101 denotes Scutellaria barbata extract of the present invention.
  • cytokines were assayed by multiplex in duplicates on sups collected at 24 h, including TNF-a, IL-10, IL-6, IL-1b, INFg, IL-4 and TGF-b.
  • Test Items encompasses Scutellaria barbata extract or fraction thereof or at least one terpene or at least one cannabinoid compound or a mixture thereof.
  • cytokine release The effect on the activation of the immune system is tested by measurement of cytokine release.
  • pro inflammatory cytokines measured include TNF, INFg, interleukins IL-1b, IL-4, IL-6, IL-10, IL-12, IL-18, CCL4/RANTES and TGFb.
  • the composition tested comprises about 10% w/w or wt.% of Scutellaria barbata extract, i.e. lOOg/L.
  • the experiment described above shows that the combination of Scutellaria barbata extract with at least one terpene compound and/or at least one cannabinoid compound provides an effect on activating the immune system or an anti-inflammatory effect, as measured by cytokine release relative to control.
  • the effect may be an additive effect or a synergistic effect, which is more than additive.
  • composition of the present invention comprising Scutellaria barabata extract, terpenes and/or Cannabis extract or a fraction or compound thereof, on cell viability.
  • Test Items were used as defined below.
  • Test Item 1 WSB 101 (excluding preservative)
  • composition of the present invention comprising Scutellaria barabata extract in combination with at least one terpene compound (e.g. Alpha Pinene, Beta Pinene, Beta Caryophyllene and Limonene) and/or with a Cannabis extract, provides a significant cytotoxic effect on cancerous cells (i.e. Breast cancer cells).
  • the cytotoxic effect illustrated in the present invention is surprisingly synergistic, as the cytotoxicity observed as a results of exposure of the cells to the combination of Scutellaria barabata extract with a terpene compound (e.g. Alpha Pinene, Beta Pinene and Beta Caryophyllene) is more effective in lower concentrations (higher dilution rate) as compared to the effect provided by each of the components administered separately in a similar concentration.
  • FIG. 4 schematically illustrating the experimental design of the study, performed according to the following protocol:
  • mice were randomly separated into 6 groups, 5 mice per group:
  • Group 1- Oral Control Each mouse was orally administered with vehicle 6 days a week. Drug administration (oral)-6 days a week. Days 0-14
  • Group 2- Oral S. barbata only (Treatment A): Each mouse was orally administered with S. barbata, dose 50mg/kg. Drug administration (oral)-6 days a week. Days 0-14
  • Treatment B Each mouse was orally administered with the chosen treatment, (dose 50mg/kg+ 2mM of each terpene - formula). Drug administration (oral)- 6 days a week. Days 0-14
  • IP Intraperitoneal injection
  • Group 6- IP S. barbata + Terpenes (Treatment B): Each mouse was orally administered with the chosen treatment (dose 12mg/kg+ 0.5mM of each terpene). Dmg administration (IP)-6 days a week, Days 0-14. 2. Mice received sub-lethal whole-body irradiation by single exposure to 6 Gy (Gamma radiation) and were clinically evaluated (weight, survival) for 21 days.
  • Treatments were administrated, once a day, 6 days a week, for two weeks.
  • FIG. 6 graphically presenting platelets recovery following irradiation in response to oral administration of S. barbata extract with or without terpenes (Treatment B, or Treatment A, respectively).
  • FIG. 6A is graphically presenting platelets recovery one week following irradiation in response to oral administration of S. barbata only (Treatment A) as compared to oral administration of the formula including S. barbata + Terpenes (Treatment B).
  • FIG. 6B is graphically presenting time dependent platelets recovery following irradiation in response to oral administration of the formula including S. barbata + Terpenes (Treatment B).
  • Fig. 7 graphically presenting lymphocytes recovery following irradiation in response to oral (Fig. 7A) or IP (Fig.7B) administration of S. barbata extract with or without terpenes (Treatment B, or Treatment A, respectively). It can be seen that in both administration routs, treatment with S. barbata extract only (Treatment A) had higher effect on improvement of lymphocytes recovery following irradiation than S. barbata + Terpenes treatment (Treatment B).
  • platelets also called thrombocytes
  • thrombocytes are made in the bone marrow and help the blood to clot.
  • Thrombocytopenia is a condition caused by a low number of platelets in the blood (low platelet count). People with a low number of platelets may bleed or bruise easily, even after a minor injury. A low platelet count increases the risk of bleeding, especially from the mouth, nose and gastrointestinal tract. Therefore rapid recovery of platelets is of great importance.
  • platelet count is a biomarker, which is independently associated with disease severity and risk of mortality in the intensive care unit (ICU).
  • ICU intensive care unit
  • a low platelet count correlates with higher disease severity scores.
  • SARS severe acute respiratory syndrome
  • thrombocytopenia was reported to occur in up to 55% of patients and was identified as a significant risk factor for mortality.
  • composition of the present invention comprising S. barbata ingredients or extract, and especially the formulation comprising S. barbata + Terpenes (e.g. as exemplified in Example 5 below), significantly increase (by about 2 fold relative to control) platelets rate and recovery.
  • lymphocytopenia With respect to low lymphocyte count (lymphocytopenia), it is herein acknowledged that lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphopenia makes patients susceptible to common and unusual infections. An association between treatment-related lymphopenia (TRL) and decreased survival was demonstrated in patients. Therefore, rapid recovery of lymphocytes is highly important.
  • TRL treatment-related lymphopenia
  • the present invention shows that the composition comprising S. barbata ingredients or extract improves recovery of lymphocytes 1 week following irradiation as compared to a control treatment.
  • cancer treatments that can affect the bone marrow and lead to Thrombocytopenia/Lymphocytopenia include:
  • composition of the present invention comprising S. barbata ingredients or extract, and especially the formulation comprising S. barbata + Terpenes (e.g. as exemplified in Example 5 below), significantly improve hematopoietic recovery of platelets and/or lymphocyte count and thus may be used to treat diseases, conditions or treatments such as cancer treatments, associated with bone marrow dysfunction or disorders, for example leading to Thrombocytopenia/Lymphocytopenia.
  • This example provides a pre- clinical study presenting evaluation of Test Items (TIs) anti inflammatory effect on human Peripheral Blood Mononuclear (PBMC) and RAW Cells (monocyte/macrophage-like cell line).
  • TIs Test Items
  • PBMC Peripheral Blood Mononuclear
  • RAW Cells monocyte/macrophage-like cell line
  • Test items were added to the culture medium of PBMC and RAW derived from a single donor before the addition of LPS (or similar) stimulation. Cytokine secretion was quantitated in supernatants by multiplex and viability was evaluated by XTT following microscopic observation.
  • NO secretion was evaluated in the RAW cell study (e.g. nitric oxide (NO) production by LPS- stimulated macrophages).
  • NO nitric oxide
  • Viability was evaluated by XTT at 24.
  • Fig. 8A graphically presenting NO secretion (mM) by RAW cells exposed to different S. barbata (WSB 101) treatments/formulations (e.g. as disclosed in Example 5 below).
  • stimulated monocyte/macrophage-like cell RAW line treated by alcohol based S. barbata extract with CBD, or by alcohol based S. barbata extract combined with terpenes (i.e. D-limonene, a-pinene and b- pinene) and CBD showed significantly reduced activity (NO secretion) of the immune system cells as compared to RAW cells exposed to vehicle or exposed to any combination of the terpenes or combination of the terpenes with CBD alone.
  • the mixture or combination of alcohol based S. barbata extract with CBD has a dramatic inhibitory effect on stimulated immune system cells.
  • alcohol based S. barbata extract with CBD has a dramatic inhibitory effect on stimulated immune system cells.
  • barbata extract with CBD in combination with terpenes has an inhibitory synergistic effect on stimulated immune system cells as compared to the effect of the terpenes or mixtures thereof administered alone and as compared to the inhibitory effect of terpenes with CBD administered alone.
  • Fig. 8A it was surprisingly shown in Fig. 8A that exposure of immune system cells to water based S. barbata extract combined with any one of the terpenes D-limonene, a-pinene and b- pinene or any of their combinations resulted in significant increase in the activity (NO secretion) of the stimulated RAW cells as compared to cells treated with water based vehicle.
  • This effect may be synergistic or additive as the stimulation is significantly incased also with respect to any combination of the terpenes administered without S. barbata extract.
  • Fig. 8B viability of the tested immune system cells was not affected (not reduced) by exposure to any of the treatments described in Fig. 8A and the tables above.
  • Fig. 8C graphically presents the NO secretion results of Fig. 8A, as % of vehicle.
  • Fig. 8D presents the NO secretion results of Fig. 8A, as (% from vehicle )/normalized to the viability results of Fig. 8B.
  • Figs 8A-D alcohol based S. barbata extract together with CBD significantly inhibited (by more than 50%) immune system cells activity.
  • the inhibitory effect of treatment of stimulated immune system cells (e.g. RAW or PBMC CELLS) with S. barbata extract, CBD and terpenes was synergistic as compared to treatment with the combination of terpenes (i.e. D- limonene, a-pinene and b- pinene) or partial combinations thereof which caused slight increase in immune system activity relative to control; and as compared to terpenes and CBD combination which showed similar effect as the control (only vehicle).
  • the results presented further demonstrate that water based S.
  • barbata extract with terpenes i.e. D-limonene, a-pinene and b- pinene
  • terpenes i.e. D-limonene, a-pinene and b- pinene
  • partial combinations thereof increase or stimulate immune system cells activity by at least 2 fold (up to at least 2.5. fold) relative to control (vehicle only). It is noted that similar correlations or trends were found with the tested doses/concentrations.
  • composition of the present invention comprising alcohol based S. barbata extract with CBD may be useful for treatment of autoimmune diseases by inhibiting the immune system cells when administered in a therapeutic dose to a patient with such a disease.
  • composition of the present invention comprising water based S. barbata extract with terpenes may be useful for therapies and conditions where immune system activation is needed in a patient.
  • the current example describes product specifications of a formulation containing aqueous extract of Scutelaria barbata (also referred to as 'SB extract'), enriched by terpenes in syrup form.
  • the product is ready to drink.
  • Table 8 Ingredients of S. barbata formulation
  • Table 11 presenting ingredients of samples derived from Scutellaria barbata formulation.
  • Table 12 is presenting Terpenes emulsion ingredients.
  • incorporating terpene compounds into an aqueous solution/formulation/composition requires a preliminary stage of formulating an emulsion with the terpenes, as an alternative solution requires alcohol use and therefore has been disqualified.
  • the emulsion may be prepared with the same technology and raw materials used for cloudy emulsions in the beverage industry (including natural beverages).
  • Oil phase preparation Includes terpenes, vegetable oil (preferably MCT vegetable oil) and Ester gum. The vegetable oil is heated together with the Ester gum until fully dissolved in 50 °C. The terpenes are then added.
  • stage A Adding predetermined amount of the emulsion prepared in stage A (e.g. 0.1% w/w of the final preparation or formulation)

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Abstract

La présente invention concerne une composition comprenant (a) un extrait de Scutellaria barbata ou une partie de ce dernier, et (b) un composé sélectionné dans le groupe constitué par : au moins un composé terpène ou un dérivé de ce dernier, au moins un composé cannabinoïde ou un dérivé de ce dernier, et une combinaison de ces derniers. Selon un aspect essentiel de la présente invention, la composition susmentionnée confère un effet d'activation ou d'inhibition à au moins un des deux types de cellules suivants : les cellules souches hématopoïétiques (CSH) ou les cellules sanguines. La présente invention concerne également des méthodes permettant de traiter des affections médicales à l'aide de la composition susmentionnée.
PCT/IL2020/050675 2019-06-18 2020-06-17 Nouvelles préparations thérapeutiques comprenant du scutellaria barbata WO2020255133A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030211180A1 (en) * 2000-03-09 2003-11-13 Yung-Chi Cheng Herbal composition phy906 and its use in chemotheraphy
US20150181925A1 (en) * 2013-12-26 2015-07-02 John Turner Herbal smoking blend
US20180344661A1 (en) * 2015-11-24 2018-12-06 Constance Therapeutics, Inc. Cannabis oil compositions and methods for preparation thereof
EP3472307A1 (fr) * 2016-06-15 2019-04-24 Ojai Energetics PBC Procédés et compositions de potentialisation de thérapies de cellules souches

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030211180A1 (en) * 2000-03-09 2003-11-13 Yung-Chi Cheng Herbal composition phy906 and its use in chemotheraphy
US20150181925A1 (en) * 2013-12-26 2015-07-02 John Turner Herbal smoking blend
US20180344661A1 (en) * 2015-11-24 2018-12-06 Constance Therapeutics, Inc. Cannabis oil compositions and methods for preparation thereof
EP3472307A1 (fr) * 2016-06-15 2019-04-24 Ojai Energetics PBC Procédés et compositions de potentialisation de thérapies de cellules souches

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