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EP3071190A1 - Curcumine synthétique (s-curcumine) intraveineuse pour le traitement de troubles prolifératifs - Google Patents

Curcumine synthétique (s-curcumine) intraveineuse pour le traitement de troubles prolifératifs

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Publication number
EP3071190A1
EP3071190A1 EP14864686.2A EP14864686A EP3071190A1 EP 3071190 A1 EP3071190 A1 EP 3071190A1 EP 14864686 A EP14864686 A EP 14864686A EP 3071190 A1 EP3071190 A1 EP 3071190A1
Authority
EP
European Patent Office
Prior art keywords
curcumin
composition
subject
disease
proliferative disorders
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP14864686.2A
Other languages
German (de)
English (en)
Other versions
EP3071190A4 (fr
Inventor
Lawrence Helson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Signpath Pharma Inc
Original Assignee
Signpath Pharma Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Signpath Pharma Inc filed Critical Signpath Pharma Inc
Priority claimed from PCT/US2014/066944 external-priority patent/WO2015077640A1/fr
Publication of EP3071190A1 publication Critical patent/EP3071190A1/fr
Publication of EP3071190A4 publication Critical patent/EP3071190A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • 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
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/593—Polyesters, e.g. PLGA or polylactide-co-glycolide

Definitions

  • the present invention relates in general to the field of treatment of proliferative disorders, and more particularly to administering topically, or systemically a therapeutic amount of synthetic curcumin (S-curcumin) to a subject afflicted with proliferative disorders such as breast, uterine cervical, ophthalmic, and pancreatic cancer.
  • S-curcumin synthetic curcumin
  • compositions comprising curcumin, synthetic curcumin and analogues and derivatives thereof.
  • U.S. Patent No. 7,220,438 discloses a topical pharmaceutical composition comprising an water soluble Curcuma extract, and suitable excipients for said topical administration; the process for obtaining said pharmaceutical compositions; the use of different Curcuma extracts as photosensitizing agents for the treatment of proliferative diseases; and the use of Curcuma extract or curcuminoids in combination with a radiation for the treatment of proliferative diseases on eukaryote cells.
  • U.S. Patent Application Publication No. 20090047371 discloses a pharmaceutical composition containing curcumin and resveratrol and its application in the medical field.
  • the composition according to the invention can be advantageously employed for preventing aging and vascular diseases, for the treatment and the prophylaxis of cancers as prostate carcinoma, of skin diseases as psoriasis, and of the piliferous system as hair loss.
  • U.S. Patent Application Publication No. 20100286585 (Dimauro et al. 2010) relates to a method for reducing or preventing a human brain disorder relating to the presence of a pathogenic substance in cerebrospinal fluid by selecting a human for treatment as a patient and placing a proximal end of a first catheter, having at least a first lumen, in a first sub-dural location within the brain of the patient to establish open communication between the first lumen and cerebrospinal fluid of the patient.
  • a curcumin agent selected from at least one of curcumin, a curcumin hybrid and a curcumin analog is delivered to the cerebrospinal fluid to interact with the pathogenic substance to attenuate its effect on the brain.
  • the present invention relates to pharmaceutical compositions and treatment methods comprising synthetic curcumin (S-curcumin).
  • the invention further describes the use of the pharmaceutical composition for the treatment of proliferative disorders.
  • the present invention includes a composition for ameliorating symptoms or treating one or more proliferative disorders in a subject comprising: one or more spherical liposomes comprising a lipid or a phospholipid wall, wherein the liposome encloses a synthetic curcumin (S-curcumin) or derivatives and modifications thereof dissolved or dispersed in an aqueous or a non-aqueous solvent with one or more optional related co-factors, proteins, antibodies, pain medications, and other pharmaceutically active agents dissolved, dispersed, or suspended in the solvent; a suitable aqueous or non-aqueous dispersion medium, wherein the one or more spherical liposomes are dispersed in the dispersion medium; and one or more optional excipients, diluents, extended or controlled
  • the one or more proliferative disorders are selected from the group consisting of breast, uterine, cervical, ophthalmic, pancreatic, or any combinations thereof.
  • the lipid or the phospholipid is selected from the group consisting of phosphatidylcholine (lecithin), lysolecithin, lysophosphatidylethanol-amine, phosphatidylserine, phosphatidylinositol, sphingomyelin, phosphatidylethanolamine (cephalin), cardiolipin, phosphatidic acid, cerebrosides, dicetylphosphate, phosphatidylcholine, and dipalmitoyl-phosphatidylglycerol, stearylamine, dodecylamine, hexadecyl-amine, acetyl palmitate, glycerol ricinoleate, hexadecyl stearate, isopropyl myri
  • composition is adapted for enteral, parenteral, intravenous, sub-cutaneous, intra-muscular, or intra-peritoneal injection in the subject.
  • one or more liposomes have a size of about 100 nm.
  • the present invention includes a composition for ameliorating symptoms or treating one or more proliferative disorders in a subject comprising: a biodegradable polymer conjugate dissolved or dispersed in a suitable aqueous or nonaqueous solvent, wherein the conjugate comprises a synthetic curcumin (S-curcumin) or derivatives and modifications thereof conjugated to one or more polymers selected from the group consisting of polyesters, polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyorthoesters, polyphosphoesters, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acids), copolymers, terpolymers, and combinations or mixtures thereof; and
  • the one or more proliferative disorders are selected from the group consisting of breast, uterine, cervical, ophthalmic, pancreatic, or any combinations thereof.
  • the composition adapted for enteral, parenteral, intravenous, sub-cutaneous, intra-muscular, or intra-peritoneal injection in the subject.
  • the composition is used for the treatment of one or more neurological or neurodegenerative conditions selected from the group consisting of Parkinson's disease (PD), Alzheimer's disease, stress disorders, senile dementia, vascular dementias, Pick's disease, Creutzfeldt- Jacobs disease, and aging.
  • the synthetic curcumin is 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 or 96% pure diferuloylmethane.
  • the present invention includes a method of ameliorating symptoms or treating one or more proliferative disorders in a subject comprising the steps of: identifying the subject in need of amelioration of symptoms or treatment of the one or more proliferative disorders; and administering intravenously one or more pharmaceutical compositions comprising a therapeutically effective amount of a synthetic curcumin (S-curcumin) or derivatives and modifications thereof dissolved or dispersed in a suitable aqueous or non-aqueous medium, wherein the curcumin is enclosed in one or more spherical liposomes or is conjugated to one or more biodegradable polymers.
  • S-curcumin synthetic curcumin
  • the one or more proliferative disorders are selected from at least one of breast, uterine, cervical, ophthalmic, pancreatic, or any combinations thereof.
  • the liposomes comprise a lipid or a phospholipid wall.
  • the lipid or the phospholipid is selected from the group consisting of phosphatidylcholine (lecithin), lysolecithin, lysophosphatidylethanol-amine, phosphatidyls erine, phosphatidylinositol, sphingomyelin, phosphatidylethanolamine (cephalin), cardiolipin, phosphatidic acid, cerebrosides, dicetylphosphate, phosphatidylcholine, and dipalmitoyl-phosphatidylglycerol, stearylamine, dodecylamine, hexadecyl-amine, acetyl palmitate, glycerol ricinoleate, hexadecyl stearate, isopropyl myristate, amphoteric acrylic polymers, fatty acid, fatty acid amides, cholesterol, cholesterol ester, diacylglycerol, and diacylglyce
  • the therapeutically effective amount comprises 50 nM/kg, 10 to 100 nM/kg, 25 to 75 nM/kg, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 nM/kg of body weight of the subject.
  • the synthetic curcumin is 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 or 96% pure diferuloylmethane.
  • the present invention includes a composition for ameliorating symptoms or treating breast cancer in a human subject comprising synthetic curcumin (S-curcumin) or derivatives and modifications thereof dissolved or dispersed in a suitable aqueous or non-aqueous medium, wherein the S-curcumin is enclosed in one or more spherical liposomes or is conjugated to one or more biodegradable polymers.
  • S-curcumin synthetic curcumin
  • the liposome comprises a lipid or phospholipid, wherein lipid or the phospholipid is selected from the group consisting of phosphatidylcholine (lecithin), lysolecithin, lysophosphatidylethanol-amine, phosphatidylserine, phosphatidylinositol, sphingomyelin, phosphatidylethanolamine (cephalin), cardiolipin, phosphatidic acid, cerebrosides, dicetylphosphate, phosphatidylcholine, and dipalmitoyl- phosphatidylglycerol, stearylamine, dodecylamine, hexadecyl-amine, acetyl palmitate, glycerol ricinoleate, hexadecyl stearate, isopropyl myristate, amphoteric acrylic polymers, fatty acid, fatty acid amides, cholesterol, cholesterol ester,
  • the biodegradable polymer is selected from the group consisting of polyesters, polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyorthoesters, polyphosphoesters, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acids), copolymers, terpolymers, and combinations or mixtures thereof.
  • the composition adapted for intravenous, sub-cutaneous, intra-muscular, or intra-peritoneal injection in the subject.
  • the present invention includes a composition for ameliorating symptoms or treating at least one of proliferative disorders, neurological disorders, or neurodegenerative conditions, in a subject comprising: curcumin, synthetic curcumin (S-curcumin), curcumin analogues, curcumin derivatives or combinations thereof dissolved or dispersed in a suitable aqueous or non-aqueous medium, wherein the curcumin or the S-curcumin is enclosed in one or more spherical liposomes or is conjugated to one or more biodegradable polymer, wherein the liposome comprises a lipid or phospholipid, wherein lipid or the phospholipid is selected from the group consisting of phosphatidylcholine (lecithin), lysolecithin, lysophosphatidylethanol-amine, phosphatidylserine, phosphatidyl
  • the one or more proliferative disorders are selected from the group consisting of breast, uterine, cervical, ophthalmic, pancreatic, or any combinations thereof.
  • the neurological disorder or the neurodegenerative condition is selected from the group consisting of Parkinson's disease (PD), Alzheimer's disease, stress disorders, post traumatic stress disorder (PTSD), senile dementia, vascular dementias, Pick's disease, Creutzfeldt-Jacobs disease, and aging.
  • the composition adapted for enteral, parenteral, intravenous, sub-cutaneous, intra-muscular, or intra-peritoneal injection in the subject.
  • the composition is administered along with related co-factors, proteins, antibodies, pain medications, and other pharmaceutically active agents selected from at least one of L-dopa, Carbidopa, benserazide, Tolcapone, dopamine agonists bromocriptine, pergolide, pramipexole, ropinirole , piribedil, cabergoline, apomorphine, lisuride, MAO inhibitors, serotonin reuptake inhibitors, sertraline, paroxetine, selegiline, or rasagiline.
  • the synthetic curcumin is 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 or 96% pure diferuloylmethane.
  • the present invention includes a method of ameliorating symptoms or treating one or more proliferative disorders, neurological disorders, neurodegenerative conditions, or any combinations thereof in a subject comprising the steps of: identifying the subject in need of amelioration of symptoms or treatment of the one or more proliferative disorders, neurological disorders, neurodegenerative conditions, or any combinations thereof; and administering intravenously one or more pharmaceutical compositions comprising a therapeutically effective amount of curcumin, synthetic curcumin (S-curcumin), curcumin analogues, curcumin derivatives or combinations thereof dissolved or dispersed in a suitable aqueous or non-aqueous medium, wherein the curcumin or the S-curcumin is enclosed in one or more spherical liposomes or is conjugated to one or more biodegradable polymers.
  • S-curcumin synthetic curcumin
  • the neurological disorder or the neurodegenerative condition is selected from the group consisting of Parkinson's disease (PD), Alzheimer's disease, stress disorders, post traumatic stress disorder (PTSD), senile dementia, vascular dementias, Pick's disease, Creutzfeldt-Jacobs disease, and aging.
  • the synthetic curcumin is 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 or 96% pure diferuloylmethane.
  • FIG. 1 shows wound healing (inhibition of growth) of human breast cancer cells between S- curcumin-PLGA and C3-curcumin PLGA at a 12 hour exposure time in the breast cancer cell line MCF 10AT;
  • FIG. 2 shows wound healing (inhibition of growth) of human breast cancer cells between S- curcumin-PLGA and C3-curcumin PLGA at a 12 hour exposure time in the breast cancer cell line MCF lOACAlH cell line.
  • Curcumin (diferuloyl methane; l,7-bis(4-hydroxy-3-methoxyphenyl)-l,6- heptadiene-3,5-dione) is a naturally occurring compound which is the main coloring principle found in the rhizomes of the plant Curcuma longa (U.S. Pat. No. 5,679,864 (Krackov et al.)).
  • the synthetic curcumin is 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 or 96% pure diferuloylmethane.
  • liposome refers to a capsule wherein the wall or membrane thereof is formed of lipids, especially phospholipid, with the optional addition therewith of a sterol, especially cholesterol.
  • in vivo refers to being inside the body.
  • in vitro as used in the present application is to be understood as indicating an operation carried out in a non-living system.
  • treatment refers to the treatment of the conditions mentioned herein, particularly in a patient who demonstrates symptoms of the disease or disorder.
  • treatment refers to any administration of a compound of the present invention and includes (i) inhibiting the disease in an animal that is experiencing or displaying the pathology or symptomatology of the diseased (i.e., arresting further development of the pathology and/or symptomatology) or (ii) ameliorating the disease in an animal that is experiencing or displaying the pathology or symptomatology of the diseased (i.e., reversing the pathology and/or symptomatology).
  • controlling includes preventing treating, eradicating, ameliorating or otherwise reducing the severity of the condition being controlled.
  • the terms "effective amount” or “therapeutically effective amount” described herein means the amount of the subject compound that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by the researcher, veterinarian, medical doctor or other clinician.
  • the therapeutically effective amount comprises 50 nM/kg, 10 to 100 nM/kg, 25 to 75 nM/kg, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 nM/kg of body weight of the subject.
  • administering a should be understood to mean providing a compound of the invention to the individual in need of treatment in a form that can be introduced into that individual's body in a therapeutically useful form and therapeutically useful amount, including, but not limited to: oral dosage forms, such as tablets, capsules, syrups, suspensions, and the like; injectable dosage forms, such as intravenous (IV), intramuscular (IM), or intraperitoneal (IP), and the like; enteral or parenteral, transdermal dosage forms, including creams, jellies, powders, or patches; buccal dosage forms; inhalation powders, sprays, suspensions, and the like; and rectal suppositories.
  • oral dosage forms such as tablets, capsules, syrups, suspensions, and the like
  • injectable dosage forms such as intravenous (IV), intramuscular (IM), or intraperitoneal (IP), and the like
  • enteral or parenteral, transdermal dosage forms including creams, jellies, powders, or patches
  • buccal dosage forms inhal
  • intravenous administration includes injection and other modes of intravenous administration.
  • pharmaceutically acceptable as used herein to describe a carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
  • the present invention discloses compositions and methods for the treatment of proliferative disorders using synthetic curcumin (S-curcumin).
  • Curcumin is the active principle of the turmeric plant which has been synthesized to near purity (99.2%). 1 It is formulated with liposomes 2 , polymers 3 , or PLGM to render it capable of being administered intravenously as a bolus or as a continuous infusion over 1-72 hours in combination with other active agents (for e.g. a calcium channel blocker). Curcumin has antioxidant and antiinflammatory activity, and can block autonomous intracellular signaling pathways abnormally responsive to extracellular growth factors, uncontrolled proliferation of cells and fibrosis-associated and tissue degenerative conditions. Specifically, Curcumin reacts negatively with components of key signaling pathways commanding proliferation, metabolism, survival and death.
  • Curcumin as an extract of turmeric root is available to researchers as a mixture of three curcuminoids and to the public as a food supplement or spice according to the FDA.
  • the extract is 79.2% curcumin (diferuloylmethane), 18.27% demethoxycurcumin, and 2.53 % bisdemethoxycurcumin.
  • the synthesized curcumin is GMP grade 99.2% pure diferuloylmethane produced for non-human experimental study and future Phase I clinical trials. There are obvious differences between the C3 three component extract and the single component synthesized S-curcumin that extend to discernable analytic, physicochemical, and biological characteristics.
  • the diferuloylmethane is 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 or 96% pure diferuloylmethane.
  • the present invention relates to synthetic curcumin (S-curcumin) and compares the properties and the activity of S-curcumin with liposomal curcumin, Nanocurc®, and PLGA-curcumin (hereinafter C3-complex).
  • Liposomal curcumin The initial studies of liposomal curcumin were done using material bought as the complex. 6"7 Studies with S-curcumin are Mach CM, et al (2009) 8 and Mach CM et al (2010) 9 .
  • Nanocurc® The initial study of Nanocurc® was done using product bought as the complex Savita Bisht et al (2007) 10 used a non-sabinsa source. Since then studies with S-curcumin are used in the remainder of Nanocurc® publications. 11"13
  • PLGA-curcumin The initial studies of PLGA-curcumin were done using product manufactured as the C3-complex. 14 18 Studies included PLGA -curcumin C3 complex and PLGA-S-curcumin pharmacokinetic studies in rat brains.
  • Table 1 Solubilities of S-curcumin and C3 -complex curcumin in different organic solvents.
  • Residual solvents complies complies Micro -total Plate count ⁇ 100cfug lOcfu/g
  • Table 3 Mean Brain tissue and Plasma Curcumin Levels in Rats Following Intravenous PLGA- curcumin: 20 mg/kg.
  • curcumin-PLGA the purity of free curcumin is 99.2 % and the relative ratio of free curcumin to the PLGA copolymer is 1 :9, hence the intravenous dose of free curcumin in the CurcuminPLGA formulation is 2 mg/kg.
  • Scratch assay The lack of a significant difference in interference with wound healing (inhibition of growth) of human breast cancer cells between S-curcumin-PLGA and C3-curcumin PLGA at a 12 hour exposure time in the breast cancer cell line MCF IOAT appears to be due to the sensitivity to curcumin of this cell line (Table 4 and FIG. 1). In the MCF10ACA1H cell line (Table 5 and FIG. 2) the S -curcumin is 30% more effective than C3 -curcumin in interfering with wound healing.
  • Table 4 Differences in wound healing between S-curcumin-PLGA and C3 -curcumin PLGA at a 12 hour exposure time in the breast cancer cell line MCFIOAT.
  • Table 5 Differences in wound healing between S-curcumin-PLGA and C3-curcumin PLGA at a 12 hour exposure time in the breast cancer cell line MCF10ACA1H.
  • Hemolytic toxicity in Dogs This is a unique adverse reaction observed at concentrations equal to or greater the 20 mg/kg "first-in dog" with the liposomal curcumin.
  • the physiopathologic cause appears to involve disruption of homeostatic mechanisms in the red blood cell membrane following exposure to liposome alone or the high concentration of pure curcumin or both.
  • this adverse effect may be a heretofore unknown effect of pure curcumin or curcuminoids in specific to dog red blood cells.
  • compositions of the invention can be used to achieve methods of the invention.
  • the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), "including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
  • A, B, C, or combinations thereof refers to all permutations and combinations of the listed items preceding the term.
  • A, B, C, or combinations thereof is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB.
  • expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth.
  • BB BB
  • AAA AAA
  • AB BBC
  • AAABCCCCCC CBBAAA
  • CABABB CABABB
  • compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des compositions et méthodes pour le traitement de troubles prolifératifs tels que le cancer du sein, le cancer du col de l'utérus, le cancer ophtalmique, et le cancer du pancréas par administration de curcumine synthétique (s-curcumine) intraveineuse.
EP14864686.2A 2013-11-22 2014-11-21 Curcumine synthétique (s-curcumine) intraveineuse pour le traitement de troubles prolifératifs Withdrawn EP3071190A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361907825P 2013-11-22 2013-11-22
PCT/US2014/066944 WO2015077640A1 (fr) 2013-11-22 2014-11-21 Curcumine synthétique (s-curcumine) intraveineuse pour le traitement de troubles prolifératifs

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EP3071190A1 true EP3071190A1 (fr) 2016-09-28
EP3071190A4 EP3071190A4 (fr) 2017-05-31

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Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10029770A1 (de) * 2000-06-16 2001-12-20 Transmit Technologietransfer Verwendung von Curcuminen zur Behandlung von soliden Tumoren,insbesondere von Hirntumoren
DE10031955A1 (de) * 2000-06-30 2002-01-17 Deutsches Krebsforsch Curcumin-Derivate mit gegenüber Curcumin verbesserter Wasserlöslichkeit und diese enthaltende Arzneimittel
US8784881B2 (en) * 2004-03-05 2014-07-22 Board Of Regents, The University Of Texas System Liposomal curcumin for treatment of diseases
EP2685963A4 (fr) * 2011-03-16 2014-11-19 Signpath Pharma Inc Association de la curcumine avec des antidiabétiques du diabète de type 2 utilisée pour prévenir et traiter les séquelles d'une maladie, les réactions indésirables associées à un traitement, et pour améliorer le contrôle de la glycémie

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