WO2012035480A2 - Pharmaceutical compositions of curcumin - Google Patents
Pharmaceutical compositions of curcumin Download PDFInfo
- Publication number
- WO2012035480A2 WO2012035480A2 PCT/IB2011/053974 IB2011053974W WO2012035480A2 WO 2012035480 A2 WO2012035480 A2 WO 2012035480A2 IB 2011053974 W IB2011053974 W IB 2011053974W WO 2012035480 A2 WO2012035480 A2 WO 2012035480A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- curcumin
- surfactant
- pharmaceutical composition
- oil
- solvent
- Prior art date
Links
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/121—Ketones acyclic
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
Definitions
- the present invention is related to stable liquid pharmaceutical compositions of curcumin or its pharmaceutically acceptable salts or its derivatives.
- Curcumin a potent natural anti-oxidant and anti-inflammatory agent, has shown therapeutic potential against many diseases. These include cancers (colon, prostate, breast, skin, leukemia, etc.), atherosclerosis, stroke, CNS alcohol toxicity, traumatic brain injury, Huntington's disease, Marie- Charcot Tooth, multiple sclerosis and Alzheimer's disease.
- Curcumin in this specification is referred as total curcuminoids containing curcumin, desmethoxycurcumin and bis-desmethoxycurcumin.
- Curcumin is a crystalline compound and poorly soluble in water at pH less than 7. Major reasons contributing to the lower plasma and tissue levels of curcumin are due to poor absorption, high first pass metabolism and rapid systemic elimination. Most of the curcumin is not absorbed and simply passes through the Gl tract and is excreted. Garcea, G. et al. (2004) reported that patients taking 3.6 g of curcumin a day (as a standard powder supplied by Sabinsa Corporation), drug levels in blood and liver were found to be negligible.
- Curcumin is not soluble at acidic pH and breaks down in solution at neutral or alkaline pH (e.g., in the Gl tract, after the small intestine), In addition, curcumin is susceptible to rapid glucuronidation/sulfation.
- WO2007103435 discloses the compositions comprising curcuminoid, antioxidant (to stabilize curcumin against hydrolysis), water-soluble pharmaceutically acceptable carrier and optionally glucuronidation inhibitor.
- the said formulation with 35% w/w curcumin resulted in improved bioavailability.
- CN100352430C discloses self-micro-emulsified curcumin preparation comprising curcumin, surfactant, co-surfactant, oil phase and solid adsorbent providing self- micro-emulsified system having liquid drops with size below 100 nm.
- Such compositions show increase in curcumin solubility and absorption in gastrointestinal tract with higher bioavailability.
- the concentration of curcumin in composition is in the range of 0.33 to 1 .56% w/v.
- WO2010010431 discloses self nano-emulsion compositions comprising curcumin (0.1 to 10% w/w), a lipidic carrier system with a hydrophilic-lipophilic balance (HLB) between 3 to 14 and a pH buffer.
- the lipidic carrier system is selected from one or more mono- and di- esters of saturated or unsaturated long chain fatty acids with low and medium molecular weight polyoxyethylene glycerol ethers or combinations thereof.
- the composition further comprises molecular aggregation inhibitor(s), a surface active agent and a co-solvent.
- the group of excipients used as lipidic carrier system belongs to alkyl-glycerol ether surfactants category (M. J. Lawrence et. al.
- the main object of the invention is to provide stable liquid pharmaceutical compositions of curcumin or its pharmaceutically acceptable salts or its derivatives with higher curcumin concentration and improved bioavailability.
- Another object of the invention is to provide stable pharmaceutical compositions wherein the concentration of curcumin in solution is 2 to 20% w/w.
- Another object of the invention is to provide the said pharmaceutical compositions without the use of pH buffer and/or molecular aggregation inhibitor(s).
- the stable liquid pharmaceutical compositions with higher curcumin concentration comprises of curcumin or pharmaceutically acceptable salts or derivatives thereof, surfactant, solvent, oil and optionally antioxidant wherein the concentration of surfactant is not more than 60% w/w.
- compositions comprise 2 to 20% w/w of curcumin, oil, solvent, surfactant and optionally antioxidant, wherein the ratio of oil to solvent, surfactant to solvent and surfactant to curcumin is in the range of 0.83 to 10, 1 to 60 and 3 to 15, respectively.
- composition is prepared without the use of pH buffer and/or molecular aggregation inhibitor(s).
- the oil is selected from: (1 ) fractionated coconut oil, caprylic/capric triglyceride or oil containing fatty acid triglycerides, preferably medium chain fatty acid triglycerides (2) isopropyl myristate, isopropyl palmitate, ethyl linoleate or oil containing ethyl oleate esters of fatty acids and monovalent alkanols (3) propyleneglycol dicaprylate, propyleneglycol dilaurate or oil containing propyleneglycol di-fatty acid esters.
- the surfactant is selected from polysorbate, vitamin E TPGS and cremophor, preferably cremophor.
- the solvent is selected from glycofurol, polyethylene glycol (PEG 200, 400), glycerol, polypropylene glycol, propylene glycol, N-methyl-2-pyrolidone and ethyl alcohol or mixture thereof, preferably from propylene glycol and ethyl alcohol or mixture thereof.
- the anti-oxidant is selected from ascorbyl palmitate, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, sodium ascorbate, tocopheryl derivative such as alpha-tocopherol and mixtures thereof.
- the pharmaceutical composition as per the invention shows improved bioavailability.
- the present invention provides a process for the preparation of the said composition comprising
- step (ii) adding surfactant to the curcumin dispersion of step (i);
- step (iv) adding oil to the solution of step (iii) to obtain the liquid pharmaceutical composition.
- step (ii) adding solvent to the curcumin dispersion of step (i); and dissolving curcumin by mixing and heating;
- step (iii) mixing oil to the solution of step (ii) to obtain the stable liquid pharmaceutical composition.
- step (ii) adding solvent to the curcumin dispersion of step (i);
- step (iii) mixing surfactant to the dispersion of step (ii) and dissolving curcumin by mixing and heating to obtain the stable liquid pharmaceutical composition.
- step (ii) adding curcumin to blend of step (i) and dissolving curcumin by mixing and heating to obtain stable liquid pharmaceutical composition.
- compositions according to the present invention can be administered by oral, topical or parenteral route; preferably the compositions are administered by oral route.
- Example 1 A pharmaceutical composition of curcumin was prepared as given in table 1 .
- Curcumin was dispersed in ethyl alcohol and propylene glycol.
- Cremophore RH 40 was added to curcumin dispersion of step 1 with mixing and heating to dissolve the curcumin.
- Example 2 A pharmaceutical composition of curcumin was prepared as given in table 2.
- Curcumin was dispersed in ethyl alcohol. 2. Cremophore RH 40 was added to the curcumin dispersion of step 1 with mixing and heating to dissolve the curcumin.
- Particle size of the resulting microemulsion was found to be 222 nm.
- Examples 3-8 Pharmaceutical compositions of curcumin were prepared as given in table 3.
- Curcumin was dispersed in ethyl alcohol.
- Cremophore RH 40 was added to the curcumin dispersion of step 1 with mixing and heating.
- composition of example 1 was subjected to accelerated stability study as per ICH guideline. The product was found to be stable for 6 months at 40 °C /75% RH as shown in table 5.
- the pharmaceutical composition comprising curcumin, surfactant, solvent, oil and anti-oxidant was found to exhibit high bioavailability as shown in table 6.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hospice & Palliative Care (AREA)
- Toxicology (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Biochemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/822,539 US9474727B2 (en) | 2010-09-15 | 2011-09-12 | Pharmaceutical compositions of curcumin |
EP11824671.9A EP2616053B1 (en) | 2010-09-15 | 2011-09-12 | Pharmaceutical compositions of curcumin |
ES11824671.9T ES2616022T3 (en) | 2010-09-15 | 2011-09-12 | Curcumin pharmaceutical compositions |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN2553MU2010 | 2010-09-15 | ||
IN2553/MUM/2010 | 2010-09-15 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2012035480A2 true WO2012035480A2 (en) | 2012-03-22 |
WO2012035480A3 WO2012035480A3 (en) | 2012-07-05 |
Family
ID=45832022
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2011/053974 WO2012035480A2 (en) | 2010-09-15 | 2011-09-12 | Pharmaceutical compositions of curcumin |
Country Status (4)
Country | Link |
---|---|
US (1) | US9474727B2 (en) |
EP (1) | EP2616053B1 (en) |
ES (1) | ES2616022T3 (en) |
WO (1) | WO2012035480A2 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150342904A1 (en) * | 2012-10-22 | 2015-12-03 | Briu Gmbh | Pharmaceutical composition containing curcumin |
US9517249B2 (en) | 2012-11-26 | 2016-12-13 | Access Business Group International Llc | Antioxidant dietary supplement and related method |
CN106667912A (en) * | 2017-02-08 | 2017-05-17 | 何德海 | Preparation method of curcumin nanometer emulsion |
CN110693833A (en) * | 2019-10-31 | 2020-01-17 | 上海交通大学医学院附属新华医院 | Method for preparing nano curcumin composite preparation by using ultra-concentrated emulsion |
CN110960516A (en) * | 2018-09-27 | 2020-04-07 | 广州汝丽多食品科技有限公司 | Curcumin compound and preparation method thereof |
WO2021016576A1 (en) * | 2019-07-25 | 2021-01-28 | Skin Medicinals LLC | Topical compositions |
EP3225112B1 (en) | 2016-04-01 | 2021-08-18 | TriOptoTec GmbH | Photosensitiser dispersion and use of the same |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3203992A4 (en) * | 2014-10-08 | 2018-11-07 | Boston Biopharm, Inc. | Compositions and methods for increasing the bioavailability of one or more compounds |
US10085951B2 (en) | 2014-12-11 | 2018-10-02 | Designs For Health, Inc. | Curcuminoid formulations and related methods of treatment |
US20200383933A1 (en) * | 2017-09-05 | 2020-12-10 | Universidad De Chile | Method for obtaining nanostructures with carotenoids and nanostructures obtained |
CN110538167A (en) * | 2018-05-29 | 2019-12-06 | 冉文萍 | Curcumin composition and preparation method and application thereof |
US20210308074A9 (en) * | 2019-03-06 | 2021-10-07 | Renibus Therapeutics, Inc. | Novel tetrahydrocurcumin compositions, methods of making, and methods of using the same |
CN115176989A (en) * | 2022-07-12 | 2022-10-14 | 河南中大恒源生物科技股份有限公司 | Transparent curcumin oil solution and preparation method and application thereof |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8784881B2 (en) * | 2004-03-05 | 2014-07-22 | Board Of Regents, The University Of Texas System | Liposomal curcumin for treatment of diseases |
CN100352430C (en) | 2005-03-09 | 2007-12-05 | 山东大学 | Self microemulsifying preparation of curcumin and its preparing process |
EP1993365B1 (en) | 2006-03-06 | 2013-05-08 | The Regents of the University of California | Bioavailable curcuminoid formulations for treating alzheimer's disease and other age-related disorders |
WO2010010431A1 (en) | 2008-07-24 | 2010-01-28 | National Institute Of Pharmaceutical Education And Research | Self-nano-emulsifying curcuminoids composition with enhanced bioavailability |
WO2010045395A2 (en) * | 2008-10-14 | 2010-04-22 | Danyang Chen | Curcumin analog compositions and related methods |
CN101627969B (en) * | 2009-07-30 | 2011-06-29 | 浙江工业大学 | Novel curcumin self-emulsifying drug delivery system and preparation method thereof |
-
2011
- 2011-09-12 WO PCT/IB2011/053974 patent/WO2012035480A2/en active Application Filing
- 2011-09-12 EP EP11824671.9A patent/EP2616053B1/en active Active
- 2011-09-12 US US13/822,539 patent/US9474727B2/en active Active
- 2011-09-12 ES ES11824671.9T patent/ES2616022T3/en active Active
Non-Patent Citations (1)
Title |
---|
See references of EP2616053A4 * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150342904A1 (en) * | 2012-10-22 | 2015-12-03 | Briu Gmbh | Pharmaceutical composition containing curcumin |
US11382871B2 (en) | 2012-10-22 | 2022-07-12 | Briu Gmbh | Pharmaceutical composition containing curcumin |
US9517249B2 (en) | 2012-11-26 | 2016-12-13 | Access Business Group International Llc | Antioxidant dietary supplement and related method |
US10201583B2 (en) | 2012-11-26 | 2019-02-12 | Access Business Group International Llc | Antioxidant dietary supplement and related method |
EP3225112B1 (en) | 2016-04-01 | 2021-08-18 | TriOptoTec GmbH | Photosensitiser dispersion and use of the same |
CN106667912A (en) * | 2017-02-08 | 2017-05-17 | 何德海 | Preparation method of curcumin nanometer emulsion |
CN110960516A (en) * | 2018-09-27 | 2020-04-07 | 广州汝丽多食品科技有限公司 | Curcumin compound and preparation method thereof |
CN110960516B (en) * | 2018-09-27 | 2023-01-06 | 广州汝丽多食品科技有限公司 | Curcumin compound and preparation method thereof |
WO2021016576A1 (en) * | 2019-07-25 | 2021-01-28 | Skin Medicinals LLC | Topical compositions |
CN110693833A (en) * | 2019-10-31 | 2020-01-17 | 上海交通大学医学院附属新华医院 | Method for preparing nano curcumin composite preparation by using ultra-concentrated emulsion |
Also Published As
Publication number | Publication date |
---|---|
EP2616053A2 (en) | 2013-07-24 |
US9474727B2 (en) | 2016-10-25 |
ES2616022T3 (en) | 2017-06-09 |
WO2012035480A3 (en) | 2012-07-05 |
US20130225689A1 (en) | 2013-08-29 |
EP2616053A4 (en) | 2014-01-15 |
EP2616053B1 (en) | 2016-11-02 |
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