NZ746802A - Curcuminoid chlorophyllin (chl) compositions and methods of preparation and use - Google Patents
Curcuminoid chlorophyllin (chl) compositions and methods of preparation and useInfo
- Publication number
- NZ746802A NZ746802A NZ746802A NZ74680218A NZ746802A NZ 746802 A NZ746802 A NZ 746802A NZ 746802 A NZ746802 A NZ 746802A NZ 74680218 A NZ74680218 A NZ 74680218A NZ 746802 A NZ746802 A NZ 746802A
- Authority
- NZ
- New Zealand
- Prior art keywords
- composition
- weight
- curcuminoid
- chl
- solubilization matrix
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 194
- 235000019805 chlorophyllin Nutrition 0.000 title claims abstract description 123
- 229940099898 chlorophyllin Drugs 0.000 title claims abstract description 123
- VFLDPWHFBUODDF-FCXRPNKRSA-N Curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 title claims abstract description 107
- UVOXKYYHMDAWNK-UHFFFAOYSA-L magnesium;3-[20-(carboxylatomethyl)-18-(dioxidomethylidene)-8-ethenyl-13-ethyl-3,7,12,17-tetramethyl-2,3-dihydroporphyrin-23-id-2-yl]propanoate;hydron Chemical compound [H+].[H+].[H+].[Mg+2].C1=C([N-]2)C(CC)=C(C)C2=CC(C(=C2C)C=C)=NC2=CC(C(C2CCC([O-])=O)C)=NC2=C(CC([O-])=O)C2=NC1=C(C)C2=C([O-])[O-] UVOXKYYHMDAWNK-UHFFFAOYSA-L 0.000 title claims abstract 17
- 238000002360 preparation method Methods 0.000 title description 5
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- 238000005063 solubilization Methods 0.000 claims abstract description 59
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- PTADZZOCKJDRAG-UHFFFAOYSA-L magnesium;[18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-18,23-dihydro-17H-porphyrin-2-ylidene]methanediolate Chemical compound [Mg+2].N1=C(C(CC(O)=O)=C2C(C(C)C(C=C3C(=C(C=C)C(=C4)N3)C)=N2)CCC(O)=O)C(=C([O-])[O-])C(C)=C1C=C1C(CC)=C(C)C4=N1 PTADZZOCKJDRAG-UHFFFAOYSA-L 0.000 description 109
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Abstract
Provided herein are solid form water soluble curcuminoid compositions, including a curcuminoid; and a solubilization matrix, wherein the solubilization matrix is selected from one or more of the following: (i) chlorophyllin (CHL); (ii) green tea extract; (iii) epigallocatechin gallate (EGCG); (iv) Rutin; and (v) an aromatic amino acid. Alternatively, the solubilization matrix may include methylsulfonylmethane (MSM). Also provided herein are methods for producing curcuminoid compositions. Rutin; and (v) an aromatic amino acid. Alternatively, the solubilization matrix may include methylsulfonylmethane (MSM). Also provided herein are methods for producing curcuminoid compositions.
Description
CURCUMINOID CHLOROPHYLLIN (CHL) COMPOSITIONS AND METHODS OF
PREPARATION AND USE
This application claims priority from US Application No. 62/564,819 filed on 28 September
2017, the contents of which are to be taken as incorporated herein by this reference.
TECHNICAL FIELD
This invention relates to the field of curcuminoids. In particular, the invention relates to
water soluble curcuminoid compositions and methods for preparing water-soluble curcuminoid
compositions.
BACKGROUND
Curcumin is the major curcuminoid of the Indian curry spice turmeric. Curcuminoids
provide the major yellow color pigment of turmeric, which is derived from the rhizome of the
Curcuma longa linn plant and it has been traditionally used in the treatment of skin wounds,
inflammation, tumors et al.
Although raw turmeric contains more than 100 components, its characteristic yellow
color is derived from various curcuminoids. Curcuminoids have a chemical structure consisting
of 2 aromatic rings joined by a 7-carbon chain with various substituents.
Curcumin (1,7bis (4-hydroxymethoxy phenyl)-1,6 heptadiene-3,5-dione) is a
hydrophobic polyphenol derivative which is a potent antioxidant derived from the spice
turmeric. Commercial “curcumin” is a mixture of diarylheptanoid compounds, that usually a
combination of about 77% diferuloylmethane (i.e. curcumin), 17% demethoxycurcumin, and 6%
of bisdemethoxycurcumin.
Curcuminoids are the primary active ingredients of Cucuma longa rhizome (the turmeric
plant). These curcuminoids are often identified as curcumin 1 (diferuylmethane), curcumin 2
(demethoxycurcumin), curcumin 3 (didemethoxycurcumin) and cyclocurcumin (A. Goel and A.
B. Kunnumakkara, 2008). Curcumin 1 (diferuylmethane) is the most potent of the naturally
occurring curcuminoids.
Curcuminoids are natural phenolic compounds that are responsible for the yellow color
of turmeric. Curcumin exists in several tautomeric forms.
Curcuminoids are generally hydrophobic compounds thought to have a variety of
therapeutic benefits (for example, anti-inflammatory, anti-oxidant, anti-cancerous activities).
2
However, their therapeutic use has been limited by their hydrophobicity which results in poor
solubility and rapid elimination from the body (i.e. low bioavailability).
While the poor bioavailability of curcumin is attributable to its poor absorption in the
body, it is also quickly metabolized and rapidly eliminated from the body.
Curcuminoids have been shown to have potent activity against pancreatic cancer, to
inhibit gastrointestinal carcinogenesis, and to protect against oxidative stress. It is also reported
to have chemopreventative, chemotherapeutic, chemosensitizing, and radio-protective in
normal cells and radiosensitizing in cancer cells. Curcumin has been reported to exhibit antitumor and anti-apoptotic properties and to suppress the growth of a variety of cancer cell lines
in the laboratory and prevent the appearance of cancers in animal studies (Araujo and Leon,
2001).
In order to overcome the poor bioavailability of curcuminoid compounds, various efforts
have been made to increase their bioavailability through complexing with cyclodextrins, micelles
and nanoparticles.
Curcumin has chemo preventive, anti-neoplastic and anti-inflammatory properties in
preclinical animal models (Gary J. Kelloff New Agents for Cancer Chemoprevention Journal of
Cell Biochemistry (1996) 63 Supplement S26:1–28).
S.K Kulkarni demonstrate a role for curcumin in enhancing neurogenesis, notably in the
frontal cortex and hippocampal regions of the brain (“Potentials of Curcumin as an
Antidepressant” Scientific World Journal (2009) 9:1233–1241).
The synthesis and physiochemical characterization of a polymer based nanoparticle of
curcumin called ‘nanocurcumin’ with less than 100 nm particle size was described by Savita
Bisht et al. (“Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): a novel strategy
for human cancer therapy Journal of Nanobiotechnology (2007)5:3). The nanocurcumin was
found to have similar in vitro activity as that of free curcumin in pancreatic cell lines.
WO2013175507 titled “Novel highly bioavailable, water soluble and sustained release
nano-formulations of hydrophobic plant derived compounds and extracts” describes a nanoemulsified composition to enhance bioavailability of curcuminoids. The concentration of the
emulsifier phase in the nanoformulations ranges from 60% to 95%. In addition, the application
describes the use of emulsifiers which are anionic, cationic or non-ionic selected from but not
limited to Polysorbates preferably Polysorbate 80 and Polysorbate 20, Polyethylene glycols
preferably Polyethylene glycol 200 and Polyethylene glycol 400, Polyethylene glycol esters and
Glycerol esters and also tabulates a series of composition of nanoformulations using
hydrophobic compounds and also disclosed a process of pre-heating the emulsifier phase to a
3
temperature below the melting point of the hydrophobic active ingredient. Analytical results for
the particle size of CurQlife (curcumin), morphological characteristics of CurQlife are provided,
along with an aqueous phase curcumin concentration ranging from 5 to 20%. Furthermore, the
maximum curcumin concentration achieved in human pharmacokinetic study was about
25ng/mL.
US patent 7,883,728 titled “Composition to enhance the bioavailability of curcumin”
provides a method to improve bioavailability of curcumin preparation of a composition
containing purified curcuminoid and purified oil and discloses a methodology to prepare a
composition for enhanced bioavailability. The composition comprises a curcuminoid mixture
consisting of demethoxycurcumin and bisdemethoxycurcumin and the essential oil arturmerone. The percent ratios of the composition consist of a range of 24% to 96% of
curcuminoids combined with a range of 4% to 50% of the essential oil. The bioavailability of
curcumin in human was shown to reach a maximum of about 93 ng/g.
WO2012024405 titled “Curcumin compositions and uses thereof” describes a
composition and a method of increasing the bioavailability of curcumin. The composition is
suitable for modifying DNA methylation and for treatment of cancer. The composition
comprises curcumin and excipient polymers like polyethoxylated castor oil,
polyoxyethylenesorbitan ester and polyethylene glycol. The application described the increased
bioavailability of curcumin by using gel formulation and the formulation is safe, tolerated and
effective in treatment of leukemia and breast cancer. The plasma level of curcumin was high in
human volunteers thus increasing the bioavailability of curcumin. However, the invention is
silent with respect to the absorption of curcumin from blood and its dispersibility, which affects
the bioavailability.
WO2014068597, titled “Formulation of curcumin with enhanced bioavailability of
curcumin and method of preparation and treatment thereof”, provides a medicinal
composition useful for the treatment of head and neck cancer premalignant lesions comprising
(a) curcuminoid mixture and (b) an essential oil of turmeric. The weight ratios of curcuminoid
mixtures to turmeric essential oil ranging from about 1:3 to about 99:1. Also disclosed, is a
method of treating head and neck oral premalignant lesion by the administration of medicinal
composition comprising curcuminoid mixture and added essential oil of turmeric to patients
suffering from such disease.
WO2015025263 titled “A novel composition of curcumin with enhanced
bioavailability”, discloses a curcumin composition for increasing the bioavailability of
curcumin, which consists of curcumin mixture and a water extract of turmeric in a ratio of
4
70:30, wherein the curcumin mixture comprises curcumin dry crystals, volatile oil, fixed oil and
the water extract comprises soluble proteins, dietary fibers and carbohydrates extracted from
turmeric, and the composition also consists of a natural emulsifier isolated from Quillaja
saponaria and lecithin and a method of preparing the composition.
US patent publication US2010/0316631 titled “Water Soluble Curcumin-based
Compositions” discloses the design and synthesis of water soluble curcumin-based
compositions, methods for synthesizing the compositions and methods of treatment using the
compositions.
US patent publication US2013/0274343 titled “Water Soluble Composition comprising
Curcumin having enhanced bioavailability and process thereof” describes a water soluble
composition having enhanced bioavailability and a process for its preparation.
US patent 8,551,507, titled “Terpene glycosides and their combinations as solubilizing
agents” discloses methods and compositions for enhancing solubility of organic compounds
including curcuminoids with terpene glycosides, wherein combinations include curcuminoids
with 1% to 40% w/v mogroside V and curcuminoids with 1% to 40% w/v geniposide. Stevioside
was shown to enhance the solubility of clofazinine, digoxin, oleandrin, nifedipine, and
amiodarone, but does not appear to have been combined with curcumin.
US patent publication US2011/0033525, titled “Diterpene Glycosides as Natural
Solubilizers” discloses methods for enhancing curcuminoid solubility by mixing it with water
and a diterpene glycoside such as rubusoside, rebaudioside, steviol monoside and stevioside.
Rubusoside was used to increase the solubility of curcumin in water by a factor of 285 and
another example discloses that 5% stevioside in water was equally effective to rubusoside in
solubilizing curcumin. All of the compositions disclosed as enhancing solubility were aqueous
solutions and no solid form composition was disclosed.
PCT/US2013/053585 describes water soluble compositions of curcumin were
formulated containing macrogolglycerol hydroxystearate (polyoxyl 40 castor oil) and curcumin
extract that is 99% pure l,7-Bis(4-hydroxymethoxyphenyl)-l,6-heptadiene-3,5-dione by
HPLC, wherein the polyoxyl 40 castor oil (non-ionic surfactant) was heated and stirred to a
temperature of about 125°F (about 52°C), and the curcumin powder was slowly mixed with the
polyoxyl castor oil until a clear viscous solution was formed containing dissolved curcumin
powder. The curcumin emulsion was then slowly added to warm water (100-125°F) until a
crystal clear solution was formed.
US patent 8,187,615 discloses non-aqueous compositions for oral delivery of insoluble
bioactive agents (for example, curcumin) wherein polyethylene glycol is one of the
pharmaceutically acceptable water-miscible non-aqueous solvents.
SUMMARY
The present invention is based, in part, on the discovery that curcuminoids are made
more water soluble and thus more bioavailable to a subject when combined with a solubilization
matrix as described herein.
In one aspect, there is provided a method of producing a solid form water soluble
curcuminoid composition, the method including: (a) mixing a curcuminoid and a solubilization
matrix to form a mixture; (b) adjusting the temperature of the mixture to between about 37°C
and about 190°C to dissolve the curcuminoid; and (c) cooling the mixture to permit the
curcuminoid and the solubilization matrix composition to achieve a solid form; wherein the
solubilization matrix is selected from one or more of the following: (i) chlorophyllin (CHL); (ii)
green tea extract; (iii) epigallocatechin gallate (EGCG); (iv) Rutin; and (v) an aromatic amino
acid.
The solubilization matrix may further include methylsulfonylmethane (MSM). The
aromatic amino acids may be tyrosine, tryptophan, or phenylalanine. The mixture may further
include an organic solvent. The organic solvent may be selected from: methanol; ethanol;
propanol; butanol; acetonitrile; and acetone. The organic solvent may be added: (a) before
adjusting the temperature of the mixture in (b); (b) during the adjusting the temperature of the
mixture in (b); or (c) the curcumin may be dissolved in the organic solvent before mixing with
the solubilization matrix. The temperature of the mixture may be kept between about 60°C and
about 90°C for 20 to 200 minutes to facilitate organic solvent evaporation. The temperature of
the mixture may be kept between about 70°C and about 90°C for 20 to 200 minutes to facilitate
organic solvent evaporation. The temperature of the mixture may be kept between about 80°C
and about 90°C for 20 to 200 minutes to facilitate organic solvent evaporation. The
temperature of the mixture may be kept between about 60°C and about 90°C for 40 to 200
minutes to facilitate organic solvent evaporation. The temperature of the mixture may be kept
between about 60°C and about 90°C for 50 to 200 minutes to facilitate organic solvent
evaporation. The temperature of the mixture may be kept between about 60°C and about 90°C
for 60 to 200 minutes to facilitate organic solvent evaporation. The temperature of the mixture
may be kept between about 60°C and about 90°C for 70 to 200 minutes to facilitate organic
solvent evaporation. The temperature of the mixture may be kept between about 60°C and
6
about 90°C for 80 to 200 minutes to facilitate organic solvent evaporation. The temperature of
the mixture may be kept between about 60°C and about 90°C for 90 to 200 minutes to facilitate
organic solvent evaporation. The temperature of the mixture may be kept between about 60°C
and about 90°C for 10 to 120 minutes to facilitate organic solvent evaporation.
The curcuminoid component of the solid form water soluble curcuminoid composition
may be between about 5% and about 70% by weight. The curcuminoid component of the solid
form water soluble curcuminoid composition, may be between about 10% and about 60% by
weight. The curcuminoid component of the solid form water soluble curcuminoid composition
may be between about 10% and about 50% by weight. The curcuminoid component of the solid
form water soluble curcuminoid composition may be between about 10% and about 40% by
weight. The curcuminoid component of the solid form water soluble curcuminoid composition
may be between about 10% and about 30% by weight. The curcuminoid component of the solid
form water soluble curcuminoid composition may be between about 10% and about 20% by
weight.
The solid form water soluble curcuminoid composition may be isolated. The
curcuminoid component of the solid form water soluble curcuminoid composition may be
between about 5% and about 80% by weight. The curcuminoid component of the solid form
water soluble curcuminoid composition may be between about 5% and about 90% by weight.
The solubilization matrix component of the solid form water soluble curcuminoid
composition, may be between about 30% and about 95% by weight. The solubilization matrix
component of the solid form water soluble curcuminoid composition, may be between about
40% and about 80% by weight. The solubilization matrix component of the solid form water
soluble curcuminoid composition, may be between about 40% and about 70% by weight. The
solubilization matrix component of the solid form water soluble curcuminoid composition, may
be between about 40% and about 60% by weight. The solubilization matrix component of the
solid form water soluble curcuminoid composition may be between about 50% and about 70%
by weight.
The solubilization matrix component of the solid form water soluble curcuminoid
composition, may be between about 20% and about 95% by weight. The solubilization matrix
component of the solid form water soluble curcuminoid composition, may be between about
% and about 95% by weight.
7
One of the solubilization matrix components may be a CHL and the CHL may be
between about 30% and about 90% by weight. One of the solubilization matrix components
may be a CHL and the CHL may be between about 40% and about 80% by weight. One of the
solubilization matrix components may be a CHL and the CHL may be between about 40% and
about 70% by weight. One of the solubilization matrix components may be a green tea extract
and the green tea extract may be between about 30% and about 90% by weight. One of the
solubilization matrix components may be a green tea extract and the green tea extract may be
between about 40% and about 80% by weight. One of the solubilization matrix components
may be a green tea extract and the green tea extract may be between about 40% and about 70%
by weight. One of the solubilization matrix components may be a EGCG and the EGCG may be
between about 30% and about 90% by weight. One of the solubilization matrix components
may be a EGCG and the EGCG may be between about 40% and about 80% by weight. One of the
solubilization matrix components may be a EGCG and the EGCG may be between about 40%
and about 70% by weight. The solubilization matrix component may be Rutin and the Rutin
may be between about 30% and about 90% by weight. The solubilization matrix component
may be Rutin and the Rutin may be between about 40% and about 80% by weight. The
solubilization matrix component may be Rutin and the Rutin may be between about 40% and
about 70% by weight. The solubilization matrix component may be an aromatic amino acid and
the aromatic amino acid may be between about 30% and about 90% by weight. The
solubilization matrix component may be an aromatic amino acid and the aromatic amino acid
may be between about 40% and about 80% by weight. The solubilization matrix component
may be an aromatic amino acid and the aromatic amino acid may be between about 40% and
about 70% by weight.
The organic solvent may be between 3 and 90 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 80 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 70 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 60 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 50 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 40 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 30 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 20 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 10 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 9 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 8 times the total curcumin mixture by
8
weight. The organic solvent may be between 3 and 7 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 6 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 5 times the total curcumin mixture by
weight. The organic solvent may be between 3 and 4 times the total curcumin mixture by
weight. The organic solvent may be 3 times the total curcumin mixture by weight.
The organic solvent may be ethanol and the ethanol may be evaporated for about 30 to
about 120 minutes. The organic solvent may be ethanol and the ethanol may be evaporated for
about 30 to about 110 minutes. The organic solvent may be ethanol and the ethanol may be
evaporated for about 30 to about 100 minutes. The organic solvent may be ethanol and the
ethanol may be evaporated for about 30 to about 90 minutes. The organic solvent may be
ethanol and the ethanol may be evaporated for about 30 to about 80 minutes. The organic
solvent may be ethanol and the ethanol may be evaporated for about 30 to about 70 minutes.
The organic solvent may be ethanol and the ethanol may be evaporated for about 30 to about 60
minutes. The temperature for evaporation of the ethanol may be between about 60°C and
about 85°C. The temperature for evaporation of the ethanol may be between about 60°C and
about 80°C.
In another embodiment, there may be provided a method of producing a solid form
water soluble curcuminoid composition, the method may include: (a) curcuminoid may be
dissolved in ethanol to about 20% w/w concentration; (b) CHL may be mixed and heated in a
vacuum chamber to at least about 50°C; (c) the curcumin and ethanol solution may be sprayed
into the vacuum chamber slowly; and (d) the contents of the vacuum chamber may be dried
under vacuum.
The method may further include encapsulation. The product may be encapsulated with
lubricants and fillers.
In a further embodiment, there may be provided a product produced by one of the above
methods.
In a further embodiment, there may be provided a composition, the composition
including: (a) a curcuminoid; and (b) a solubilizer, wherein the solubilizer may be selected from
one or more of: (i) chlorophyllin (CHL); (ii) green tea extract; (iii) epigallocatechin gallate
(EGCG); (iv) Rutin; and (v) an aromatic amino acid.
The curcuminoid may be between 10-30% w/w and the solubilizer may be between 70-
90% w/w. The weight percentage of curcuminoid may be between about 5% and about 70%.
9
The solubilizer may be chlorophyllin. The chlorophyllin may be sodium magnesium
chlorophyllin, sodium zinc chlorophyllin, sodium copper chlorophyllin, chlorophyll paste or oilsoluble chlorophyll.
The weight percentage of solubilizer may be between about 10% and about 50%. The
weight percentage of solubilizer may be between about 20% and about 50%. The weight
percentage of solubilizer may be between about 30% and about 50%. The weight percentage of
solubilizer may be between about 40% and about 50%. The weight percentage of solubilizer
may be between about 10% and about 40%. The weight percentage of solubilizer may be
between about 10% and about 30%. The weight percentage of solubilizer may be between about
% and about 20%. The solubilizer may be green tea extract. The solubilizer may be
chlorophyllin (CHL). The solubilizer may be epigallocatechin gallate (EGCG). The solubilizer
may be rutin. The solubilizer may be an aromatic amino acid. The weight percentage of
solubilizer may be between about 10% and about 90%. The weight percentage of solubilizer may
be between about 10% and about 80%. The weight percentage of solubilizer may be between
about 10% and about 70%. The weight percentage of solubilizer may be between about 10% and
about 60%. The weight percentage of solubilizer may be between about 10% and about 50%.
The weight percentage of solubilizer may be between about 10% and about 40%. The weight
percentage of solubilizer may be between about 10% and about 30%. The weight percentage of
solubilizer may be between about 10% and about 20%. The weight percentage of solubilizer may
be between about 20% and about 90%. The weight percentage of solubilizer may be between
about 30% and about 90%. The weight percentage of solubilizer may be between about 40%
and about 90%. The weight percentage of solubilizer may be between about 50% and about
90%. The weight percentage of solubilizer may be between about 60% and about 90%. The
weight percentage of solubilizer may be between about 70% and about 90%. The weight
percentage of solubilizer may be between about 80% and about 90%.
In a further embodiment, there may be provided a composition, the composition
including: (a) a curcuminoid, wherein the curcuminoid may be between 10-30% w/w; and (b) a
solubilizer, wherein the solubilizer may be selected from one or more of: (i) chlorophyllin
(CHL); (ii) green tea extract; (iii) epigallocatechin gallate (EGCG); (iv) Rutin; and (v) an
aromatic amino acid wherein the solubilizer may be between 70-90% w/w.
The composition may be encapsulated. The composition may be encapsulated with
pharmaceutically acceptable lubricants and fillers.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGURE 1 shows a flow chart of the extracting process for plasma sample.
FIGURE 2 shows a flow chart of extracting process for blood sample.
FIGURE 3A shows a graph comparing curcumin absorption overtime for a CHL
composition and two reference compositions.
FIGURE 3B shows a graph comparing total area under the curve (AUC) curcumin
absorption for a CHL composition and two reference compositions.
FIGURE 4A shows a plot comparing HPLC results for curcumin and compositions of
CHL with GT.
FIGURE 4B shows a graph of total amount of curcumin component for curcumin and
composition of CHL with GT by HPLC analysis.
FIGURE 5A shows a plot comparing HPLC results for curcumin and compositions of
CHL with MSM.
FIGURE 5B shows a graph of total amount of curcumin component for curcumin and
composition of CHL with MSM by HPLC analysis.
FIGURE 6A shows a plot comparing HPLC results for curcumin and compositions of
CHL with Rutin.
FIGURE 6B shows a graph of total amount of curcumin component for curcumin and
composition of CHL with Rutin by HPLC analysis.
11
DETAILED DESCRIPTION
Any terms not directly defined herein shall be understood to have the meanings
commonly associated with them as understood within the art of the invention.
The term “curcuminoid” as used herein, is meant to encompass a variety of linear
diarylheptanoid compounds of natural and synthetic origins or even compounds of natural
origin that are subsequently synthetically modified. A diarylheptanoid consists of two aromatic
rings (aryl groups) joined by a seven carbons chain (heptane) or seven carbons forming a ring
and linear linker (for example, see cyclocurcumin) and allowing for various substituents.
Common curcuminoids may include one or more of the following:
curcumin;
demethoxycurcumin;
bisdemethoxycurcumin;
cyclocurcumin;
tetrahydrocurcumin;
dihydrocurcumin;
12
curcumin-glucuronoside;
dihydrocurcumin-glucuronoside;
tetrahydrocurcumin-glucuronoside;
curcuminsulphate; and
hexahydrocurcumin.
The Indian spice turmeric, which is derived from the rhizome of the plant Curcuma
longa, is a natural source of the curcumin. However, curcuminoids are found in many other
plant families and the extracted curcuminoids may be modified to form curcuminoids
derivatives. The most common curcuminoid derivatives are substituted on the phenyl groups,
but may also have variations in the linking chain as shown above.
The term “chlorophyllin” (CHL) as used herein refers to a semi-synthetic food additive
derived from chlorophyll, which may be extracted, for example, from alfalfa (Medicago sativa)
or spinach (Spinacia oleracea), using any one or a combination of the solvents acetone, ethanol,
13
and hexane. The particular CHL (i.e. CAS Number: 110061) is determined by the identity of
the cations associated with the anion. The most common form is a sodium/copper CHL
derivative. Sodium copper CHL is a green to black powder prepared from chlorophyll by
saponification and replacement of magnesium by copper. The structure of sodium copper CHL
is:
.
However, the sodium/magnesium CHL derivative is an alternative CHL. Similarly,
sodium/zinc CHL derivative, chlorophyll paste or oil-soluble chlorophyll may be selected.
The term “green tea extract” as used herein is meant to encompass a tea extract from Camellia
sinensis. For example, powdered decaffeinated green tea extract is available in numerous forms
and purities from Millipore Sigma™ (i.e. CAS Number: 846502). The primary ingredient of
which is epigallocatechin gallate (EGCG), is most abundant catechin in tea (i.e. for example, CAS
Number 9895), which has the general structure .
The term “Rutin” or “rutoside” as used herein is refers to the glycoside combining the
flavonol quercetin and the disaccharide rutinose (α-L-rhamnopyranosyl-(1→6)-β-Dglucopyranose). It is a citrus flavonoid found in wide variety of plants including citrus fruit.
14
.
The term “methylsulfonylmethane” (MSM) as used herein refers to an organosulfur
compound with the formula (CH3)2SO2. MSM is also known by several other names including
DMSO2, methyl sulfone, and dimethyl sulfone. The structure of MSM is .
The term “solubilization matrix” as used herein is meant to encompass a particular
subset of solubilizers or a single solubilizer, in particular, wherein the solubilization matrix is
selected from one or more of the following:
(i) chlorophyllin (CHL); (ii) green tea extract; (iii) epigallocatechin gallate (EGCG); (iv) Rutin;
(v) or combinations of any of (i)-(iv).
The terms "solubilizer" as used herein refers to a substance that improves the solubility
of a curcuminoid in water.
The term "solubility" as used herein refers to the property of a solid, liquid, or gaseous
chemical substance (“solute”) to dissolve in a solid, liquid, or gaseous solvent. The solubility of a
substance fundamentally depends on the physical and chemical properties of the solute and
solvent as well as on temperature, pressure and the pH of the solution.
The term “organic solvent” as used herein is refers to any solvent having at least 1 carbon
atom and 1 hydrogen atom, a low molecular weight, lipophilicity, and volatility, and exist in
liquid form at room temperature. Organic solvents may further be grouped as aliphatic or
aromatic. Organic solvents are useful because they can dissolve oils, fats, resins, rubber, and
plastics. An organic solvent may be selected from: methanol; ethanol; propanol; butanol;
acetonitrile; and acetone.
Curcuminoids may be fully solubilized in chlorophyllin (CHL) at about 5% to about 70%
by weight of a curcuminoid powder may be blended with a mixture of CHL and green tea extract
or CHL alone. Alternatively, about 10% w/w to about 30% w/w of a curcuminoid powder may
be blended with a mixture of CHL and green tea extract or CHL alone. A further alternative
may include about 10% w/w to about 20% w/w of a curcuminoid powder is blended with a
mixture of CHL and green tea extract or CHL alone. The content of CHL as a solubilizer may be
from about 10% to about 95% by weight, or about 40% to about 80% by weight. The green tea
extract used as a solubilizer may be from about 5% to about 90% by weight, or may be from
about 20% to about 90% by weight, or may be from about 40% to about 90% by weight. The
curcuminoid powder may be visually distinguishable in the chlorophyllin and green tea extract
(if used) mixture as yellow particulates in the solution. However, when heat is applied (for
example, until the solution reaches about 60-90°C or at about 80°C), the curcuminoid may
become fully dissolved in chlorophyllin and green tea extract mixture as the particulates
disappear and the solution turns to a transparent orange color. An organic solvent, or mixtures
of solvents, including but not limited to methanol, ethanol, acetonitrile, acetone, propanol, and
butanol may be added before or during the heating process and allowed to evaporate when
heated. The solution of curcuminoid, chlorophyllin and green tea extract would then be allowed
to cool to room temperature and return to solid form.
Solubility testing of the curcuminoid composition may proceeded as follows: 1 gram of
curcuminoid composition added to 99mL of water, and shaken vigorously in order to mix; then
about 3mL of solution is removed; then centrifuged at 6000*g for 5 minutes or, alternatively
filtered through 0.2µm filter; the top layer of the centrifuged solution or the filtrate may be used
for HPLC analysis; and the filtrate after 0.2µm filtration contains only water soluble curcumin
particles smaller than 200nm.
Curcuminoids are fully solubilized in chlorophyllin (CHL)
About 5% to about 70% by weight of a curcuminoids powder was blended with a mixture
of chlorophyllin and green tea extract. Alternatively, about 10% w/w to about 30% w/w of a
curcuminoids powder was blended with a mixture of chlorophyllin and green tea extract.
Alternatively, about 10% w/w to about 20% w/w of a curcuminoids powder was blended with a
mixture of chlorophyllin and green tea extract. The content of chlorophyllin as a solubilizer may
be from about 10% to 95% by weight, or most preferably from about 40% to about 80% by
weight. The green tea extract used as a solubilizer may be from about 5% to about 90% by
weight, or may be from about 20% to about 90% by weight, or may be from about 40% to about
90% by weight. At first, the curcuminoid powder is visually distinguishable in the chlorophyllin
and green tea extract mixture as yellow particulates in the solution. However, when heat is
applied to raise the solution temperature to about 60-90°C, or about 80°C, the curcuminoids
become fully dissolved in chlorophyllin and green tea extract mixture as the particulates
completely disappear and the solution turns to a transparent but orange color. An organic
16
solvent, or mixtures of solvents, including but not limited to methanol, ethanol, acetonitrile,
acetone, propanol, and butanol may be added before or during the heating process and allowed
to evaporate during the process. The solution of curcuminoids, chlorophyllin and green tea
extract is then allows to cool to room temperature and return to solid form.
Various alternative embodiments and examples are described herein. These
embodiments and examples are illustrative and should not be construed as limiting the scope of
the invention.
17
EXAMPLES
EXAMPLE 1: BIOAVAILABILITY OF A CURCUMIN AND CHLOROPHYLLIN (CHL)
COMPOSITION
Seven volunteer subjects aged between 25 and 55 years of age as the test subject are
selected. Initially, all of volunteers were advised to take a curcumin/CHL formula capsule as
shown in TABLE 1 below. Blood samples were then collected before ingesting the capsules and
then periodically at 1hr up to 4 hrs. and then at 2hr intervals for the remaining 4 hrs. until the
end of 8 hours (see TABLE 2). After all blood samples were collected, the blood samples were
processed as described below.
It is devised a method of manufacturing for novel curcumin-based composition. An
exemplary method for producing a water-soluble curcumin having the properties is as follow:
(1) curcumin powder was dissolved in the same weight of ethanol, then mixed with CHL;
(2) dissolving and mixing in (1) was performed at a temperature of 80°C; and
(3) once dissolved, increase the temperature of the mixture above the boiling point of
ethanol for a period 30-90 minutes to evaporate as much of the ethanol as much as possible.
TABLE 1: CURCUMIN AND CHL
Ingredient Input
Amounts (g)
Input Ratios
(% w/w)
Dried Wt (g) Dried Ratios
(% w/w)
Curcumin 2 1.0 2 10.0
Ethanol 180 90.0 0 0
CHL
composition
(Sodium copper)
.4 2.7 5.4 27.0
Green tea
extract
12.6 6.3 12.6 63.0
Total 200 100.0 20 100.0
EXAMPLE 2: COMAPARISON CURCUMIN AND CHL COMPOSITION TO
COMMERCIAL PRODUCTS
Commercial curcumin products (reference #1 - Theracurmin™ 30%. A commercial
product made with micronized curcuminoids and gum ghatti, JP 2009-263638 A; reference #2 -
Longvide™ Curcumin. A commercial product with lipid micelles of curcuminoids and
antioxidants) were compared against the curcuminoid/CHL composition set out in TABLE 1.
18
Seven volunteers aged between 25 and 55 years of age as the test subject were selected
and first were advised to take a curcuminoid capsule reference #1 (Theracurmin™) or reference
#2 (Longvide™ Curcumin). Blood samples were then collected before ingesting the capsules
and then periodically at 1 hr up to 4 hrs. and then at 2hr intervals for the remaining 4 hrs. until
the end of 8 hours (see TABLE 2). After all blood samples were collected, the blood samples
were processed as described FIGURE 2.
TABLE 2: DATA COLLECTION TIME POINTS FOR TEST SUBJECTS 1-7
Name V01 V02 V03 V04 V05 V06 V07
Curcumin(mg) 180 180 180 180 180 180 180
0Hr V1-0 V2-0 V3-0 V4-0 V5-0 V6-0 V7-0
1Hr V1-1 V2-1 V3-1 V4-1 V5-1 V6-1 V7-1
2Hr V1-2 V2-2 V3-2 V4-2 V5-2 V6-2 V7-2
3Hr V1-3 V2-3 V3-3 V4-3 V5-3 V6-3 V7-3
4Hr V1-4 V2-4 V3-4 V4-4 V5-4 V6-4 V7-4
6Hr V1-6 V2-6 V3-6 V4-6 V5-6 V6-6 V7-6
8Hr V1-8 V2-8 V3-8 V4-8 V5-8 V6-8 V7-8
*V01-07 refers to each of the seven (7) volunteer test subjects.
Existing commercial curcumin products (Reference #1 and #2 as described above) were
compared against a curcumin and CHL composition using the same procedure with a wash out
period of at least one week. The curcuminoid and CHL composition (TABLE 1) showed higher
total plasma concentrations of curcumin than commercial curcumin products (see FIGURE
3B) and showed higher plasma concentrations over a longer time course than commercial
curcumin products (see FIGURE 3A). The CHL water-soluble curcumin composition shows
superior performance compared to other commercial compositions. The results described
herein show that the curcuminoid CHL composition provides an improvement of at least 88%
compared to other commercially available compositions.
EXAMPLE 3: HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC)
ANALYSIS OF CHL COMPOSITIONS WITH THREE ALTERNATIVE
SOLUBILIZERS
Human subjects were administered composition prepared comprising (1) curcuminoid
and chlorophyllin (CHL) with green tea extract (GT); (2) curcuminoid and chlorophyllin (CHL)
with methylsulfonylmethane (MSM); and (3) curcuminoid and chlorophyllin (CHL) with Rutin.
19
Furthermore, HPLC was used to compare three ratios of CHL to the second solubilizer (i.e. GT,
MSM or Rutin (i.e. ratios of either 1:9, 2:8 and 3:7). Blood sampling and extraction was
conducted as set out in FIGURE 2, prior to HPLC (High Performance Liquid Chromatography)
analysis of the extract. As shown in FIGURE 4A and FIGURE 4B, CHL with GT was
compared at three ratios (i.e. 1:9, 2:8 and 3:7). The highest concentrations of curcuminoid was
found in compositions having higher CHL relative to GT (i.e. 3:7 ratio). Similarly, as shown in
FIGURE 5A and FIGURE 5B, CHL with MSM was compared at three ratios (i.e. 1:9, 2:8 and
3:7). Although the total curcuminoid concentration was lower than in for CHL with GT, there
was still a trend towards increased concentrations of curcuminoid in compositions having
higher CHL relative to MSM (i.e. 2:8 and 3:7 ratio). Similar to the CHL with MSM, as shown in
FIGURE 6A and FIGURE 6B, CHL with Rutin was compared at three ratios (i.e. 1:9, 2:8 and
3:7). Although the total curcuminoid concentration was lower than in for CHL with GT and
CHL with MSM, there was still a trend towards increased concentrations of curcuminoid in
compositions having higher CHL relative to Rutin (i.e. 2:8 and 3:7 ratio).
The use of CHL increases the amount of curcuminoid component present in the blood
and plasma when compared to other commercially available curcumin products. Accordingly,
the use of CHL has positive role the delivery of curcuminoids.
The optimal ratio of CHL and GT for maximum absorption of curcumin is 3:7.
Compared with other ratios tested, the composition with 3:7 ratio shows about 8 times the
amount of curcumin.
TABLE 3: Water Solubilities of Various Curcuminoid Compositions
Description
Water
(g)
MSM
(g)
TYR
(g)
Green
Tea
extract
(g)
TRP
(g)
PHE
(g)
CHL
-Mg
(g)
Curcumin
(g)
Water Solubility
or Curcumin
Solubility in
Water (%, HPLC)
MSM only (10%
Curcumin) 8.1 0.9 0.1 Grade 1
MSM + Green tea
Ext (10%
Curcumin) 7.2 0.9 0.9 0.2 Grade 3
*CHL(Mg) +
Tyrosine(3:7) 0.63 0.27 0.1 1.21
*CHL(Mg) +
Tyrosine(4:6) 0.54 0.36 0.1 2.27
*CHL(Mg) +
Tyrosine(5:5) 0.45 0.45 0.1 3.25
*CHL(Mg) + Green
tea(3:7) 0.63 0.27 0.1 3.8
*CHL(Mg) + Green
tea(4:6) 0.54 0.36 0.1 3.69
*CHL(Mg) + Green
tea(5:5) 0.45 0.45 0.1 4.3
*CHL(Mg) +
Tryptophan(7:3) 0.27 0.63 0.1 1.31
*CHL(Mg) +
Tryptophan(6:4) 0.36 0.54 0.1 1.66
*CHL(Mg) +
Tryptophan(5:5) 0.45 0.45 0.1 1.09
*CHL(Mg) +
Phenylalanine(7:3) 0.27 0.63 0.1 1.53
*CHL(Mg) +
Phenylalanine(6:4) 0.36 0.54 0.1 1.66
*CHL(Mg) +
Phenylalanine(5:5) 0.45 0.45 0.1 1.54
*EtOH suspension
The optimal ratio of CHL and MSM for maximum absorption of curcumin is 3:7.
Compared with other ratio of composition, the composition with 3:7 ratio shows about 1.7 times
the amount of curcumin.
The optimal ratio of CHL and Rutin for maximum absorption of curcumin is 3:7.
Compared with other ratio of composition, the composition with 3:7 ratio shows about 2.3 times
the amount of curcumin.
EXAMPLE 4: ANALYTICAL METHOD FOR DETERMINING CURCUMIN IN BLOOD
The present application also discloses an analytical method for determining curcumin in
a subject’s plasma sample (see FIGURE 1) as set out below:
1. 0.05mL aliquot of each plasma sample collected from rats and human subjects is
transferred to a 1mL glass tube.
2. 0.11mL of 0.1M sodium acetate buffer (pH 5.0) containing 0.01mL β-glucuronidase is
added.
3. The resulting solutions (2) are incubated to hydrolyze the curcumin conjugated at 37
degree Celsius for 1 hr.
4. 0.01mL of mepronil working solution (20ng/mL in 50% MeOH) is added.
. 0.5mL of chloroform as an extraction solvent is added.
6. The sample is vortexed for 1 min, followed by ultrasonic vibrations for 15 min and then
centrifugation at 13000*g for 5 min.
7. The organic layer is transferred to a new 1mL glass tube and evaporated to dryness
using a centrifuge concentrator.
8. The treatment (5-7) is repeated once again. (add the organic layer to the same tube)
9. The dried extract is reconstituted in 0.1mL of 50% MeOH and then centrifuged at
21
13000*g for 5 min.
. 0.002mL aliquot of supernatant of reconstituted sample solution is injected into a
chromatographic system.
Although various embodiments are described herein, many adaptations and
modifications may be made within the scope of the invention in accordance with the common
general knowledge of those skilled in this art. Such modifications include the substitution of
known equivalents for any aspect of the invention in order to achieve the same result in
substantially the same way. Numeric ranges are inclusive of the numbers defining the range.
The word “comprising” is used herein as any open-ended term, substantially equivalent to the
phrase “including, but not limited to”, and the words “comprise” and “comprises” have a
corresponding meaning. As used herein, the singular forms “a”, “an” and “the” include plural
referents unless the context clearly dictates otherwise. Thus, for example, reference to “a thing”
includes more than one such thing. The invention includes all embodiments and variations
substantially as hereinbefore described and with reference to the examples and drawings.
Citation of references herein is not an admission that such references are prior art nor
does it constitute any admission as to the contents or date of these documents.
Claims (52)
1. A method of producing a solid form water soluble curcuminoid composition, the method comprising: (a) mixing a curcuminoid and a solubilization matrix to form a mixture; (b) adjusting the temperature of the mixture to between about 37°C and about 190°C to dissolve the curcuminoid; and (c) cooling the mixture to permit the curcuminoid and the solubilization matrix composition to achieve a solid form; wherein the solubilization matrix is selected from one or more of the following: (i) chlorophyllin (CHL); (ii) green tea extract; (iii) epigallocatechin gallate (EGCG); (iv) Rutin; and (v) an aromatic amino acid.
2. The method of claim 1, wherein the solubilization matrix further comprises methylsulfonylmethane (MSM).
3. The method of claim 1 or 2, wherein the aromatic amino acids is tyrosine, tryptophan, or phenylalanine.
4. The method of claim 1, 2 or 3, wherein the mixture further comprises an organic solvent.
5. The method of claim 4, wherein the organic solvent is selected from: methanol; ethanol; propanol; butanol; acetonitrile; and acetone.
6. The method of claim 4 or 5, wherein the organic solvent is added: (a) before adjusting the temperature of the mixture in (b); (b) during the adjusting the temperature of the mixture in (b); or (c) the curcumin is dissolved in the organic solvent before mixing with the solubilization matrix.
7. The method of claims 4, 5 or 6, where the temperature of the mixture is kept between about 60°C and about 90°C for 20 to 200 minutes to facilitate organic solvent evaporation. 23
8. The method of any one of claims 1-7, wherein the solid form water soluble curcuminoid composition is isolated.
9. The method of any one of claims 1-8, wherein the curcuminoid component of the solid form water soluble curcuminoid composition, is between about 5% and about 70% by weight.
10. The method of any one of claims 1-9, wherein the curcuminoid component of the solid form water soluble curcuminoid composition, is between about 10% and about 60% by weight.
11. The method of any one of claims 1-10, wherein the curcuminoid component of the solid form water soluble curcuminoid composition, is between about 10% and about 50% by weight.
12. The method of any one of claims 1-11, wherein the curcuminoid component of the solid form water soluble curcuminoid composition, is between about 10% and about 40% by weight.
13. The method of any one of claims 1-12, wherein the curcuminoid component of the solid form water soluble curcuminoid composition, is between about 10% and about 30% by weight.
14. The method of any one of claims 1-13, wherein the curcuminoid component of the solid form water soluble curcuminoid composition, is between about 10% and about 20% by weight.
15. The method of any one of claims 1-14, wherein the solubilization matrix component of the solid form water soluble curcuminoid composition, is between about 30% and about 95% by weight.
16. The method of any one of claims 1-15, wherein the solubilization matrix component of the solid form water soluble curcuminoid composition, is between about 40% and about 80% by weight.
17. The method of any one of claims 1-16, wherein the solubilization matrix component of the solid form water soluble curcuminoid composition, is between about 40% and about 70% by weight.
18. The method of any one of claims 1-17, wherein the solubilization matrix component of the solid form water soluble curcuminoid composition, is between about 40% and about 60% by weight.
19. The method of any one of claims 1-17, wherein the solubilization matrix component of the solid form water soluble curcuminoid composition, is between about 50% and about 70% by weight. 24
20. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a CHL and the CHL is between about 30% and about 90% by weight.
21. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a CHL and the CHL is between about 40% and about 80% by weight.
22. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a CHL and the CHL is between about 40% and about 70% by weight.
23. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a green tea extract and the green tea extract is between about 30% and about 90% by weight.
24. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a green tea extract and the green tea extract is between about 40% and about 80% by weight.
25. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a green tea extract and the green tea extract is between about 40% and about 70% by weight.
26. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a EGCG and the EGCG is between about 30% and about 90% by weight.
27. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a EGCG and the EGCG is between about 40% and about 80% by weight.
28. The method of any one of claims 1-15, wherein one of the solubilization matrix components is a EGCG and the EGCG is between about 40% and about 70% by weight.
29. The method of any one of claims 1-15, wherein the solubilization matrix component is Rutin and the Rutin is between about 30% and about 90% by weight.
30. The method of any one of claims 1-15, wherein the solubilization matrix component is Rutin and the Rutin is between about 40% and about 80% by weight.
31. The method of any one of claims 1-15, wherein the solubilization matrix component is Rutin and the Rutin is between about 40% and about 70% by weight. 25
32. The method of any one of claims 1-15, wherein the solubilization matrix component is an aromatic amino acid and the aromatic amino acid is between about 30% and about 90% by weight.
33. The method of any one of claims 1-15, wherein the solubilization matrix component is an aromatic amino acid and the aromatic amino acid is between about 40% and about 80% by weight.
34. The method of any one of claims 1-15, wherein the solubilization matrix component is an aromatic amino acid and the aromatic amino acid is between about 40% and about 70% by weight.
35. The method of any one of claims 2-34, wherein the organic solvent is between 3 and 90 times the total curcumin mixture by weight.
36. The method of claim 35, wherein organic solvent is ethanol and the ethanol is evaporated for about 30 to about 120 minutes.
37. The method of claim 36, wherein temperature for evaporation of the ethanol is between about 60°C and about 85°C.
38. A method of producing a solid form water soluble curcuminoid composition, the method comprising: (a) curcuminoid is dissolved in ethanol to about 20% w/w concentration; (b) CHL is mixed and heated in a vacuum chamber to at least about 50°C; (c) the curcumin and ethanol solution is sprayed into the vacuum chamber slowly; and (d) the contents of the vacuum chamber are dried under vacuum.
39. The method of claim 38, further comprising encapsulation.
40. The method of claim 38, wherein the product is encapsulated with lubricants and fillers.
41. A composition, the composition comprising: (a) a curcuminoid; and (b) a solubilizer, wherein the solubilizer is selected from one or more of: 26 (i) chlorophyllin (CHL); (ii) green tea extract; (iii) epigallocatechin gallate (EGCG); (iv) Rutin; and (v) an aromatic amino acid.
42. The composition of claim 41, wherein the curcuminoid is between 10-30% w/w and the solubilizer is between 70-90% w/w.
43. The composition of claim 41, wherein the weight percentage of curcuminoid is between about 5% and about 70%.
44. The composition of claim 41, wherein the solubilizer is chlorophyllin.
45. The composition of claim 41, wherein the weight percentage of solubilizer is between about 10% and about 50%.
46. The composition of claim 41, wherein the solubilizer is green tea extract.
47. The composition of claim 46, wherein the weight percentage of solubilizer is between about 10% and about 90%.
48. The composition of claim 41 or 43, wherein the solubilizer is rutin.
49. The composition of claim 48, wherein the weight percentage of solubilizer is between about 10% and about 90%.
50. A composition, the composition comprising: (a) a curcuminoid, wherein the curcuminoid is between 10-30% w/w; and (b) a solubilizer, wherein the solubilizer is selected from one or more of: (i) chlorophyllin (CHL); (ii) green tea extract; (iii) epigallocatechin gallate (EGCG); (iv) Rutin; and (v) an aromatic amino acid wherein the solubilizer is between 70-90% w/w. 27
51. The composition of claim 50, wherein the composition is encapsulated.
52. The composition of claim 50, wherein the composition is encapsulated with pharmaceutically acceptable lubricants and fillers.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US62/564,819 | 2017-09-28 |
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