Claims:We Claim:
1. A composition to increase the bioavailability of curcuminoid, the composition comprising:
a. a polar molecule, wherein the polar molecule comprises aqueous extract of turmeric at a concentration in the range of 42%-46%; and
b. a plurality of non-polar molecules, wherein non-polar molecules comprise an essential oil at the concentration in the range of 3%-6% and curcuminoids at the concentration of 50%-55%.
2. The composition as claimed in claim 1, wherein the essential oil is extracted from turmeric.
3. The composition as claimed in claim 1, wherein the composition passes through a lipid membrane as curcuminoid is lipidic in nature thus decreasing the rate of absorption of curcuminoid.
4. A method (200) for preparing curcuminoid composition, the method comprising the steps of:
a. grinding 95% curcuminoid and micronizing in a mill (201);
b. mixing a polar fraction of aqueous extract of turmeric with a non-polar fraction of turmeric essential oil to form a mixture (202);
c. micronizing the mixture with curcuminoid using a bead milling allowing to form a polar-nonpolar soup (203);
d. grinding the polar-nonpolar soup with curcuminoid to form a powder (204);
e. converting the powder into an emulsion using water (205); and
f. spray drying and granulating the emulsion (206).

5. The method as claimed in claim 4, wherein the concentration of aqueous extract of turmeric is in the range of in the range of 42%-46%.
6. The method as claimed in claim 4, wherein the concentration of essential is in the range of 3%-6% and curcuminoids at the concentration of 50%-55%.
7. The method as claimed in claim 4, wherein the method allows sandwich of curcuminoid between a polar and plurality of non-polar molecules.
8. The method as claimed in claim 4, wherein the method allows the controlled release of curcuminoid into a blood stream thus increasing the bioavailability.
, Description:[0001] PRIORITY CLAIM
[0002] This is an application for patent of addition for the patent application numbered 3646/CHE/2013 filed with Indian patent Office, Chennai on 19th August 2013 entitled “A novel composition of curcumin with enhanced bioavailability”, the entirety of which is expressly incorporated herein by reference.
[0003] Preamble to the Description
[0004] The following specification describes the invention and the manner in which it is to be performed:
[0005] DESCRIPTION OF THE INVENTION
[0006] Technical field of the invention
[0007] The present invention relates to a composition to increase the bioavailability of natural curcuminoids using the combination of polar and non-polar molecules. The present invention particularly describes the mechanism to increase the bioavailability of curcuminoids using a unique blend of polar and non-polar matrices to increase the absorption of the active molecule.
[0008] Background of the invention
[0009] Bioavailability refers to an extent and rate at which the active molecule enters systemic circulation, thereby accessing the site of action. Bioavailability is a measure of absorption and is the fraction of the administered dose of unaltered drug that enters the systemic circulation. The bioavailability of the active ingredient or any biological molecule varies with the mode of administration, type of the active molecule, physicochemical properties of the drug and the presence of excipients etc.
[0010] Bioavailability of a component varies with the mode of administration. When a medication is administered intravenously, its bioavailability is nearly 100%. However, when the medication is administered through alternative routes, its bioavailability generally decreases due to incomplete absorption and first-pass metabolism of the drug. The bioavailability also varies with individual. Bioavailability is one of the essential tools in pharmacokinetics and must be considered while calculating dosages for non-intravenous routes of administration. Bioavailability of a drug is largely determined by the properties of the dosage form, which depends partly on its design and manufacture. Differences in bioavailability of formulation of a given drug may also have clinical significance and hence it is essential to know the equivalence of the formulation.
[0011] The reasons for low bioavailability of any molecule are poor absorption, high rate of metabolism resulting in rapid rate of elimination and clearance from the human body. Orally administered drugs exhibit low bioavailability. Orally administered drugs must pass through the intestinal wall and then to the portal circulation to the liver, both are common sites of first-pass metabolism. Thus, many drugs are metabolized before adequate plasma concentrations are reached. Low bioavailability is most common with oral dosage forms of poorly water-soluble, slowly absorbed drugs.
[0012] Curcuminoid is isolated from the popular Indian spice Curcuma longa commonly known as turmeric. Curcuminoid is derived from the rhizome of Curcuma longa and traditionally known for its use in treatment of skin wounds, inflammation, etc. and also as antiseptic, antioxidant, anti-inflammatory, anti-angionenic and immunomodulatory effects. Curcuminoid is also used as an active ingredient in various formulations.
[0013] Bioavailability of curcuminoid is an important aspect to be considered for the formulations containing curcuminoid as the active ingredient. Curcuminoid exhibits low bioavailability due to its short half-life, low serum concentration, tissue distribution, rapid metabolism etc.
[0014] Liver is the major organ involved in the metabolism of curcuminoids. For example, curcuminoid undergoes various chemical reactions such as sulfation, glucuronidation etc. resulting in formation of different metabolites. However, these metabolites are less active compared to curcuminoid and hence the activity of the curcuminoid is lost after metabolism.
[0015] The low bioavailability of curcuminoid is also due to insufficient time for absorption in the gastrointestinal tract. If the drug does not dissolve readily or cannot penetrate the epithelial membrane due to high rate of ionization or polarity, time at the absorption site may be insufficient leading to low bioavailability.
[0016] The following components describe the different steps of the metabolic pathway, which result in altered bioavailability:
1. Release of the drug from the physicochemical dietary matrix;
2. Effects of digestive enzymes in the intestine;
3. Binding and uptake by the intestinal mucosa;
4. Transfer across the gut wall (passing through the cells, in-between them or both) to the blood or lymphatic circulation;
5. Systemic distribution and deposition;
6. Metabolic and functional use; and
7. Excretion
[0017] In addition to the above factors, other factors such as age, gender, genetic phenotype, stress also influence bioavailability of the active molecule.
[0018] Physical agents or chemical reactions that reduce the rate of absorption increase the bioavailability of the active ingredient. The chemical reactions include formation of a complex between tetracycline and polyvalent metal ions, hydrolysis by gastric acid or use of digestive enzymes such as penicillin and chloramphenicol palmitate hydrolysis, conjugation in the intestinal wall such as sulfoconjugation of isoproterenol, adsorption to other drugs such as digoxin to cholestyramine and also metabolism by luminal microflora.
[0019] In addition to this, systemic excretion of curcuminoid from the body is also a major factor for low bioavailability of curcuminoid.
[0020] To overcome the problem of low bioavailability of curcuminoid, different formulations and approaches were proposed, which includes the use of adjuvants such as nanoparticles, liposomes, micelles, phospholipids etc. The adjuvants usually increase the bioavailability of curcuminoid by blocking the metabolic activity.
[0021] The US patent application numbered US 12/073,864 titled “Composition to enhance the bioavailability of curcumin” discloses a composition containing purified curcuminoid and purified essential oil for enhanced bioavailability of curcumin. The application also discloses a method to prepare a composition for enhanced bioavailability of curcumin. The composition comprises curcuminoid mixture consisting of demethoxycurcumin and bisdemethoxycurcumin and the essential oil ar-turmerone. The percentage of curcuminoid mixture used is in the range between 24% to 96% and the essential oil in the range between 4%-50%. The dosage is suitable for oral administration and is in the form of a gelatin capsule. The application also discloses the method of extraction of curcuminoid from turmeric and also a method of preparing the composition including a curcuminoid and the essential oil of turmeric. The application also tabulates the results of bioavailability of curcumin in human volunteers. Even though the bioavailability is increased in blood, the application is silent with respect to prevention or elimination of curcumin from blood and also with respect to the stability of curcumin in blood.
[0022] The US patent application numbered US 13/645,031 titled “Formulation of Curcumin with Enhanced Bioavailability of Curcumin and Method of Preparation and Treatment Thereof” discloses a formulation of curcuminoid with essential oil of turmeric to enhance the bioavailability of curcumin and to augment the biological activity of curcumin. The application also discloses a method of preparation of curcuminoid formulation and also oral supplementation for treatment of various diseases. The formulation of curcuminoid mixture comprises curcumin, demethoxycurcumin and bisdemethoxycurcumin and essential oil ar-turmerone. The application evidenced increased bioavailability in human volunteer. Even though the patent application confirms the enhanced bioavailability in the range between 5-16 fold, the application is silent with respect to the stability of curcumin in blood.
[0023] Even though different formulations and methods are disclosed in the state of art to increase the bioavailability of curcuminoid using different adjuvants etc., the bioavailability of the curcuminoid is not increased significantly.
[0024] Hence, there is need for a different technology to increase the bioavailability of curcuminoid and other active ingredients.
[0025] Summary of the invention
[0026] The present invention relates to a composition to increase the bioavailability of natural curcuminoid using the combination of polar and non-polar molecules. The present invention particularly describes the mechanism to increase the bioavailability of curcuminoid using a unique blend of polar and non-polar matrices to increase the absorption of the active molecule.
[0027] The composition of the present invention includes the polar molecules and non-polar molecules. The polar molecule comprises an aqueous extract of turmeric at the concentration in the range of 42% to 46%. The non-polar molecules comprise turmeric essential oil and aromatic curcuminoid at the concentration in the range of 3% to 6% and 50% to 55% respectively. The polar molecules comprise aqueous extract of turmeric mainly comprising protein, dietary fiber, and carbohydrate.
[0028] The present invention further discloses a method of preparation of polar-nonpolar composition. The polar-nonpolar composition is called as polar-nonpolar soup and curcuminoid is sandwiched in polar-nonpolar soup, in which curcuminoid is protected as a single molecule. The method of preparation of polar-nonpolar composition involves grinding 95% curcuminoid and micronizing in a mill. The polar fractions of aqueous extract of turmeric are mixed with non-polar fractions of turmeric essential oil to form a mixture and the mixture is micronized using bead milling together with curcuminoid. The curcuminoid is sandwiched between the polar and non-polar matrices to obtain a curcuminoid composition. The polar-nonpolar soup with curcuminoid is grinded to form a powder, which is converted into an emulsion using water. Finally, the emulsion is spray dried and granulated. The composition easily passes through the lipid membrane as curcuminoid is lipidic in nature thus increasing the rate of absorption.
[0029] This novel concept of sandwiching the active ingredient with polar and non-polar matrices results in increased absorption and thus increased bioavailability of the active ingredient. The concept of formulating the curcuminoid or other active ingredients with polar and non-polar matrices is useful to improve the bioavailability of the active ingredients.
[0030] Brief description of drawings
[0031] FIG 1 illustrates the composition of polar and non-polar molecules.
[0032] FIG 2 illustrates the flow chart for the method of preparation of polar-nonpolar composition.
[0033] Detailed description of the invention
[0001] In order to more clearly and concisely describe and point out the subject matter of the claimed invention, the following definitions are provided for specific terms, which are used in the following written description.
[0034] The term “Bioavailability” means one of the principal pharmacokinetic properties of any compound. It is the measure of presence of drug in the systemic circulation once the drug is administered.
[0035] The present invention discloses a novel composition to improve the bioavailability of curcuminoid and other active ingredients using the polar-non-polar conjugation matrices.
[0036] In order to achieve good bioavailability, the nutrient molecule should have stability in the blood stream and must traverse the inner intestinal wall to access the blood stream. In order to achieve this, the nutrient molecule must pass through the walls of surface epithelial cells, followed by walls of the capillaries. Generally, the cell walls are made up of lipids and the molecules which are easily absorbed by them are termed as ‘fat soluble molecules’.
[0037] Curcuminoid is a fat soluble molecule and hence accumulates in the form of relatively large, undissolved particles rather than as individual molecule in the cell walls resulting in poor absorption.
[0038] The present invention discloses the use of combination of polar and non-polar molecules to increase the bioavailability of the curcuminoid. The composition of curcuminoid comprises combination of polar and non-polar molecules and curcuminoid is sandwiched between the polar and non-polar molecules to form a matrix. The matrix withheld the curcuminoid and gradually releases into the blood stream.
[0039] FIG 1 illustrates the composition of polar and non-polar molecules. The polar molecules comprise aqueous extract of turmeric at the concentration in the range of 42% to 46%. The non-polar molecules comprise turmeric essential oil and curcuminoids at the concentration in the range of 3% to 6% and 50% to 55% respectively. The polar molecules comprise aqueous extract of turmeric mainly comprising protein, dietary fiber, and carbohydrate. The essential oil is extracted from pure form of turmeric using steam distillation method.
[0040] FIG 2 illustrates the flow chart for the method of preparation of polar-nonpolar composition. The polar-nonpolar composition is called as polar-nonpolar soup and curcuminoid is sandwiched in polar-nonpolar soup, in which curcuminoid is protected as a single molecule. The method (200) of preparation of polar-nonpolar composition starts at step (201) of grinding the 95% curcuminoid and micronizing in a mill. At step (202), polar fractions of aqueous extract of turmeric are mixed with non-polar fractions of turmeric essential oil to form a mixture. At step (203), the mixture is micronized using bead milling together with curcuminoid. In this step, curcuminoid is sandwiched between the polar and non-polar matrices to obtain a curcuminoid composition. At step (204), the polar-nonpolar soup with curcuminoid is grinded to form a powder. At step (205), the powder is converted into an emulsion using water. The emulsion is water soluble in nature and makes the curcuminoid as a single molecule without forming an aggregate. At step (206), the emulsion is spray dried and granulated.
[0041] The composition easily passes through the lipid membrane as curcuminoid is lipidic in nature thus decreasing the rate of absorption.
[0042] The present invention discloses a composition of curcuminoid with polar and non-polar molecules to overcome the low bioavailability. This novel concept of sandwiching the active ingredient with polar and non-polar matrices results in increased absorption and thus increased bioavailability of the active ingredient.
[0043] The concept of formulating the curcuminoid or other active ingredients with polar and non-polar matrices is useful to improve the bioavailability of the active ingredients. The present invention is useful in preparation of various compositions, which consists of active ingredient with low bioavailability.
[0044] The present invention is not only restricted to the use of curcuminoid as active ingredient. The present invention is also applicable for other active ingredients to improve the bioavailability.