Patent Application
20190083565
The present disclosure generally relates to the field of processed pharmaceutical and nutraceutical additives. More particularly, the present disclosure relates to enhanced solubility leading to increased bioavailability of curcuminoids for effective usage in applicable areas.
Curcumin (1,7-bis [4-hydroxy-3methoxyphenyl]-1,6-heptadiene-3,5-Dione) is the principal curcuminoid of turmeric, which is a member of the ginger family (Zingiberaceae). Curcuminoid is an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcuminoid is obtained by extraction with solvent from the rhizome of Curcuma longa dried, and the extract must be separated from the flavourings i.e purification by crystallisation. It is accompanied by small amounts of its demethoxy- and bis-demethoxy-derivatives. As a group these compounds and their derivatives for pharmaceutical use are referred to as curcuminoids.
There have been recent evidences through studies conducted on the use of curcuminoids as dietary supplement in treating a variety of clinical disorders. Medicinal use of curcuminoids have been limited because the compound is virtually insoluble (dissolution of only ca. 600 ng/mL) in water at acidic and physiological pH and hydrolyzes rapidly at alkaline pH. Plasma concentrations from high human oral doses (8-12 g/day) of curcuminoids are just in the nano molar range.
Various clinical trials have shown that curcuminoids exhibit very poor bio-availability. Major reasons contributing to the low plasma and tissue levels of curcuminoids appear to be due to poor water solubility, poor absorption, rapid metabolism, and rapid systemic elimination.
Despite the lower bio-availability, therapeutic efficacy of curcuminoids against various human diseases, including cancer, Alzheimer's disease, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented.
Curcuminoids are water insoluble (Solubility: 0.6 mcg/ml), so application in aqueous based foods, beverages is not feasible. Moreover, due to insolublity in water, absorption of curcuminoids is very low. So improvement in solubility of curcuminoids in water is desirable to get wide range of benefits. Disadvantages of existing products in market are explained below:
Most of the products (Capsules & Tablets) are required to take up more doses up to 1-2 g/day due to low bioavailabilty.
Some of the products are in nano form, but still in water dispersible form which may hinder absorption. Some products are water soluble powder form, but not feasible for some applications as turbidity issues are not being addressed due to improper solubility.
Chinese patent number CN100352430C discloses curcuminoids in the form of micro emulsion formulation and a preparation process for the same. The formulation consists of curcuminoids, surface active agents, surfactants, oil phase and a solid sorbent composition and can be made into capsules or granules for oral administration. Post entering the body it is believed that under the influence of self-micro emulsifying gastrointestinal fluid forming droplets the nano particle size of 100nm or less, one can increase the solubility of curcuminoid and promote its absorption in the gastrointestinal tract to improve bioavailability.
WO 2013171270 discloses gastro resistant formulations of curcuminoid combined with absorption promotors (chitosan, black pepper extract, N-acetylcysteine, grapefruit extract). Said formulations are not controlled-release or extended-release formulations.
US 20140161915 discloses a process for solubilizing and stabilizing curcuminoid in an aqueous solution, comprising: (a) providing a quantity of water; (b) providing over 0.008 mg curcuminoids per mL water; (c) optionally providing at least 0.01 ml lower alcohol per ml of water; (d) optionally providing at least 0.01 ml polyalkyleneoxide per ml of water; (e) 6 combining the water, curcuminoid and optional lower alcohol in any order and optionally with mixing; and (f) heating the combined water, curcuminoid and optional lower alcohol to a temperature in excess of 100%, optionally at a pressure exceeding 1 atmosphere; wherein steps (a), (b) and (c) may be done in any order, and wherein the process includes at least one of combining the lower alcohol or optional polyalkyleneoxide in step (e) and applying a pressure exceeding 1 atmosphere in step (f).
US 2011/0274809 disclose a method for masking curcuminoid flavour which comprises mixing curcuminoids with a modified starch.
CN101361713B discloses the invention relates to a curcuminoid nano crystal formulation and a preparation thereof. The nano crystal can increase the solubility of the curcuminoid, promote the absorption thereof in gastrointestinal tract and improve bioavailability.
WO2014/111956 discloses a sustained release curcuminoid composition comprising a bioavailable curcuminoid composition and a release rate controlling excipient.
CN103442703B/U.S. Pat. No. 9,259,401B2 discloses water-soluble composition having enhanced bioavailability useful for the treatment of depression comprising curcuminoid, a synergistic combination of at least one anti-oxidizing agent, a hydrophilic carrier and fats.
In the light of aforementioned discussion there exists a need of enhanced water solubility in turn increasing the bio-availability of curcuminoid in order to bring curcuminoid and its derivatives to the forefront of therapeutic agents for treatment of various diseases.
The following presents a simplified summary of the disclosure in order to provide a basic understanding to the reader. This summary is not an extensive overview of the disclosure and it does not identify key/critical elements of the invention or delineate the scope of the invention. Its sole purpose is to present some concepts disclosed herein in a simplified form as a prelude to the more detailed description that is presented later.
An exemplary objective of the present disclosure is, to provide water soluble formulation of curcuminoids, preferably in liquid form without using any organic solvents to enhance bioavailability of curcuminoids in vivo.
Another objective according to an exemplary embodiment of the present disclosure is, to provide an amorphous form of water soluble formulation of curcuminoids in order to achieve higher solubility resulting in higher bioavailability.
Another objective according to an exemplary embodiment of the present disclosure is, to provide water soluble formulation of curcuminoids, to facilitate easy miscibility with water, aqueous based beverages, foods, and dietary supplements and to eliminate problem of sedimentation which is associated with dispersible formulations in beverage application with existing products in the market.
Yet another objective according to an exemplary embodiment of the present disclosure is, to provide water soluble formulation of curcuminoids, using excipients having E-Number/generally recognised as safe (GRAS) status that ensures safety of human beings for long term administration.
Further objective of the present invention is to provide water soluble formulation of curcuminoids, preferably in liquid form with easy process to reduce the cost and time of the process.
An exemplary aspect of the present subject matter is, to provide a water soluble formulation of curcuminoids and methods employed thereof.
Another exemplary aspect of the present subject matter is to provide water soluble formulation of curcuminoids in an amorphous form and high storage stability.
Another exemplary aspect of the present subject matter is to provide water soluble formulation of curcuminoids capable of acting as natural colourants for consumables and being non-carcinogenic.
Yet another exemplary aspect of the present subject matter is to provide water soluble formulation of curcuminoids required in low dosage due to enhanced bioavailability.
Other objects and advantages of the present invention will become apparent to those skilled in the art upon reading the following detailed description of the preferred embodiments, in conjunction with the accompanying drawings, wherein like reference numerals have been used to designate like elements, and wherein:
It is to be understood that the present disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The present disclosure is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.
The use of “including”, “comprising” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. The terms “a” and “an” herein do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced item. Further, the use of terms “first”, “second”, and “third”, and the like, herein do not denote any order, quantity, or importance, but rather are used to distinguish one element from another.
The present disclosure provides water soluble formulations of Curcuminoids comprising of;
The terms “curcuminoid” and “curcuminoids” used herein refers to one or a mixture of curcuminoid, demethoxy curcuminoid, and bis demethoxy curcuminoid.
The Surfactants and/or Emulsifiers used are selected from sodium lauryl sulfate, Polysorbate 80 (Tween 80), docusate sodium or mixture thereof and the like without limiting the scope of the disclosure. The vehicles incorporated may include but not limited to Purified Water, Polyethylene Glycol, preferably PEG 400, and Propylene Glycol, Polysorbate 80 or mixture thereof. The hydrophilic polymers used are selected from hydroxy propyl methyl cellulose, polyvinyl pyrollidone, Copovidone (vinylpyrrolidone-vinyl acetate copolymer) or mixture thereof and the like without limiting the scope of the disclosure.
The preservatives used are selected from sodium benzoate, benzoic acid, potassium sorbate, sodium sorbate or mixture thereof and the like without limiting the scope of the disclosure. The acidulants used may include but not limited to citric acid, acetic acid, lactic acid, malic acid, tartaric acid or mixture thereof. The overages are added which may be less than 1% of the total formulation.
An exemplary embodiment for the composition for the manufacture of water soluble formulation of curcuminoids is represented in the following table:
Referring to
The water soluble formulation of curcuminoids is in the form of viscous liquid can be easily soluble/miscible in aqueous based beverages, foods, cosmetics and pharmaceutical products. The water soluble formulation of curcuminoids is in the form of viscous liquid enabled to provide a light yellow to orange shades as colorant.
The water soluble formulation of curcuminoids in the form of viscous liquid when dissolved provides clear solutions in water, with almost nil undissolved particles settled at the bottom.
The method employed for the preparation of water soluble formulation of curcuminoids transforms the crystalline form of curcuminoids to amorphous form which is soluble in water.
Referring to
The difference in the solubility pattern of native curcuminoid and water soluble formulation of curcuminoids refers to higher availability of water soluble formulation of curcuminoids. This result in higher bioavailability making the water soluble formulation of curcuminoids appropriate for pharmaceutical and nutraceutical compositions.
The increase in bioavailability leads to faster action of the drug at the site of action thus leading to more effective treatment for any specific medical condition. The higher solubility leads to clarity in the solution when mixed with water thus eliminating turbidity leading to better usage in food processing industries like beverages, aqueous based foods and the like without limiting the scope of the disclosure.
Although the present disclosure has been described in terms of certain preferred embodiments and illustrations thereof, other embodiments and modifications to preferred embodiments may be possible that are within the principles and spirit of the invention. The above descriptions and figures are therefore to be regarded as illustrative and not restrictive.
Thus the scope of the present disclosure is defined by the appended claims and includes both combinations and sub combinations of the various features described herein above as well as variations and modifications thereof, which would occur to persons skilled in the art upon reading the foregoing description.
| Number | Date | Country | Kind |
|---|---|---|---|
| 201641012270 | Apr 2016 | IN | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2017/051315 | 3/7/2017 | WO | 00 |
