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"Bio Potentiated Beta Carotene Composition With Enhanced Bioavailability And Efficacy"

Abstract: The present invention relates to highly bioavailable beta-carotene compositions and environmentally benign method for the preparation thereoenvironmentally benign and simple process for preparation thereof. The bio-potentiated beta carotene composition is useful in the nutritional supplement preferably in eye health and immune health.f. Particularly, the invention pertains to bio-potentiated beta-carotene composition, wherein the bioavailability and solubility of beta-carotene is improved by using natural bio-potentiator. Further it describes the

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
29 December 2017
Publication Number
37/2020
Publication Type
INA
Invention Field
BIO-CHEMISTRY
Status
Email
Parent Application
Patent Number
Legal Status
Grant Date
2024-04-15
Renewal Date

Applicants

ZeusHygia Lifesciences Private Ltd.
FIRST FLOOR, PLOT NO. 47, RAVIRAJA INDUSTRIES, TECHNOCRATS INDUSTRIAL ESTATE, BALANAGAR, HYDERABAD, TELANGANA - 5000037, INDIA.

Inventors

1. Jeyakodi,Shankaranarayanan
Geetha Palace-II,Plat No.104/1A, Flat No.302, Sector 8A, Airoli, Navi Mumbai, Maharashtra India- 400708
2. Nair,Arunkanth Krishnakumaran
FIRST FLOOR, PLOT NO. 47, RAVIRAJA INDUSTRIES, TECHNOCRATS INDUSTRIAL ESTATE, BALANAGAR, HYDERABAD, TELANGANA - 5000037, INDIA.

Specification

Technical Field: The present invention relates to highly bioavailable beta-carotene compositions and environmentally benign method for the preparation thereof. Particularly, the invention pertains to bio potentiated beta-carotene composition, wherein the bioavailability and solubility of beta-carotene is improved by using natural bio-potentiator. Further it describes the environmentally benign and simple process for preparation thereof. The bio-potentiated beta carotene composition is useful in the nutritional supplement preferably in eye health and immune health. Prior art and Background: Certain functional nutrients have been discovered to have beneficial health effects. Lipophilic nutrients form an important part of the human diet and prescribed by nutritionists for curing certain deficiencies in the body. Owing to their lipophilic nature, these nutrients exhibit low aqueous solubility and permeability through body membranes. Since the gastrointestinal tract is an aqueous environment, and smee only dissolved molecules can be taken up by the body, these nutrients often show limited bioavailability. O Lipophilic carotenoid nutrient is at least one selected from the group consisting of lutein, lutein esters, alpha carotene, beta-carotene, zeaxanthin, mesozeaxanthin, betacryptoxanthin, zeaxanthin esters, astaxanthin, lycopene and mixtures thereof. Among the carotenoids that can be converted to vitamin A in the human body, so-called 'provitaminA carotenoids', beta-carotene is the most abundant and most efficient one found in foods. Beta-carotene plays vital biological roles that may be independent of its provitaminA status. Beta carotene is a member of the carotenoid family belonging to the isoprenoid compounds, which are polyunsaturates with antioxidant properties. The formula for beta carotene is C4oHs6 and it can exist as cis- or trans-isomers. Most of the naturally-occurring and synthesized forms of beta exists as the all-trans isomer. Beta-carotene is a pigment found in plants that gives yellow and orange fruits and vegetables their color. It's converted in the body to vitamin A, a powerful antioxidant that plays a critical role in maintaining healthy vision, skin and neurological function. It is essential for normal growth and development, immune system function, and vision. High intake of beta carotene foods helps to relieve respiratory ailments, Consumption of adequate levels of beta carotene (15mg) along with other nutrients can slow down the progression of age related macular degeneration (ARMD).Beta carotene strengthens immune system of human body by activating the thymus gland which is one of the most important sources of immune protection. Further foods containing beta carotene or supplements can be coupled with sunscreen to enhance its effectiveness. It protects the skin against damage also useful for hair growth. Having such multiple applications, the use of beta carotene is restricted in nutritional, pharmaceutical, food sectors due to its poor bioavailability and solubility. Bioaccesability of beta-carotene is also improved by using long chain triglyceride,nano-emulsions, and bioenahncers. US5744161A discloses that bioavailability of beta-carotene enhanced by adding effective amount of a bioavailability enhancer comprising at least 98% of the alkaloid piperine. WO2004067018A8 relates to composite bioenhancer comprising an effective amount of an aqueous extract or a bioactive fraction of Carumcarvi and at least one other bioenhancer useful for enhancing the bioavailability of a drug, neutraceutical, vitamin, antioxidant, natural herbal products and essential nutritional components. US6007856 relates to oil-in-water dispersions of (3-carotene and other carotenoids that are stable against oxidation which are prepared from water-dispersible beadlets comprising higher concentrations of colloidal p-carotene. Ratndeep Singh et al (Phcog Rev. Vol, 3, Issue 5, 80-82, 2009) are reported some of the herbal bioenhancers and their applications in human and veterinary practices such as Ginger, Niaziridin, Glycyrrhizin., Cumin, Aloe vera etc.. Bharat Jhanwar et al in (International journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.6, No.2, pp 443-454, April-June 2014) describe bioenhancers with their brief mechanism of action and pharmacotherapeutics application when supplemented with therapeutic ingredients. Shailendra Wadhwa et al. (A Review. Asian Journal of Biomedical and Pharmaceutical Sciences; 04 (36); 2014,1-8.) report bioavailability enhancing property of piperine towards poorly bioavailable drugs. Poor bioavailable drugs remain sub-therapeutic because a major portion of a dose never reaches the plasma or exerts its pharmacological effect unless and until very large doses are given which may lead to serious side effects. Any significant improvement in bioavailability will result in lowering the dose or the dose frequency of that particular drug. Several approaches have been adopted in the past to maximize oral bioavailability controlled release formulation, using complexing agent, surfactant, nano emulsion, particle size reduction, prodrugs. Among all the approaches use of bioenhancers seems to be a fruitful method for bioenhancement of an orally administered pharmaceutical compound/ nutrient and leads to improved formulation. Based on a traditional system of Indian medicine, bioenhancers constitute modern theory and sensible use of them can lead to reductions in drug cost, toxicity, environmental impact and other adverse effects. Present day research on natural occurring actives preferably nutrients that exhibit poor bioavailability demands the use of an ideal bioenhancer which should be safe, effective, economical, easily procured, non-addictive etc. To fulfill the need of improvement of bioavailability of lipophilic nutrients the present invention provides natural bio-potentiator to enhance the bioavailability and solubility of poorly water soluble nutrients along with the therapeutic efficacy thereof. The composition containing natural bio-potentiator with enhanced bioavailability and efficacy of active nutrient, unlocks new prospect in pharmaceutical and healthcare sector. Further the reduced dose and cost along with safety and efficacy is the unique benefit of present composition. Summary: In an aspect the invention provides, the composition of poorly water soluble nutrients coupled with natural biopotentiator to enhance bioavailability and efficacy of nutrient. In another aspect the invention provides, the Cytochrome P450 3A (CYP3A) inhibitors as biopotentiator derived from natural resources to enhance the bioavailability of poorly soluble carotenoids. Moreover it describes the Cytochrome P450 3A [CYP3A) inhibitors combination with therapeutically active beta-carotene. In yet another aspect the invention provides, the bio-potentiated beta carotene composition with high bioavailability and efficacy, wherein the bio-potentiator is Naringin. In yet another aspect the invention affords, the environmentally benign and simple, cost effective process for preparation of bio potentiated beta carotene composition. In another aspect the invention offers, the application of said beta carotene composition as nutritional supplement particularly in eye health and immune health. Detailed Description: A bio-potentiator is an agent capable of enhancing bioavailability and efficacy of active substance with which it is co-administered, without any pharmacological activity of its own at therapeutic dose used. It increases bioavailability of active across the membrane of enhancing bioavailability and bioefficacy of a particular drug with which it is combined. Biopotentiators can belong to any of the classes based on their mechanism of action by which they increase the bioavailability of active compounds/drugs/ nutrients and vitamins etc. According to the invention the term 'bio-potentiator 'refers to an agent or element used for enhancing the bioavailability and efficacy of water insoluble or fat soluble active nutrients. In an embodiment the present invention provides, the use of bioenhancer to enhance bioavailability and efficacy of poorly water soluble or fat soluble nutrients. The poorly water soluble or fat soluble nutrients consisting of carotenoids, vitamins, omega fatty acids, glycerides, capsaicin, curcumin, Co- Enzyme Q-10; wherein the poorly water soluble carotenoid nutrientsare selected from the group consisting of lutein, lutein esters, alpha carotene, beta-carotene, zeaxanthin, mesozeaxanthin, betacryptoxanthin, zeaxanthin esters, astaxanthin, lycopene and mixtures thereof. In preferred embodiment the poorly water soluble nutrient used in the invention is beta carotene. In another embodiment of the invention, the bio-potentiator can be selected from the group consisting of Solubilizers, P-GP inhibitors, CYP3A4 inhibitors, BCRP inhibitors, Permeability enhancers, Lysergol, Cow urine distillate, Nitrile glycoside, Glycyrrhizin. The Inhibitors of cytochrome P450 3A drug biotransformation as bio-potentiator are hitherto unexploited category of bio-potentiator in nutritional domain, whereinCYP450 are composed of at least 207 genes that have been named based on the evolutionary relationships of the cytochromes P450. Inhibition of CYP3A by bio-potentiator in gut epithelia will lead to a total increase in drug bioavailability in the serum. In an another preferred embodiment, the invention provides environmentally benign process for the preparation of bio-potentiated beta carotene composition with high bioavailability, wherein the process comprises steps of; a) Preparing aqueous solution of polymer under constant stirring at elevated temperature; b) Preparing organic solution of fat soluble active nutrient in presence of antioxidant and organic solvent and cytochrome P 450 (CYP) enzyme inhibitor ; c) Mixing of organic solution of step b) to aqueous solution of step a] under stirring to get homogenous emulsion; d} Spray drying the emulsion under optimum condition to obtain fine particles; In another embodiment, the use of non-polar solvent to solubitize fat soluble active nutrient is optional, wherein the fat soluble active nutrient can be used in aqueous phase in presence of suitable surfactant to enhance the solubility of active nutrient in water. The surfactants employed in the invention may be ionic or nonionic and selected from the group consisting of Tween 20, Tween 40, Tween 80,Dimethyl sulfoxide. Sodium Lauryl Sulphate, Triethanolamine, Glycerol esters and like thereof. In another embodiment, the bio-potentiated beta carotene composition can be further formulated in beadlets, wherein the process comprises additional step of coating of homogenized emulsion on non-pareil seeds under optimum condition. Non-Pareil Seeds or Placebo pellets are spherical particles of uniform diameter which are practically inert. They are mainly composed of Sugar pellets [Sugar Spheres) .Cellulose pellets ,Mannitol pellets , Potato Starch Pellets (Starch Spheres). In one embodiment of the invention, the fat soluble active nutrient of the invention is not limited to beta carotene but it can also be selected from alpha-carotene, beta- carotene, 8'- apo-beta-carotenal, 8'-apo-beta-carotenoic acid esters, canthaxanthin, astaxanthin, astaxanthin ester, betacryptoxanthin, tycopene, lutein, lutein (di) ester, zeaxanthin or crocetin, mesozeaxanthin, alpha or beta-zeacarotene or mixtures thereof), curcumin, vitamins (A, D, E, K, CoQ 10) or esters or derivatives thereof, capsaicin, dihydrocapsaicin, derivatives thereof, polyunsaturated fatty acids (PUFAs) or derivatives thereof, and triglycerides rich in polyunsaturated fatty acids such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or gamma-linolenic acid (GLA), Omega 3, Omega 6 oils or derivatives thereof, extracts of Terminalia. Salacia, Green coffee, and or mixtures thereof. In another embodiment, the polymer used in the composition is preferably water soluble polymer which is not limited to starch but also cellulose, polyethylene glycols, cellulose ethers, casein, gelatin, xanthan gum, guar gum, carrageenan, and pectin and like thereof, wherein concentration of polymer with respect to active nutrient ranges from 1:5 to 1: 8. Particularly the modified starch gives desired matrix formation for poorly soluble carotenoids. In another embodiment of the invention, the organic solvents are polar or non-polar solvents wherein non-polar solvents are selected from the group consisting of hexane, dichloromethane, toluene, ether , esters , chloroform , pentane or combination thereof, and polar solvents are Tetrahydrofuran (THF), Ethyl acetate, Acetone, Dimethylformamide[DMF), Acetonitrile (MeCN), Dimethyl sulfoxide (DMSO), Isopropy! alcohol (IPA), n-propanol,n- butanol, ethanol, methanol, Acetic acid,polar acid and water or combinations thereof. According to the invention the concentration of organic solvent used in the ratio of 1:10 to 1:20 with respect to beta carotene. In another preferred embodiment of the invention, the Cytochrome P450 3A (CYP3A) inhibitors are used as bio-potentiators. It may be selected from the group consisting of

Documents

Orders

Section Controller Decision Date
Section 15 Vijay T. Doye 2023-08-18
section 15 Vijay T. Doye 2024-04-15

Application Documents

# Name Date
1 Form2 Title Page_Provisional_29-12-2017.pdf 2017-12-29
2 Form 1_As Filed_29-12-2017.pdf 2017-12-29
3 Description Provisional_As Filed_29-12-2017.pdf 2017-12-29
4 Correspondence by Applicant_ As Filed_29-12-2017.pdf 2017-12-29
5 Abstract_As Filed_29-12-2017.pdf 2017-12-29
6 Form5_After Provisional_24-12-2018.pdf 2018-12-24
7 Form3_After Provisional_24-12-2018.pdf 2018-12-24
8 Form2 Title Page_Complete_24-12-2018.pdf 2018-12-24
9 Drawings_After Provisional_24-12-2018.pdf 2018-12-24
10 Description Complete_After Provisional_24-12-2018.pdf 2018-12-24
11 Correspondence by Applicant_After Provisional_24-12-2018.pdf 2018-12-24
12 Claims_After Provisional_24-12-2018.pdf 2018-12-24
13 Abstact_After Provisional_24-12-2018.pdf 2018-12-24
14 201741047150-FORM-26 [21-09-2020(online)].pdf 2020-09-21
15 201741047150-FORM 18 [21-09-2020(online)].pdf 2020-09-21
16 201741047150-FER.pdf 2021-10-17
17 201741047150-FORM FOR SMALL ENTITY [23-01-2022(online)].pdf 2022-01-23
18 201741047150-FER_SER_REPLY [23-01-2022(online)].pdf 2022-01-23
19 201741047150-EVIDENCE FOR REGISTRATION UNDER SSI [23-01-2022(online)].pdf 2022-01-23
20 201741047150-US(14)-HearingNotice-(HearingDate-25-05-2023).pdf 2023-05-11
21 201741047150-Correspondence to notify the Controller [21-05-2023(online)].pdf 2023-05-21
22 201741047150-Written submissions and relevant documents [09-06-2023(online)].pdf 2023-06-09
23 201741047150-Annexure [09-06-2023(online)].pdf 2023-06-09
24 201741047150-Information under section 8(2) [26-07-2023(online)].pdf 2023-07-26
25 201741047150-Response to office action [02-08-2023(online)].pdf 2023-08-02
26 201741047150-Annexure [02-08-2023(online)].pdf 2023-08-02
27 201741047150-NBA INTIMATION TO APPLICANT COMPLY WITH REQUIREMENT-18-08-2023.pdf 2023-08-18
28 201741047150-PatentCertificate15-04-2024.pdf 2024-04-15
29 201741047150-NBA Approval Submission [15-04-2024(online)].pdf 2024-04-15
30 201741047150-IntimationOfGrant15-04-2024.pdf 2024-04-15
31 201741047150-FORM FOR SMALL ENTITY [04-07-2024(online)].pdf 2024-07-04
32 201741047150-EVIDENCE FOR REGISTRATION UNDER SSI [04-07-2024(online)].pdf 2024-07-04

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