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WO2018179011A1 - Composition to enhance bioavailability of natural compounds - Google Patents

Composition to enhance bioavailability of natural compounds Download PDF

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Publication number
WO2018179011A1
WO2018179011A1 PCT/IN2018/050180 IN2018050180W WO2018179011A1 WO 2018179011 A1 WO2018179011 A1 WO 2018179011A1 IN 2018050180 W IN2018050180 W IN 2018050180W WO 2018179011 A1 WO2018179011 A1 WO 2018179011A1
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WO
WIPO (PCT)
Prior art keywords
oil
composition
liquid
essential oil
natural
Prior art date
Application number
PCT/IN2018/050180
Other languages
French (fr)
Inventor
Nirvanashetty Somashekara
Sripathy RAViCHANDRAN
Nilima MOHANTY
Sanjib Kumar PANDA
Vivek Anand PARACHUR
Original Assignee
Olene Life Sciences Private Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
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Publication of WO2018179011A1 publication Critical patent/WO2018179011A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Definitions

  • the present invention relates to a bioavailable composition of natural compounds. More specifically, the invention relates to a composition which uses a synergistic combination of an essential oil and an emulsifier for enhancing bioavailability and slow release profile of the natural compounds.
  • the bioavailability of the drugs or pharmaceutical compounds is majorly based on solubility of said compounds in water, since water solubility of the natural compounds plays a major role in determining the amount of compounds which may be absorbed after oral administration.
  • Bioavailability enhancers are drug facilitators, which by themselves do not show any drug activity but when used in combination with drugs or active ingredients they enhance the activity of the drug molecule by increasing penetration of the drug across the cell membrane, potentiating the drug molecule by conformational interaction, improving the solubility of the drug molecule, and making target cells more receptive to drugs.
  • Essential oils are generally isolated from plant material by distillation methods, usually steam or hydro-distillation. Essential oils are variable mixtures of principally terpenoids, specifically monoterpenes [Cio], sesquiterpenes [C15], diterpenes [C20] and a variety of other low molecular weight aliphatic hydrocarbons (linear, ramified, saturated and unsaturated), acids, alcohols, aldehydes, acyclic esters or lactones and exceptionally nitrogen- and sulphur-containing compounds, coumarins and homologues of phenylpropanoids.
  • terpenoids specifically monoterpenes [Cio], sesquiterpenes [C15], diterpenes [C20] and a variety of other low molecular weight aliphatic hydrocarbons (linear, ramified, saturated and unsaturated), acids, alcohols, aldehydes, acyclic esters or lactones and exceptionally nitrogen- and sulphur-containing compounds, cou
  • curcumin essential oil comprising Ar-turmerone
  • emulsifiers have also proved to be effective for enhancing the bioavailability.
  • emulsifiers have also proved to be effective for enhancing the bioavailability.
  • a right blend of emulsifier(s) is necessary to achieve a better bioavailability, as can be seen from article titled "Preparation and In Vitro Evaluation of Self-Nanoemulsifying Drug Delivery System (SNEDDS) Containing Clopidogrel" by Pathak, Chirag Vilas et al in "Int. J. Pharm. Sci. Rev. Res., 25(1), Mar - Apr 2014; Article No. 02, Pages: 10-15"
  • compositions which contains natural compound(s) combined with an essential oil and an emulsifier with a view of enhancing the bioavailability of the natural compound(s) and provide an economical method for manufacturing the composition of invention.
  • Essential oil and emulsifier synergistically enhance the bioavailability of the natural compound(s).
  • the invention provides a novel pharmaceutical, nutraceutical, dietary supplement, food/feed supplement or additive and/or herbal composition which comprises of a natural compound(s), an essential oil(s) and an emulsifier(s).
  • a natural compound(s) an essential oil(s)
  • an emulsifier(s) an emulsifier(s).
  • the composition of the invention demonstrates enhanced bioavailability and also achieves slow/sustained release of the natural compound(s).
  • the enhanced bioavailability is due to the synergistic activity of the essential oil and the emulsifier, wherein essential oil has a dual purpose of aiding in enhancing the bioavailability, acting as co-solvent in the composition and directly enhancing the bioavailability as a permeation enhancer, thereby synergistically working with emulsifier to enhance the bioavailability of natural compound(s).
  • the viscosity of the synergistic composition leads to sustained release of the active ingredient.
  • the invention provides a process for preparation of the composition of the invention.
  • Fig. 1 illustrates release profile of luetin from Marigold oleoresin formulation of Example 1.
  • Fig. 2 illustrates release profile of myristicin in Nutmeg oleoresin formulation of Example 5.
  • Fig. 3 illustrates release profile of silymarin in Silymarin formulation of Example 17.
  • Fig. 4 illustrates release profile of lutein in luetin formulation of Example 18.
  • Fig. 5 illustrates release profile of 6-gingerol in Gingerol oleoresin formulation of Example 19.
  • Fig. 6 illustrates release profile of Catechin in Accacia catechu formulation of Example 20.
  • Fig. 7 illustrates release profile of Ellagic acid in Ellagic acid formulation of Example 21.
  • Fig. 8 illustrates release profile of zeaxanthin in zeaxanthin formulation of Example 22.
  • compositions which contains a natural compound(s) extracted from plant or animal source, an essential oil and an emulsifier.
  • the natural compound can also be crude or partially purified or purified or natural compound(s) containing component derived from plant or animal extract.
  • the composition of invention exhibits a synergistically enhanced bioavailability along with slow release profile of the active.
  • the present invention discloses a highly bioavailable, slow/sustained release composition
  • a highly bioavailable, slow/sustained release composition comprising of a natural compound(s), an essential oil and an emulsifier.
  • the composition of the invention may be in solid, semi-solid or liquid form.
  • the natural compound is a purified natural compound derived from plant or animal extract or crude or partially purified natural compound containing component derived from plant or animal extract.
  • the natural compound is selected from, but not limited to, liquid or semisolid/soft or solid extract, liquid or semisolid or solid oleoresins, liquid or semisolid or solid oleo gum resins, resin, resinoids and liquid or semisolid or solid gum resins, fractionated liquid extract and purified extract/compounds either alone or in combination.
  • Said natural compound may be a synthetically manufactured or obtained from a natural source.
  • the plant extract or plant oleoresin is obtained from plant source selected from, but not limited to, Boswellia serrata, Bacopa monnieri, Marigold, Ginger, Glycyrrhiza glabra, Cinnamon species, Terminalia chebula, Scutellaria baicalensis, Terminalia arjuna, Grifolia simplicifolia, Echinacea, Pinus pinaster (Maritime pine bark), Euterpe oleracea,Acacia catechu, Silybum marianum, Viscum album, Punica granatum, Camellia sinensis (Green Tea), Green coffee bean, Commiphora Mukul (Guggul), Architoke Oleoresin, Cassia fistula, Carica papaya, Centella asiatica, Cinnamomum zeylanicum, Cissus quadrangularis, Chlorophytum tuberosum, Colius forskohlii, Emblica officinalis, Eugenia
  • the animal extract is obtained from animal source selected from but not limited to Krill oil, Fish oil, Squalamine etc.
  • liquid or semisolid or solid oleoresins including, but not limited to Clove Oleoresins, Curry leaf Oleoresins, Pepper Oleoresins, Cardamom Oleoresins, Chilli Oleoresins, Capsicum Oleoresins, Paprika Oleoresins, Ginger Oleoresins, Coleus Oleoresin, Milk Thistle Oleoresin (Sylimarin), Terminalia arjuna, Grifolia simplicifolia, Echinacea, Bearberry Leaf Extract, Coriander Oleoresins, Cumin Oleoresins, Celery Oleoresins, Dill Oleoresins, Fenugreek Oleoresins, Garlic Oleoresins, Mace Oleoresins, Garcinia Extract, Fennel Oleoresins, Tamarind Oleoresin
  • the purified natural compounds are selected from but not limited to group of flavonoids, phenolic compounds, terpene, resins, alkaloids, stilbenes, lignins, proanthocyanidins, and their metabolites or derivatives such as boswellic acids, bacosides, lutein, berberine, ellagic acid, resveratrol, catechin, quercetin, gingerols, caffeine, pterostilbene, allicin, astaxnathin, silymarin, beta-cryptoxanthin, daidzein, geni stein, huperzin, Ellagic acid, Geraniol, caffeine, alkamides etc.
  • extract, purified extract or compounds, oleoresin, oleo gum resin, gum resin, rosin is extracted from the spice and plant(s) or animal parts using alcoholic, hydro alcoholic, organic, inorganic solvents such as ethanol, methanol, hexane, ether, 1,2-dichloroethane, dichloromethane, ethyl acetate, acetone, chloroform, toluene, CO2 (supercritical extract), ethanol and/or combinations thereof.
  • the extract may contain active ingredients, essential oils and resins in natural proportions, where the active ingredients content is 0.001 to 99.9%, Essential oil content is 0 to 50% and resin content is 0 to 99.9%.
  • the plant or animal extract as used herein is a crude extract, partially purified extracts or purified extract/compounds involving solvent extraction or CO2 extraction.
  • the essential oils of the oleoresin may be preserved in the final extract obtained.
  • said essential oil may be natural essential oil, either alone or in combination can include, but not limited to, Turmeric essential oil, Ginger essential oil, Cinnamon essential oil, Orange essential oil, Annua essential oil, Boswellia serrata oil, cardamom oil, Chamomile oil, Citronella oil, Olibanum oil, Fennel oil, Garlic oil, Jojoba oil, Lemon oil, Lemongrass oil, Pepper oil, Myrrh oil, Nutmeg oil, Oregano oil, Rosemary oil, Tea tree oil, Mint oil, Cedar oil, Thyme oil, Wintergreen oil, Ylang ylang oil, Calendula oil, Eugenol (Clove oil), Lippia sidoides, Origanum dictamnus, Artemisia arborecens, etc.
  • the essential oil performs a dual function of a co-solvent and a permeation enhancer.
  • the essential oil is obtained by steam distillation or supercritical extraction and other organic and inorganic solvents from plant, spice or other source.
  • the emulsifier present in the composition of invention can be a natural emulsifier or synthetic emulsifier and their derivatives, either alone or in combination.
  • the natural emulsifier may be selected from, but not limited to soya/sunflower phospholipids, soya/sunflower lecithin, lysolecithin, Lysophospholipids, phospholipids from marine source, and egg phospholipids.
  • the synthetic emulsifier may be selected from, but not limited to, Polysorbates, polyethylene glycols and derivatives, glyceryl monooleates and derivatives, Brij- 65, D-a-Tocopheryl Polyethylene Glycol 1000 Succinate, Span 80etc.
  • the phospholipids has purity in the range of 10 to 100%. This can also be in the hydrolysed or partially hydrolysed form.
  • the herbal composition of the invention contains
  • the composition of the invention is in solid or semisolid or liquid form.
  • Said solid, liquid or semisolid herbal composition can be formulated in the form of soft gelatine capsules, hard gelatine capsules, syrup, ointments, gels, patches, liquid sachets, eye drops, bottles and/or any other suitable packing material.
  • the liquid composition has higher viscosity (at 25°C) ranging from 1000 centipoise (cps) to 2500000 centipoise (cps) which gives sustained release profile.
  • Suitable excipients may be added to have desired viscosity in the product.
  • the composition may also contains suitable solid and liquid excipients such as, but not limited to suitable diluents, viscosity enhancers, Olive oil, Gingili oil, Omega 3 fatty acids, Krill oil, Lard Oil, Salmon oil, Medium Chain Triglycerides, Microcrystalline cellulose, poly vinyl pyrrollidone, silica, Magnesium stearate, Hydroxypropyl methyl cellulose, Natural Gums, Synthetic gums, calcium silicate, silicon dioxide, antioxidants, preservatives, pH modifiers, acidifiers, viscosity modifiers etc.
  • suitable solid and liquid excipients such as, but not limited to suitable diluents, viscosity enhancers, Olive oil, Gingili oil, Omega 3 fatty acids, Krill oil, Lard Oil, Salmon oil, Medium Chain Triglycerides, Microcrystalline cellulose, poly vinyl pyrrollidone, silica, Magnesium stearate, Hydroxypropyl methyl cellulose, Natural Gu
  • the solid/liquid/semisolid composition can be used as pharmaceutical, nutraceutical, dietary supplement, feed supplements/additives, food supplement/additives, beverage supplement, flavours, colouring agents, cosmetic compositions, special health supplement/food, gym supplements and other medicaments.
  • the said the solid/liquid/semisolid composition is useful in the prevention, management and treatment of all animal and human disease such as bone disease, eye diseases/disorders, cancers, blood diseases, diabetes, CNS diseases, Gut health/Digestive health , Immune health, oral health and hygiene, metabolic syndrome, glucose health, Age Related Macular Degeneration (AMD), Glaucoma, joint health, cardiovascular diseases, brain diseases, anti-aging, inflammatory diseases, weight management, skin health, hair health, infectious diseases, Bacterial and fungal diseases, injuries, sports nutrition, Alzheimer's disease, depression, Hyperactive disorders, Attention deficit hyperactivity disorder (ADHD), Male Health, Female health, sexual health, Fertility, Delayed Onset of Muscle Soreness etc.
  • animal and human disease such as bone disease, eye diseases/disorders, cancers, blood diseases, diabetes, CNS diseases, Gut health/Digestive health , Immune health, oral health and hygiene, metabolic syndrome, glucose health, Age Related Macular Degeneration (AMD), Glaucoma, joint health
  • the invention provides a process for manufacturing the composition of the invention, the process comprises of following steps:
  • step (b) optionally heating the natural compound(s) or natural compound containing component of step (a) in a vessel to desired temperature;
  • step (c) adding emulsifier to reaction mixtures of step (a) or (b) and mixing the same for 5 to 180 minutes at 30°C to 180°C to get uniform mixture;
  • step (d) adding essential oil to mixture of step (c) at 30 to 80°Cand mixing the reaction mixture for 5 to 180 minutes to obtain a solid/liquid/semisolid product;
  • Step (e) adding optional excipients/carriers to Step (d)to obtain a free flowing solid/liquid/semi solid product
  • step (f) mixing with optional antioxidants and preservatives to product of step (e);
  • step (g) filling the final product of step (f) into HDPE jerry cans or any suitable packaging material
  • the invention provides a process for manufacturing the composition of the invention with purified natural compounds, the process comprises of following steps:
  • step (b) adding purified natural compound (s) to step (a) at 30 to 130°C and mixing the reaction mixture for 5 to 180 minutes
  • step (c) adding emulsifier to reaction mixtures of step (b) and mixing the same for 5 to 180 minutes at 30 to 130°C
  • step (d) adding optional excipients/carriers to Step (d) to obtain a free flowing solid/liquid/semi solid product
  • step (e) mixing with optional antioxidants and preservatives to product of step (e);
  • step (f) filling the final product of step (f) into HDPE jerry cans or any suitable packaging material
  • the composition forms spherical structures in aqueous media having essential oil and natural compound(s) at the core surrounded by molecules of emulsifier, which is optionally suspended in resin suspension, wherein the essential oil has a dual role of co-solvent and bioavailability enhancer in synergy with emulsifier.
  • the composition enhances the bioavailability and therapeutic efficacy of natural compound(s) present in plant or animal extracts.
  • the composition of invention comprises ginger plant extract that contains ginger oleoresin containing 0.1% to 60% total Gingerols and Shogaols.
  • the composition of invention comprises marigold extract /marigold oleoresin containing 0.1% to 80% total xanthophylls and lutein up to 100% was used as an active.
  • Marigold oleoresin composition was made using the below process
  • Marigold oleoresin was taken in a glass reactor fitted with stirrer;
  • Ginger essential oil was added and mixed for 10 minutes for uniform mixing, and
  • the formulation was tested for its solubility in water by adding 500mg of marigold oleoresin formulation (from composition example-I) in water, samples were drawn up to four hours and absorbance was measured at 445 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted (Fig. 1). Result indicates solubility and slow release of luetin from the formulation.
  • Ginger oleoresin composition was made using the below process
  • Fenugreek oleoresin composition was made using the below process
  • Cinnamon oleoresin
  • Cinnamon oleoresin composition was made using the below process
  • Cinnamon oleoresin was taken in a glass reactor fitted with stirrer
  • Ginger essential oil and olive oil was added and mixed for 10 minutes for uniform mixing, and
  • the formulation was tested for its solubility in water by adding lOmg of nutmeg oleoresin formulation (from composition Example -V) in water, samples were drawn up to two hours and absorbance was measured at 210 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of myristicin from the formulation into the water Example 6:
  • Paprika oleoresin composition was made using the below process
  • Ginger essential oil and olive oil was added and mixed for 10 minutes for uniform mixing, and
  • Coleus forskohlii oleoresin composition was made using the below process; a. Coleus forskohlii oleoresin was taken in a glass reactor fitted with stirrer b. Oleoresin was heated to 50°C while stirring
  • Boswellia gum resin composition was made using the below process
  • Boswellia gum resin was taken in a glass reactor fitted with stirrer b. Resin was heated to 80°C while stirring
  • Lutein composition was made using the below process
  • Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 50°C while stirring c. Lutein was added and continued stirring for 20 minutes at 50°C d. the mixture was allowed to cool
  • Bacopa extract composition was made using the below process
  • Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 80°C while stirring c. Bacopa extract was added and continued stirring for 20 minutes at 80°C d. the mixture was allowed to cool
  • Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Berberine was added and continued stirring for 20 minutes at 60°C d. the mixture was allowed to cool
  • Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Coleus Forskohlii extract was added and continued stirring for 20 minutes at 60°C
  • Silymarin composition was made using the below process
  • Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Silymarin extract and Ellagic acid was added and continued stirring for 20 minutes at 60°C d. the mixture was allowed to cool
  • Silymarin composition was made using the below process
  • Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Silymarin extract , Ellagic acid and acacia catechu was added and continued stirring for 20 minutes at 60°C
  • Silymarin composition was made using the below process
  • Thyme essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Silymarin extract was added and continued stirring for 20 minutes at 60°C d. The mixture was allowed to cool
  • the formulation was tested for its solubility in water by adding 500mg of Sylemarin formulation (from example XVII) in water, samples were drawn up to two hours and absorbance was measured at 287 nm using UV-Vis
  • Lutein composition was made using the below process
  • Thyme essential oil was taken in a glass reactor fitted with stirrer;
  • the formulation was tested for its solubility in water by adding 50mg of Lutein powder formulation (from composition XVIII) in water, samples were drawn up to two hours and absorbance was measured at 445 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of lutein from the formulation into the water
  • Example 19
  • Ginger oleoresin composition was made using the below process
  • Ginger oleoresin was taken in a glass reactor fitted with stirrer and heated to 40°C
  • Liquid Lecithin was added followed by powder lecithin and the mixture was stirred.
  • the formulation was tested for its solubility in water by adding 400mg of ginger oleoresin formulation (from example XIX) in water, samples were drawn up to two hours and absorbance was measured at 282 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of 6-gingerol from the formulation into the water.
  • Example 20
  • Thyme essential oil was taken in a glass reactor fitted with stirrer b. Polysorbate was added and the mixture was heated to 80°C while stirring c. Acacia Catechu extract was added and continued stirring for 20 minutes at 80°C
  • the formulation was tested for its solubility in water by adding 50mg of Acacia Catechu formulation (from example XX) in water, samples were drawn up to two hours and absorbance was measured at 276 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of catechin from the formulation into the water.
  • Example 21
  • Ellagic acid extract composition was made using the below process
  • Thyme essential oil was taken in a glass reactor fitted with stirrer b. Polysorbate was added and the mixture was heated to 80°C while stirring c. Ellagic acid extract was added and continued stirring for 20 minutes at 80°C d. the mixture was allowed to cool
  • Zeaxanthin composition was made using the below process
  • Thyme essential oil was taken in a glass reactor fitted with stirrer b. Polysorbate was added and the mixture was heated to 80°C while stirring c. Zeaxanthin was added and continued stirring for 20 minutes at 80°C d. the mixture was allowed to cool
  • the formulation was tested for its solubility in water by adding 50mg of zeaxanthin formulation (from example XXII) in water, samples were drawn up to two hours and absorbance was measured at 446nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of zeaxanthin from the formulation into the water

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Abstract

The invention discloses a novel composition for a natural compound. The composition described herein comprises of an natural active compound present in range of 0.01 – 98%; an essential oil present in range of 1 – 98%, and an emulsifier in range of 1 – 98%. Said composition exhibits an enhanced bioavailability and slow release of natural active compound.

Description

COMPOSITION TO ENHANCE BIOAVAILABILITY OF NATURAL
COMPOUNDS"
Field of Invention:
The present invention relates to a bioavailable composition of natural compounds. More specifically, the invention relates to a composition which uses a synergistic combination of an essential oil and an emulsifier for enhancing bioavailability and slow release profile of the natural compounds.
Background of Invention:
The bioavailability of the drugs or pharmaceutical compounds is majorly based on solubility of said compounds in water, since water solubility of the natural compounds plays a major role in determining the amount of compounds which may be absorbed after oral administration.
Despite the tentative popularity of natural compounds, as alternative treatment means, demonstrable efficacy has remained elusive for many of these compounds because of their hydrophobic nature. Due to their hydrophobic nature, said natural compounds demonstrate a low solubility. The low solubility, in turn, results in poor systemic absorption of these natural compounds and hence low bioavailability.
A number of techniques have been employed to enhance the bioavailability of the hydrophobic compounds. One such technique is addition of certain components which are classified as 'bioavailability enhancers' or 'bioenhancers' . Bioavailability enhancers are drug facilitators, which by themselves do not show any drug activity but when used in combination with drugs or active ingredients they enhance the activity of the drug molecule by increasing penetration of the drug across the cell membrane, potentiating the drug molecule by conformational interaction, improving the solubility of the drug molecule, and making target cells more receptive to drugs. Chen, Jun, et al in their article titled "Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea" published in Molecules, 2015, have clearly established the potential use of the plant essential oils as effective permeation enhancers, However, the article focused, in particular, on the use of Essential Oils as permeation enhancers for ibuprofen. The Article observes that essential oils and their constituents can easily penetrate through the skin into the blood stream.
Essential oils are generally isolated from plant material by distillation methods, usually steam or hydro-distillation. Essential oils are variable mixtures of principally terpenoids, specifically monoterpenes [Cio], sesquiterpenes [C15], diterpenes [C20] and a variety of other low molecular weight aliphatic hydrocarbons (linear, ramified, saturated and unsaturated), acids, alcohols, aldehydes, acyclic esters or lactones and exceptionally nitrogen- and sulphur-containing compounds, coumarins and homologues of phenylpropanoids.
The effectiveness of terpenes as skin penetration enhancers has been established by Williams, A. C. and Barry, B. W. in their article titled "Terpenes and the Lipid- Protein-Partitioning Theory of Skin Penetration Enhancement" published in
Pharmaceutical Research, January 1991, Volume 8, Issue 1, pp 17-24.
The same has been further highlighted by Sapra, B. et al in their article titled "Percutaneous permeation enhancement by terpenes: mechanistic view" published in AAPS J., 10 (1) (2008), pp. 120-132. According to Sapra et al, Terpenes are included in the list of Generally Recognized as Safe (GRAS) substances and have low irritancy potential. Their mechanism of percutaneous permeation enhancement involves increasing the solubility of drugs in skin lipids, disruption of lipid/protein re-organization and/or extraction of skin micro constituents that are responsible for maintenance of barrier status. Hence, they appear to offer great promise for use in transdermal compositions. US5716928, assigned to Avmax, Inc., further establishes the use of Essential oils for enhancing the bioavailability of various pharmaceutical actives.
Therefore, the use of Essential Oils as permeation enhancers has been concretely established in past few years. This has made them an attractive and safe option for various synthetic permeation enhancers.
950/CHE/2010, of Arjuna Natural Extracts Ltd., tried using curcumin essential oil, comprising Ar-turmerone, for increasing the bioavailability of curcumin.
Additionally, emulsifiers have also proved to be effective for enhancing the bioavailability. Especially in case of Self-Nanoemulsifying Drug Delivery System, wherein a right blend of emulsifier(s) is necessary to achieve a better bioavailability, as can be seen from article titled "Preparation and In Vitro Evaluation of Self-Nanoemulsifying Drug Delivery System (SNEDDS) Containing Clopidogrel" by Pathak, Chirag Vilas et al in "Int. J. Pharm. Sci. Rev. Res., 25(1), Mar - Apr 2014; Article No. 02, Pages: 10-15"
Therefore, the present inventor describe compositions which contains natural compound(s) combined with an essential oil and an emulsifier with a view of enhancing the bioavailability of the natural compound(s) and provide an economical method for manufacturing the composition of invention. Essential oil and emulsifier synergistically enhance the bioavailability of the natural compound(s).
Summary of Invention:
The invention provides a novel pharmaceutical, nutraceutical, dietary supplement, food/feed supplement or additive and/or herbal composition which comprises of a natural compound(s), an essential oil(s) and an emulsifier(s). In main aspect, the composition of the invention demonstrates enhanced bioavailability and also achieves slow/sustained release of the natural compound(s).
The enhanced bioavailability is due to the synergistic activity of the essential oil and the emulsifier, wherein essential oil has a dual purpose of aiding in enhancing the bioavailability, acting as co-solvent in the composition and directly enhancing the bioavailability as a permeation enhancer, thereby synergistically working with emulsifier to enhance the bioavailability of natural compound(s).
The viscosity of the synergistic composition leads to sustained release of the active ingredient.
In another aspect, the invention provides a process for preparation of the composition of the invention.
Brief Description of Drawings:
Fig. 1 illustrates release profile of luetin from Marigold oleoresin formulation of Example 1.
Fig. 2 illustrates release profile of myristicin in Nutmeg oleoresin formulation of Example 5.
Fig. 3 illustrates release profile of silymarin in Silymarin formulation of Example 17.
Fig. 4 illustrates release profile of lutein in luetin formulation of Example 18.
Fig. 5 illustrates release profile of 6-gingerol in Gingerol oleoresin formulation of Example 19. Fig. 6 illustrates release profile of Catechin in Accacia catechu formulation of Example 20.
Fig. 7 illustrates release profile of Ellagic acid in Ellagic acid formulation of Example 21.
Fig. 8 illustrates release profile of zeaxanthin in zeaxanthin formulation of Example 22.
Detailed Description of Invention:
Described herein is a composition which contains a natural compound(s) extracted from plant or animal source, an essential oil and an emulsifier. The natural compound can also be crude or partially purified or purified or natural compound(s) containing component derived from plant or animal extract. The composition of invention exhibits a synergistically enhanced bioavailability along with slow release profile of the active.
Accordingly, in one embodiment, the present invention discloses a highly bioavailable, slow/sustained release composition comprising of a natural compound(s), an essential oil and an emulsifier. The composition of the invention may be in solid, semi-solid or liquid form.
In an embodiment, the natural compound is a purified natural compound derived from plant or animal extract or crude or partially purified natural compound containing component derived from plant or animal extract. The natural compound is selected from, but not limited to, liquid or semisolid/soft or solid extract, liquid or semisolid or solid oleoresins, liquid or semisolid or solid oleo gum resins, resin, resinoids and liquid or semisolid or solid gum resins, fractionated liquid extract and purified extract/compounds either alone or in combination. Said natural compound may be a synthetically manufactured or obtained from a natural source. In accordance with above embodiment, the plant extract or plant oleoresin is obtained from plant source selected from, but not limited to, Boswellia serrata, Bacopa monnieri, Marigold, Ginger, Glycyrrhiza glabra, Cinnamon species, Terminalia chebula, Scutellaria baicalensis, Terminalia arjuna, Grifolia simplicifolia, Echinacea, Pinus pinaster (Maritime pine bark), Euterpe oleracea,Acacia catechu, Silybum marianum, Viscum album, Punica granatum, Camellia sinensis (Green Tea), Green coffee bean, Commiphora Mukul (Guggul), Architoke Oleoresin, Cassia fistula, Carica papaya, Centella asiatica, Cinnamomum zeylanicum, Cissus quadrangularis, Chlorophytum tuberosum, Colius forskohlii, Emblica officinalis, Eugenia jambolana, Eurycoma longifolia Root, Garcinia cambogia, Garcinia mangostana, Gymnema sylvestre, Indigofera tinctoria, Momordica charantia Fruit (Chamomile), Morinda citrifolia, Moringa oleifera, Mucuna pruriens, Piper nigrum Fruit, Phyllanthus niruri, Salacia oblonga, Salacia reticulata, Sphaeranthus indicus, Sida cordifolia, Tagetes erecta Flower, Tamarindus indica, Terminalia arjuna, Terminalia chebula, Tribulus terrestris, Trigonellafoenum-graecum, Asthaxanthin, Zeaxanthin, Lutein,Cannabis extract, Triphala, Ashwagandha, Resveratrol, Huperzine containing extract and/or Curry leaf extract.
In accordance with above embodiment, the animal extract is obtained from animal source selected from but not limited to Krill oil, Fish oil, Squalamine etc.
Further in accordance with above embodiment the liquid or semisolid or solid oleoresins, liquid or semisolid or solid oleo gum resins and liquid or semisolid or solid gum resins, and rosins including, but not limited to Clove Oleoresins, Curry leaf Oleoresins, Pepper Oleoresins, Cardamom Oleoresins, Chilli Oleoresins, Capsicum Oleoresins, Paprika Oleoresins, Ginger Oleoresins, Coleus Oleoresin, Milk Thistle Oleoresin (Sylimarin), Terminalia arjuna, Grifolia simplicifolia, Echinacea, Bearberry Leaf Extract, Coriander Oleoresins, Cumin Oleoresins, Celery Oleoresins, Dill Oleoresins, Fenugreek Oleoresins, Garlic Oleoresins, Mace Oleoresins, Garcinia Extract, Fennel Oleoresins, Tamarind Oleoresins, Cinnamon Oleoresins, Nutmeg Oleoresins, Cassia Oleoresins, Galangal Oleoresins, Parsley Oleoresins, Thyme Oleoresins, Marigold Oleoresins, Rosemary Oleoresins, Salacia extract, Mustard Oleoresins, and Vanilla Oleoresins either alone or in combination.
In further accordance with above embodiment, the purified natural compounds are selected from but not limited to group of flavonoids, phenolic compounds, terpene, resins, alkaloids, stilbenes, lignins, proanthocyanidins, and their metabolites or derivatives such as boswellic acids, bacosides, lutein, berberine, ellagic acid, resveratrol, catechin, quercetin, gingerols, caffeine, pterostilbene, allicin, astaxnathin, silymarin, beta-cryptoxanthin, daidzein, geni stein, huperzin, Ellagic acid, Geraniol, caffeine, alkamides etc.
In further accordance with above embodiment, extract, purified extract or compounds, oleoresin, oleo gum resin, gum resin, rosin is extracted from the spice and plant(s) or animal parts using alcoholic, hydro alcoholic, organic, inorganic solvents such as ethanol, methanol, hexane, ether, 1,2-dichloroethane, dichloromethane, ethyl acetate, acetone, chloroform, toluene, CO2 (supercritical extract), ethanol and/or combinations thereof.
The extract may contain active ingredients, essential oils and resins in natural proportions, where the active ingredients content is 0.001 to 99.9%, Essential oil content is 0 to 50% and resin content is 0 to 99.9%.
In accordance with above embodiment, the plant or animal extract as used herein is a crude extract, partially purified extracts or purified extract/compounds involving solvent extraction or CO2 extraction. As the consequence of above process, the essential oils of the oleoresin may be preserved in the final extract obtained.
In accordance with above embodiment, said essential oil may be natural essential oil, either alone or in combination can include, but not limited to, Turmeric essential oil, Ginger essential oil, Cinnamon essential oil, Orange essential oil, Annua essential oil, Boswellia serrata oil, cardamom oil, Chamomile oil, Citronella oil, Olibanum oil, Fennel oil, Garlic oil, Jojoba oil, Lemon oil, Lemongrass oil, Pepper oil, Myrrh oil, Nutmeg oil, Oregano oil, Rosemary oil, Tea tree oil, Mint oil, Cedar oil, Thyme oil, Wintergreen oil, Ylang ylang oil, Calendula oil, Eugenol (Clove oil), Lippia sidoides, Origanum dictamnus, Artemisia arborecens, etc.
In an embodiment, the essential oil performs a dual function of a co-solvent and a permeation enhancer. The essential oil is obtained by steam distillation or supercritical extraction and other organic and inorganic solvents from plant, spice or other source.
In further embodiment, the emulsifier present in the composition of invention can be a natural emulsifier or synthetic emulsifier and their derivatives, either alone or in combination. The natural emulsifier may be selected from, but not limited to soya/sunflower phospholipids, soya/sunflower lecithin, lysolecithin, Lysophospholipids, phospholipids from marine source, and egg phospholipids. The synthetic emulsifier may be selected from, but not limited to, Polysorbates, polyethylene glycols and derivatives, glyceryl monooleates and derivatives, Brij- 65, D-a-Tocopheryl Polyethylene Glycol 1000 Succinate, Span 80etc.The phospholipids has purity in the range of 10 to 100%. This can also be in the hydrolysed or partially hydrolysed form.
In an embodiment, the herbal composition of the invention contains
a. 0.01 to 99% at least one natural compound or natural compound containing component;
b. 1 to 98%) at least one essential oil, and
c. 1 to 98%o at least one natural or synthetic emulsifier.
In an embodiment, the composition of the invention is in solid or semisolid or liquid form. Said solid, liquid or semisolid herbal composition can be formulated in the form of soft gelatine capsules, hard gelatine capsules, syrup, ointments, gels, patches, liquid sachets, eye drops, bottles and/or any other suitable packing material.
In an embodiment, the liquid composition has higher viscosity (at 25°C) ranging from 1000 centipoise (cps) to 2500000 centipoise (cps) which gives sustained release profile. Suitable excipients may be added to have desired viscosity in the product.
In an embodiment, the composition may also contains suitable solid and liquid excipients such as, but not limited to suitable diluents, viscosity enhancers, Olive oil, Gingili oil, Omega 3 fatty acids, Krill oil, Lard Oil, Salmon oil, Medium Chain Triglycerides, Microcrystalline cellulose, poly vinyl pyrrollidone, silica, Magnesium stearate, Hydroxypropyl methyl cellulose, Natural Gums, Synthetic gums, calcium silicate, silicon dioxide, antioxidants, preservatives, pH modifiers, acidifiers, viscosity modifiers etc.
In another embodiment, the solid/liquid/semisolid composition can be used as pharmaceutical, nutraceutical, dietary supplement, feed supplements/additives, food supplement/additives, beverage supplement, flavours, colouring agents, cosmetic compositions, special health supplement/food, gym supplements and other medicaments.
In another embodiment, the said the solid/liquid/semisolid composition is useful in the prevention, management and treatment of all animal and human disease such as bone disease, eye diseases/disorders, cancers, blood diseases, diabetes, CNS diseases, Gut health/Digestive health , Immune health, oral health and hygiene, metabolic syndrome, glucose health, Age Related Macular Degeneration (AMD), Glaucoma, joint health, cardiovascular diseases, brain diseases, anti-aging, inflammatory diseases, weight management, skin health, hair health, infectious diseases, Bacterial and fungal diseases, injuries, sports nutrition, Alzheimer's disease, depression, Hyperactive disorders, Attention deficit hyperactivity disorder (ADHD), Male Health, Female health, Sexual health, Fertility, Delayed Onset of Muscle Soreness etc.
In one of the embodiments of the invention, the invention provides a process for manufacturing the composition of the invention, the process comprises of following steps:
(a) Taking measured amount of natural compound(s)or natural compound containing component in a reaction vessel;
(b) optionally heating the natural compound(s) or natural compound containing component of step (a) in a vessel to desired temperature;
(c) adding emulsifier to reaction mixtures of step (a) or (b) and mixing the same for 5 to 180 minutes at 30°C to 180°C to get uniform mixture;
(d) adding essential oil to mixture of step (c) at 30 to 80°Cand mixing the reaction mixture for 5 to 180 minutes to obtain a solid/liquid/semisolid product;
(e) adding optional excipients/carriers to Step (d)to obtain a free flowing solid/liquid/semi solid product;
(f) mixing with optional antioxidants and preservatives to product of step (e);
(g) filling the final product of step (f) into HDPE jerry cans or any suitable packaging material, and
(h) filling the final product into soft gelatine or hard gelatine or HPMC capsules or sachets or formulating it to suitable dosage form.
In one of the embodiments of the invention, the invention provides a process for manufacturing the composition of the invention with purified natural compounds, the process comprises of following steps:
(a) Taking measured amount of essential oil in a reaction vessel;
(b) adding purified natural compound (s) to step (a) at 30 to 130°C and mixing the reaction mixture for 5 to 180 minutes
(c) adding emulsifier to reaction mixtures of step (b) and mixing the same for 5 to 180 minutes at 30 to 130°C (d) adding optional excipients/carriers to Step (d) to obtain a free flowing solid/liquid/semi solid product;
(e) mixing with optional antioxidants and preservatives to product of step (e);
(f) filling the final product of step (f) into HDPE jerry cans or any suitable packaging material, and
(g) filling the final product into soft gelatine or hard gelatine or HPMC capsules or sachets or formulating it to suitable dosage form.
In an advantageous embodiment, the composition forms spherical structures in aqueous media having essential oil and natural compound(s) at the core surrounded by molecules of emulsifier, which is optionally suspended in resin suspension, wherein the essential oil has a dual role of co-solvent and bioavailability enhancer in synergy with emulsifier.
In another advantageous embodiment, the composition enhances the bioavailability and therapeutic efficacy of natural compound(s) present in plant or animal extracts.
In an exemplary embodiment, the composition of invention comprises ginger plant extract that contains ginger oleoresin containing 0.1% to 60% total Gingerols and Shogaols.
In yet another exemplary embodiment, the composition of invention comprises marigold extract /marigold oleoresin containing 0.1% to 80% total xanthophylls and lutein up to 100% was used as an active.
EXAMPLES:
The composition as given in tables I through XIV are exemplary in nature and in no way limit the scope of the invention. It will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit or scope of the appended claims. Example 1:
Marigold Oleoresin Composition:
Table I
Figure imgf000013_0001
Process:
Marigold oleoresin composition was made using the below process;
a. Marigold oleoresin was taken in a glass reactor fitted with stirrer;
b. Oleoresin was heated to 70°C while stirring;
c. Lecithin and lecithin powder was added and continued stirring for 20 minutes; d. Oleoresin and lecithin mixture was allowed to cool to achieve 40°C;
e. Ginger essential oil was added and mixed for 10 minutes for uniform mixing, and
f. The final product was transferred to HDPE container and stored Solubility of the Marigold oleoresin formulation in Water:
The formulation was tested for its solubility in water by adding 500mg of marigold oleoresin formulation (from composition example-I) in water, samples were drawn up to four hours and absorbance was measured at 445 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted (Fig. 1). Result indicates solubility and slow release of luetin from the formulation.
Example 2:
Ginger Oleoresin Composition: Table II
Figure imgf000014_0001
Process:
Ginger oleoresin composition was made using the below process;
a. Ginger oleoresin was taken in a glass reactor fitted with stirrer
b. Oleoresin was heated to 70°C while stirring
c. Lecithin and lecithin powder was added and continued stirring for 20 minutes d. Oleoresin and lecithin mixture was allowed to cool to achieve 40°C
e. Turmeric essential oil was added and mixed for 10 minutes for uniform mixing. f. The final product was transferred to HDPE container and stored
Example 3:
Fenugreek oleoresins:
Table III
Sr. No. Ingredients Quantity (g)
1. Fenugreek oleoresin 75.0
2. Cinnamon oil 15.0
3. Lecithin Powder/Polysorbate 80 5.0
4. Nutmeg essential oil 5.0
Total 100.0 Process:
Fenugreek oleoresin composition was made using the below process;
a. Fenugreek oleoresin was taken in a glass reactor fitted with stirrer
b. Oleoresin was heated to 50°C while stirring
c. Polysorbate 80 powder was added and continued stirring for 20 minutes d. Oleoresin and polysorbate mixture was allowed to cool to achieve 40°C e. Cinnamon oil and Nutmeg essential oil was added and mixed for 10 minutes for uniform mixing.
f. The final product was transferred to FIDPE container and stored
Example 4:
Cinnamon oleoresin:
Table IV
Figure imgf000015_0001
Process:
Cinnamon oleoresin composition was made using the below process;
a. Cinnamon oleoresin was taken in a glass reactor fitted with stirrer
b. Oleoresin was heated to 70°C while stirring
c. Lecithin was added and continued stirring for 20 minutes
d. Oleoresin and lecithin mixture was allowed to cool to achieve 40°C
e. Annua essential oil was added and mixed for 10 minutes for uniform mixing. f. The final product was transferred to FIDPE container and stored Example 5:
Nutmeg oleoresin
Table V
Figure imgf000016_0001
Process:
Nutmeg oleoresin composition was made using the below process;
a. Nutmeg oleoresin was taken in a glass reactor fitted with stirrer;
b. Oleoresin was heated to 50°C while stirring;
c. Lecithin was added and continued stirring for 20 minutes;
d. Oleoresin and lecithin mixture was allowed to cool to achieve 40°C;
e. Ginger essential oil and olive oil was added and mixed for 10 minutes for uniform mixing, and
f. The final product was transferred to HDPE container and stored.
Solubility of the Nutmeg oleoresin formulation in Water:
The formulation was tested for its solubility in water by adding lOmg of nutmeg oleoresin formulation (from composition Example -V) in water, samples were drawn up to two hours and absorbance was measured at 210 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of myristicin from the formulation into the water Example 6:
Paprika oleoresin
Table VI
Figure imgf000017_0001
Process:
Paprika oleoresin composition was made using the below process;
a. Paprika oleoresin was taken in a glass reactor fitted with stirrer;
b. Oleoresin was heated to 60°C while stirring;
c. Deoiled Lecithin was added and continued stirring for 20 minutes at 60°C; d. Oleoresin and lecithin mixture was allowed to cool to achieve 40°C;
e. Ginger essential oil and olive oil was added and mixed for 10 minutes for uniform mixing, and
f. The final product was transferred to HDPE container and stored.
Example 7:
Capsicum oleoresin
Table VII
Sr. No. Ingredients Quantity (g)
1. Capsicum oleoresin 75.0
2. Ginger essential oil 10.0
3. De-oiled lecithin 5.0 4. Olive oil 10.0
Total 100.0
Example 8:
Coleus forskohlii oleoresin:
Table VIII
Figure imgf000018_0001
Process:
Coleus forskohlii oleoresin composition was made using the below process; a. Coleus forskohlii oleoresin was taken in a glass reactor fitted with stirrer b. Oleoresin was heated to 50°C while stirring
c. Deoiled Lecithin was added and continued stirring for 20 minutes at 50°C d. Oleoresin and lecithin mixture was allowed to cool to achieve 40°C e. Ginger essential oil was added and mixed for 10 minutes for uniform mixing. f. The final product was transferred to HDPE container and stored
Example 9:
Boswellia gum resin
Table LX
Sr. No. Ingredients Quantity (g)
1. Boswellia gum resin 60.0
2. Ginger Essential Oil 25.0 3. De-oiled lecithin/Polysorbate 15.0
Total 100.0
Process:
Boswellia gum resin composition was made using the below process;
a. Boswellia gum resin was taken in a glass reactor fitted with stirrer b. Resin was heated to 80°C while stirring
c. Deoiled Lecithin was added and continued stirring for 20 minutes at 80°C d. Oleoresin and lecithin mixture was allowed to cool to achieve 40°C e. Ginger essential oil was added and mixed for 10 minutes for uniform mixing. f. The final product was transferred to HDPE container and stored
Example 10:
Lutein composition
Table X
Figure imgf000019_0001
Process:
Lutein composition was made using the below process;
a. Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 50°C while stirring c. Lutein was added and continued stirring for 20 minutes at 50°C d. the mixture was allowed to cool
e. The final product was transferred to HDPE container and stored
Example 11:
Bacopa composition
Table XI
Figure imgf000020_0001
Process:
Bacopa extract composition was made using the below process;
a. Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 80°C while stirring c. Bacopa extract was added and continued stirring for 20 minutes at 80°C d. the mixture was allowed to cool
e. The final product was transferred to HDPE container and stored
Example 12:
Berberine composition
Table XII
Sr. No. Ingredients Quantity (g)
1. Berberin extract 30.0
Ginger Essential Oil/ Annua essential
2. 30.0
oil/Orange oil 3. Polysorbate 80/Lecithin 40.0
Total 100.0
Process:
Berberine composition was made using the below process;
a. Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Berberine was added and continued stirring for 20 minutes at 60°C d. the mixture was allowed to cool
e. The final product was transferred to HDPE container and stored Example 13:
Coleus Forskohlii composition
Table XIII
Figure imgf000021_0001
Process:
Coleus Forskohlii composition was made using the below process;
a. Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Coleus Forskohlii extract was added and continued stirring for 20 minutes at 60°C
d. the mixture was allowed to cool
e. The final product was transferred to FIDPE container and stored Example 14:
Krill oil composition
Table XIV
Figure imgf000022_0001
Example 15:
Silymarin composition
Table XV
Figure imgf000022_0002
Process:
Silymarin composition was made using the below process;
a. Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Silymarin extract and Ellagic acid was added and continued stirring for 20 minutes at 60°C d. the mixture was allowed to cool
e. The final product was transferred to HDPE container and stored
Example 16:
Silymarin composition
Table XVI
Figure imgf000023_0001
Process:
Silymarin composition was made using the below process;
a. Ginger essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Silymarin extract , Ellagic acid and acacia catechu was added and continued stirring for 20 minutes at 60°C
d. the mixture was allowed to cool
e. The final product was transferred to HDPE container and stored Example 17:
Silymarin composition
Table XVII
Figure imgf000024_0001
Process:
Silymarin composition was made using the below process;
a. Thyme essential oil was taken in a glass reactor fitted with stirrer b. Lecithin was added and the mixture was heated to 60°C while stirring c. Silymarin extract was added and continued stirring for 20 minutes at 60°C d. The mixture was allowed to cool
e. The final product was transferred to HDPE container and stored Solubility of the Silymarin formulation in Water:
The formulation was tested for its solubility in water by adding 500mg of Sylemarin formulation (from example XVII) in water, samples were drawn up to two hours and absorbance was measured at 287 nm using UV-Vis
spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of Silymarin from the formulation into the water Example 18:
Lutein composition
Table XVIII
Figure imgf000025_0001
Process:
Lutein composition was made using the below process;
a. Thyme essential oil was taken in a glass reactor fitted with stirrer;
b. Lecithin was added and the mixture was heated to 80°C while stirring; c. Lutein extract was added and continued stirring for 20 minutes at 80°C; d. the mixture was allowed to cool, and
e. The final product was transferred to HDPE container and stored. Solubility of the Lutein formulation in Water:
The formulation was tested for its solubility in water by adding 50mg of Lutein powder formulation (from composition XVIII) in water, samples were drawn up to two hours and absorbance was measured at 445 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of lutein from the formulation into the water Example 19:
Table XIX
Figure imgf000026_0001
Process:
Ginger oleoresin composition was made using the below process;
a. Ginger oleoresin was taken in a glass reactor fitted with stirrer and heated to 40°C
b. Liquid Lecithin was added followed by powder lecithin and the mixture was stirred.
c. Turmeric oil was added and continued stirring for 20 minutes
d. The mixture was allowed to cool
e. The final product was transferred to HDPE container and stored
HPLC analysis for 6-Gingerol test results:
The test result for the above product was found to be 9.02%
Solubility of the Ginger oleoresin formulation in Water
The formulation was tested for its solubility in water by adding 400mg of ginger oleoresin formulation (from example XIX) in water, samples were drawn up to two hours and absorbance was measured at 282 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of 6-gingerol from the formulation into the water. Example 20:
Table XX
Figure imgf000027_0001
Process:
Acacia catechu composition was made using the below process;
a. Thyme essential oil was taken in a glass reactor fitted with stirrer b. Polysorbate was added and the mixture was heated to 80°C while stirring c. Acacia Catechu extract was added and continued stirring for 20 minutes at 80°C
d. the mixture was allowed to cool
e. The final product was transferred to HDPE container and stored Solubility of the Acacia Catechu formulation in Water
The formulation was tested for its solubility in water by adding 50mg of Acacia Catechu formulation (from example XX) in water, samples were drawn up to two hours and absorbance was measured at 276 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of catechin from the formulation into the water. Example 21:
Ellagic acid composition
Table XXI
Figure imgf000028_0001
Process:
Ellagic acid extract composition was made using the below process;
a. Thyme essential oil was taken in a glass reactor fitted with stirrer b. Polysorbate was added and the mixture was heated to 80°C while stirring c. Ellagic acid extract was added and continued stirring for 20 minutes at 80°C d. the mixture was allowed to cool
e. The final product was transferred to HDPE container and stored Solubility of the Ellagic acid formulation in Water
The formulation was tested for its solubility in water by adding 50mg of Ellagic acid formulation (from example XXI) in water, samples were drawn up to two hours and absorbance was measured at 256 nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of Ellagic acid from the formulation into the water. Example 22:
Zeaxanthin composition
Table XXII
Figure imgf000029_0001
Process:
Zeaxanthin composition was made using the below process;
a. Thyme essential oil was taken in a glass reactor fitted with stirrer b. Polysorbate was added and the mixture was heated to 80°C while stirring c. Zeaxanthin was added and continued stirring for 20 minutes at 80°C d. the mixture was allowed to cool
e. The final product was transferred to HDPE container and stored Solubility of the zeaxanthin formulation in Water:
The formulation was tested for its solubility in water by adding 50mg of zeaxanthin formulation (from example XXII) in water, samples were drawn up to two hours and absorbance was measured at 446nm using UV-Vis spectrophotometer. Absorbance vs. time graph was plotted. Result indicates solubility and slow release of zeaxanthin from the formulation into the water

Claims

We Claim,
1. A composition comprising:
a. a natural active compound present in range of 0.01 - 98%;
b. an essential oil present in range of 1 - 98%, wherein the essential oil performs dual function of co-solvent and permeation enhancer, and c. an emulsifier in range of 1 - 98%.
wherein, the composition exhibits enhanced bioavailability and slow release of the natural compound.
2. The composition of Claims 1, wherein the essential oil is selected from Turmeric essential oil, Ginger essential oil, Cinnamon essential oil, Orange essential oil, Annua essential oil, Boswellia serrata oil, cardamom oil, Chamomile oil, Citronella oil, Olibanum oil, Fennel oil, Garlic oil, Jojoba oil, Lemon oil, Lemongrass oil, Pepper oil, Myrrh oil, Nutmeg oil, Oregano oil, Rosemary oil, Tea tree oil, Mint oil, Cedar oil, Thyme oil, Wintergreen oil, Ylang ylang oil, Calendula oil, Eugenol (Clove oil), Lippia sidoides, Origanum dictamnus, Artemisia arborecens, or combinations or mixtures thereof.
3. The composition of Claim 1, wherein the natural active compound is selected from a natural compound(s) or a natural compound containing component.
4. The composition of Claim 4, wherein the natural active compound is selected from group of liquid or semisolid or solid plant or animal extract, liquid or semisolid or solid oleoresins, liquid or semisolid or solid oleo gum resins and liquid or semisolid or solid gum resins, fractionated liquid extract purified compounds and purified extract.
5. The composition of Claim 1, wherein the emulsifier is a natural emulsifier or synthetic emulsifier or combination and mixtures thereof.
6. The composition of Claim 1, wherein the composition is solid, liquid or semisolid.
7. The composition of Claim 6, wherein the composition can be formulated in the form of soft gelatine capsules, hard gelatine capsules, syrup, ointments, gels, patches, liquid sachets, eye drops, bottles and/or any other suitable packing material.
8. The composition of Claim 6, wherein the liquid composition has higher viscosity (at 25°C) ranging from 1000 centipoise (cps) to 2500000 centipoise (cps) which gives sustained release profile.
9. The composition of Claim 1, wherein the composition can be used as pharmaceutical, nutraceutical, dietary supplement, feed supplements / additives, food supplement / additives, beverage supplement, flavours, colouring agents, cosmetic compositions, special health supplement / food, gym supplements and other medicaments.
10. The composition of Claim 1, is manufactured by process comprising:
a. Taking measured amount of natural compound(s) or natural compound containing component in a reaction vessel;
b. optionally heating the natural compound(s) or natural compound containing component of step (a) in a vessel to desired temperature;
c. adding emulsifier to reaction mixtures of step (a) or (b) and mixing the same to get uniform mixture;
d. adding essential oil to mixture of step (c) and mixing the reaction mixture to obtain a solid/liquid/semisolid product;
e. adding optional excipients/carriers to Step (d) to obtain a free flowing solid/liquid/semi solid product, and
f. mixing with optional antioxidants and preservatives to product of step (e).
11. The composition of Claim 1, wherein the process comprises of:
(a) Taking measured amount of essential oil in a reaction vessel;
(b) adding purified natural compound (s) to step (a) at 30 to 130°C and mixing the reaction mixture for 5 to 180 minutes
(c) adding emulsifier to reaction mixtures of step (b) and mixing the same for 5 to 180 minutes at 30 to 130°C
(d) adding optional excipients/carriers to Step (d) to obtain a free flowing solid/liquid/semi solid product;
(e) mixing with optional antioxidants and preservatives to product of step (e);
(f) filling the final product of step (f) into HDPE jerry cans or any suitable packaging material, and
(g) filling the final product into soft gelatine or hard gelatine or HPMC capsules or sachets or formulating it to suitable dosage form.
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US11464816B2 (en) 2019-04-16 2022-10-11 The Procter & Gamble Company Supplement for menopause
KR20220115275A (en) * 2021-02-10 2022-08-17 주식회사 바이오의생명공학연구소 Skin useful composition for antiaging
KR102530638B1 (en) 2021-02-10 2023-05-10 주식회사 바이오의생명공학연구소 Skin useful composition for antiaging

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