WO1996040262A2 - Process for preparing encapsulated water soluble beta-carotene - Google Patents

Process for preparing encapsulated water soluble beta-carotene Download PDF

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Publication number
WO1996040262A2
WO1996040262A2 PCT/US1996/006981 US9606981W WO9640262A2 WO 1996040262 A2 WO1996040262 A2 WO 1996040262A2 US 9606981 W US9606981 W US 9606981W WO 9640262 A2 WO9640262 A2 WO 9640262A2
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Prior art keywords
beta
carotene
solution
cyclodextrin
organic solvent
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PCT/US1996/006981
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French (fr)
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WO1996040262A3 (en
Inventor
Nancy Elaine Fortier
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The Procter & Gamble Company
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Publication of WO1996040262A2 publication Critical patent/WO1996040262A2/en
Publication of WO1996040262A3 publication Critical patent/WO1996040262A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
    • C07C403/24—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/02—Halogenated hydrocarbons
    • A61K31/035—Halogenated hydrocarbons having aliphatic unsaturation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Definitions

  • the present invention relates to water soluble carotenoid compositions and to a method for preparing such compositions. More particularly the present invention relates to dry beta-carotene compositions which exhibit superior resistance to oxidative and thermal degradation.
  • the carotenoids particularly, beta-carotene
  • beta-carotene are well known and the most commonly used source of vitamin A for nutritional supplementation.
  • beta-carotene is reported to protect cells from the reactive species (free radicals) that are suggested as causes of cancer and atherosclerosis.
  • beta-carotene To be acceptable as a nutritional supplement in foods, the beta-carotene must be reasonably soluble and bioavailable. Although beta-carotene is considered to be oil soluble, it is poorly soluble in vegetable oils and insoluble in water. For example, beta-carotene has a solubility of about 0.08% by weight in vegetable oils at room temperature. The solubility of the beta-carotene has severely hindered its absorbability from food products having an aqueous base, for example, beverages, puddings, and soups and from fat substitutes (i.e., non-absorbable, non-digestible polyol polyesters, e.g., sugar fatty acid esters or sugar alcohol fatty acid esters and the like). Beta-carotene is sufficiently soluble in polyol fatty acid polyesters such that it remains with the oil as it passes through the body undigested.
  • beta-carotene Methods for preparing "water dispersible" beta-carotene are well known in the art .
  • One method of forming a water dispersible beta-carotene includes binding the carotenoid material with soluble starch, see for example U. S. 3,790,688 issued February 5, 1974.
  • the starch coating helps disperse and keep the beta-carotene in the solution.
  • the beta-carotene is "dispersed” rather than "dissolved” in the aqueous media.
  • Another method comprises the steps of forming a solution of a carotenoid in a volatile organic solvent and emulsifying the solution with an aqueous solution containing sodium lauryl sulfate (SLS), other dispersing agents and stabilizers, using a high speed, high shear mixer, see for example, U. S. 3,998,753, issued December 21, 1976.
  • SLS sodium lauryl sulfate
  • This method requires an additional step to remove the volatile solvent from the emulsion.
  • Still another method comprises the steps of reacting the beta-carotene with cyclodextrin to form an encapsulated beta- carotene.
  • this product when placed in water forms an obvious dispersion, with particles visible to the naked eye and the beta-carotene separates from the water within a few days.
  • beta-carotene While water dispersible beta-carotenes are suitable for some applications (e.g., beverages) they are not suitable for others (e.g., fat substitutes) because the beta-carotene itself is still oil soluble. Only a few processes for the manufacture of "water soluble" beta-carotene have been suggested in the art. For example, Japanese Patent 410109178, prepares water soluble beta-carotene by treating the carotenoids and methylcellulose with powdered water soluble polysaccharides. In this method, the carbohydrate is coated with beta-carotene, butylhydroxyanisole, dibutylhydroxytoluene and chloroform. When produced by this process the beta-carotene is distributed over the surface of the particle, where it can be exposed to oxygen and light, thus being capable of increased degradation.
  • Japanese Patent 410109178 prepares water soluble beta-carotene by treating the carotenoids and methylcellulose with powdered water soluble polysaccharides. In
  • beta-carotene i.e. crystal structure, melting point, solubility
  • oil soluble vitamins i.e., vitamin A, vitamin E, vitamin D
  • Another object of the present invention is to prepare bioavailable beta-carotene in a powder form which can be used in oil based products, water based products and products containing polyol fatty acid polyesters or other nondigestible fat substitutes.
  • the present invention is directed to a novel method for preparing water soluble beta- carotene compositions in the form of a dry powder. These compositions can be used in pharmaceuticals, aqueous food products, fat substitutes and products which contain fat substitutes.
  • the method comprise the steps of : a) heating an aqueous solution of cyclodextrin or cyclodextrin derivatives and mixtures thereof ; b) adding a second solution of beta-carotene or beta-carotene derivatives and mixtures thereof in an organic solvent to solution (a) with stirring for a time sufficient to remove the organic solvent; c) removing any excess beta-carotene from the resultant solution; and e) evaporating the resultant solution to dryness.
  • the products of the present invention are "water soluble" complexes of beta-carotene in cyclodextrin.
  • water soluble means that the compounds of the present invention shows UV-visible absorbance characteristic of ⁇ -carotene after dissolution in water and filtration.
  • the complexed beta-carotene has characteristic, i.e., beta-carotene, UV-visible spectroscopy absorbance when dissolved in water whereas the prior art products, having similar ingredients, exhibit no absorbance in this region.
  • An additional benefit is that the particle size of the complex can be reduced without affecting the water-soluble properties.
  • Beta-carotene is a naturally occurring precursor to vitamin A and it's often used as an orange/yellow pigment. The molecular structure is similar to that of vitamin A. Beta-carotene is typically derived by extraction from plant sources such as algae. The extraction processes are well known in the art Beta-carotene may also be synthesized using known chemical processes such as that disclosed in U. S. 4,504,499. Beta-carotene is easily degraded when subjected to air, UV light or high temperatures. Therefore, beta-carotene is generally sold in stabilized forms. Stabilized beta-carotene is readily available from several commercial sources, for example, BASF Corporation and Hoffinan LaRoche, Nutley, NJ. In the practice of the present invention, it is preferred to use neat beta-carotene crystals. However, neat beta-carotene crystals are not commercially available except by special arrangement with a supplier.
  • the beta-carotene is dissolved in an organic solvent.
  • the organic solvents suitable for use herein are known solvents for the carotenoids.
  • the solvent must boil below boiling point of water or codistill with water.
  • Such solvents include acetone, alcohols, ethers, hexane and methyl ethyl ketone.
  • Other solvents also can be used, but are less preferred for food applications, for example hydrocarbons, halogenated aliphatic hydrocarbons, petroleum ether, polyhalogenated methane, chloroform, carbon tetrachloride, methylene chloride, benzene and carbon disulfide.
  • the preferred solvent for use herein is acetone.
  • the compositions of the present invention which are in a powder form contain from about
  • the cyclodextrins for use herein are water soluble derivatives of beta-cyclodextrin capable of forming inclusion complexes with beta-carotene and similar carotenoids.
  • Beta-cyclodextrins for use in the present invention include, for example, beta-cyclodextrin, heptakis (2,6-di-O-methyl)- beta-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, 2,3-dihydroxy propyl-beta-cyclodextrin, poly- beta-cyclodextrin and mixtures thereof.
  • the cyclodextrins for use herein have molecular weights of at least 972 grams/mole and a water solubility of at least 1.8 grams/100 milliliters at 25°C.
  • the cyclodextrins are dissolved in water at a concentration of from about 0.5% to about 50%.
  • the preferred cyclodextrin derivatives are ⁇ - cyclodextrin and 2-hydroxypropyl-beta- cyclodextrin.
  • antioxidants may be dissolved in the solvent containing the beta-carotene to further enhance the stability against deterioration caused by heat, air, light and moisture.
  • Any antioxidant approved for food use may be used in the present invention, including, but not limited to, propyl gallate, ascorbyl palmitate, butylated hydroxy anisole (herein after referred to as "BHA”), butylated hydroxy toluene (herein after referred to as "BHT”), ascorbic acid, erythorbic acid, gallic acid, alpha-tocopherol and mixtures thereof.
  • BHA butylated hydroxy anisole
  • BHT butylated hydroxy toluene
  • the antioxidants may also be used with compounds having little or no antioxidative properties themselves (e.g. citric acid, lecithin, etc.) which when admixed, act in synergy to prevent oxidation.
  • the preferred antioxidant is ⁇ -tocopherol.
  • the amount of antioxidant used may be as high as 100 times the level of beta-carotene.
  • the amount of anti-oxidant used is from about 1 to 3 times the amount of ⁇ -carotene.
  • the amount of antioxidant should at least be equal to the amount of ⁇ -carotene.
  • the powdered water soluble beta-carotene compositions are prepared by initially forming an aqueous solution of cyclodextrin.
  • the beta-cyclodextrin solution is heated to a temperature of from about 45°C to about 95°C.
  • beta-carotene, and if desired the antioxidant is dissolved in an organic solvent, preferably forming a saturated solution of beta-carotene.
  • the concentration of ⁇ -carotene in the organic solvent may be lower than saturated.
  • the cyclodextrin solution is heated to the desired temperature.
  • the reaction may be done under vacuum however, a vacuum is not required.
  • the solvent/beta-carotene solution is slowly added to the hot solution of beta-cyclodextrin with rapid stirring.
  • the organic solvent evaporates.
  • any free beta-carotene present in the combined aqueous solution is removed by a separation method known in the art (i.e. filtration, decanting, centrifugation etc.).
  • the preferred method of separation is filtration.
  • the remaining aqueous solution containing the complexed beta-carotene is evaporated to dryness, using methods known in the art, for example freeze- drying, spray- drying or rotary- evaporating.
  • the resulting powder can be reduced to the desired particle size by methods known in the art.
  • the water soluble powders produced herein contain from about 0.1% to about 32%, preferably from about 1% to about 32% beta-carotene in cyclodextrin.
  • hydroxypropyl-beta-cyclodextrin 0.1 grams is added to 25 mL water.
  • the cyclodextrin is solubilized by stirring at ambient temperature.
  • the following solution is prepared by dissolving 0.005 grams alpha-tocopherol in 50 mL of acetone at ambient temperature.
  • Beta carotene is weighed under a nitrogen atmosphere and dissolved in acetone/ ⁇ -tocopherol solution.
  • This solution is then added dropwise to the boiling solution of hydroxypropyl-beta- cyclodextrin.
  • the solution containing the reacted beta-carotene and beta-cyclodextrin is removed by filtration from the unreacted beta-carotene and evaporated to dryness at ambient temperature.

Abstract

A process for preparing a powdered water soluble beta-carotene is disclosed. The carotenoid composition is prepared by combining an aqueous solution of cyclodextrin or derivatized cyclodextrins, and a solution of beta-carotene, beta-carotene derivatives or mixtures thereof, dissolved in an organic solvent. The beta-carotene solution is added to the cyclodextrin solution with stirring for a time sufficient to remove the organic solvent. Excess beta-carotene is removed and the remaining solution is evaporated to dryness.

Description

PROCESS FOR PREPARING ENCAPSULATED WATER SOLUBLE BETA-CAROTENE FIELD OF THE INVENTION
The present invention relates to water soluble carotenoid compositions and to a method for preparing such compositions. More particularly the present invention relates to dry beta-carotene compositions which exhibit superior resistance to oxidative and thermal degradation.
BACKGROUND OF THE INVENTION Supplementation of food products and animal feed with vitamin A is well known in the art.
The carotenoids, particularly, beta-carotene, are well known and the most commonly used source of vitamin A for nutritional supplementation. In humans, beta-carotene is reported to protect cells from the reactive species (free radicals) that are suggested as causes of cancer and atherosclerosis.
To be acceptable as a nutritional supplement in foods, the beta-carotene must be reasonably soluble and bioavailable. Although beta-carotene is considered to be oil soluble, it is poorly soluble in vegetable oils and insoluble in water. For example, beta-carotene has a solubility of about 0.08% by weight in vegetable oils at room temperature. The solubility of the beta-carotene has severely hindered its absorbability from food products having an aqueous base, for example, beverages, puddings, and soups and from fat substitutes (i.e., non-absorbable, non-digestible polyol polyesters, e.g., sugar fatty acid esters or sugar alcohol fatty acid esters and the like). Beta-carotene is sufficiently soluble in polyol fatty acid polyesters such that it remains with the oil as it passes through the body undigested.
Methods for preparing "water dispersible" beta-carotene are well known in the art . One method of forming a water dispersible beta-carotene includes binding the carotenoid material with soluble starch, see for example U. S. 3,790,688 issued February 5, 1974. The starch coating helps disperse and keep the beta-carotene in the solution. However, the beta-carotene is "dispersed" rather than "dissolved" in the aqueous media. Another method comprises the steps of forming a solution of a carotenoid in a volatile organic solvent and emulsifying the solution with an aqueous solution containing sodium lauryl sulfate (SLS), other dispersing agents and stabilizers, using a high speed, high shear mixer, see for example, U. S. 3,998,753, issued December 21, 1976. This method requires an additional step to remove the volatile solvent from the emulsion. Still another method comprises the steps of reacting the beta-carotene with cyclodextrin to form an encapsulated beta- carotene. However, this product when placed in water forms an obvious dispersion, with particles visible to the naked eye and the beta-carotene separates from the water within a few days. While water dispersible beta-carotenes are suitable for some applications (e.g., beverages) they are not suitable for others (e.g., fat substitutes) because the beta-carotene itself is still oil soluble. Only a few processes for the manufacture of "water soluble" beta-carotene have been suggested in the art. For example, Japanese Patent 410109178, prepares water soluble beta-carotene by treating the carotenoids and methylcellulose with powdered water soluble polysaccharides. In this method, the carbohydrate is coated with beta-carotene, butylhydroxyanisole, dibutylhydroxytoluene and chloroform. When produced by this process the beta-carotene is distributed over the surface of the particle, where it can be exposed to oxygen and light, thus being capable of increased degradation.
Although many of these compounds are described as being "water soluble," the β carotene itself is only dispersed in the water and can be removed by simple filtration techniques. It has also been suggested by the art that water solubility of certain vitamins could be achieved by forming inclusions complexes with cyclodextrins. U.S. 4,727,064 (1988) describes a process for encapsulating pharmaceuticals which requires stirring a solution for 24 hours.
Surprisingly, it has been found that the process used to prepare the complexed beta- carotene is critical to its water solubility and therefore its bioavailability. The difference in the physical properties of beta-carotene (i.e. crystal structure, melting point, solubility) and the oil soluble vitamins (i.e., vitamin A, vitamin E, vitamin D) are such that the methods used to encapsulate/complex these other oil soluble vitamins with cyclodextrin are ineffective for complexing/encapsulating beta-carotene. In fact, two complexes, both comprising cyclodextrin and beta-carotene, have suprisingly different water solubilities thereby affecting their bioavailability and use in certain foods and pharmaceutical preparations. It is an object of the present invention to provide a simple process for manufacturing water soluble beta-carotene.
Another object of the present invention is to prepare bioavailable beta-carotene in a powder form which can be used in oil based products, water based products and products containing polyol fatty acid polyesters or other nondigestible fat substitutes. These and other objects will become apparent from the following detailed description. All percentages herein are by weight unless otherwise specified.
SUMMARY OF THE INVENTION
The present invention is directed to a novel method for preparing water soluble beta- carotene compositions in the form of a dry powder. These compositions can be used in pharmaceuticals, aqueous food products, fat substitutes and products which contain fat substitutes. The method comprise the steps of : a) heating an aqueous solution of cyclodextrin or cyclodextrin derivatives and mixtures thereof ; b) adding a second solution of beta-carotene or beta-carotene derivatives and mixtures thereof in an organic solvent to solution (a) with stirring for a time sufficient to remove the organic solvent; c) removing any excess beta-carotene from the resultant solution; and e) evaporating the resultant solution to dryness.
DETAILED DESCRIPTION OF THE INVENTION
The products of the present invention are "water soluble" complexes of beta-carotene in cyclodextrin. As used herein the term "water soluble" means that the compounds of the present invention shows UV-visible absorbance characteristic of β-carotene after dissolution in water and filtration. These products are significantly different from the prior art products in that the complexed beta-carotene has characteristic, i.e., beta-carotene, UV-visible spectroscopy absorbance when dissolved in water whereas the prior art products, having similar ingredients, exhibit no absorbance in this region. An additional benefit is that the particle size of the complex can be reduced without affecting the water-soluble properties.
Beta-Carotene
Beta-carotene is a naturally occurring precursor to vitamin A and it's often used as an orange/yellow pigment. The molecular structure is similar to that of vitamin A. Beta-carotene is typically derived by extraction from plant sources such as algae. The extraction processes are well known in the art Beta-carotene may also be synthesized using known chemical processes such as that disclosed in U. S. 4,504,499. Beta-carotene is easily degraded when subjected to air, UV light or high temperatures. Therefore, beta-carotene is generally sold in stabilized forms. Stabilized beta-carotene is readily available from several commercial sources, for example, BASF Corporation and Hoffinan LaRoche, Nutley, NJ. In the practice of the present invention, it is preferred to use neat beta-carotene crystals. However, neat beta-carotene crystals are not commercially available except by special arrangement with a supplier.
The beta-carotene is dissolved in an organic solvent. The organic solvents suitable for use herein are known solvents for the carotenoids. The solvent must boil below boiling point of water or codistill with water. Such solvents include acetone, alcohols, ethers, hexane and methyl ethyl ketone. Other solvents also can be used, but are less preferred for food applications, for example hydrocarbons, halogenated aliphatic hydrocarbons, petroleum ether, polyhalogenated methane, chloroform, carbon tetrachloride, methylene chloride, benzene and carbon disulfide. The preferred solvent for use herein is acetone. The compositions of the present invention which are in a powder form contain from about
0.1% to about 32%, preferably from about 1% to about 32% and more preferably from about 10% to about 32% by weight, beta-carotene, the remainder being cyclodextrins.
CYCLODEXTRIN The cyclodextrins for use herein are water soluble derivatives of beta-cyclodextrin capable of forming inclusion complexes with beta-carotene and similar carotenoids. Beta-cyclodextrins for use in the present invention include, for example, beta-cyclodextrin, heptakis (2,6-di-O-methyl)- beta-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, 2,3-dihydroxy propyl-beta-cyclodextrin, poly- beta-cyclodextrin and mixtures thereof. The cyclodextrins for use herein have molecular weights of at least 972 grams/mole and a water solubility of at least 1.8 grams/100 milliliters at 25°C.
The cyclodextrins are dissolved in water at a concentration of from about 0.5% to about 50%. The preferred cyclodextrin derivatives are β- cyclodextrin and 2-hydroxypropyl-beta- cyclodextrin.
ADDITIONAL INGREDIENTS Because beta-carotene is sensitive to oxidation, preservatives and antioxidants may be dissolved in the solvent containing the beta-carotene to further enhance the stability against deterioration caused by heat, air, light and moisture. Any antioxidant approved for food use may be used in the present invention, including, but not limited to, propyl gallate, ascorbyl palmitate, butylated hydroxy anisole (herein after referred to as "BHA"), butylated hydroxy toluene (herein after referred to as "BHT"), ascorbic acid, erythorbic acid, gallic acid, alpha-tocopherol and mixtures thereof. The antioxidants may also be used with compounds having little or no antioxidative properties themselves (e.g. citric acid, lecithin, etc.) which when admixed, act in synergy to prevent oxidation.
The preferred antioxidant is α-tocopherol. When used in the present invention the amount of antioxidant used may be as high as 100 times the level of beta-carotene. Preferably the amount of anti-oxidant used is from about 1 to 3 times the amount of β-carotene. The amount of antioxidant should at least be equal to the amount of β -carotene.
METHOD OF PREPARATION
The powdered water soluble beta-carotene compositions are prepared by initially forming an aqueous solution of cyclodextrin. The beta-cyclodextrin solution is heated to a temperature of from about 45°C to about 95°C. Separately, beta-carotene, and if desired the antioxidant, is dissolved in an organic solvent, preferably forming a saturated solution of beta-carotene. However, the concentration of β-carotene in the organic solvent may be lower than saturated.
The cyclodextrin solution is heated to the desired temperature. The reaction may be done under vacuum however, a vacuum is not required. The solvent/beta-carotene solution is slowly added to the hot solution of beta-cyclodextrin with rapid stirring. The organic solvent evaporates.
It is critical that the solvent containing beta-carotene be added to the cyclodextrin solution at a rate sufficient to prevent the accumulation of solvent in the reaction vessel.
After all organic solvent has evaporated, any free beta-carotene present in the combined aqueous solution is removed by a separation method known in the art (i.e. filtration, decanting, centrifugation etc.). The preferred method of separation is filtration. The remaining aqueous solution containing the complexed beta-carotene is evaporated to dryness, using methods known in the art, for example freeze- drying, spray- drying or rotary- evaporating. The resulting powder can be reduced to the desired particle size by methods known in the art.
The water soluble powders produced herein contain from about 0.1% to about 32%, preferably from about 1% to about 32% beta-carotene in cyclodextrin.
The following examples are given to illustrate the invention and are not intended to limit it in any way.
EXAMPLE I
0.1 grams of hydroxypropyl-beta-cyclodextrin is added to 25 mL water. The cyclodextrin is solubilized by stirring at ambient temperature. In a separate vessel, the following solution is prepared by dissolving 0.005 grams alpha-tocopherol in 50 mL of acetone at ambient temperature. Beta carotene is weighed under a nitrogen atmosphere and dissolved in acetone/α-tocopherol solution.
Beta-carotene 0.005 g
Alpha-tocopherol 0.005 g
Acetone 50 mL
This solution is then added dropwise to the boiling solution of hydroxypropyl-beta- cyclodextrin. The solution containing the reacted beta-carotene and beta-cyclodextrin is removed by filtration from the unreacted beta-carotene and evaporated to dryness at ambient temperature.

Claims

1. A process for producing a water soluble beta-carotene characterized in that it comprises the steps of : a) heating an aqueous solution of cyclodextrin or cyclodextrin derivative and mixtures thereof; b) adding a second solution of beta-carotene dissolved in an organic solvent to the aqueous solution with stirring for a time sufficient to remove the organic solvent; c) removing any excess beta-carotene from the resulting solution; and d) evaporating the solution to dryness.
2. The process of Claim 1 characterized in that the addition of solution (b) to solution
(a) is dropwise.
3. The process of any of Claims 1-2 characterized in that the solution (d) is subjected to a freeze-drying or spray-drying process or evaporated to dryness using a rotary evaporator.
4. A process for producing a water soluble beta-carotene characterized in that it comprises the steps of: a) preparing an aqueous solution of cyclodextrin or cyclodextrin derivative and mixtures thereof wherein the concentration of cyclodextrin or cyclodextrin derivative is from about 0.5% to about 50%. b) heating the aqueous solution of (a); c) preparing a second solution of an antioxidant and beta-carotene dissolved in an organic solvent wherein the amount of said antioxidant is at least equivalent to the amount of beta-carotene. d) adding the solution of (c) to the solution of (b) with stirring for a time sufficient to remove the organic solvent at a temperature of from 45°C to 95°C; e) removing any excess beta-carotene from solution (d); and f) evaporating the solution of (e) to dryness.
5. The process of Claim 4 characterized in that the addition of solution (c) to solution (b) is dropwise.
6. The process of any of Claims 4 or 5 characterized in that the antioxidant is alpha-tocopherol or ascorbyl palmitate or mixtures thereof.
7. The process of any of Claims 4, 5 or 6 characterized in that the addition of solvent (c) to solution (b) is done under vacuum.
8. The process of any of Claims 1, 2, 3, 4, 5, 6 or 7 characterized in that the cyclodextrin derivative is 2-hydroxypropyl beta-cyclodextrin.
9. The process of any of Claims 1-8 characterized in that the organic solvent is acetone.
10. The process of any of Claims 1-9 characterized in that the cyclodextrin or derivative has a water solubility of at least 1.8 grams/100 milliliters at 25°C
PCT/US1996/006981 1995-06-07 1996-05-16 Process for preparing encapsulated water soluble beta-carotene WO1996040262A2 (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6007856A (en) * 1997-08-08 1999-12-28 The Procter & Gamble Company Oil-in-water dispersions of β-carotene and other carotenoids stable against oxidation prepared from water-dispersible beadlets having high concentrations of carotenoid
WO2003095498A1 (en) * 2002-05-10 2003-11-20 Yunqing Liu Complex of organic medicines and beta-cyclodextrin derivatives and its preparing process
WO2004005353A1 (en) * 2002-07-04 2004-01-15 Poltec As Complexes of cyclodextrins and carotenoids
EP1931361A2 (en) * 2005-10-05 2008-06-18 Pharmanex, Llc Nanosized carotenoid cyclodextrin complexes
US10117823B2 (en) 2013-03-12 2018-11-06 Primal Therapies, Inc. Dental composition comprising chelator and base

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US11491100B2 (en) 2013-03-12 2022-11-08 Primal Therapies, Inc. Dermal composition comprising chelator and base

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