Classifications

• • 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
  • A61K31/01—Hydrocarbons
  • A61K31/015—Hydrocarbons carbocyclic
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/15—Vitamins
  • A23L33/155—Vitamins A or D
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
  • A23L5/40—Colouring or decolouring of foods
  • A23L5/42—Addition of dyes or pigments, e.g. in combination with optical brighteners
  • A23L5/43—Addition of dyes or pigments, e.g. in combination with optical brighteners using naturally occurring organic dyes or pigments, their artificial duplicates or their derivatives
  • A23L5/44—Addition of dyes or pigments, e.g. in combination with optical brighteners using naturally occurring organic dyes or pigments, their artificial duplicates or their derivatives using carotenoids or xanthophylls
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
  • A23P10/00—Shaping or working of foodstuffs characterised by the products
  • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
  • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
  • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/02—Nutrients, e.g. vitamins, minerals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
  • A61P39/06—Free radical scavengers or antioxidants
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
  • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

• the present invention relates to granules containing carotenoids and a process for their production. More particularly, the present invention relates to encapsulated carotenoids, especially ⁇ -carotene, obtained using various kinds of food starches and formulated in granules with improved handling properties, compression capacity, color release and appearance, and which They are useful for coloring beverages, for formulating solid and semi-solid pharmaceutical preparations and for stimulating the growth of fish.
• ⁇ -carotene is used in various forms as a natural coloring agent for food, cosmetics, fish food and the like, as an additive for healthy foods and as a material to regulate vital functions, as a supplement nutritious dietary
• carotenoids ⁇ -carotene, one of the compounds in the provitamin A group, is easily oxidizable because it contains a chain with conjugated double bonds. It is also a poorly soluble compound in water.
• US 5364563 describes a process for producing a powder carotenoid preparation, which comprises forming a suspension of a carotenoid in a high boiling oil without the presence of organic solvent.
• the suspension is superheated with steam for a maximum period of thirty seconds to form a carotenoid solution in oil.
• the solution is emulsified in an aqueous solution of a colloid and then the emulsion is spray dried forming a powder.
• WO93 / 04598 proposed the use of
• SUBSTITUTE SHEET (RULE 26) natural additives, such as stabilizers, acidulants and emulsifiers.
• US5714658 described the use of a mixture of different solvents that included esters of acetic acid, C1-C4 alcohols and oils compatible with the other solvents. In this procedure, there were two problems: first, the low solubility of carotenoids in the solvent mixture, which implies the need for a large amount of oil and solvents, especially if a high concentration of carotenoids is demanded, and second the environmental risks entailed by residual solvents.
• EP807431 describes a procedure for obtaining an aqueous solution of carotenoids with a protective colloid, at high temperature (180-250 ° C) and pressure (96.6-2.759 bar), obtaining an emulsion that after drying produces the Carotenoid in the form of a dry powder.
• US5780056 describes microcapsules that are constituted by a core material comprising a natural carotenoid, an edible oil, and a wall that is made of a gelatin-based coating material, the particles having an average particle size of 0.01. -5 ⁇ m.
• the microcapsule has sufficient strength to protect the natural carotenoid against oxidation and deterioration for a long time and to withstand the pressing pressure.
• the colloid used is gelatin from warm-blooded animals and such origin is usually problematic. For example, preparations based on this type of jelly cannot be used for religious reasons worldwide.
• SUBSTITUTE SHEET (RULE 26) of these proteins being carriers of infections and more particularly of the disease known as the mad cow syndrome.
• the particles In order to obtain maximum benefit from carotenoids, the particles must either dissolve rapidly, or be sufficiently wettable to be easily absorbed.
• the first strategy was to manufacture microcapsules such as those in US5478569 and US5780056.
• the resulting microcapsules have low resistance and the stabilizing effect of the gelatin against oxidation as a protective coating is not fully exercised. Then, the natural carotenoid is vulnerable to oxidation and deterioration.
• the low resistance of the microcapsules poses another problem. When the microcapsules are mixed with a vehicle and pressed to form tablets, the microcapsules can break during pressing, allowing the carotenoid to escape. Therefore, it is difficult to mix carotenoid tablets in a stable manner.
• the second strategy could be the spray coating of the carotenoid with aqueous solutions containing approximately 0.5% to approximately 10% by weight of a material that confers hydrophilic character, selected from the group consisting of methyl cellulose, hydroxyethyl- methyl cellulose and hydroxypropyl methyl cellulose.
• a material that confers hydrophilic character selected from the group consisting of methyl cellulose, hydroxyethyl- methyl cellulose and hydroxypropyl methyl cellulose.
• the limitation is that the procedure whereby the material that confers hydrophilic character is applied to the surface of the individual particles must be carried out in a way that ensures that the particles do not agglomerate.
• the resulting powder is a freely circulating powder and is also capable of being compressed by direct pressing or encapsulated in a hard capsule. A method for manufacturing such granulation and formulations is also described.
• An object of the present invention is to provide a water dispersible carotenoid formulation 25 containing approximately 1 to 25 parts by weight of dry carotenoid powder encapsulated in a food grade starch matrix that provides ⁇ -carotene included in the encapsulated powder In a stable condition.
• Formulations containing natural carotenoids have satisfactory physiological activity for the human body and a resistance high enough to prevent the carotenoid from being oxidized or damaged during storage.
• SUBSTITUTE SHEET (RULE 26) long term.
• the formulations are suitable to be mixed in capsules or tablets, or the like, stably, and in applications such as additives for food and pharmaceuticals.
• Another object of this invention is to provide a process for producing the formulation, which comprises the following steps: adding ⁇ -carotene to a mixture of natural or synthetic tocopherols in vegetable oil and dissolving the resulting mixture in isobutyl acetate or n-butyl acetate , dissolve a mixture of two different starches in deionized water, prepare an emulsion by mixing both phases and remove organic solvent at temperatures between 50 and 80 ° and reduced pressure, until 15-25% of dry matter is obtained, and dry to obtain the Final product.
• the initial temperature was in the range of 100 to 190 ° C, while the final temperature was in the range of 80 to 150 ° C.
• a fluidized bed granulator in a fluidized bed granulator the planting material is placed, that is, typical inert material such as sugar particles, as well as dusting powder or fine powder obtained in previous granulation procedures or in a spray drying process.
• the particles are kept moving by air, and the initial and final temperature of the same is adjusted between 30 and 90 ° C.
• a solution of the liquid formulation (15-25% dry matter) is sprayed into the dryer at a rate that ensures that the particles to be coated do not get too wet or conglomerate. Once the spraying is finished, the particles can be coated.
• the invention also relates to spray coating with approximately 0.5% to approximately 10% by weight of aqueous concentrated sugar solutions or with a selected material that confers hydrophilic character, ie methyl cellulose, hydroxyethyl methyl cellulose and hydroxypropyl -methyl cellulose.
• the particles can be dried directly
• the invention also relates to pharmaceutical preparations in powder form or in the form of tablets containing the carotenoid granulate in combination with pharmaceutically acceptable and conventional pharmaceutically acceptable adjuvants and / or excipients.
• Pharmaceutically acceptable and suitable pharmaceutically acceptable adjuvants and excipients are microcrystalline cellulose, dextrose, lactose, sucrose, mannitol, glucose and sorbitol; lubricants such as calcium stearate, stearic acid or magnesium stearate as well as mixtures thereof. Talc, corn starch, etc. can be mixed with the lubricants. flavoring agents and coloring agents can also be used.
• the process for producing tablets containing ⁇ -carotene comprises the following steps: mixing and / or granulating the water dispersible formulation with adjuvants and / or excipients, and pressing in an eccentric or rotary tablet press at a pressure applied between 30 and 200 MPa.
• the ⁇ -carotene remained in the starch matrix after compression in a stable condition and released ⁇ -carotene in a very short time.
• the products of the present invention are solid, water dispersible ⁇ -carotene formulations.
• water dispersible means that the formulations of the present invention show a characteristic UV-visible spectrum of ⁇ -carotene after its dissolution and filtration. Due to the interaction of light with very small particles, the crystals appear more yellow the smaller their size. ⁇ - crystals
• SUBSTITUTE SHEET (RULE 26) Carotene about 3-5 ⁇ m in size are tomato red. The color changes to orange if the particle size is approximately 1 ⁇ m and the dispersion is yellow if the particle diameter is as small as approximately 0.6 ⁇ m. This effect is caused by shifts in the light absorption spectrum.
• ⁇ -carotene is a natural precursor of Vitamin A and is often used as an important dye in the beverage industry.
• ⁇ -Carotene is typically obtained by extraction from fermentation sources or is synthesized using known chemical procedures. However, ⁇ -carotene degrades easily when exposed to air, light or temperature. Therefore, ⁇ -carotene is stabilized and available in various formulations, such as those developed by BASF Corporation or Hoffman LaRoche. In the present invention, it is preferred to use ⁇ -carotene crystals.
• the ⁇ -carotene is dissolved in an organic solvent.
• the ⁇ -carotene was suspended in iso-butyl acetate (IBA).
• IBA iso-butyl acetate
• the suspension was ground in a ball mill (Netzch minizeta) at 1,500 rpm for approximately 10-15 minutes.
• the viscous paste was transferred to hot IBA and continuously stirred at 60 ° C.
• the suspension in IBA was rapidly heated to 105 ° C. The temperature was maintained for 5 minutes.
• the ⁇ -carotene solution was then formed and cooled to 85-90 ° C.
• the composition of the present invention comprises about 1 to 25 parts by weight of ⁇ -carotene in the dry powder, the rest being starches-OSA.
• SUBSTITUTE SHEET (RULE 26)
• the starches used are a modified food grade corn starch of high molecular weight, which allows a simple emulsification of the organic phase in water. After separating the solvent, the dispersion satisfies the color range of ⁇ -carotene.
• This modified food starch does not produce enough redispersability of dry powder. Therefore, another starch is also added.
• the second variety is a mixture of food grade starches of different molecular weights in a range of 1,000-700,000; This second type of starch provides good dispersibility of the final product.
• antioxidants can be dissolved in the solvent containing ⁇ -carotene to enhance stability against deterioration.
• any authorized antioxidant can be used in foods, including but not limited to el-tocopherol of natural or synthetic origin.
• the antioxidant level will be sufficient to protect ⁇ -carotene. This will have to be 0.1 to 0.3 times the amount of ⁇ -carotene.
• Ascorbyl palmitate can also be added to the formulation due to the synergistic antioxidant effect of the association of both antioxidants.
• the next step is emulsification.
• the solution of ⁇ -carotene with antioxidants in the mentioned solvent and at 85-90 ° C is poured into the solution of starch in water.
• the dark brown solution has a temperature below 50 ° C and is homogenized immediately after using a rotor-stator system (IKA MF45) for 10 min.
• IKA MF45 rotor-stator system
• SUBSTITUTE SHEET (RULE 26) Emulsion takes a dark orange color during the first minute.
• Evaporation of the solvent / micronization is carried out at 40-45 ° C and reduced pressure (approximately 65 mbar) in about 30 minutes.
• the solvent residues are separated by evaporating the water for several hours.
• the preferred method is the fluidized bed.
• the planting material that is, a typical inert material such as sugar particles, as well as a dusting or fine powder obtained from prior granulation procedures or a spray drying process, are placed in a fluidized bed granulator.
• the particles are kept moving by air, whose inlet and outlet temperature is adjusted accordingly within the range of 30-90 ° C.
• a solution of the liquid formulation (15-25% dry matter) is sprayed at a rate that ensures that the particles to be coated do not get too wet or conglomerate.
• SUBSTITUTE SHEET (RULE 26) ⁇ -carotene content of 2.4% in solution (12.7% of ⁇ -carotene based on dry mass).
• the dispersion was granulated and dried in a fluidized bed (UniGlatt) of sugar crystals. A freely circulating powder was obtained, wettable with water and dispersible very quickly.
• Table 1 Ingredients of the ⁇ -carotene formulation.
• the dispersion was diluted with water and the iso-butyl acetate evaporated rapidly in a range of 30 min at 40-45 ° C and 65 mbar. The solvent residues were separated by evaporating the water for several hours.
• the dispersion was granulated and dried in a continuous AGT 150 fluidized bed granulator (Glatt) without planting material. A freely circulating powder was obtained, wettable with water and dispersible very quickly.
• Table 2 Ingredients of the ⁇ -carotene formulation.

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• Health & Medical Sciences (AREA)
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• General Health & Medical Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Engineering & Computer Science (AREA)
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• Food Science & Technology (AREA)
• Epidemiology (AREA)
• Polymers & Plastics (AREA)
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• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
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• 2000
  • 2000-07-13 JP JP2002514089A patent/JP2004514419A/ja active Pending
  • 2000-07-13 AT AT00949487T patent/ATE259351T1/de not_active IP Right Cessation
  • 2000-07-13 EP EP00949487A patent/EP1300394B1/en not_active Revoked
  • 2000-07-13 WO PCT/ES2000/000250 patent/WO2002008182A1/es not_active Ceased
  • 2000-07-13 PT PT00949487T patent/PT1300394E/pt unknown
  • 2000-07-13 DE DE60008299T patent/DE60008299T2/de not_active Revoked
  • 2000-07-13 AU AU2000262820A patent/AU2000262820A1/en not_active Abandoned
  • 2000-07-13 ES ES00949487T patent/ES2215696T3/es not_active Expired - Lifetime
• 2003
  • 2003-01-03 US US10/336,658 patent/US20050169999A1/en not_active Abandoned

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