US20050080136A1 - Powder of amino acids and method for producing the same - Google Patents

Powder of amino acids and method for producing the same Download PDF

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US20050080136A1
US20050080136A1 US10/921,895 US92189504A US2005080136A1 US 20050080136 A1 US20050080136 A1 US 20050080136A1 US 92189504 A US92189504 A US 92189504A US 2005080136 A1 US2005080136 A1 US 2005080136A1
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powder
amino acid
amino acids
trehalose
spray drying
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Aiji Watanabe
Junichi Katouno
Teruo Yoshida
Susumu Tsujimoto
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Ajinomoto Co Inc
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Ajinomoto Co Inc
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Assigned to AJINOMOTO CO., INC. reassignment AJINOMOTO CO., INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: YOSHIDA, TERUO, KATOUNO, JUNICHI, TSUJIMOTO, SUSUMU, WATANABE, AIJI
Publication of US20050080136A1 publication Critical patent/US20050080136A1/en
Priority to US12/168,566 priority Critical patent/US7662799B2/en
Abandoned legal-status Critical Current

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    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • 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
    • A23P10/40—Shaping or working of foodstuffs characterised by the products free-flowing powder or instant powder, i.e. powder which is reconstituted rapidly when liquid is added
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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 powders of amino acids, which is a microfine or granulated amino acid powder containing trehalose.
  • the present invention further relates to methods for producing such powders.
  • amino acids amino acid salts, and amino acid derivatives (simply referred to as amino acids hereinafter) are widely used in medical diets for nutrition supplements, disease-specific amino acid preparations for oral administration and infusion for subject patients with renal impairment and liver disorders, infantile nutritious compositions, diet food materials, health foods, and functional foods. Further, amino acids are used in cosmetics and in veterinary preparations for dosing to animals, after being mixed in feeds and the like.
  • Trehalose when contained in amino acids, not only serves as a saccharide nutrient but also suppresses the bittern taste of amino acids, advantageously, without any occurrence of the Maillard reaction (browning reaction). Therefore, the presence of trehalose therein is recommended. Specifically, those formulations described below are known.
  • trehalose-coated (film) powders of amino acids are known, and may be prepared by one of the following methods.
  • a binder is added to a powder of amino acids in mixture to prepare granules by an extrusion granulation process, and the granules surfaces are then coated with trehalose as a coating material by fluid granulation.
  • trehalose and a binder are added to a powder of amino acids in mixture for coating by fluid granulation, and spraying an aqueous ethanol solution over the resulting coated powder for granulation (see, JP-A-6-227975).
  • amino acid food products containing trehalose which are adjusted to a pH 3.0 to 6.0 by the addition of sour agents such as citric acid so as to prevent flavor deterioration due to heating of the amino acid, or flavor modification or color modification of the amino acid during long-term storage.
  • sour agents such as citric acid
  • compositions for use in the suppression of blood amino acid variation following vigorous athletic motion a hydrous solution of a composition of amino acids and sugar is disclosed, which contains at least 13 types of amino acids and trehalose.
  • the hydrous solution is said to be effective for the improvement of athletic potential and the amelioration of fatigue (see, JP-A-2000-72669).
  • the spray drying method is capable of producing microfine particles, and is a dry method for recovering a dry powder of spherical and spherical shell-shaped powder, by dispersing a solution or a particle slurry into the form of microfine particles in hot air, where the spray method uses pressure nozzle, rotating disk, and two-fluid nozzle and the like.
  • the mean particle size of the dry powder is about 20 ⁇ m to 500 ⁇ m (see, Handbook of Chemistry and Engineering , revised sixth edition, p. 770, p.
  • an inhalation dry composition containing the pharmacologically active component, interferon, as the essential component and containing a hydrophobic amino acid selected from leucine, isoleucine, and valine at 60% or more to less than 100% (mean particle size (volume-based distribution) of 0.1 ⁇ m or more to 10 ⁇ m or less) is disclosed for the purpose of avoiding the deliquescence of the inhalation dry composition, when left at a high humidity (see, JP-A-9-235238).
  • Example 2 of JP-A-9-2352308 a dry particle powder is obtained as a control, by preparing a solution containing 3.5 g of isoleucine, 0.7 g of serum albumin, 695.8 g of deionized water, and 300 g of ethanol for spray drying, and then spraying the resulting solution with a spray dryer (aerodynamic mean particle size of 0.9897 ⁇ m).
  • a spray dryer anodynamic mean particle size of 0.9897 ⁇ m.
  • this Example does not include any description of oral meltability, solubility, and taste masking.
  • novel dry powders meaning microfine powder or granulated powder
  • amino acids which have great oral meltability and solubility and a high masking effect of the taste.
  • a method for producing a powder of amino acids comprising spray drying a hydrous liquid of amino acids to produce a powder of amino acids, where the hydrous liquid of amino acids is prepared into the form of microfine liquid droplets in the presence of trehalose for spray drying to prepare a powder having a mean particle size (Mean Volume Diameter) of 0.1 ⁇ m to 15 ⁇ m.
  • a method for producing a powder of amino acids comprising spray drying a hydrous liquid of amino acids to produce a powder of amino acids, where the hydrous liquid of amino acids is prepared into the form of microfine liquid droplets in the presence of trehalose for spray drying, and the resulting powder is then granulated and dried during spray drying or after spray drying, to prepare a granulated powder having a mean particle size (Mean Volume Diameter) of 20 ⁇ m to 1,000 ⁇ m.
  • FIG. 1 depicts two X-ray diffraction charts, in which the upper line is the X-ray powder diffraction pattern of the spray dry granulated powder of Example 1 and the lower line is the X-ray powder diffraction pattern of the mixed powder before drying of Comparative Example 2; and
  • FIG. 2 depicts three X-ray diffraction charts, in which the upper line is the X-ray diffraction pattern of trehalose; the middle line is the X-ray diffraction pattern of “the mix powder of amino acids” used as the raw materials of Comparative Example 2; and the lower line is the X-ray diffraction pattern of hydroxypropyl cellulose.
  • the present invention provides novel powders comprising amino acids and methods of producing such powders.
  • novel powders comprising amino acids and methods of producing such powders.
  • the various aspects of the present invention are specifically described below.
  • amino acids to be used in accordance with the present invention include amino acids, salts of amino acid, and amino acid derivatives, for example branched amino acids such as leucine, isoleucine, and valine, sulfur-containing amino acids such as cystine and methionine, aromatic amino acids such as phenylalanine and tyrosine, heterocyclic amino acids such as tryptophan and histidine, acidic amino acids such as aspartic acid and glutamic acid, and various amino acid derivatives such as sulfur-containing amino acid derivatives including taurine. These amino acids may be used singly or in combination of two or more thereof.
  • the subject hydrous solution of the amino acid(s) is in the solution state or a particle slurry solution state (for example, a slurry containing particles having a mean particle size (Mean Volume Diameter) of 0.1 ⁇ m to 15 ⁇ m), and the solvent may contain ethyl alcohol and the like.
  • a particle slurry solution state for example, a slurry containing particles having a mean particle size (Mean Volume Diameter) of 0.1 ⁇ m to 15 ⁇ m
  • the solvent may contain ethyl alcohol and the like.
  • the amino acids to which the present invention is effectively applied include amino acids relatively slightly soluble in water, such as amino acids with a solubility of 9 g or less in 10 g of water at 20° C.
  • the amino acids preferable for the application of the present invention are slightly soluble amino acids.
  • the present invention is preferably applied to amino acids with a solubility of 5 g or less in 100 g of water at 20° C.
  • the present invention is applicable to leucine, isoleucine, cystine, phenylalanine, tyrosine, tryptophan, and aspartic acid, and salts thereof and derivatives thereof, in particular.
  • the amount of the amino acid(s) to be used generally includes but is not specifically limited to 20% by weight to 95% by weight in the dry powder. If necessary, the amount may be at 50% by weight to 95% by weight, 60% by weight to 95% by weight, or 70% by weight to 95% by weight.
  • the amount to be used may satisfactorily be determined, taking account of the conditions of product design, namely the balance between the amount of amino acid(s) required as effective ingredients and the specific volume of the dry powder of amino acids.
  • the raw material trehalose for use in accordance with the invention includes ⁇ , ⁇ -trehalose, ⁇ , ⁇ -trehalose, and ⁇ , ⁇ -trehalose.
  • ⁇ , ⁇ -Trehalose is preferable, because ⁇ , ⁇ -trehalose is a naturally occurring substance and is now not costly. If necessary, the dihydrate thereof with almost no hygroscopicity over time may be used, satisfactorily.
  • a commercially available “Treha” (Hayashibara, Co., Ltd.) is listed and may be used.
  • the amount of trehalose (on an anhydride basis) is 5% by weight to 80% by weight in the dry powder, satisfactorily. If necessary, the content can be 5% by weight to 50% by weight, 5% by weight to 40% by weight and 5% by weight to 30% by weight.
  • the amount of trehalose to be used may be adjusted to the conditions for product design, as described above.
  • the trehalose and the amino acid(s) may be mixed together to prepare a mixture solution prior to spray drying. Otherwise, a hydrous solution containing the amino acid(s) as the main components and a hydrous solution containing trehalose as the main component may be simultaneously sprayed together during spray drying. Alternatively, after a hydrous solution containing the amino acid(s) as the main component(s) has been spray dried, a hydrous solution containing trehalose as the main component may be sprayed and/or granulated as a coating agent and a binder, satisfactorily. If necessary, further additives, other than trehalose, may be added satisfactorily as a matter of course.
  • the spray drying apparatus for use in accordance with the present invention, commercially available apparatus can be used.
  • a spray drying apparatus which has a vertical parallel flow function is preferable.
  • the productivity can be maintained, even under drying conditions with dehumidification at low temperature, and the quality of the resulting dry powder can be maintained at a high level, preferably.
  • an apparatus capable of blowing a high volume of dry dehumidified gas at 1% RH or less is particularly preferable as the dehumidifying apparatus, which is for example a dry dehumidifier BX series manufactured by Munsters K. K., and HCS series and HCP series manufactured by Nichias Corporation.
  • suitable spray drying apparatus include the micromist dryer MD series and the hybrid granulator series manufactured by Fujisaki Electric Co., Ltd., the FSD spray dryer with internal fluid layer as manufactured by Niro Corporation, the fluid granulation spray dryer and L-8 type spray dryer manufactured by O-gawara Chemical Engineering Machine Corporation, and the DL-21 type and GB-21 type manufactured by Yamato Scientific Co., Ltd.
  • a spray nozzle capable of generating a liquid droplet (microfine particle, single particle) having a mean particle size (Mean Volume Diameter) of 0.1 ⁇ m or more to less than 20 ⁇ m.
  • a spray dryer or a spray dry granulation apparatus with a spray nozzle capable of generating a large volume of liquid droplets having a mean particle size (Mean Volume Diameter) of 0.1 ⁇ m or more to less than 20 ⁇ m, preferably 0.1 ⁇ m to 10 ⁇ m, and more preferably 1 ⁇ m to 8 ⁇ m.
  • a dry powder having a mean particle size (Mean Volume Diameter) of 0.1 ⁇ m to 15 ⁇ m, preferably 0.1 ⁇ m to 7 ⁇ m, and more preferably 0.7 ⁇ m to 6 ⁇ m is obtained.
  • This is preferable with the respect to the control of the product quality and productivity, because such liquid droplets can be dried under low-temperature conditions within a short time.
  • the four-fluid nozzle manufactured by Fujisaki Electric Co., Ltd. which can spray a large volume (for example, 1 kg/min) of liquid droplets of several micrometers (see, U.S. Pat. No. 2,797,080; Chemical Apparatus, 2000, No. 6, pp.
  • the three-fluid nozzle manufactured by Fukusen Production Corporation, which can spray a large volume (for example, 150 g/min) of liquid droplets of 1 ⁇ m to 10 ⁇ m (see, Japanese Patent Publication Sho 63-5146) are included.
  • the four-fluid nozzle is particularly preferable because a large volume can be sprayed from the nozzle.
  • the spray dryer is preferably an apparatus with a granulation function or is additionally mounted with a granulation dryer if the spray dryer does not have such granulation function (referred to as “spray dry granulation apparatus”).
  • the resulting apparatus is of a specification to enable the granulated powder (aggregate particle powder) to be finally dried to the desired moisture.
  • particles with such a small specific gravity such as those of amino acids for use in accordance with the present invention
  • particles (Mean Volume Diameter) of 0.1 ⁇ m to 15 ⁇ m disadvantageously involve difficulty in handling. Therefore, preferably, a granulation dryer is additionally mounted in the inside of the spray dryer or in a state in communication with the spray dryer.
  • the granulation size is 20 ⁇ m to 1,000 ⁇ m, and preferably 20 ⁇ m to 500 ⁇ m (Mean Volume Diameter). Satisfactorily, granulation is sometimes effected almost simultaneously with spray drying or in other cases, fluid granulation is effected after spray drying or both fluid granulation and spray drying are effected simultaneously.
  • the apparatus can carry out the final drying during granulation or immediately after granulation.
  • the conditions such as the outlet temperature (also referred to as “drying temperature” or “exhaust gas temperature”) of the spray dry granulation apparatus, the inlet temperature thereof, the outlet relative humidity thereof and the inlet relative humidity thereof are almost identical to those of spray drying conditions described below.
  • the outlet temperature of the spray dry granulation apparatus is 20° C. to less than 97° C., preferably 20 to 80° C., and more preferably 20 to 60° C.
  • the outlet relative humidity of the spray dry granulation apparatus is 1% RH to 50% RH, preferably 3% RH to 35% RH, and more preferably 6% RH to 30% RH.
  • the inlet temperature of the spray dry granulation apparatus is 60 to 300° C., and preferably 70 to 180° C. Under conditions lower than 60° C., the productivity is undesirably lowered. Under conditions above 300° C., the quality of the resulting dry powder is undesirably deteriorated.
  • the inlet relative humidity of the spray dry granulation apparatus of the invention is 35% RH or less, preferably 15% RH or less, more preferably 7% RH or less, and most preferably 1% RH or less.
  • Spray drying granulation apparatus with such granulation function include for example the “Hybrid Granulator Series as granulation apparatus on filter cloth with spray drying function equipped” manufactured by Fujisaki Electric Co., Ltd.
  • the outlet temperature (also referred to as “drying temperature” or “exhaust gas temperature”) of the spray dryer is 20° C. to less than 97° C., preferably 20 to 80° C., and more preferably 20 to 60° C. At temperatures lower than 20° C., the productivity is undesirably lowered. Furthermore because the melting point of trehalose in the dihydrate form is 97° C., the outlet temperature is preferably set within a range not exceeding the melting point, with respect to quality control.
  • the outlet relative humidity of the spray dryer set in the present invention is 1% RH to 50% RH, preferably 1% RH to 35% RH, and more preferably 1% RH to 30% RH.
  • the outlet relative humidity of the spray dryer as referred to in accordance with the present invention means the relative humidity in the vicinity of the powder collection part of the spray dryer.
  • the outlet relative humidity exhaust gas humidity
  • the outlet relative humidity means the relative humidity at the exhaust part thereof.
  • the outlet relative humidity means the relative humidity (exhaust gas humidity) in the vicinity of the filter cloth at the powder collection part of the apparatus.
  • the inlet temperature of the spray dryer is 60 to 300° C., and preferably 70 to 180° C. Under conditions lower than 60° C., the productivity is undesirably lowered. Under conditions above 300° C., the quality of the resulting dry powder is undesirably deteriorated.
  • the inlet relative humidity of the spray dryer of the present invention is 35% RH or less, preferably 15% RH or less, more preferably 7% RH or less, and most preferably 1% RH or less.
  • the volume of dry gas for example dry air for use in accordance with the present invention is preferably 0.5 m/min or more, more preferably 1 m/min to 5 m/min, and still more preferably 1 m/min to 3.5 m/min, with respect to the improvement of the productivity of the dry powder.
  • the volume of dry air means the air rate (m/min) in the spray dryer or at the cylinder part (the trunk part) of the body of the spray dry granulation apparatus.
  • the volume means the filtration rate.
  • the liquid transfer rate of the raw material solutions such as the hydrous solution of amino acids and the hydrous trehalose solution can be preset appropriately, in relation with the inlet temperature, the outlet temperature, the exhaust gas humidity, the types of the raw material solutions, the desired particle size and the like.
  • the spraying pressure is preferably 0.5 kg/cm 2 or more, more preferably 1 kg/cm 2 to 5 kg/cm 2 , and still more preferably 1 kg/cm 2 to 3 kg/cm 2 .
  • the gas to be used in accordance with the invention is preferably air, but may be a gas other than air, depending on the case.
  • Inert gases for example nitrogen gas and carbonate gas, can be used.
  • an inert gas is effective and may be preferred.
  • the moisture content (loss on drying) of the dry powder thus produced is preferably 5 wt. % or less when dried at 60° C. for 5 hours.
  • spray drying the hydrous solution containing trehalose and amino acids or the hydrous solution containing amino acids and the hydrous solution containing trehalose in the form of liquid droplets having a mean particle size of 0.1 ⁇ m or more to less than 20 ⁇ m, and preferably 0.1 ⁇ m to 10 ⁇ m the liquid droplet is instantly dried.
  • instant drying at a temperature lower than 97° C., and preferably at a temperature of 20 to 60° C. the trehalose in the dry powder exists in a structure of an almost amorphous state.
  • the existence in the amorphous state may possibly generate excellent effects such as oral meltability of the dry powder, the solubility thereof, and the taste-masking effect thereof. Furthermore, some of amino acids are observed to have low crystallinity, according to the method of the present invention, which suggests an increase of amorphous materials.
  • the dry powder thus produced can be used as it is or as an intermediate material, in the pharmaceutical field of, for example, oral or infusion amino acid preparations specific to individual diseases for subject patients with renal impairment or liver disorders, and the cosmetic field, and the like.
  • the dry powder can be used in the form of powders, tablets, and capsules, as individual materials for foods such as sport drinks, diet food materials, health foods and functional foods, and amino acid-series cosmetics.
  • the mean particle size of the microfine powders (single particle powder generated from liquid droplet) were measured visually with a microscope, while the mean particle size (Mean Volume Diameter) of the granulated powders were measured with a dry particle size distribution measurement system of laser diffraction & scattering microtruck, 9320 HRA manufactured by Honeywell Co., Ltd.).
  • the flow of dehumidified hot air having a relative humidity of 1% RH at 25° C. was preset to 5.5 m 3 /min (filtration rate of about 3 m/min), and spray drying and granulation were carried out with a “HGL-130 type as granulation apparatus on filter cloth with spray drying function equipped” manufactured by Fujisaki Electric Co., Ltd. using the conditions of the inlet temperature of the spray dry granulation apparatus described below as set to 131 to 139° C. and the feed rate of the aqueous solution of amino acids as set to 6.7 to 7.3 kg/hr. With the exhaust gas temperature (outlet temperature) at 49 to 58° C.
  • the mean particle size of the microfine powder (single particle powder generated from the liquid droplets) was about 2 ⁇ m to 3 ⁇ m (diameter), as observed with a microscope. Then, the microfine powder was densified under pressure into granules on the filter membrane for particle collection, so that the dry powder granulated as the final product was a powder of amino acids, which had a mean particle size (Mean Volume Diameter) of 40 ⁇ m (moisture content of 4 wt. %).
  • the flow of dehumidified hot air having a relative humidity of 1% RH at 25° C. was preset to 5.5 m 3 /min (filtration rate of about 3 m/min), and spray drying and granulation were carried out with a “HGL-130 type as granulation apparatus on filter cloth with spray drying function equipped” manufactured by Fujisaki Electric Co., Ltd., using the conditions of the inlet temperature of the spray dry granulation apparatus described below set to 130 to 137° C., and the supply rate of aqueous amino acids solution set to 6.1 to 7.7 kg/hr. With the exhaust gas temperature (outlet temperature) at 49 to 61° C.
  • the mean particle size (diameter) of the microfine powder (single particle powder generated from the liquid droplets) was about 2 ⁇ m to 3 ⁇ m, as observed with a microscope. Then, the microfine powder was densified under pressure into granules on the filter membrane for particle collection, so that the dry powder granulated as the final product was a powder of amino acids, which had a mean particle size (Mean Volume Diameter) of 32 ⁇ m (moisture content of 1 wt. %).
  • Leucine, isoleucine, and valine were individually pulverized to a mean particle size (Mean Volume Diameter) of 20 ⁇ m, and were then mixed together uniformly at 47% by weight, 24% by weight and 29% by weight, respectively. Then, 47.8% by weight of the powder of the amino acid mixture, 47.8% by weight of trehalose ⁇ dihydrate (“Treha” manufactured by Hayashibara, Co., Ltd.), and 4.4% by weight of hydroxypropyl cellulose powder were uniformly mixed together.
  • Example 1 Example 2 Oral meltability 5 2 3 Bitterness masking 5 2 3 Solubility 5.5 min 6.00 min 14 min Solidification no problem no problem no problem no problem Notes: The oral meltability and the degree of bitterness masking were evaluated, while the scores of those of Comparative Example 2 were ranked as 3. 1. Oral meltability (5: very good; 4: relatively good; 3: normal; 2: slightly poor; 1: poor) 2.
  • the granulated powder containing trehalose had great oral meltability, great solubility, and a great effect on bitterness masking.
  • the granulated powder containing sugar had good solubility but poor oral meltability without any masking effect of bitterness. Additionally, the granulated powder tasted very powdery and had bad aftertaste.
  • the spray dry granulated powder containing trehalose (Example 1) is compared with the mixed powder of the powders and of the same composition (Comparative Example 2).
  • the oral meltability and the bitterness-masking effect of the mix powder of the powders of Comparative Example 2 were more or less worse than those of the spray dry granulated powder (Example 1).
  • the spray dry granulated powder containing trehalose (Example 1), the mixed powder of the powders (Comparative Example 2) and the individual raw material powders such as trehalose were analyzed by powder X ray diffraction. The results are shown in FIGS. 1 and 2 . It was clearly verified that trehalose in the spray dry granulated powder of Example 1 was in an amorphous state, which apparently makes contributions to the oral meltability and the bitterness-masking effect. Additionally, the spray dry granulated powder (Example 1) lost the crystallinity essential to amino acids. The spray dry granulated powder (Example 1) exhibits partial crystallinity, but contains an amorphous fraction at a high content, when compared with Comparative Example 2.
  • a dry powder of amino acids of high quality such as improved oral meltability, solubility, and a taste-masking effect, can be obtained.

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EP1839502A1 (de) * 2004-12-07 2007-10-03 Ajinomoto Co., Inc. Feines aminosäurepulver und suspension davon
US20080028632A1 (en) * 2006-04-24 2008-02-07 Daniel Py Needle penetrable and laser resealable lyophilization device and related method
US20080132604A1 (en) * 2006-11-30 2008-06-05 Terumo Kabushiki Kaisha Poly-(alpha-hydroxy acid) composition and method of producing molded article using the same
US20080172902A1 (en) * 2006-06-20 2008-07-24 Octapharma Ag Lyophilisation targeting defined residual moisture by limited desorption energy levels
US8272411B2 (en) 2003-04-28 2012-09-25 Medical Instill Technologies, Inc. Lyophilization method and device
WO2013109863A1 (en) * 2012-01-20 2013-07-25 Milk Specialties Company Method of instantizing amino acids

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JP2004305201A (ja) * 2002-11-27 2004-11-04 Hayashibara Biochem Lab Inc アクリルアミドの生成抑制方法とその用途
DE112006002215A5 (de) * 2005-08-23 2008-07-03 Leweling, Hans, Dr. Proteinzusammensetzung zur Behandlung von Proteinmangelzuständen
PL1916913T3 (pl) * 2005-08-23 2011-04-29 Armand Herberger Preparat białkowy do leczenia uwarunkowanego fizjologicznie klinicznie nie zwracającego uwagi, zwiększonego zapotrzebowania na białko
JP5438287B2 (ja) * 2008-05-30 2014-03-12 日本理化学薬品株式会社 難溶性アミノ酸類含有混合組成物及びその製造方法、並びに皮膚外用剤
CN102149374B (zh) 2008-09-09 2013-06-12 味之素株式会社 含有支链氨基酸的口服制剂
US20110305798A1 (en) * 2008-12-17 2011-12-15 Igelosa Nutrition Science AB Nutritional supplement with specific amino acid profile
WO2011043647A1 (en) * 2009-10-09 2011-04-14 N.V. Nutricia Amino acid composition with improved dispersibility
JP5917964B2 (ja) 2012-03-19 2016-05-18 富士ゼロックス株式会社 錠剤、錠剤の製造方法、錠剤管理装置、錠剤照合装置及びプログラム
CN102908337B (zh) * 2012-10-12 2014-03-05 大连医诺生物有限公司 微囊化氨基酸组合物及其制备方法
CN103734716A (zh) * 2013-12-16 2014-04-23 无锡金维氨生物科技有限公司 一种支链氨基酸
MX2017005692A (es) 2014-10-31 2017-08-07 Glaxosmithkline Ip Dev Ltd Formulacion en polvo.
CN105288638B (zh) * 2015-10-27 2018-07-06 江苏金维氨生物工程有限公司 一种提高支链氨基酸粉剂堆积密度的方法
WO2023222797A1 (en) * 2022-05-18 2023-11-23 Société des Produits Nestlé S.A. Method for the preparation of a nutritional powder

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US5538883A (en) * 1993-07-20 1996-07-23 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Maltose-trehalose converting enzyme
US6455511B1 (en) * 1994-09-22 2002-09-24 Quadrant Holdings Cambridge Limited Compositions for use in rehydration and nutrition during athletic exercise and methods of making same
US6254889B1 (en) * 1995-07-26 2001-07-03 Kyowa Hakko Kogyo Co., Ltd. Solid dispersion dosage form of amorphous xanthine derivative and enteric-coating polymer
US20010006939A1 (en) * 1997-10-03 2001-07-05 Ralph W. Niven Secretory leukocyte protease inhibitor dry powder pharmaceutical compositions
US6743443B1 (en) * 1998-10-05 2004-06-01 Eisai Co., Ltd. Tablets immediately disintegrating in the oral cavity
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US8272411B2 (en) 2003-04-28 2012-09-25 Medical Instill Technologies, Inc. Lyophilization method and device
EP1839502A1 (de) * 2004-12-07 2007-10-03 Ajinomoto Co., Inc. Feines aminosäurepulver und suspension davon
US20070286887A1 (en) * 2004-12-07 2007-12-13 Ajinomoto Co., Inc Fine powder of amino acid and suspension thereof
EP1839502A4 (de) * 2004-12-07 2010-03-24 Ajinomoto Kk Feines aminosäurepulver und suspension davon
US20080028632A1 (en) * 2006-04-24 2008-02-07 Daniel Py Needle penetrable and laser resealable lyophilization device and related method
US7966746B2 (en) * 2006-04-24 2011-06-28 Medical Instill Technologies, LLC Needle penetrable and laser resealable lyophilization method
US8171652B2 (en) 2006-04-24 2012-05-08 Medical Instill Technologies, Inc. Penetrable and resealable lyophilization method
US9222728B2 (en) 2006-04-24 2015-12-29 Medinstill Development Llc Penetrable and resealable lyophilization device
US20080172902A1 (en) * 2006-06-20 2008-07-24 Octapharma Ag Lyophilisation targeting defined residual moisture by limited desorption energy levels
US8769841B2 (en) 2006-06-20 2014-07-08 Octapharma Ag Lyophilisation targeting defined residual moisture by limited desorption energy levels
US20080132604A1 (en) * 2006-11-30 2008-06-05 Terumo Kabushiki Kaisha Poly-(alpha-hydroxy acid) composition and method of producing molded article using the same
WO2013109863A1 (en) * 2012-01-20 2013-07-25 Milk Specialties Company Method of instantizing amino acids

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JPWO2003070023A1 (ja) 2005-06-09
BR0306741A (pt) 2004-12-28
US20080275124A1 (en) 2008-11-06
DE60329744D1 (de) 2009-12-03
EP1479300A4 (de) 2005-09-14
EP1479300A1 (de) 2004-11-24
CN100356871C (zh) 2007-12-26
MY140392A (en) 2009-12-31
JP4482925B2 (ja) 2010-06-16
EP1479300B1 (de) 2009-10-21
CN1625346A (zh) 2005-06-08
US7662799B2 (en) 2010-02-16
AU2003207244A1 (en) 2003-09-09

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