KR101736654B1 - A liquid suspension composition comprising branched chain amino acids and a preparation method thereof - Google Patents

A liquid suspension composition comprising branched chain amino acids and a preparation method thereof Download PDF

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KR101736654B1
KR101736654B1 KR1020160006822A KR20160006822A KR101736654B1 KR 101736654 B1 KR101736654 B1 KR 101736654B1 KR 1020160006822 A KR1020160006822 A KR 1020160006822A KR 20160006822 A KR20160006822 A KR 20160006822A KR 101736654 B1 KR101736654 B1 KR 101736654B1
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branched chain
chain amino
amino acid
solution
amino acids
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KR1020160006822A
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Korean (ko)
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최승준
홍시락
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서울과학기술대학교 산학협력단
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    • 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
    • A61K9/08—Solutions
    • 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
    • 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, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • 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
    • A23V2250/00—Food ingredients
    • A23V2250/02—Acid
    • A23V2250/06—Amino acid
    • A23V2250/0626—Isoleucine
    • 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
    • A23V2250/00—Food ingredients
    • A23V2250/02—Acid
    • A23V2250/06—Amino acid
    • A23V2250/0628—Leucine
    • 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
    • A23V2250/00—Food ingredients
    • A23V2250/02—Acid
    • A23V2250/06—Amino acid
    • A23V2250/0654—Valine

Abstract

The present invention relates to a liquid suspension composition comprising a surfactant-based stabilizer and branched chain amino acids formed of leucine, isoleucine, and valine. The present invention additionally relates to a preparation method of the liquid suspension composition which comprises the following steps: producing a stabilizer solution by mixing a pH regulator and a surfactant-based stabilizer; mixing the stabilizer solution with branched chain amino acids formed of leucine, isoleucine, and valine to obtain a branched chain amino acid solution; stirring the branched chain amino acid solution; passing the stirred solution through a microfluidizer; and cooling the solution passed through the microfluidizer.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a liquid suspension composition comprising a branched chain amino acid and a branched chain amino acid,

The present invention relates to a liquid suspension composition comprising a branched chain amino acid and a method for producing the same.

Three branched chain amino acids, leucine, isoleucine and valine, are important nutrients for the human body contained in essential amino acids. In addition, it has an effect of improving nitrogen discharge by adjusting imbalance of amino acid in muscle tissue and plasma of cirrhotic patients. It is also effective in improving symptoms such as fatigue and ascites in liver disease patients, and degradation of muscle protein and hepatic secretion protein . It also shows effects such as antioxidation, anti-cancer and anti-inflammation.

Leucine, isoleucine, and valine are generally recommended to be taken at a ratio of 2: 1: 1, and the recommended daily intake for the general population is over 5 g. However, the branched chain amino acids show poor solubility in the aqueous phase and thus show a great difficulty in the production process.

The general characteristics of poorly soluble materials are that they have little or no solubility in the aqueous phase, and some of them are soluble in some organic solvents, but are inevitably edible. In addition, most of the medicines produced mainly in the pharmaceutical field show this difficulty, and product development is limited due to these problems.

Therefore, the liquefaction method of such incompatible materials is one of the biggest requirements of the market, and methods using physical methods and chemical agents are used. However, liquefied liquefied liquefied petrochemicals have been treated with expensive chemical agents, resulting in very unreasonable price competition. The complexity of the production process and its focus on low-volume production make it difficult I can not do that.

Korean Patent Laid-Open Publication No. 10-2013-0110669 discloses a composition for oral administration comprising a branched chain amino acid of isoleucine, leucine and valine, an increasing agent, a pH adjusting agent and an additive, which is a liquid phase having a particle size of 35 mesh to 100 mesh A suspension composition has been proposed. However, this publication focuses on alleviating an unpleasant taste and feeling such as a bitter taste peculiar to branched chain amino acids, and does not mention at all the improvement in solubility and dispersion stability of branched chain amino acids.

US Patent Publication No. US 2011/0124702 A1 discloses a nano-suspension of a poorly soluble drug prepared by a microfluidization process, but does not disclose any branched-chain amino acids at all.

Korean Patent Publication No. 10-2013-0110669 (published Oct. 10, 2013) U.S. Published Patent Application No. US 2011/0124702 A1 (published May 26, 2011)

The present invention overcomes the problems of conventional branched chain amino acid granules, and it relates to a liquid suspension composition having improved solubility and dispersion stability, including a branched chain amino acid consisting of leucine, isoleucine and valine, and a surfactant series stabilizer, The present invention is directed to a method of manufacturing a semiconductor device.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that a liquid suspension composition comprising a branched chain amino acid composed of leucine, isoleucine and valine and a surfactant-based stabilizer achieves the above- .

The present invention also provides a method for preparing a stabilizer solution, comprising: preparing a stabilizer solution by mixing a pH adjusting agent and a surfactant-based stabilizer; Preparing a branched chain amino acid solution by mixing a branched chain amino acid composed of leucine, isoleucine and valine and the stabilizer solution; Stirring the branched chain amino acid solution; Passing the stirred solution through a microfluidizer; And cooling the passed solution. The present invention also provides a method for producing a liquid suspension composition.

The liquid suspension composition comprising the branched chain amino acid according to the present invention and the preparation method thereof provide a liquid suspension composition having improved solubility and dispersion stability. It also simplifies the liquefaction process and provides cost savings and convenience for the process.

1 is a flow chart of a branched chain amino acid high concentration liquefaction process in accordance with an embodiment of the present invention.
FIG. 2 to FIG. 8 are graphs showing the results of measurement of dispersion stability of a branched chain amino acid solution and a conventional branched chain amino acid powder solution according to an embodiment of the present invention.

The branched chain amino acids, which are widely used as pharmaceuticals and health supplements, are used for medical purposes in patients with liver disease and as part of the health supplement supplement for the general public. In general, the powder is directly dissolved in a solvent such as water, and therefore, it is in a very uncomfortable situation due to the foreign matter of the powder which is not dissolved in the drink. In addition, since users can directly prepare and take a solution, the amount of water, temperature, mixing time, etc., are different, and it is impossible to take a certain amount of branched chain imanosane, so that it is difficult to expect the same effective effect.

Currently, there are few branched chain amino acid solutions in the form of powder in the form of branched chain amino acids that are generally available in the market. The reason why it is difficult to commercialize in liquid form is because the concentrations of the three kinds of branched chain amino acids are less than the doses that can be expected to have effective effects due to the poor solubility properties and when the branched chain amino acids liquefied by the present technology are used, And this can lead to inconvenience due to abdominal bloating of the users.

Current branched-chain amino acid formulations have the disadvantage that complete liquefaction is not possible and mass production processes for commercial sale through additional processing steps are not possible. The powdered or granular branched chain amino acids are not suitable for the production process due to the floating nature of the solution in the upper phase of the solution when dissolved in the aqueous phase and the turbidity of the branched chain amino acid solution is remarkably lowered when developed for beverage, As a result, the development of liquid formulations has not yet been achieved.

In addition, the present liquefaction production process of branched chain amino acids causes an increase in production cost due to the use of excessive additives, complicates the process, requires a long process time, and requires a lot of energy.

As a result, the three branched chain amino acids of leucine, isoleucine and valine are difficult to develop for liquid formulations due to their poor solubility and low solubility, increased floatability and turbidity in the production process, and high production cost of the product Which is a problem in commercial mass production.

Any of the three kinds of branched chain amino acids contained as an active ingredient in the liquid suspension composition of the present invention can be used as long as it is conventionally used in the manufacture of pharmaceutical products containing such branched chain amino acids, . Generally, in the case of leucine, particles having a particle size of 50 to 150 mesh prepared by fermentation or extraction are used. In the case of isoleucine, particles having a particle size of 50 to 150 mesh prepared by a fermentation method are used. In the case of valine, Particles having a particle size of 50 to 150 mesh prepared by the synthetic method are used, and the milling temperature at the time of milling these branched chain amino acids is preferably 30 占 폚 or less.

According to one aspect of the present invention, the content of the branched chain amino acid is 4 to 5% by weight with respect to the whole composition. The content of branched chain amino acids should be within the recommended range above and is suitable for drinking when considering the recommended daily intake and the solubility of the branched chain amino acids in the present invention.

When dispersing or dissolving the branched chain amino acid of the present invention in a liquid medium, it is generally possible to dissolve at room temperature or elevated temperature using a high-speed stirrer. The temperature is not particularly limited, but it is preferably in the range of 30 to 70, It is preferable in terms of maintaining integrity.

According to one aspect of the liquid suspension composition of the present invention, the mixing ratio of the three kinds of branched chain amino acids comprising leucine, isoleucine and valine ranges from 1.5 to 2.5 / 0.5 to 1.5 / 0.5 to 1.5 Lt; / RTI > The compounding ratio of leucine, isoleucine and valine is effective against liver disease, foods rich in protein and eggs and milk, composition of milk widely known to have ideal amino acid composition, essential amino acid And the weight ratio of the branched chain amino acid in the amount of the food to be consumed.

The liquid suspension compositions of the present invention comprise stabilizers of the surfactant series. The surfactant-based stabilizer is added to improve the solubility and dispersion stability of the branched chain amino acid to be achieved in the present invention. The surfactant may be a synthetic surfactant, a natural surfactant, a nonionic surfactant, a cationic surfactant, Anionic surfactants, and amphoteric surfactants.

According to one aspect of the present invention, at least one selected from the group consisting of Span 80, Tween 80 and lysolecithin is used as the surfactant-based stabilizer.

The liquid suspension composition of the present invention may further comprise a pH adjusting agent (phosphate buffer solution). The Korean Pharmacopoeia No. 9 revision discloses a process for preparing a disodium phosphate citrate buffer which can control pH. But are not limited to, at least one selected from the group consisting of monosodium phosphate monohydrate and disodium phosphate heptahydrate is appropriately used as a pH adjusting agent to adjust the pH to a range of 3 to 7 Can be manufactured. Within this range, the three branched chain amino acids tend to be stable.

The liquid suspension composition of the present invention may contain at least one additive conventionally used in the manufacture of medicines, for example, an acidic agent, a sweetener, a flavoring agent, a binder, a defoamer, a dispersing agent, a suspending agent, an excipient and a preservative.

Any acidic agent that can be used is acceptable as long as it can be used in the production of pharmaceuticals. However, ascorbic acid, citric acid (citric acid) and malic acid are preferable from the viewpoint of improving flavor and decreasing bitter taste. The amount of the acid to be added is not particularly limited, but is generally appropriately added in the range of 0.01 to 0.5% by weight based on the whole composition. Acids can be used alone in amino acid mixtures and may be added with other additives.

Usable sweeteners include natural sweeteners such as sucrose, stevioside and oligosaccharides, artificial sweeteners such as saccharine, aspartame, acesulfame K, and alitam, and sugar alcohols such as xylitol, sorbitol, isomalt and maltitol.

Examples of the flavor agent that can be used include an odor improving agent such as apple or strawberry flavor.

There are no particular restrictions on the binding agent that can be used in the manufacture of pharmaceutical products, such as whole-cell sorting, synthetic polymers, natural polymers, etc. However, Alginic acid, carrageenan and the like are preferable. The amount of the binder to be added may be determined by a method known per se, but is preferably included in the range of 0.01 to 0.5 parts by weight per 1 part by weight of the branched chain amino acid.

As the antifoaming agent, antifoaming agents such as myristic acid, palmitic acid, simethicone, and silicone antifoaming agents may be appropriately selected from those generally known and may be contained in the range of 0.01 to 0.5% by weight based on the total amount of the composition.

A bitter tasting amino acid mixture with bitter tasting citric acid, vitamin C, and an excipient with bitter and sour taste can be mixed to produce a liquid composition in which the bitter taste is best masked.

The liquid suspension compositions of the present invention may contain preservatives commonly used in liquid preparations for safety reasons. Preservatives that can be used include sorbic acid and its salts, benzoic acid and its salts, and p-hydroxybenzoic acid and salts thereof.

The present invention also provides a method for producing the above liquid suspension composition.

The preparation method comprises: preparing a stabilizer solution by mixing a pH adjusting agent and a surfactant-based stabilizer;

Preparing a branched chain amino acid solution by mixing a branched chain amino acid composed of leucine, isoleucine and valine and the stabilizer solution;

Stirring the branched chain amino acid solution;

Passing the stirred solution through a microfluidizer; And

And cooling the passed solution.

1 is a flow chart of a branched chain amino acid high concentration liquefaction process in accordance with an embodiment of the present invention.

The microfluidization technique is based on the use of a microfluidizer and the microfluidizer is a jet flow homogenizer of two fluid flow at full speed under high pressure. Turbulence and high shear forces cause particles to collide, reducing the particle size to the nanometer range. The high pressures and high flow rates of lipids applied can cause cavitation and can also contribute to size reduction. In order to maintain the particle size, stabilization with phospholipids or other surfactants and stabilizers is required. A major drawback of the microfluidization process is the required manufacturing time. In many cases, 50 to 100 time-consuming passes are required for sufficient particle size reduction (see, for example, U.S. Patent Nos. 6,018,080 and 5,091,187). High pressure homogenization / microfluidization techniques have been studied over the years (Muller RH, "Nanosuspensions as particulate drug formulations in therapy: rationale for development ", Adv. Drug Delivery Rev. 2001, 47: 3-19; " Nanosuspensions in drug delivery ", Nature Reviews: Drug Delivery 2004, 3: 785-796; Pace S. et al., "Novel injectable formulations of insoluble drugs ", Pharm. , 23: 116-134; and Panagiotou T. et al., "Production of stable nanosuspensions using mircofluidics reaction technology ", Nanotech. 2007, 4: 246-249). Also, high energy wet milling is known (Bottomley K, "NanoTechnology for Drug Delivery: a Validated Technology ", Drug Delivery Report, 2006: 20-21).

In the present invention, the poor solubility of the branched chain amino acid is eliminated by using the micro-fluidization technique, and the dispersion stability and turbidity are improved to prepare a transparent liquid suspension containing the branched chain amino acid at a high concentration.

According to one aspect of the present invention, at least one selected from the group consisting of Span 80, Tween 80 and lysolecithin is used as the surfactant-based stabilizer.

According to one aspect of the present invention, the stirring step is performed at 20 to 40 캜. Stirring is preferably carried out at a temperature within the recommended range to homogenize the pre-injection sample in the micro-fluidizer.

According to one aspect of the present invention, the step of passing through the microfluidizer to microfluidize is performed at a pressure of 100 to 130 MPa and a temperature of 50 to 90 ° C. The microfluidization should be carried out in the recommended range of the above-mentioned pressure and temperature in order to improve the solubility.

According to an aspect of the present invention, passage to the microfluidizer is repeated five or more times, preferably five to seven times. It should be passed in the recommended number of times in order to improve dispersion stability.

According to one aspect of the present invention, the cooling is carried out at 10 to 40 占 폚 in the cooling step.

The liquid suspension composition of the present invention can be formulated into a liquid preparation by a conventional method in the field of pharmaceutical production, and can be formulated into liquid form preparations such as liquid preparations, drop preparations, syrup preparations, And can be administered in the same manner as a conventional oral liquid preparation.

The liquid suspension composition of the present invention can be formulated and used as a therapeutic agent for patients requiring administration of three kinds of branched chain amino acids, for example, cirrhosis patients, or as a health functional food in the form of beverage, drink, etc. have. In the case of pharmaceuticals, a single dose is an amount such that the total content of the three kinds of branched chain amino acids in the preparation is about 5 g, and is administered three times a day. In the case of a health functional food, the dose may be smaller than that of a medicine, and generally, the product contains about 1 to 5 g of all three kinds of branched chain amino acids.

Hereinafter, the liquid suspension composition of the present invention and the method for producing the same will be described in detail by way of the following examples, but the scope of the present invention is not limited thereto.

[Examples] Preparation of branched chain amino acid-containing liquid suspension compositions according to the present invention

First, 1 kg of distilled water was added to 0.584 g of monosodium phosphate monohydrate and 1.584 g of disodium phosphate monohydrate to adjust the pH to 3 and 6 using hydrochloric acid to adjust the pH at the isoelectric point and below A branched chain amino acid solution was prepared and the optimum process could be derived by comparing the original amino acid form and the salt form. Span 80, Tween 80 and lysolecithin were then added as stabilizers in accordance with the ratios in Table 1 in an amount of 0.5 g, 0.33 g, 0.25 g and 0.2 g and 50 g of branched chain amino acids (25 g leucine, 12.5 g isoleucine and 12.5 g isoline) g) was added to a phosphate buffer solution to prepare a 5 wt% branched chain amino acid solution.

The concentration of added stabilizer according to the ratio of branched chain amino acid to stabilizer Concentration of branched chain amino acids (%) The ratio of branched chain amino acid: stabilizer and
Concentration of stabilizer (%) 100: 1 100: 0.67 100: 0.50 100: 0.40 5 0.050 0.033 0.025 0.020

Subsequently, the branched chain amino acid solution was stirred at 25 ° C for 1 hour, and the mixture was applied to a micro-fluidizer (Micronox, MN400BF) and repeatedly passed through 100 MPa at 70 ° C for 5 times to prepare a high concentration branched chain amino acid solution. Lt; / RTI > for 1 hour.

The resulting solubility enhancement results are shown in Tables 2 to 5 below.

pH 6, storage stability at 25 ° C for 20 days Type of stabilizer Concentration of stabilizer (%) Content of branched chain amino acids (%) 0 days past One day past Five days past 10 days past 20 days past Span 80 0.060 4.52 4.48 4.38 4.17 4.19 0.040 4.33 4.51 4.24 4.17 4.12 0.030 4.47 4.23 4.35 4.24 4.08 0.024 4.41 4.35 4.30 4.08 4.08 Lysolecithin 0.060 4.92 4.61 4.75 4.69 4.59 0.040 4.91 4.76 4.78 4.73 4.62 0.030 4.84 4.58 4.74 4.73 4.64 0.024 4.57 4.65 4.56 4.47 4.36 Tween 80 0.060 4.97 4.89 4.89 4.80 4.76 0.040 4.96 4.83 4.91 4.82 4.72 0.030 4.94 4.69 4.84 4.79 4.69 0.024 4.93 4.84 4.92 4.70 4.67

 pH 6, storage stability at 20 ° C during storage at 4 ° C Type of stabilizer Concentration of stabilizer (%) Content of branched chain amino acids (%) 0 days past One day past Five days past 10 days past 20 days past Span 80 0.060 4.52 4.38 4.41 4.25 4.21 0.040 4.33 4.60 4.26 4.22 4.14 0.030 4.47 4.37 4.31 4.27 4.11 0.024 4.41 4.39 4.29 4.18 4.09 Lysolecithin 0.060 4.92 4.56 4.81 4.76 4.69 0.040 4.91 4.65 4.86 4.79 4.71 0.030 4.84 4.64 4.85 4.75 4.65 0.024 4.57 4.47 4.48 4.38 4.28 Tween 80 0.060 4.97 4.94 4.89 4.71 4.77 0.040 4.96 4.92 4.86 4.72 4.67 0.030 4.94 4.67 4.83 4.67 4.66 0.024 4.93 4.60 4.78 4.71 4.62

 pH 3, at 25 ° C. Type of stabilizer Concentration of stabilizer (%) Content of branched chain amino acids (%) 0 days past One day past Five days past 10 days past 20 days past Span 80 0.060 4.46 4.34 4.51 4.49 4.18 0.040 4.28 4.34 4.43 4.51 4.47 0.030 4.51 4.40 4.50 4.23 4.58 0.024 4.34 4.50 4.52 4.35 4.53 Lysolecithin 0.060 4.61 4.35 4.61 4.43 3.85 0.040 4.71 4.37 4.63 4.56 4.12 0.030 4.63 4.35 4.70 4.50 3.98 0.024 4.63 4.59 4.67 4.52 4.12 Tween 80 0.060 4.71 4.38 4.44 4.19 4.12 0.040 4.34 4.39 4.53 4.19 4.32 0.030 4.58 4.52 4.59 4.50 4.10 0.024 4.49 4.64 4.46 4.05 4.06

pH 3, at 4 ° C. Type of stabilizer Concentration of stabilizer (%) Content of branched chain amino acids (%) 0 days past One day past Five days past 10 days past 20 days past Span 80 0.060 4.46 4.53 4.57 4.47 4.11 0.040 4.28 4.36 4.61 4.45 4.32 0.030 4.51 4.69 4.60 4.15 4.52 0.024 4.34 4.51 4.53 4.26 3.82 Lysolecithin 0.060 4.61 4.39 4.48 4.70 3.97 0.040 4.71 4.44 4.52 4.65 3.75 0.030 4.63 4.27 4.54 4.57 3.48 0.024 4.63 4.24 4.35 4.52 3.73 Tween 80 0.060 4.71 4.65 4.47 4.11 3.94 0.040 4.34 4.68 4.49 4.09 3.87 0.030 4.58 4.49 4.49 4.06 4.00 0.024 4.49 4.28 4.41 4.07 3.59

[Comparative Example] A conventional branched chain amino acid powder

The solubilities of branched chain amino acids in the form of branched chain amino acids mixed with 1.5% by weight of leucine, 0.75% by weight of isoleucine and 0.75% by weight of valine are shown in Tables 6 and 7.

Results of 20 days of solubility observation at 25 ℃ storage Type of stabilizer Concentration of stabilizer (%) Content of branched chain amino acids (%) 0 days past One day past Five days past 10 days past 20 days past No stabilizer 2.89 2.75 2.73 2.70 2.71

Results of 20 days of solubility observation at 4 ℃ storage Type of stabilizer Concentration of stabilizer (%) Content of branched chain amino acids (%) 0 days past One day past Five days past 10 days past 20 days past No stabilizer 2.89 2.70 2.65 2.66 2.41

As contrasted in Tables 2 to 5 and Tables 6 to 7, the liquid suspension composition prepared according to the present invention exhibits a solubility improvement effect of about 71% over the conventional powder form. This makes it possible to reduce the amount of the food to be ingested by the user, and as a high-concentration raw material in the process, convenient transportation and the like are provided.

The dispersion stability of the high concentration branched chain amino acid solution was measured by measuring the transmittance and reflectance of the light source (880 nm), which is an optical method, by measuring the turbidity of the solution, and measuring the transmittance of the lower layer, The stability was measured.

2 to 8 show the results of measurement of dispersion stability.

It was observed that the sample not using the process of the present invention had a very low dispersion stability than the sample using the process of the present invention.

As can be seen from the above experimental results, the greatest advantage of the present invention is that the solubility and dispersion stability of the branched chain amino acid solution are improved, thereby providing ease of raw material transportation and use in a mass production process and inconvenience of users taking it directly But also facilitates further processing into a transparent liquid solution.

It can be used as a final product with a high concentration of liquid solution. It can be used as raw material of product. It reduces the inconvenience of transportation in mass production process and removes the floating property of branched chain amino acid, can do. In addition, users who take a branched-chain amino acid solution directly can reduce the inconvenience of unnecessary abdominal swelling due to a reduction in the volume due to the high concentration of the solution, and it is possible to reduce the discomfort of the naked eye due to the transparent liquid material, And it is not necessary for the user to manufacture it directly, so that it is possible to exhibit the effect of taking the constant and the same branched chain amino acid.

Claims (13)

delete delete delete delete delete delete delete preparing a stabilizer solution by mixing a pH adjusting agent and a surfactant-based stabilizer;
Preparing a branched chain amino acid solution by mixing a branched chain amino acid composed of leucine, isoleucine and valine and the stabilizer solution;
Stirring the branched chain amino acid solution;
Passing the stirred solution through a microfluidizer; And
Cooling the passed solution
, ≪ / RTI &
Wherein the surfactant-based stabilizer is at least one selected from the group consisting of Span 80, Tween 80, and lysolecithin.
delete 9. The method of claim 8, wherein the stirring step occurs at 20 to 40 < 0 > C.
9. The method of claim 8, wherein said passing is from 100 to 130 MPa.
9. The method of claim 8, wherein said passing is at 50 to 90 < 0 > C.
9. The method of claim 8, wherein the passage through the microfluidizer is repeated five or more times in the passing step.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20210063746A (en) 2019-11-25 2021-06-02 씨제이제일제당 (주) Method for crystallization of branched chain amino acids with a sustainable cycle of ammonia

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1334722A1 (en) 2000-10-26 2003-08-13 Ajinomoto Co., Inc. Granular drug preparations containing branched amino acids and process for producing the same
KR100927254B1 (en) 2009-04-02 2009-11-16 제삼바이오잠(주) Liquid compositions comprising branched amino acids and preparation methods thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1334722A1 (en) 2000-10-26 2003-08-13 Ajinomoto Co., Inc. Granular drug preparations containing branched amino acids and process for producing the same
KR100927254B1 (en) 2009-04-02 2009-11-16 제삼바이오잠(주) Liquid compositions comprising branched amino acids and preparation methods thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20210063746A (en) 2019-11-25 2021-06-02 씨제이제일제당 (주) Method for crystallization of branched chain amino acids with a sustainable cycle of ammonia
WO2021107451A1 (en) 2019-11-25 2021-06-03 씨제이제일제당(주) Branched-chain amino acid crystallization method capable of sustainably cycling ammonia

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