WO2013147451A1 - Composition pharmaceutique contenant un acide aminé à chaîne ramifiée, et son procédé de production - Google Patents

Composition pharmaceutique contenant un acide aminé à chaîne ramifiée, et son procédé de production Download PDF

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Publication number
WO2013147451A1
WO2013147451A1 PCT/KR2013/002304 KR2013002304W WO2013147451A1 WO 2013147451 A1 WO2013147451 A1 WO 2013147451A1 KR 2013002304 W KR2013002304 W KR 2013002304W WO 2013147451 A1 WO2013147451 A1 WO 2013147451A1
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liquid suspension
branched chain
chain amino
suspension composition
amino acids
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PCT/KR2013/002304
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English (en)
Korean (ko)
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이단비
정용혁
김현수
연규정
박진규
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주식회사 서울제약
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Publication of WO2013147451A1 publication Critical patent/WO2013147451A1/fr

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    • 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 or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/10—Dispersions; Emulsions

Definitions

  • the present invention relates to a pharmaceutical liquid suspension composition containing a branched chain amino acid as an active ingredient and concealing the high content of the active ingredient, and a method for producing the same.
  • the present invention relates to a pharmaceutical liquid suspension composition containing three branched chain amino acids, specifically, isoleucine, leucine, and valine, as an active ingredient, and concealing the gluten of the active ingredient, and a method for preparing the same.
  • the present invention contains three branched chain amino acids with controlled particle size distribution, specifically, isoleucine, leucine, and valine as active ingredients, and includes a specific thickener or a combination of specific thickeners.
  • the present invention relates to a liquid suspension composition having a dispersing ability and a preparation method thereof.
  • the present invention relates to a method for preparing a liquid suspension composition, characterized in that the three branched chain amino acids are introduced under specific temperature conditions in a specific order in mass production for commercial use of the liquid suspension composition.
  • liquid suspension compositions are used to improve the nutritional status of patients or healthy people, are widely used in the medical field, etc., and are usually taken in a dissolved or suspended state in a solvent such as water.
  • a solvent such as water.
  • the pharmaceutical liquid suspension composition containing three branched chain amino acids has a bitter taste, which is a burden on the patient or the like taking it.
  • suspending agents comprising three branched chain amino acids of isoleucine, leucine and valine have been proposed.
  • Japanese Laid-Open Patent Publication No. 2002-114674 discloses a pharmaceutical suspension containing a branched chain amino acid and at least one organic acid as an acidulant.
  • simply adding an organic acid does not have enough masking effect of bitterness, and therefore it is difficult to put it to commercial use.
  • Patent Publication No. 10-2005-0095833 (published Oct. 4, 2005) states that in order to obtain an oral composition having a bitter taste in fact, the branched chain amino acid mixture should be taken immediately after the preparation of the solution or suspension. Since it is necessary to prepare a solution or suspension directly at the time of taking, it is not only cumbersome when taking, but the amount of water, the mixing time, and the mixing method vary depending on the user, so it is difficult to expect the same and effective drug efficacy.
  • Patent No. 10-0927254 registered on November 10, 2009
  • three kinds of branched chain amino acids are mixed with aloe vera, gum and acidulant to reduce unpleasant taste and feeling such as bitterness peculiar to branched chain amino acids and at the same time, branched chain amino acids. It is described to improve the convenience of taking by formulating the into a liquid suspension composition.
  • commercially available suspensions are prepared in fixed doses or weights and are sold in pouches, usually in units of 5 mL to 20 mL (specific gravity 0.8 to 1.2 g / mL).
  • the doses of branched chain amino acids are 474 mg of isoleucine, leucine 952 mg, and valine 572 mg per 20 mL.
  • this method does not complete the composition of a liquid suspension composition suitable for therapeutic treatment due to the large amount of one-time use of three branched chain amino acids constituting the suspension. This is also a result of not completely eliminating bitter taste, foreign matter in the oral cavity derived from powder, and troubles in the mass production process for commercial sale.
  • compositions containing three branched chain amino acids consisting of isoleucine, leucine and valine as active ingredients are known as effective therapeutic drugs for liver disease.
  • These branched chain amino acids have the effect of correcting the imbalance of plasma amino acids in patients with cirrhosis, thereby improving the nitrogen balance.
  • it improves the perception and cognitive symptoms of cirrhosis, fatigue, etc. of patients with cirrhosis, increases plasma protein and albumin, improves protein nutrition status, inhibits muscle protein degradation and hepatic secretory protein reduction, and prevents platelet count reduction. It shows an effect.
  • granules are generally used by pulverizing the active ingredient in order to satisfy the requirements of securing content uniformity and improving solubility.
  • a solid preparation containing particles of the three branched chain amino acids In order to cope by reducing only the particle size of the raw material amino acid particles, the specific volume thereof increases, resulting in a large volume per dose, making it difficult to swallow due to a large volume in the mouth at the time of taking it. The same problem arises.
  • granules thus prepared generally have a specific volume of 2.0 mL / s. g or more, since the single dose of branched chain amino acid is about 4 to 5 g, when the granule formulation is prepared by pulverizing to 50 ⁇ m or less, its volume becomes about 8 to 10 mL and becomes large in the mouth, making it very difficult to swallow. .
  • pouch packaging is commercially available in volumes of 5 mL to 20 mL (specific gravity 0.8 to 1.2 g / mL), but
  • the three chain amino acids isoleucine, leucine and valine
  • a fluid liquid formulation that can be easily eaten when taken is not made in a sufficient concentration, and should be taken with water when taken.
  • the side effects of bloating can be brought about, and when the branched chain amino acid preparation is administered to liver disease patients in need of water control such as ascites, difficulty in controlling water can cause a patient's symptoms to worsen.
  • the three branched chain amino acids consisting of isoleucine, leucine and valine, have a strong bitter taste and a characteristic amino acid odor, and once they have adequate fluidity but should not be large in dosage volume, it is difficult to formulate them. It has become a problem in commercial use.
  • the present invention relates to a liquid suspension composition
  • a liquid suspension composition comprising three branched chain amino acids of isoleucine, leucine, and valine, and a method for preparing the same.
  • a branched chain amino acid is mixed with a thickener, a pH adjusting agent, and a sweetener to provide a branched chain amino acid.
  • the purpose is to provide a liquid suspension composition to reduce the unpleasant taste and feeling, such as bitter taste.
  • Another problem is to formulate three branched chain amino acids (isoleucine, leucine and valine) into liquid suspension compositions by solving problems in the mass production process for commercial sale.
  • the branching A liquid suspension composition comprising three branched chain amino acids of isoleucine, leucine and valine, a thickening agent, a pH adjusting agent and a pharmaceutically acceptable additive
  • the branching A liquid suspension composition characterized in that the particle size of the chain amino acids is from 35 mesh to 100 mesh.
  • the thickener is provided with a liquid suspension composition, characterized in that selected from the group consisting of hydroxypropyl cellulose, microcrystalline cellulose sodium carboxymethyl cellulose, and polyvinylpyrrolidone.
  • the pH adjusting agent is provided with a liquid suspension composition, characterized in that selected from the group consisting of citric acid and anhydrous sodium hydrogen phosphate.
  • liquid suspension composition characterized in that the pH range of 5 to 7.
  • hydroxypropyl cellulose is 0.2 to 2.0% (w / w) based on the weight of the liquid suspension composition
  • microcrystalline cellulose-carboxymethyl cellulose sodium is 1.0 to 3.4% (w / w) by weight of the liquid suspension composition.
  • a liquid suspension composition containing 2.0% to 4.0% (w / w) of polyvinylpyrrolidone by weight of the liquid suspension composition is provided.
  • liquid suspension composition dissolving or suspending a thickener selected from the group consisting of hydroxypropyl cellulose, microcrystalline cellulose carboxymethyl cellulose sodium and polyvinylpyrrolidone in purified water at room temperature or mild temperature ; Adding and dispersing one amino acid selected from isoleucine, leucine and valine to the suspension solution; Adding the remaining two amino acids to the suspension solution at 50 ° C.
  • a thickener selected from the group consisting of hydroxypropyl cellulose, microcrystalline cellulose carboxymethyl cellulose sodium and polyvinylpyrrolidone in purified water at room temperature or mild temperature ; Adding and dispersing one amino acid selected from isoleucine, leucine and valine to the suspension solution; Adding the remaining two amino acids to the suspension solution at 50 ° C.
  • an orally administrable liquid suspension composition comprising three branched chain amino acids of isoleucine, leucine and valine, comprising dissolving by adding a preservative, a sweetener, and a pH adjusting agent to the suspension solution. .
  • the pharmaceutical liquid suspension composition of the present invention may contain 4 g to 5 g of three branched chain amino acids in a volume of about 20 mL, thereby providing a liquid suspension composition with a convenient flavor and minimized taste to the patient for therapeutic purposes. .
  • there is no process, such as coating the main ingredient is generally used for high concealment can be easily manufactured by a low cost simplified manufacturing method.
  • FIG. 1 is a view showing a manufacturing process diagram of the manufacturing method of the present invention.
  • 2 and 3 is a view comparing the aggregation phenomenon according to the manufacturing process.
  • composition of the present invention is a liquid suspension containing one or more additives commonly used in the manufacture of pharmaceuticals, for example, acidulant, sweetener, flavoring agent, binder, antifoaming agent, dispersing agent, suspending agent, stabilizer, excipient, preservative, etc. It may be included in an amount suitable for preparing the composition.
  • additives commonly used in the manufacture of pharmaceuticals, for example, acidulant, sweetener, flavoring agent, binder, antifoaming agent, dispersing agent, suspending agent, stabilizer, excipient, preservative, etc. It may be included in an amount suitable for preparing the composition.
  • Branched chain amino acids contained in the pharmaceutical liquid suspension composition of the present invention include isoleucine, leucine, and valine, which are commonly used in medicines and foods.
  • branched chain amino acids composed of three kinds of amino acids, isoleucine, leucine and valine are known to play an important role as an energy source during exercise and to increase protein, and include various branched chain amino acids. Has been developed and released.
  • the amino acid can be any of L-form, D-form, and DL-form, but preferably L-form, DL-form, and more preferably L-form.
  • an amino acid can use not only a free body but a salt form, and in this invention, an amino acid is a concept containing both a free body and a salt.
  • salts include acid addition salts and salts with bases, and it is preferable to select salts that are acceptable as pharmaceuticals of amino acids.
  • permitted as a medicine in addition to an amino acid For example, inorganic acids, such as hydrogen chloride, hydrogen bromide, sulfuric acid, phosphoric acid; And organic acids such as acetic acid, lactic acid, citric acid, tartaric acid, maleic acid, fumaric acid, and monomethyl sulfuric acid.
  • permitted as a medicament of an amino acid For example, Inorganic bases, such as hydroxide or carbonate of metal, such as sodium, potassium, calcium, or ammonia; And organic bases such as ethylenediamine, propylenediamine, ethanolamine, monoalkylethanolamine, dialkylethanolamine, diethanolamine and triethanolamine.
  • the pharmaceutical liquid suspension composition of the present invention contains three branched chain amino acids of isoleucine, leucine and valine together, preferably in the range of 19% to 21% (w / w) based on the weight of the pharmaceutical liquid suspension composition.
  • the pharmaceutical composition of the present invention may contain a thickener.
  • Cellulose derivatives such as methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and hydroxypropyl methyl cellulose phthalate Starch such as corn starch, wheat starch, etc .: Synthesis of polyvinylpyrrolidone, polyvinyl alcohol, acrylic acid polymer Polymers: Natural polymers such as agar, xanthan gum, gum arabic and gelatin, microcrystalline cellulose, cellulose polymers, microcrystalline cellulose and sodium carboxymethyl cellulose.
  • the quality of the suspension liquid is not constant depending on the combination of the thickeners, and in particular, polyvinylprolidone, microcrystalline cellulose, carboxymethylcellulose sodium and hydroxide as thickeners. It has been found that the suspension state is excellent when used in combination with oxypropyl cellulose.
  • the content of the thickener may be within the range in which the usual liquid suspension composition can be prepared.
  • hydroxypropyl cellulose is 0.2 to 2.0% (w / w) based on the weight of the liquid suspension composition, and microcrystalline cellulose and carboxymethyl cellulose sodium are used.
  • polyvinylpyrrolidone is preferably included 2.0 to 4.0% (w / w) of the weight of the liquid suspension composition.
  • the pharmaceutical composition of the present invention may contain a pH adjusting agent.
  • a pH adjusting agent such as citric acid and anhydrous sodium hydrogen phosphate may be appropriately used to range from pH3.0 to pH9.0, preferably pH4.0 to pH8.0, more preferably pH5.0 to pH7. It can be produced in the 0 range.
  • Three branched chain amino acids of the present invention show a tendency to be stable near pH 5.0 to 7.0, and also minimize the bitter or unpleasant taste in the same range.
  • any one that can be used for the manufacture of a pharmaceutical product is acceptable, but ascorbic acid, citric acid (citric acid) and malic acid are preferable from the viewpoint of improving the flavor and reducing the bitter taste.
  • acidulant any one that can be used for the manufacture of a pharmaceutical product is acceptable, but ascorbic acid, citric acid (citric acid) and malic acid are preferable from the viewpoint of improving the flavor and reducing the bitter taste.
  • There is no particular limitation on the amount of acid added and it may be used alone in the amino acid mixture and may be added together with other additives.
  • Flavors that can be used include odor enhancers such as apple or strawberry flavors.
  • the pharmaceutical composition of the present invention may contain a sweetening agent.
  • sweeteners sugar, glucose, maltose, oligosaccharide, galactose, syrup, sorbitol, maltitol, invert sugar, xylitol, erythritol, hydrogenated syrup, mannitol, trehalose, aspartame, acesulfame salt, sucralose, saccharin salt, neotime, tao
  • It may be one or more high sweetening sweeteners selected from the group consisting of martin, tomatin mixtures, cyclate salts, taumartin, Nahan fruit extract, licorice extract, stevioside, enzyme treatment stevioside, neohesperidine and monelin.
  • the antifoaming agent may be appropriately selected from among those generally known as medical antifoaming agents such as myristic acid, palmitic acid, simethicone, silicone antifoaming agent, and the amount of use may vary depending on the composition of the active ingredient.
  • medical antifoaming agents such as myristic acid, palmitic acid, simethicone, silicone antifoaming agent, and the amount of use may vary depending on the composition of the active ingredient.
  • the liquid suspension composition of the present invention may include a preservative commonly used in liquid formulations for safety.
  • Preservatives that can be used include sorbic acid and salts thereof, benzoic acid and salts thereof, and paraoxybenzoic acid and salts thereof.
  • the pharmaceutical composition of the present invention may also comprise perfume. Since the pharmaceutical composition of the present invention is a product to be taken through the oral cavity, it is necessary to add an appropriate flavor.
  • the flavor may be natural flavors, artificial flavors or mixtures thereof. Natural flavors may be extracts from the leaves, flowers, fruits and the like of plants, oils of plants and the like. Plant oils include spearmint oil, cinnamon oil, peppermint oil, lemon oil, clove oil, bay oil, thyme oil, cedar leaf oil, nutmeg oil, sage ( sage) oil, almond oil and the like.
  • artificial flavors of fruits such as lemons, oranges, grapes, limes, strawberries and artificial synthetic flavors such as vanilla, chocolate, coffee, cocoa, pine needles, ginseng, red ginseng, citrus may be used.
  • the pharmaceutical composition of the present invention may include a pigment suitable for the product.
  • the pigment may be appropriately adjusted in amount as necessary, and in general, 0.1 to 1.0% by weight (w / w) may be added to the weight of the pharmaceutical liquid suspension composition.
  • the pigment may be a natural or synthetic pigment.
  • the pharmaceutical composition of the present invention may also further comprise a cooling agent.
  • the refreshing agent may be, but is not limited to, for example, l-menthol, WS3, WS23, or Questais-L.
  • the refreshing agent can be appropriately adjusted in accordance with the content, if necessary, in general, may be added up to 10% by weight (w / w) relative to the total weight of the pharmaceutical composition.
  • the pharmaceutical composition of the present invention may further include a bad breath remover to reduce oral odor.
  • the bad breath remover may be a metal salt.
  • the metal salt may be, for example, one or more components selected from the group consisting of metal salts of chlorite, copper gluconate, zinc chloride, zinc citrate and zinc gluconate. Another example is nium chloride, red ginseng extract, green tea extract, seaweed extract, herbal extract, grapefruit extract, apple extract, time oil, thymol, antibiotic, geraniol, carbachol, citral, hinokithiol, One or more components selected from the group consisting of eucalyptol, catechol, methylsalicylate and hydrogen peroxide. Such one or more bad breath remover components may be used together or independently with the one or more metal salts.
  • the viscosity was measured using a No. 62 spindle containing about 40 mL of the pharmaceutical liquid suspension in a centrifuge tube of about 3 cm in diameter and 50 mL.
  • BROOKFIELD model name: DV-2 + Pro, USA, measurement method: cup and bob, measurement temperature: room temperature
  • the particle size of the three branched chain amino acids was used as commercially available raw materials without separate classification, and the mixed three branched chain amino acids had a wide distribution of coarse particles of 18 mesh or more and fine particles of 100 mesh or less.
  • a liquid suspension composition was prepared in the same manner as in Comparative Example 1 with the exception of the three branched chain amino acids, but the particle size distribution of the three branched chain amino acids as the main component was shown in Table 1 and Table 2.
  • Commercial corporation, Korea to prepare a liquid suspension composition for each particle size.
  • Comparative Example 1 three main ingredients were used commercially as raw materials without separate classification, and Comparative Examples 2 to 8 were prepared by classifying only L-isoleucine, and Comparative Examples 9 to 12, L-leucine. It was prepared by classifying only, in the case of Comparative Examples 13 to 17 was prepared by classifying only L-valine.
  • Each 20 g of pharmaceutical liquid suspension was prepared.
  • the prepared solution was evaluated in accordance with the evaluation criteria described above in terms of suspension state, viscosity, bitter taste and foreign matter.
  • a liquid suspension composition was prepared in the same process as in Comparative Example 1 (prescription is shown in Table 3), and the particle sizes of the three branched chain amino acids were classified using a standard sieve network (TESTING SIEVE, Cheonggye Sangpo, Korea) and 35mesh.
  • a liquid suspension composition was prepared from three branched chain amino acids remaining at 100 mesh. It is also one selected from the group of hydroxypropyl cellulose, polyvinylpyrrolidone, hydroxypropyl methyl cellulose and microcrystalline carboxymethyl cellulose sodium as shown in Table 3 to prepare a branched chain amino acid suspension. Or more than one thickener was used. Unexpectedly, the quality of the suspension was not constant according to the combination of the thickeners, and as a result, the suspension was found to be excellent when used in combination with PVPK30, AvicelRC591, HPC-L as the thickener.
  • Example 4 Example 5
  • Example 6 Example 7
  • Example 8 Example 9
  • Example 10 Example 11
  • Example 12 Example 13
  • Example 14 Example 15
  • Example 16 Example 17
  • a liquid suspension composition was prepared in the same process as in Comparative Example 1 (prescription is described in Tables 4 and 5), and the particle size of the three branched chain amino acids was classified using a standard sieve network (TESTING SIEVE, Cheonggye Sangpo, Korea).
  • the liquid suspension composition was prepared from three branched chain amino acids remaining in 100 mesh through 35 mesh. It was prepared as described in Tables 4 and 5 below to find the appropriate component ratios with PVPK30, AvicelRC591 and HPC-L selected in Table 3, and the suspensions were evaluated.
  • PVPK30 as a thickener was 2.0 to 4.0% (w / w) based on the weight of the pharmaceutical liquid suspension composition
  • AvicelRC591 was 1.0 to 3.4% by weight of the pharmaceutical liquid suspension composition ( w / w)
  • HPC-L was found to be excellent in suspension state when used in combination with 0.2 to 2.0% (w / w) relative to the weight of the pharmaceutical liquid suspension composition.
  • production scale For commercial use, mass production at the factory is essential and the production scale may be in accordance with separate scale provisions relating to the manufacturer or distributor's situation or permit.
  • Example 35 Although the results of Comparative Examples 20 to 23 and the known fact of agglomeration at high temperature heating of hydroxypropyl cellulose were not unexpected at all, when manufactured by the manufacturing process described in Example 35 below, the problem was not only solved. It has been found that commercially available products can be obtained.
  • Figure 1 the manufacturing process of Example 35 is shown in Figure 1, the aggregation phenomenon of hydroxypropyl cellulose is shown in Figure 2 (a), the preparation of Example 35 of the pharmaceutical liquid suspension composition The process is shown in FIG. 3.
  • Comparative Examples 20 to 23 and 35 The preparation methods of Comparative Examples 20 to 23 and 35 are shown below.
  • the particle size of three branched chain amino acids used here used the raw material classified into 35 mesh-100 mesh.
  • the scope of the present invention is not limited to the ranges of the comparative examples and examples, and similar effects can be obtained by mixing relatively small amounts of particles larger than 35 mesh or particles smaller than 100 mesh.
  • the particle size range of the amino acid is most preferably used having a particle size of the above 35 mesh to 100 mesh.
  • the temperature is increased by setting the temperature to 90 ⁇ 5 °C. Agglomeration phenomenon starts to occur when the temperature of the preparation liquid in the preparation tank is around 45 ⁇ 50 °C.
  • the addition of three branched chain amino acids (14.280 kg L-isoleucine, 28.560 kg and 17.160 kg) does not disintegrate the mass and can no longer proceed.
  • the temperature is increased by setting the temperature to 90 ⁇ 5 °C.
  • the temperature is increased by setting the temperature to 90 ⁇ 5 °C.
  • Two kinds of branched chain amino acids are added and stirred in the vicinity of the temperature of the preparation liquid in the preparation tank of 50 to 70 ° C. Agglomeration phenomenon starts to occur when the temperature of the preparation liquid in the preparation tank is around 70 ⁇ 90 °C.
  • One branched chain amino acid (L-isoleucine) is added to the preparation tank and stirred.
  • the temperature is increased by setting the temperature to 90 ⁇ 5 °C. Agglomeration does not occur even when the temperature of the preparation liquid inside the preparation tank rises to 90 ° C.
  • a pharmaceutical liquid suspension composition of the same properties can be obtained even when the order of the three branched chain amino acids to be added to the above-described production steps 2 and 3 is changed.
  • the present invention contains three branched chain amino acid isoleucine, leucine, and valine as effective ingredients in which the particle size distribution is adjusted as described in the above embodiments, and a specific thickener or a combination of specific thickeners, specific A sweetening agent and a pharmaceutical liquid suspension composition are provided in a volume suitable for the patient's intake while concealing bitter taste and foreign body by adjusting a specific range of pH.
  • the present invention also provides a preferred process for the preparation of a pharmaceutical liquid suspension composition commercially available under sterile conditions by solving the agglomeration of thickeners arising from mass production for commercial use.
  • an excellent pharmaceutical liquid suspension composition having improved taste and volume which is easy to administer to the patient, can be easily prepared. It can be produced on an industrial scale.

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Abstract

Cette invention concerne une suspension liquide pharmaceutique qui contient un acide aminé à chaîne ramifiée et différents médicaments comme principes actifs dont le goût amer est masqué. L'invention concerne également le procédé de production de ladite suspension. L'invention concerne plus précisément une suspension liquide pharmaceutique qui contient, comme principes actifs, trois types d'acides aminés à chaîne ramifiée, à savoir l'isoleucine, la leucine et la valine, et dont le goût amer est masqué. L'invention concerne également le procédé de production de ladite suspension. L'invention concerne plus précisément une suspension liquide pharmaceutique qui contient, comme principes actifs, trois types d'acides aminés à chaîne ramifiée, à savoir l'isoleucine, la leucine et la valine, dont la répartition granulométrique est ajustée, et un épaississant spécifique ou une association spécifique d'épaississants, un édulcorant, un composé aromatique et un composé ajustant le pH. L'invention concerne également le procédé de production de ladite suspension.
PCT/KR2013/002304 2012-03-30 2013-03-20 Composition pharmaceutique contenant un acide aminé à chaîne ramifiée, et son procédé de production WO2013147451A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2952103A1 (fr) 2014-06-05 2015-12-09 Symrise AG Mixtures de matières

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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