WO2003063856A1 - Preparation de gelee contenant des acides amines ramifies - Google Patents

Preparation de gelee contenant des acides amines ramifies Download PDF

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Publication number
WO2003063856A1
WO2003063856A1 PCT/JP2003/000581 JP0300581W WO03063856A1 WO 2003063856 A1 WO2003063856 A1 WO 2003063856A1 JP 0300581 W JP0300581 W JP 0300581W WO 03063856 A1 WO03063856 A1 WO 03063856A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
leucine
isoleucine
jelly
agent
Prior art date
Application number
PCT/JP2003/000581
Other languages
English (en)
Japanese (ja)
Inventor
Hiroyuki Higuchi
Hirokazu Hagio
Chisato Makino
Tomoaki Kawano
Mitsuyasu Ida
Akira Yabuki
Original Assignee
Ajinomoto Co., Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ajinomoto Co., Inc. filed Critical Ajinomoto Co., Inc.
Publication of WO2003063856A1 publication Critical patent/WO2003063856A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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

Definitions

  • the present invention relates to a jelly agent containing, as an active ingredient, three kinds of branched-chain amino acids consisting of isoleucine, leucine and parin.
  • the jelly agent referred to in the present invention refers to a solution or suspension which is made into a semi-solid state by using a gelling agent such as agar or gelatin.
  • compositions containing three types of branched-chain amino acids of isoleucine, leucine and valine as active ingredients are effective therapeutic agents for liver diseases, and currently marketed preparations are mainly granules.
  • granules containing the above three kinds of branched-chain amino acids as active ingredients have a drawback of-about 5 g, which is remarkably large compared to general preparations, and are difficult to take.
  • granules were generally problematic from the viewpoint of ingestibility, especially for the elderly, because they were caught between teeth in the mouth when taken and could not be swallowed well.
  • jellies are the preferred dosage form for formulations containing about 4 g of leucine, isoleucine and palin as active ingredients.
  • the active ingredient is 4 g, which is much larger than that of a conventional preparation, if a jelly preparation is prepared by a usual method, a single dose will be as large as about 10 OmL, and
  • the conventional technology must meet all of the above requirements. There was no effective way to do it. Disclosure of the invention
  • the present inventors have conducted intensive studies and found that The present inventors have found that the above-mentioned problems can be solved by allowing a suspending agent to coexist in addition to the gelling agent in syn, leucine, and palin, and have completed the present invention.
  • the present invention includes the following inventions.
  • a pharmaceutical jelly preparation comprising only three types of branched-chain amino acids consisting of isoleucine, leucine and palin as an active ingredient, and further comprising a suspending agent and a gelling agent.
  • the suspending agent is hydroxypropylmethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, carmellose, carmellose sodium, carmellose calcium, crystalline cellulose and crystalline cellulose.
  • the pharmaceutical jelly preparation according to item (1) which is at least one selected from carmellose sodium.
  • the gelling agent is one selected from agar, agar powder, carrageenan, xanthan gum, guar gum, pectin, dielan gum, locust bean gum, arabic gum, arabic gum powder, tragacanth, tragacanth powder and gelatin.
  • the amount of the suspending agent is 0.0005 to 0.25 part by mass, preferably 0.2 part by mass, per 1 part by mass of the total of three types of branched-chain amino acids consisting of isoleucine, leucine and parin.
  • the concentration of three types of branched-chain amino acids consisting of isoleucine, leucine and parin is 11 to 70% (WZV), preferably 15 to 60% (W / V), more preferably 15 to 45% (W / V).
  • WZV concentration of three types of branched-chain amino acids consisting of isoleucine, leucine and parin
  • Average particle size (median size) of mixed particles of isoleucine, leucine and parin M is 1 to 200 m, preferably 5 to 120 m.
  • the organic acid is selected from citric anhydride, cunic acid, malic acid, tartaric acid, D-tartaric acid, ascorbic acid, succinic acid, maleic acid, malonic acid, L-glutamate hydrochloride, acetic acid, lactic acid and aspartic acid.
  • the pharmaceutical jelly agent according to item (8) which is at least one of the following:
  • the jelly agent of the present invention uses isoleucine, leucine and parin particles of the above-mentioned particle size in the above-mentioned mixing ratio, and is mixed with water together with a suspending agent. It is prepared by mixing with a solution in which a gelling agent is dispersed or dissolved.
  • a gelling agent is dispersed or dissolved.
  • the mixing means for preparing the jelly agent there is no particular limitation on the mixing means for preparing the jelly agent, and any mixing or pulverizing mechanism and model can be used as long as a uniform suspension can be obtained.
  • High-pressure emulsifiers such as various homogenizers and microfluidizers, colloid mills, and the like are preferably used, but universal mixers such as kneaders—pot mills, mortars, and the like can also be used.
  • the method for preparing the three types of branched-chain amino acid particles is not particularly limited, and a usual pulverization method can be employed.
  • a shock type (high-speed rotation type) pulverizer such as a hammer mill, a tumbler set (medium type) such as a pole mill, and a fluid type (air flow type) pulverizer such as a jet mill can be used.
  • the three types of branched-chain amino acid particles used in the jelly agent particles whose particle size is adjusted to 1 to 200 from particles generally produced by a fermentation method are used. If the particle size of the branched-chain amino acid particles exceeds 200, a foreign-body sensation will remain when taken, and if the particle size is smaller than 1 ⁇ , the bitterness will increase, and in any case, it will be difficult to take.
  • the particle size is preferably 1 to 200 m, more preferably 5 to 120 zm.
  • the measurement of the particle size of the branched-chain amino acid particles used in the jelly agent can be performed as follows.
  • Laser diffraction scattering particle size distribution analyzer [Horiba Seisakusho Co., Ltd. LA-920] Put about 20 OmL of 2-propanol in the circulating layer, circulate for 2 minutes while stirring and irradiating with ultrasonic wave, and then perform blank measurement (no ultrasonic irradiation during measurement). Subsequently, introduce the amino acid sample to be measured so that the transmittance is within the range of 85 ⁇ 5%. Circulate for 2 minutes while stirring and irradiating ultrasonic waves, and measure after stopping ultrasonic irradiation. The average particle diameter is a volume-based median diameter.
  • suspending agent In the jelly preparation of the present invention, a suspending agent and a gelling agent are used in combination. Substances that can be used as suspending agents and gelling agents are selected from those that are acceptable as pharmaceutical excipients. Considering the maximum usage record, it is decided whether to use it alone or multiple times.
  • the suspending agent include hydroxypropylmethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxymethylmethylcellulose, carmellose, carmellose sodium, carmellose calcium, crystalline cellulose and crystalline cellulose. At least one selected from the group consisting of loin sodium and popidone is used. Particularly preferred suspending agents are hydroxypropylmethylcellulose and crystalline cellulose 'carmel sodium'.
  • the amount of the suspending agent added to the jelly preparation is from 0.01 to 5.0% (W / V), preferably from 0.02 to 3.0% (W / V). .
  • gelling agent used in the jelly agent of the present invention examples include agar, agar powder, carrageenan, xanthan gum, guar gum, pectin, dielan gum, stoving gum, arabic gum, arabic gum, tragacanth, tragacanth and gelatin. And the like.
  • Particularly preferred gelling agents are agar and agar powder.
  • the amount of the gelling agent to be added to the jelly agent is from 0.01 to 5.0% (W / V), preferably from 0.02 to 3.0% (W / V).
  • an organic acid, a sweetener, a fragrance and the like can be further added in addition to the above three kinds of branched-chain amino acids, a suspending agent and a gelling agent.
  • Organic acids include citric anhydride, cunic acid, malic acid, tartaric acid, D-tartaric acid, ascorbic acid, succinic acid, maleic acid, malonic acid, L-glutamate, Examples include acids such as acetic acid, lactic acid, and aspartic acid, but there is no particular limitation as long as the acid is acceptable as a pharmaceutical additive.
  • Preferred acids include citric anhydride, cunic acid, malic acid, tartaric acid, D-tartaric acid, ascorbic acid and the like.
  • As a sweetener that can be added to the jelly preparation of the present invention aspartame, saccharin, saccharin sodium, erythritol, xylitol, mannitol, stevia and the like are used.
  • fragrance imparting agents such as menthol, lemon flavor, sugarless, sweet flavor, strawberry oil and the like can be optionally used.
  • Example 2 After adding 20.0 g of N-sodium hydroxide solution to adjust the pH, the mixture was uniformly suspended with Nanomizer-1 (LEN03-12B from Nanomizer-1 Co., Ltd.) and suspended. A suspension was prepared. Also, 3.9 Og of agar powder was dispersed in 190.0 Og of purified water, heated and dissolved, and 630.0 g of this suspension and 3.9 g of lemon flavor were added. In addition, the mixture mixed with the stirrer was ice-cooled to prepare a pharmaceutical jelly.
  • Nanomizer-1 LN03-12B from Nanomizer-1 Co., Ltd.
  • Example 1 Was dissolved with a stirrer. To this solution, 476.0 g of isoleucine, 952.0 g of leucine, and 572.0 of palin having the same particle size as those used in Example 1 were added, and the mixture was suspended with the above stirrer. After adjusting the pH by adding 200.0 g of a solution, the mixture was uniformly suspended with a nanomizer. To 630.0 g of this suspension, 7.8 g of xanthan gum and 3.9 g of lemon flavor were added and dispersed with a stirrer to prepare a pharmaceutical jelly. Comparative Example 1
  • Flavor ⁇ not concerned, ⁇ not very concerned, ⁇ slightly concerned, X bad Easy to take: ⁇ easy to drink, ⁇ slightly concerned, X quite concerned ⁇ table 1 ⁇
  • the jelly agent containing only isoleucine, leucine and valin as an active ingredient provided by the present invention has a small volume per volume, and can have a good taste and throat passing over. It makes it possible to supply a jelly preparation that is easy for patients to take and greatly contributes to the improvement of compliance, and is clearly useful as a pharmaceutical preparation.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une préparation de gelée contenant trois acides aminés ramifiés à savoir l'isoleucine, la leucine et la valine en tant que seuls ingrédients actifs et pouvant être administrée en une quantité réduite dans chaque dose, présentant un goût satisfaisant et passant dans la gorge sans difficulté. La préparation de gelée médicinale est caractérisée en ce qu'elle contient trois acides aminés ramifiés à savoir l'isoleucine, la leucine et la valine en tant que seuls ingrédients actifs et contenant un agent de mise en suspension et un gélifiant.
PCT/JP2003/000581 2002-01-30 2003-01-23 Preparation de gelee contenant des acides amines ramifies WO2003063856A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002021356A JP3341770B1 (ja) 2002-01-30 2002-01-30 分岐鎖アミノ酸を含有するゼリー剤
JP2002-21356 2002-01-30

Publications (1)

Publication Number Publication Date
WO2003063856A1 true WO2003063856A1 (fr) 2003-08-07

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PCT/JP2003/000581 WO2003063856A1 (fr) 2002-01-30 2003-01-23 Preparation de gelee contenant des acides amines ramifies

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JP (1) JP3341770B1 (fr)
WO (1) WO2003063856A1 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004182696A (ja) * 2002-12-05 2004-07-02 Shiseido Co Ltd 外用剤組成物
JP2004262859A (ja) * 2003-03-03 2004-09-24 Shiseido Co Ltd 外用剤組成物
JP2004262857A (ja) * 2003-03-03 2004-09-24 Shiseido Co Ltd 外用剤組成物
JP2004269459A (ja) * 2003-03-11 2004-09-30 Nippon Unicar Co Ltd アミノ酸誘導体変性シリコーンを含有する油性化粧料
CN101287458A (zh) * 2005-10-12 2008-10-15 株式会社大塚制药工场 低血糖症状抑制用组合物
TWI397418B (zh) 2006-10-10 2013-06-01 Otsuka Pharma Co Ltd 抗憂鬱劑
JP5837276B2 (ja) * 2009-09-30 2015-12-24 味の素株式会社 経口摂取用ゲル状組成物、及びその製造方法
WO2012099082A1 (fr) * 2011-01-17 2012-07-26 味の素株式会社 Gelée contenant un acide aminé à chaîne ramifiée
JP5854077B2 (ja) * 2014-04-14 2016-02-09 味の素株式会社 経口摂取用ゲル状組成物、及びその製造方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0769877A (ja) * 1993-08-31 1995-03-14 Yoshiaki Akiyama 分枝鎖アミノ酸を有効成分とする経口投与薬

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0769877A (ja) * 1993-08-31 1995-03-14 Yoshiaki Akiyama 分枝鎖アミノ酸を有効成分とする経口投与薬

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JP2003221330A (ja) 2003-08-05
JP3341770B1 (ja) 2002-11-05

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