[go: up one dir, main page]

WO2002034256A1 - Processus de production de preparation de medicament en granules contenant des acides amines ramifies - Google Patents

Processus de production de preparation de medicament en granules contenant des acides amines ramifies Download PDF

Info

Publication number
WO2002034256A1
WO2002034256A1 PCT/JP2001/009333 JP0109333W WO0234256A1 WO 2002034256 A1 WO2002034256 A1 WO 2002034256A1 JP 0109333 W JP0109333 W JP 0109333W WO 0234256 A1 WO0234256 A1 WO 0234256A1
Authority
WO
WIPO (PCT)
Prior art keywords
raw material
isoleucine
leucine
solid raw
solid
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2001/009333
Other languages
English (en)
Japanese (ja)
Inventor
Kazuhiro Takanosu
Hidetoshi Sakai
Akira Yabuki
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ajinomoto Co Inc
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 WO2002034256A1 publication Critical patent/WO2002034256A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • 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 method for producing a pharmaceutical granule preparation containing three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine as a main drug (active ingredient), and in particular, to three kinds of branching materials which are granulation raw materials for the granule preparation.
  • the present invention relates to a pulverizing method for avoiding a risk of dust explosion in a step of pulverizing particles of a chain amino acid from each solid raw material to prepare the same.
  • compositions containing three types of branched-chain amino acids consisting of isoleucine, leucine and valine as the main drug are effective therapeutic agents for liver diseases.
  • the granule formulation containing these three amino acids is ground to adjust the particle size to the specified size to ensure uniformity of the content of the three amino acids that make up the granule formulation and to improve granulation in the granulation process. Is being processed.
  • the present invention provides raw particles of three amino acids used in the manufacture of a pharmaceutical granule formulation containing three types of branched-chain amino acids consisting of isoleucine, leucine and valine, which are effective therapeutic agents for liver diseases. It is an object of the present invention to provide a safe and inexpensive means that can avoid the danger of dust explosion in the pulverization process of a solid raw material of amino acid that is carried out, does not require a large-scale device.
  • the present invention for solving the above-mentioned problems is particularly advantageous for solid-state And pulverizing at least one of two kinds of solid amino acids consisting of other solid leucine and / or solid valine at the time of pulverizing the powder, and further includes the following inventions.
  • a method for pulverizing solid isoleucine comprising mixing and pulverizing solid isoleucine with solid leucine and / or solid palin.
  • a method for producing a granulated raw material particle mixture for producing a pharmaceutical granule preparation comprising isoleucine, leucine and palin as a main ingredient, comprising mixing and grinding solid isoleucine with solid leucine and / or solid parin.
  • the solid raw material isoloisin in the step of pulverizing the solid raw material of the three kinds of branched-chain amino acids to adjust the particle size is obtained by solid raw material mouth and
  • the mixing and pulverization of the solid raw material isoleucine and the solid raw material leucine and the solid raw material palin is performed by a shock type (high-speed rotation type) pulverizer such as a hammer mill, a tumbler type (medium type) pulverizer such as a pole mill or the like.
  • a shock type (high-speed rotation type) pulverizer such as a hammer mill
  • a tumbler type (medium type) pulverizer such as a pole mill or the like.
  • the mixed ground material has a particle size of 5 to 7006 ⁇ , preferably in a range of 10 to 500, and any one of the above items (3) to (6). 4.
  • the method for producing a pharmaceutical granular preparation comprising isoleucine, leucine and valine as
  • the solid raw material isoleucine, the solid raw material leucine and the solid raw material valine in each method of the present invention are pharmaceutical granules produced by granulating particles of the three kinds of branched-chain amino acids, which are effective therapeutic agents for liver diseases. It is an amino acid useful as a raw material for pharmaceuticals.
  • isoleucine which is one of the main drugs, is generally a particle having a particle size of 1 mm or less produced by a fermentation method, and is a Japanese Pharmacopoeia; It meets any of the standards of the United States Pharmacopeia, but is not so limited.
  • Leucine is generally manufactured by fermentation or extraction and has a particle size of lmm or less and meets the standards of the Japanese Pharmacopoeia, European Pharmacopoeia or the United States Pharmacopeia. It is not limited.
  • palin which is generally produced by fermentation or synthesis and has a particle size of lmm or less and meets any of the standards of the Japanese Pharmacopoeia, European Pharmacopoeia, and US Pharmacopoeia, is used. But not limited to.
  • mixed grinding refers to a method in which isoleucine, leucine and palin are mixed in advance and then crushed, or a method in which isoleucine, leucine and parin are mixed and ground while being mixed.
  • mixing refers to a container rotary mixer such as a container mixer, an air stirring mixer such as a fluidized bed mixer, a stirring mixer by rotating stirring blades and stirring lipons, and mixing in a powder transport line.
  • a feeder type mixer installed at a raw material supply port such as a line mixer or a pulverizer is not particularly limited.
  • Pulverization here means an impact type such as a hammer mill (high-speed rotation type)
  • a tumbler set such as a pulverizer or a pole mill (medium type)
  • a fluid type (pneumatic type) such as a pulverizer or a jet mill Pulverization by a pulverizer is preferable, but not particularly limited.
  • a binder in producing the granular preparation of the present invention, can be used.
  • the binder include cellulose derivatives such as methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and hydroxypropylmethylcellulose, starches such as corn starch and wheat starch, polyvinylpyrrolidone, and acrylic acid polymers. Any molecule can be used without particular limitation as long as it can be used for medical purposes, such as molecules, natural polymers such as gum arabic and gelatin. Also, the amount used is within the range where normal granulation is possible.
  • Granules containing the three types of branched chain amino acid particles in the pharmaceutical granule preparation of the present invention include a high-speed stirring granulator, a fluidized bed granulator, a planetary mixer, a dry press granulator, a crush granulator, Any of an extrusion granulator, a tumbling granulator, a spray-drying granulator, and a coating granulator can be used, but a high-speed stirring granulator and an extrusion granulator are preferable.
  • Extrusion granulation is a method of granulating plasticized powder by extruding it through a screen with many holes.Pre-extrusion granulator, disk pellets, Yuichi granulator, ring die granulator Machine, basket type granulator, oscillating type granulator, cylinder type granulator, etc. are used.
  • the high-speed stirring granulation method is a method in which water or a binder liquid is charged or sprayed into a powder, and the powder is subjected to shearing, rolling, and compaction by rotating a stirring blade to granulate.
  • a vertical and horizontal stirring granulator is used. Is used.
  • the fluidized-bed granulation method is a granulation method performed by spraying water or a binder liquid while flowing the powder to agglomerate the powder.
  • the fluidized-bed granulator, the stirred fluidized-bed granulator, A tumbling fluidized bed type granulator and a stirring tumbling fluidized bed type granulator are used.
  • Dry press granulation is a method of compressing and molding powder without using water or a binder solution. Roll presses, pre-ketting machines, single-shot tablet presses, and one-stop tablet presses are used. used.
  • the tumbling granulation method is a method of rolling and granulating powder, and a drum-type granulator, a dish-type granulator, a vibrating granulator, and a disk-type granulator are used.
  • Figure 1 is a diagram showing the dust explosive properties of the pulverized product of three types of branched-chain amino acids (leucine, isoleucine, and palin).
  • the present invention makes it possible to safely manufacture a pharmaceutical granule preparation as a therapeutic agent for liver disease of the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (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

La présente invention concerne un processus de production de préparation de médicament en granulés contenant de l'isoleucine, de la leucine et de la valine comme agents principaux. Dans ce processus on pulvérise une matière solide d'isoleucine sous forme de mélange avec une matière solide de leucine et/ou une matière solide de valine durant l'étape de la pulvérisation de ces trois matières d'acide aminé solides de façon à en maîtriser le calibre du grain. Cette préparation de médicament en granulé contenant ces trois acides aminés (à savoir l'isoleucine, la leucine et la valine ) comme agents principaux peut ainsi être produite en sécurité avec une réduction des risques d'explosion de poussières lors de la pulvérisation de l'isoleucine solide.
PCT/JP2001/009333 2000-10-26 2001-10-24 Processus de production de preparation de medicament en granules contenant des acides amines ramifies Ceased WO2002034256A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000-326514 2000-10-26
JP2000326514A JP3228288B1 (ja) 2000-10-26 2000-10-26 分岐鎖アミノ酸含有医薬用顆粒製剤の製造方法

Publications (1)

Publication Number Publication Date
WO2002034256A1 true WO2002034256A1 (fr) 2002-05-02

Family

ID=18803687

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2001/009333 Ceased WO2002034256A1 (fr) 2000-10-26 2001-10-24 Processus de production de preparation de medicament en granules contenant des acides amines ramifies

Country Status (2)

Country Link
JP (1) JP3228288B1 (fr)
WO (1) WO2002034256A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1334722A4 (fr) * 2000-10-26 2007-05-23 Ajinomoto Kk Preparations de medicament en granules contenant des acides amines ramifies et processus de production de ce medicament

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1839502A4 (fr) * 2004-12-07 2010-03-24 Ajinomoto Kk Poudre fine d'acide amine et suspension la contenant

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0184999A2 (fr) * 1984-12-12 1986-06-18 Boehringer Mannheim Italia S.P.A. Produits diététiques granulaires à base d'amino-acides et méthode pour leur préparation
JPH08198748A (ja) * 1995-01-27 1996-08-06 Ajinomoto Co Inc アミノ酸栄養組成物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0184999A2 (fr) * 1984-12-12 1986-06-18 Boehringer Mannheim Italia S.P.A. Produits diététiques granulaires à base d'amino-acides et méthode pour leur préparation
JPH08198748A (ja) * 1995-01-27 1996-08-06 Ajinomoto Co Inc アミノ酸栄養組成物

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1334722A4 (fr) * 2000-10-26 2007-05-23 Ajinomoto Kk Preparations de medicament en granules contenant des acides amines ramifies et processus de production de ce medicament

Also Published As

Publication number Publication date
JP3228288B1 (ja) 2001-11-12
JP2002128668A (ja) 2002-05-09

Similar Documents

Publication Publication Date Title
EP1565258B1 (fr) Procede et appareil pour la granulation continue par voie humide de materiau pulverulent
JPS62174013A (ja) 直打用ビタミン顆粒、その製造法および錠剤
US20160256390A1 (en) Process for producing cellulose derivatives of high bulk density and good flowability
JP3368898B1 (ja) 分岐鎖アミノ酸含有顆粒の製造方法
JPS6191118A (ja) チアミン塩の顆粒，その製造法および錠剤
CN103705520A (zh) 一种利伐沙班固体组合物的制备方法
JP3165700B2 (ja) 高速攪拌造粒法及び高速攪拌造粒機
JP7106161B2 (ja) 粒子サイズが不揃いな原薬粒子の処理方法
EP1334722A1 (fr) Preparations de medicament en granules contenant des acides amines ramifies et processus de production de ce medicament
Shinde et al. Recent advances in granulation techniques
JP3228288B1 (ja) 分岐鎖アミノ酸含有医薬用顆粒製剤の製造方法
JP5515943B2 (ja) 分岐鎖アミノ酸を含有する顆粒、およびその製造方法
KR101829646B1 (ko) 투여형으로부터의 활성 성분의 방출을 제어하는 방법
CN114681404B (zh) 一种瑞格列奈颗粒剂药物组合物及其制备方法
JPH0818801B2 (ja) 直接的な圧縮錠剤形成のために適切な粒状リン酸三石灰組成物
JPH11137640A (ja) 生薬類の造粒方法
JP3228289B1 (ja) 分岐鎖アミノ酸を含有する医薬用顆粒の製造方法
WO2002038147A1 (fr) Preparations medicamenteuses granulees contenant des acides amines ramifies et leur procede de production
CN117964525A (zh) 一种原料药的前处理方法及其组合物
CN112190580A (zh) 用于制备依折麦布片的方法及依折麦布片
EP0533103A1 (fr) Production de cristaux de thiamine chlorohydrate de forme bêta
Madsen Pilot-Scale Investigation of Spray Dried Powders for Direct Compression

Legal Events

Date Code Title Description
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase