WO2016082413A1 - Composition pharmaceutique de dexibuprofène pour l'injection et procédé de préparation correspondant - Google Patents

Composition pharmaceutique de dexibuprofène pour l'injection et procédé de préparation correspondant Download PDF

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Publication number
WO2016082413A1
WO2016082413A1 PCT/CN2015/075844 CN2015075844W WO2016082413A1 WO 2016082413 A1 WO2016082413 A1 WO 2016082413A1 CN 2015075844 W CN2015075844 W CN 2015075844W WO 2016082413 A1 WO2016082413 A1 WO 2016082413A1
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WO
WIPO (PCT)
Prior art keywords
dextroprofen
concentration
tromethamine
injection
composition
Prior art date
Application number
PCT/CN2015/075844
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English (en)
Chinese (zh)
Inventor
林金平
宋华先
Original Assignee
北京蓝丹医药科技有限公司
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 北京蓝丹医药科技有限公司 filed Critical 北京蓝丹医药科技有限公司
Publication of WO2016082413A1 publication Critical patent/WO2016082413A1/fr

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Classifications

    • 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
    • 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
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids

Definitions

  • the present invention relates to the field of pharmacy, and in particular to a dextroprofen composition and a process for the preparation thereof.
  • Non-steroidal anti-inflammatory drugs have good anti-inflammatory, antipyretic and analgesic effects.
  • Ibuprofen was first marketed in the UK in 1968. It has been widely used because of its remarkable efficacy in antipyretic and analgesic effects, and its low toxicity, superior to aspirin and paracetamol. Despite its many advantages, one of the main drawbacks of ibuprofen is its poor solubility in water.
  • WO 03/039532 and WO 2005/065674 describe liquid pharmaceutical compositions of ibuprofen comprising an amino acid, such as arginine, for increasing the solubility of ibuprofen.
  • Ibuprofen injection was marketed in the United States in 2009, in which the concentration of ibuprofen was 100 mg/ml, and the molar ratio of the cosolvent arginine to ibuprofen was 0.92:1.
  • concentration of ibuprofen in the ibuprofen injection is 8 mg/ml, and the concentration of tromethamine is 6.04 mg/ml.
  • the ibuprofen injection is not suitable for high temperature sterilization, but can only be used. Sterile filtration is carried out to increase production costs.
  • a low concentration of ibuprofen injection is disclosed in CN102892410A, wherein the concentration of ibuprofen is 2-6 mg/ml, and the concentration of tromethamine is 1.8-5.8 mg/ml.
  • Dextroprofen is the S-(+)-isomer of ibuprofen, very soluble in ethanol, acetone, chloroform and diethyl ether, but almost insoluble in water.
  • CN102362857A discloses a dextroprofen injection comprising dextroprofen, meglumine, citric acid and trisodium citrate, wherein the concentration of dextroprofen is 50 mg/ml.
  • CN103720647A also discloses a dextroprofen injection, wherein the concentration of dextroprofen is 100 mg/ml, and the molar ratio of dextroprofen to arginine is 1:0.8-1.4, preferably 1 : 1.3. Since arginine will decompose during the sterilization process, it will not produce For the foreseeable impurities, we chose tromethamine in combination with dextroprofen.
  • the present invention provides a dextroprofen composition, which is an aqueous solution containing dextroprofen and tromethamine, wherein dextrozole
  • concentration of phenanthrene is 2-4 mg/ml
  • concentration of tromethamine is 1.0-3.4 mg/ml.
  • the present invention provides a method of preparing a dextroprofen composition according to the present invention, the method comprising:
  • the above-mentioned dextroprofen composition provided by the present invention has no significant change in the content before and after filtration, and can withstand high temperature sterilization.
  • the present invention provides a dextroprofen composition, which is an aqueous solution containing dextroprofen and tromethamine, wherein the concentration of dextroprofen is 2-4 mg/ml, the concentration of tromethamine is 1.0-3.4 mg/ml.
  • the concentration of dextroprofen is 2.5-3.5 mg/ml, and the concentration of tromethamine is 1.8. -3.0 mg/ml.
  • the concentration of the dextroprofen is 2 mg/ml, and the concentration of the tromethamine is 1.0 to 1.4 mg/ml, particularly preferably the tromethamine
  • concentration of the alcohol is 0.7-1.4 mg/ml; or
  • the concentration of dextroprofen is 3 mg/ml
  • the concentration of tromethamine is 1.5-2.7 mg/ml
  • the concentration of tromethamine is 1.5. -1.8mg/ml
  • the concentration of dextroprofen is 4 mg/ml, and the concentration of tromethamine is 2.4-3.4 mg/ml; preferably, the concentration of tromethamine is 2.4. -3.0 mg/ml.
  • the dextroprofen composition further contains a pH adjusting agent and an osmotic pressure adjusting agent (also referred to as an isotonicity adjusting agent).
  • the pH adjusting agent is sodium hydroxide and has a pH in the range of 6.5 to 8.5.
  • the isotonicity adjusting agent is sodium chloride.
  • the present invention provides a method of preparing a dextroprofen composition according to the present invention, the method comprising:
  • the dextroprofen composition of the present invention has no significant change in content before and after filtration, and can withstand high temperature sterilization.
  • the above-mentioned dextroprofen composition provided by the present invention can maintain stability and is not easily deteriorated in filtration, high temperature sterilization, and long-term storage.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the dextroprofen combination prepared in the above examples and comparative examples was determined by HPLC method.
  • the content of dextroprofen in the product is shown in Table 1:
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.
  • the glass bottle is potted and sterilized (121 ° C, F0>12), that is, the dextroprofen composition is obtained.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une composition de dexibuprofène comprenant du dexibuprofène et de la trométhamine, la concentration de dexibuprofène étant de 2-4 mg/ml, et la concentration de trométhamine de 1,0-3,4 mg/ml.
PCT/CN2015/075844 2014-11-27 2015-04-03 Composition pharmaceutique de dexibuprofène pour l'injection et procédé de préparation correspondant WO2016082413A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201410692234.7A CN104323988A (zh) 2014-11-27 2014-11-27 一种用于注射的右旋布洛芬药物组合物
CN201410692234.7 2014-11-27

Publications (1)

Publication Number Publication Date
WO2016082413A1 true WO2016082413A1 (fr) 2016-06-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2015/075844 WO2016082413A1 (fr) 2014-11-27 2015-04-03 Composition pharmaceutique de dexibuprofène pour l'injection et procédé de préparation correspondant

Country Status (2)

Country Link
CN (1) CN104323988A (fr)
WO (1) WO2016082413A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104323988A (zh) * 2014-11-27 2015-02-04 北京蓝丹医药科技有限公司 一种用于注射的右旋布洛芬药物组合物

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101978945A (zh) * 2010-10-25 2011-02-23 北京世纪博康医药科技有限公司 一种布洛芬药物组合物
CN102381986A (zh) * 2011-07-25 2012-03-21 南京特丰药业股份有限公司 一种右旋布洛芬氨丁三醇盐及其口服溶液的制备方法
CN102892410A (zh) * 2010-05-18 2013-01-23 西班牙制药公司 用于注射的布洛芬药物组合物
CN104323988A (zh) * 2014-11-27 2015-02-04 北京蓝丹医药科技有限公司 一种用于注射的右旋布洛芬药物组合物

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19912436A1 (de) * 1999-03-19 2000-09-21 Merckle Gmbh Ibuprofen-Lösung
CN101069681A (zh) * 2006-05-10 2007-11-14 汪洪湖 含有布洛芬的注射剂及其制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102892410A (zh) * 2010-05-18 2013-01-23 西班牙制药公司 用于注射的布洛芬药物组合物
CN101978945A (zh) * 2010-10-25 2011-02-23 北京世纪博康医药科技有限公司 一种布洛芬药物组合物
CN102381986A (zh) * 2011-07-25 2012-03-21 南京特丰药业股份有限公司 一种右旋布洛芬氨丁三醇盐及其口服溶液的制备方法
CN104323988A (zh) * 2014-11-27 2015-02-04 北京蓝丹医药科技有限公司 一种用于注射的右旋布洛芬药物组合物

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