WO2004054621A1 - Clathrates hydrosolubles de ziprasidone et de ses sels et procedes de preparation associes - Google Patents

Clathrates hydrosolubles de ziprasidone et de ses sels et procedes de preparation associes Download PDF

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Publication number
WO2004054621A1
WO2004054621A1 PCT/CN2003/000979 CN0300979W WO2004054621A1 WO 2004054621 A1 WO2004054621 A1 WO 2004054621A1 CN 0300979 W CN0300979 W CN 0300979W WO 2004054621 A1 WO2004054621 A1 WO 2004054621A1
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WO
WIPO (PCT)
Prior art keywords
ziprasidone
cyclodextrin
salt
clathrate
water
Prior art date
Application number
PCT/CN2003/000979
Other languages
English (en)
Chinese (zh)
Inventor
Wen Qu
Yongchu Bao
Qinghua Chen
Baoquan Zhu
Qiang Sui
Xiaomei Wang
Huilin Shi
Original Assignee
Shanghai Institute Of Pharmaceutical Industry
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 Shanghai Institute Of Pharmaceutical Industry filed Critical Shanghai Institute Of Pharmaceutical Industry
Priority to AU2003303019A priority Critical patent/AU2003303019A1/en
Publication of WO2004054621A1 publication Critical patent/WO2004054621A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Definitions

  • the invention relates to a water-soluble inclusion compound of ziprasidone and a salt thereof and a preparation method thereof. Background technique
  • Ziprasidone is a newer atypical antipsychotic drug. It is an antagonist of serotonin and dopamine receptors. It is effective for the symptoms of schizophrenia, including hallucinations, hallucinations, and delusions.
  • the chemical name of ziprasidone 5- (2- (4- (1,2-benzoisothiazol-3-yl) -piperazine) ethyl) -6-chloro-1,3-dihydro- 2H-indole-2-one.
  • FDA US Food and Drug Administration
  • Geodon a muscarinic injection of ziprasidone mesylate
  • Ziprasidone has a low water solubility, so it must be solubilized when preparing its injection solutions.
  • the currently used solubilization technology is: firstly make ziprasidone into mesylate, and then make ziprasidone mesylate with hydroxypropyl- ⁇ -cyclodextrin or sulfobutyl ether- ⁇ -cyclo Dextrin forms an inclusion compound in an aqueous solution to increase the water solubility of the drug, such as the technology disclosed in Chinese patent CN 97194242.0.
  • the technical problem to be solved by the present invention is to disclose a water-soluble package of ziprasidone and its salt. And its preparation method to overcome the above-mentioned shortcomings of the prior art.
  • the water-soluble inclusion compound of ziprasidone and its salt according to the present invention is a water-soluble inclusion compound comprising a therapeutically effective amount of the active ingredient ziprasidone and its salt and an inclusion material cyclodextrin derivative.
  • the inclusion compound is said to contain no crystal water or half or more crystal water.
  • the final application form of the inclusion compound is an aqueous solution, a lyophilizate, a tablet, a capsule, a granule, a pill, a suppository, or an inhalation powder.
  • a preferred molar ratio of ziprasidone or a salt thereof to a cyclodextrin derivative is: 0.1 100: 1.
  • the ziprasidone salt of the present invention includes mesylate, hydrochloride, benzenesulfonate, ethanesulfonate, tartrate, naphthalenesulfonate, malate, citrate, benzoate or As one of aspartate salts, the salt may be an anhydrous substance, or may be a hemihydrate or a polyhydrate.
  • the cyclodextrin derivatives include a-cyclodextrin derivatives, ⁇ -cyclodextrin derivatives, and ⁇ -cyclodextrin derivatives with various degrees of substitution.
  • the most ideal choice is hydroxypropyl- ⁇ -cyclodextrin.
  • the method for preparing the water-soluble inclusion compound of the present invention includes the following steps:
  • the organic solvent includes, but is not limited to, one or more of ethanol, methanol, acetonitrile, acetone, isopropanol, n-butanol, tetrahydrofuran, and the like.
  • the inclusion compound of the present invention can be used for acute control and short-term treatment of restless mental patients, and the dosage and method of use are the same as those of conventional ziprasidone or a salt thereof.
  • the preparation method of the inclusion compound of the present invention greatly shortens the time for preparing the inclusion compound, from 4 days to 2 hours, which is a kind of inclusion compound and inclusion technology with considerable practical value. detailed description

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Nanotechnology (AREA)
  • Neurology (AREA)
  • Biophysics (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Psychiatry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des clathrates hydrosolubles de ziprasidone et de ses sels ainsi que les procédés de préparation associés. Ces clathrates hydrosolubles de ziprasidone et de ses sels contiennent un taux efficace de ziprasidone et de ses sels en tant que principe actif et des dérivés de cyclodextrines en tant que matériaux de clathration. Les procédés de préparation des clathrates hydrosolubles selon l'invention consistent dans les étapes suivantes : on ajoute du ziprasidone ou des sels de ce dernier dans le solvant organique contenant des cyclodextrines, le mélange est chauffé afin d'être bouilli au reflux pendant une à deux heures jusqu'à ce que le ziprasidone se dissolve complètement ; le solvant organique est ensuite chauffé afin d'être volatilisé sous vide de façon que les clathrates soient acquis. Les procédés de préparation selon l'invention ne requièrent que deux heures, ce qui est beaucoup plus court que dans l'état antérieur de la technique (quatre jours).
PCT/CN2003/000979 2002-12-17 2003-11-18 Clathrates hydrosolubles de ziprasidone et de ses sels et procedes de preparation associes WO2004054621A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003303019A AU2003303019A1 (en) 2002-12-17 2003-11-18 Water-soluble clathrates of ziprasidone and its salts, and the preparation methods therefor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CNB021551391A CN1255105C (zh) 2002-12-17 2002-12-17 齐拉西酮及其盐的水溶性包合物及其制备方法
CN02155139.1 2002-12-17

Publications (1)

Publication Number Publication Date
WO2004054621A1 true WO2004054621A1 (fr) 2004-07-01

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2003/000979 WO2004054621A1 (fr) 2002-12-17 2003-11-18 Clathrates hydrosolubles de ziprasidone et de ses sels et procedes de preparation associes

Country Status (3)

Country Link
CN (1) CN1255105C (fr)
AU (1) AU2003303019A1 (fr)
WO (1) WO2004054621A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7667037B2 (en) 2003-10-24 2010-02-23 Teva Pharmaceutical Industries Ltd. Processes for preparation of ziprasidone
US7678799B2 (en) 2003-06-03 2010-03-16 Teva Pharmaceutical Industries Ltd. Crystalline ziprasidone HCl and processes for preparation thereof
US7745624B2 (en) 2005-03-11 2010-06-29 Apotex Pharma Chem Inc. Preparation of acid addition salts of ziprasidone and intermediates thereof by solid phase-gas phase reactions
WO2011148253A2 (fr) 2010-05-25 2011-12-01 Aurobindo Pharma Limited Formes posologiques solides d'antipsychotiques

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100391458C (zh) * 2006-02-07 2008-06-04 上海医药工业研究院 齐拉西酮或其盐包合物制备方法
CN102234273B (zh) * 2010-04-21 2015-08-05 上海医药工业研究院 甲磺酸齐拉西酮半水合物及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1083061A (zh) * 1992-08-26 1994-03-02 美国辉瑞有限公司 制备芳基哌嗪基-杂环化合物的方法
CN1089607A (zh) * 1992-09-01 1994-07-20 美国辉瑞有限公司 5-(2-(4-(1,2-苯并异噻唑-3-基)-1-哌嗪基)乙基)-6-氟-1,3-二氢-2h-吲哚-2-酮盐酸盐一水合物
CN1136776A (zh) * 1993-09-30 1996-11-27 詹森药业有限公司 一种抗真菌口服制剂
CN1216923A (zh) * 1996-05-07 1999-05-19 美国辉瑞有限公司 芳基杂环化合物盐的包合复合物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1083061A (zh) * 1992-08-26 1994-03-02 美国辉瑞有限公司 制备芳基哌嗪基-杂环化合物的方法
CN1089607A (zh) * 1992-09-01 1994-07-20 美国辉瑞有限公司 5-(2-(4-(1,2-苯并异噻唑-3-基)-1-哌嗪基)乙基)-6-氟-1,3-二氢-2h-吲哚-2-酮盐酸盐一水合物
CN1136776A (zh) * 1993-09-30 1996-11-27 詹森药业有限公司 一种抗真菌口服制剂
CN1216923A (zh) * 1996-05-07 1999-05-19 美国辉瑞有限公司 芳基杂环化合物盐的包合复合物

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7678799B2 (en) 2003-06-03 2010-03-16 Teva Pharmaceutical Industries Ltd. Crystalline ziprasidone HCl and processes for preparation thereof
US7667037B2 (en) 2003-10-24 2010-02-23 Teva Pharmaceutical Industries Ltd. Processes for preparation of ziprasidone
US7745624B2 (en) 2005-03-11 2010-06-29 Apotex Pharma Chem Inc. Preparation of acid addition salts of ziprasidone and intermediates thereof by solid phase-gas phase reactions
WO2011148253A2 (fr) 2010-05-25 2011-12-01 Aurobindo Pharma Limited Formes posologiques solides d'antipsychotiques

Also Published As

Publication number Publication date
CN1424037A (zh) 2003-06-18
AU2003303019A1 (en) 2004-07-09
CN1255105C (zh) 2006-05-10

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