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EP1150670A2 - Agents d'alkylation destines au traitement de proliferation cellulaire - Google Patents

Agents d'alkylation destines au traitement de proliferation cellulaire

Info

Publication number
EP1150670A2
EP1150670A2 EP00914574A EP00914574A EP1150670A2 EP 1150670 A2 EP1150670 A2 EP 1150670A2 EP 00914574 A EP00914574 A EP 00914574A EP 00914574 A EP00914574 A EP 00914574A EP 1150670 A2 EP1150670 A2 EP 1150670A2
Authority
EP
European Patent Office
Prior art keywords
stent
alkylating agent
composition according
agent
polymer
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.)
Withdrawn
Application number
EP00914574A
Other languages
German (de)
English (en)
Inventor
Angelica Alvarado
Robert Eury
Irina D. Pomerantseva
Michael Froix
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.)
Boston Scientific Scimed Inc
Original Assignee
Quanam Medical Corp
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 Quanam Medical Corp filed Critical Quanam Medical Corp
Publication of EP1150670A2 publication Critical patent/EP1150670A2/fr
Withdrawn legal-status Critical Current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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the ethyleneimines and methylmelamines include the compounds triethylenemelamine, thiotepa (triethylene thiophosphoramide) and altretamine (hexamethylmelamine).
  • Thiotepa and its primary metabolite, triethylenephosphoramide are capable of fo ⁇ ning DNA cross-links, as the aziridine rings open after protonation of the ring-nitrogen, leading to a reactive molecule.
  • the alkyl sulfonates include busulfan.
  • the nitrosoureas include carmustine and lomustine, semustine and streptozocin.
  • the triazenes include dacarbazine.
  • the alkylating agent melphalan was incorporated into polymer stents and implanted into pig coronary arteries, and this study will now be discussed.
  • stents as depicted in Fig. 3C were prepared and loaded with melphalan and then placed in the coronary arteries of pigs. Preparation of the melphalan-loaded stents is described in Example 3.
  • the stents, which carried a total drug load of 546 ⁇ g, were deployed into the pig coronary artery using a balloon catheter and positioned distally in the right coronary artery and approximately in the middle of the left circumflex artery.
  • a commercially available metal stent not carrying a polymer member was also deployed into the left anterior descending artery.
  • Stents carrying four polymer sleeve segments were prepared as described in Example 2.
  • a solution of melphalan in methanol was prepared by dissolving 0.0293 g melphalan in 1.5 mL methanol to give a solution concentration of 19.5 ⁇ g/ ⁇ L.
  • Each of the four segments was loaded with 136.5 ⁇ g of melphalan from the stock solution by pipetting 1 ⁇ L of the solution on each segment 7 times.
  • the total drug loading in the polymer stent was 546 ⁇ g.
  • the pig was euthanized and the heart and coronary arteries explanted.
  • the arteries were pressure fixed for mo ⁇ hometric analysis to determine the percent diameter stenosis and percent intimal growth.
  • the percent diameter stenosis was taken as l-[(stented vessel's minimum lumenal diameter)/(diameter of unstented reference vessel)]*100.
  • the percent intimal growth was taken as l-[(stented vessel's minimum lumenal diameter)/(diameter of stented portion prior to stent placement)]* 100.
  • the balloon to artery ratio was also determined as a measure of the degree of distension of the vessel by the balloon. The results are shown in Table 1.
  • a solution of busulfan in dimethylsulfoxide was prepared by dissolving 0.0243 g busulfan in 300 ⁇ L dimethylsulfoxide to give a solution concentration of 81 ⁇ g/ ⁇ L.
  • Each of the four segments was loaded with 81 ⁇ g of busulfan from the stock solution by pipetting 1 ⁇ L of the solution on each segment.
  • the total drug loading in the polymer stent was 162 ⁇ g-

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une méthode d'inhibition de prolifération cellulaire associée à une condition d'hyperprolifération telle que la resténose. Cette méthode consiste à administrer un agent d'alkylation. L'invention concerne aussi un extenseur destiné à administrer l'agent localement.
EP00914574A 1999-02-12 2000-02-10 Agents d'alkylation destines au traitement de proliferation cellulaire Withdrawn EP1150670A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US11995199P 1999-02-12 1999-02-12
US119951P 1999-02-12
PCT/US2000/003667 WO2000047197A2 (fr) 1999-02-12 2000-02-10 Agents d'alkylation destines au traitement de proliferation cellulaire

Publications (1)

Publication Number Publication Date
EP1150670A2 true EP1150670A2 (fr) 2001-11-07

Family

ID=22387376

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00914574A Withdrawn EP1150670A2 (fr) 1999-02-12 2000-02-10 Agents d'alkylation destines au traitement de proliferation cellulaire

Country Status (5)

Country Link
EP (1) EP1150670A2 (fr)
JP (1) JP2002536406A (fr)
AU (1) AU3594700A (fr)
CA (1) CA2362883A1 (fr)
WO (1) WO2000047197A2 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002246542A1 (en) * 2000-10-31 2002-07-30 Chemgenex Therapeutics, Inc. Antiproliferative colchicine compositions and uses thereof
DE10115740A1 (de) 2001-03-26 2002-10-02 Ulrich Speck Zubereitung für die Restenoseprophylaxe
US6613083B2 (en) 2001-05-02 2003-09-02 Eckhard Alt Stent device and method
US7041046B2 (en) 2001-05-07 2006-05-09 Xoft, Inc. Combination ionizing radiation and immunomodulator delivery devices and methods for inhibiting hyperplasia
US6537195B2 (en) 2001-05-07 2003-03-25 Xoft, Microtube, Inc. Combination x-ray radiation and drug delivery devices and methods for inhibiting hyperplasia
DE10244847A1 (de) 2002-09-20 2004-04-01 Ulrich Prof. Dr. Speck Medizinische Vorrichtung zur Arzneimittelabgabe

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2730702B2 (ja) * 1990-02-26 1998-03-25 エンドルミナル セラピューティックス，インコーポレイテッド 中空の器管およびその他の組織管腔における病巣を処置する装置
US6057367A (en) * 1996-08-30 2000-05-02 Duke University Manipulating nitrosative stress to kill pathologic microbes, pathologic helminths and pathologically proliferating cells or to upregulate nitrosative stress defenses
CA2302438A1 (fr) * 1997-05-19 1998-11-26 Sugen, Inc. Composes d'heteroarylcarboxamide actifs contre les etats pathologiques lies aux proteine tyrosine kinases
WO1998057671A2 (fr) * 1997-06-18 1998-12-23 Boston Scientific Corporation Dispersions de polycarbonate-polyurethane pour revetements thromboresistants
EP1019034A2 (fr) * 1997-07-01 2000-07-19 Atherogenics, Inc. Amelioration au moyen d'antioxydants de la therapie destinee aux etats d'hyperproliferation
US6153252A (en) * 1998-06-30 2000-11-28 Ethicon, Inc. Process for coating stents

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0047197A2 *

Also Published As

Publication number Publication date
JP2002536406A (ja) 2002-10-29
WO2000047197A3 (fr) 2001-04-05
AU3594700A (en) 2000-08-29
WO2000047197A2 (fr) 2000-08-17
CA2362883A1 (fr) 2000-08-17

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Legal Events

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PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

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Effective date: 20010821

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RIN1 Information on inventor provided before grant (corrected)

Inventor name: POMERANTSEVA, IRINA, D.

Inventor name: ALVARADO, ANGELICA

Inventor name: EURY, ROBERT

Inventor name: FROIX, MICHAEL

17Q First examination report despatched

Effective date: 20030925

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