EP0491018A1 - Utilisation de taurolidine et/ou de taurultame pour le traitement des tumeurs - Google Patents

Utilisation de taurolidine et/ou de taurultame pour le traitement des tumeurs

Info

Publication number
EP0491018A1
EP0491018A1 EP91911804A EP91911804A EP0491018A1 EP 0491018 A1 EP0491018 A1 EP 0491018A1 EP 91911804 A EP91911804 A EP 91911804A EP 91911804 A EP91911804 A EP 91911804A EP 0491018 A1 EP0491018 A1 EP 0491018A1
Authority
EP
European Patent Office
Prior art keywords
taurolidine
taurultam
tumours
treatment
administered
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Withdrawn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
EP91911804A
Other languages
German (de)
English (en)
Inventor
J. Academic Surg. United Queen Elizabeth Monson
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.)
Ed Geistlich Soehne AG fuer Chemische Industrie
Original Assignee
Ed Geistlich Soehne AG fuer Chemische Industrie
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 Ed Geistlich Soehne AG fuer Chemische Industrie filed Critical Ed Geistlich Soehne AG fuer Chemische Industrie
Publication of EP0491018A1 publication Critical patent/EP0491018A1/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Withdrawn legal-status Critical Current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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • This invention relates to the treatment of tumours by chemotherapy.
  • the antibacterial and anti-toxin drug taurolidine and the related product taurultam have recently been shown to exert a modifying effect on the toxicity of tumour necrosis factor (TNF) which is used, inter alia, in the treatment of tumours.
  • TNF tumour necrosis factor
  • Our United Kingdom Patent Application No 9005856.1 relates to combined therapy using TNF and taurolidine or taurultam.
  • taurolidine acted directly on tumours in addition to its effect on TNF.
  • taurolidine was shown to be selective in that the growth of normal cell-lines was not significantly inhibited.
  • Taurolidine and taurultam have the formulae given below:
  • Taurolidine acts by transferring three methylol groups at the site of action, taurultam being an intermediate metabolite which itself transfers a single methylol group with liberation of the very well tolerated compound taurinamide. Thus, the two compounds act by essentially the same mechanism. It should be noted that methylol transfer is to be contrasted with methyl transfer which is characteristic of many highly toxic anti-tumour drugs. Taurolidine and taurultam have low toxicity and are not cytotoxic against normal cells.
  • the taurolidine or taurultam may be administered systemically, ie. by injection or infusion, or by direct application, eg topically, to external tumours.
  • Suitable formulations for injection or infusion may comprise an isotonic solution containing one or more solubilising agents, eg polyols such as glucose, in order to provide solutions of increased taurolidine or taurultam concentration.
  • solubilising agents eg polyols such as glucose
  • concentration of taurolidine or taurultam in such solutions may be in the range 1 to 10 g/litre.
  • Taurolidine and/or taurultam may be administered in the dose range 150 to 450 mg/kg per day, preferably 300 to 450 mg/kg per day. Relatively large volumes of aqueous solutions containing taurolidine or taurultam will thus often require to be administered, containing for example lOg to 30g of taurolidine and/or taurultam. It may be convenient to administer these compounds by infusion in view of the relatively large volumes concerned, conveniently at intervals throughout the day. - 3 -
  • agents known to be involved in tumour metabolism may also advantageously be co-administered in conjunction with the above combined therapy.
  • agents include gamma-interferon, interleukin-1 and interleukin-2.
  • Cytotoxic agents such as adriamycin and actinomycin D may also be co-administered.
  • tumours to be treated may be of any type, including lymphomas, sarcomas, melanomas and carcinomas. It is particularly beneficial to use taurolidine and/or taurultam prevent the spread of metastases, especially following surgical removal of tumours.
  • the mammalian subjects are typically humans.
  • the invention also includes the use of taurolidine and/or taurultam for the treatment or prophylaxis of tumours in mammalian subjects.
  • the invention further includes the use of taurolidine and/or taurultam for the preparation of pharmaceutical compositions for the treatment or prophylaxis of tumours in mammalian subjects.
  • mice injected iv with 1.5xl0 6 B16 melanoma cells were treated with a) ip normal saline tid on days 0-10, b) ip taurolidine 4.0mg tid on days 0-10, and c) ip taurolidine 4.0mg tid on days 3-10.
  • Mice were sacrificed on day 10 and pulmonary metastases counted.
  • taurolidine treatments started on the day of tumour injection the number of pulmonary metastases was - A - significantly reduced compared either to the control group or to Group C (p ⁇ 0.05).
  • mice injected sc with 1.5 x 10 6 Meth A sarcoma cells received either no treatment or taurolidine 2mg ip bid for seven days. At seven days 90% (27/30) of the control animals had palpable tumour growth, while only 40% (12/30) of the taurolidine treated mice had detectable tumour growth (p-0.0.02).
  • Balb C mice received IP injections of meth A followed by either a)saline 0.1 ml IP BD or b) taurolidine 0.1 ml IP BD for 7 days. At 7 days 28/32 saline treated mice had ascites in comparison to 0/32 of taurolidine treated mice (p ⁇ 0.0001) . Actuarial survival of saline treated mice was also significantly impaired (p,0.005).
  • Taurolidine was tested against multiple cell lines (two tumours, one normal) using a range of doses.
  • tumour lines Preferential activity against tumour lines was demonstrated at low doses with complete cellular inhibition of tumour, but not normal cells, occurring at doses > 200 ⁇ g ml

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

Abstract

La présente invention se rapporte à un procédé de traitement ou de prophylaxie de tumeurs chez des sujets mammifères, selon lequel on administre une dose active de taurolidine et/ou de taurultame à un sujet mammifère atteint ou présentant un risque de formation tumorale.
EP91911804A 1990-07-09 1991-07-08 Utilisation de taurolidine et/ou de taurultame pour le traitement des tumeurs Withdrawn EP0491018A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9015108 1990-07-09
GB909015108A GB9015108D0 (en) 1990-07-09 1990-07-09 Chemical compositions

Publications (1)

Publication Number Publication Date
EP0491018A1 true EP0491018A1 (fr) 1992-06-24

Family

ID=10678847

Family Applications (1)

Application Number Title Priority Date Filing Date
EP91911804A Withdrawn EP0491018A1 (fr) 1990-07-09 1991-07-08 Utilisation de taurolidine et/ou de taurultame pour le traitement des tumeurs

Country Status (4)

Country Link
EP (1) EP0491018A1 (fr)
JP (1) JP3465824B2 (fr)
GB (1) GB9015108D0 (fr)
WO (1) WO1992000743A1 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19606897C2 (de) * 1996-02-13 2002-08-29 Geistlich Soehne Ag Mittel zur Verhinderung der Tumorzellverschleppung und der Entstehung von Trokarmetastasen in der offenen und laparoskopischen Chirurgie maligner Tumoren
GB9716219D0 (en) * 1997-07-31 1997-10-08 Geistlich Soehne Ag Prevention of metastases
US20030027818A1 (en) 2001-04-03 2003-02-06 Redmond H. Paul Treatment of cancers
US6479481B1 (en) * 1999-06-04 2002-11-12 Ed. Geistlich Soehne Ag Fur Chemische Industrie Methods and compositions for treating primary and secondary tumors of the central nervous system (CNS)
US8304390B2 (en) 1997-07-31 2012-11-06 Ed. Geistlich Soehne Ag Fuer Chemische Industrie Method of treatment for preventing or reducing tumor growth in the liver of patient
US7151099B2 (en) 1998-07-31 2006-12-19 Ed. Geistlich Soehne Ag Fuer Chemische Industrie Use of taurolidine and/or taurultam for treatment of abdominal cancer and/or for the prevention of metastases
US7345039B2 (en) 1999-06-04 2008-03-18 Ed. Geistlich Soehne Ag Fuer Chemische Industrie Enhancement of effectiveness of 5-fluorouracil in treatment of tumor metastases and cancer
US7892530B2 (en) 1999-06-04 2011-02-22 Ed. Geistlich Soehne Ag Fuer Chemische Industrie Treatment of tumor metastases and cancer
US8030301B2 (en) 1999-06-04 2011-10-04 Ed. Geistlich Soehne Ag Fuer Chemische Industrie Treatment of cancers with methylol-containing compounds and at least one electrolyte
US20020098164A1 (en) * 2000-10-27 2002-07-25 Redmond H. Paul Treatment of tumor metastases and cancer
JP2003515558A (ja) * 1999-12-06 2003-05-07 ロード アイランド ホスピタル， ア ライフスパン パートナー 腫瘍を治療するためのメチロール含有化合物の使用
CN100519525C (zh) 1999-12-06 2009-07-29 葛兰素集团有限公司 芳香砜类及其医疗用途
EP1797884B1 (fr) * 1999-12-06 2013-09-11 Geistlich Pharma AG Taurolidine ou de taurultame pour i' utilisation dans le traitement des tumeurs de la prostate, des poumons, du côlon et dans le traitement de la glioblastome multiforme récurrente
US6641571B2 (en) 2000-01-05 2003-11-04 Ed. Geistlich Soehne Ag Fuer Chemische Industrie Reduction of postoperative complications of cardiopulmonary bypass (CPB) surgery
CA2363973C (fr) * 2000-11-28 2009-03-10 Ed. Geistlich Sohne Ag Fur Chemische Industrie Amelioration de l'efficacite du 5-fluorouracil dans le traitement des metastases et du cancer
WO2002074294A1 (fr) * 2001-03-15 2002-09-26 Rhode Island Hospital, A Lifespan Partner Composes de taurine
WO2003028642A2 (fr) 2001-10-01 2003-04-10 Rhode Island Hospital, A Lifespan Partner Procede d'inhibition de metastases
JP5346148B2 (ja) * 2003-03-28 2013-11-20 エー・デー・ガイストリヒ・ゾーネ・アクチェンゲゼルシャフト・フュール・ヒェーミシェ・インダストリー 抗新生物性組成物および治療方法
US8236794B2 (en) 2003-09-29 2012-08-07 Ed. Geistlich Soehne Ag Fuer Chemische Industrie Treatment of mesothelioma
RU2468796C2 (ru) * 2006-09-07 2012-12-10 Эд. Гайстлих Зёне Аг Фюр Хемише Индустри Способ лечения рака костей

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8328073D0 (en) * 1983-10-20 1983-11-23 Geistlich Soehne Ag Chemical compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9200743A1 *

Also Published As

Publication number Publication date
WO1992000743A1 (fr) 1992-01-23
JPH05500973A (ja) 1993-02-25
JP3465824B2 (ja) 2003-11-10
GB9015108D0 (en) 1990-08-29

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