WO1992000743A1 - Use of taurolidine and/or taurultam for the treatment of tumours - Google Patents
Use of taurolidine and/or taurultam for the treatment of tumours Download PDFInfo
- Publication number
- WO1992000743A1 WO1992000743A1 PCT/EP1991/001269 EP9101269W WO9200743A1 WO 1992000743 A1 WO1992000743 A1 WO 1992000743A1 EP 9101269 W EP9101269 W EP 9101269W WO 9200743 A1 WO9200743 A1 WO 9200743A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- taurolidine
- taurultam
- tumours
- treatment
- administered
- Prior art date
Links
- AJKIRUJIDFJUKJ-UHFFFAOYSA-N taurolidine Chemical compound C1NS(=O)(=O)CCN1CN1CNS(=O)(=O)CC1 AJKIRUJIDFJUKJ-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 229960004267 taurolidine Drugs 0.000 title claims abstract description 36
- RJGYJMFQWGPBGM-UHFFFAOYSA-N 1,2,4-thiadiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCN1 RJGYJMFQWGPBGM-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 229950007343 taurultam Drugs 0.000 title claims abstract description 25
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 23
- 238000011282 treatment Methods 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 9
- 238000011321 prophylaxis Methods 0.000 claims abstract description 8
- 230000004614 tumor growth Effects 0.000 claims abstract description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 4
- 238000001802 infusion Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 3
- 239000002254 cytotoxic agent Substances 0.000 claims description 3
- 229940127089 cytotoxic agent Drugs 0.000 claims description 3
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 3
- 230000004060 metabolic process Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 108010092160 Dactinomycin Proteins 0.000 claims description 2
- 102000000589 Interleukin-1 Human genes 0.000 claims description 2
- 108010002352 Interleukin-1 Proteins 0.000 claims description 2
- 102000000588 Interleukin-2 Human genes 0.000 claims description 2
- 108010002350 Interleukin-2 Proteins 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 2
- 229940009456 adriamycin Drugs 0.000 claims description 2
- 229960000640 dactinomycin Drugs 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 229940079322 interferon Drugs 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 102000018594 Tumour necrosis factor Human genes 0.000 description 4
- 108050007852 Tumour necrosis factor Proteins 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 206010027458 Metastases to lung Diseases 0.000 description 3
- -1 methylol groups Chemical group 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- JIZZEHDLOQDZGP-UHFFFAOYSA-N 2-amino-1-hydroxyethanesulfonic acid Chemical compound NCC(O)S(O)(=O)=O JIZZEHDLOQDZGP-UHFFFAOYSA-N 0.000 description 1
- MVQXBXLDXSQURK-UHFFFAOYSA-N 2-aminoethanesulfonamide Chemical compound NCCS(N)(=O)=O MVQXBXLDXSQURK-UHFFFAOYSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000001382 Experimental Melanoma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000051 modifying effect Effects 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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
The present invention relates to a method of treatment or prophylaxis of tumours in mammalian subjects wherein an effective dose of taurolidine and/or taurultam is administered to a mammalian subject suffering from or at risk to tumour growth.
Description
- 1 -
USE OF TAUROLIDINE AND/OR TAURULTAM FOR THE TREATMENT OF TUMOURS
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. Our United Kingdom Patent Application No 9005856.1 relates to combined therapy using TNF and taurolidine or taurultam. In the course of these studies, it was surprisingly found that taurolidine acted directly on tumours in addition to its effect on TNF. Furthermore, such action was shown to be selective in that the growth of normal cell-lines was not significantly inhibited.
According to the present invention we provide a method of treatment or prophylaxis of tumours in mammalian subjects wherein an effective dose of taurolidine and/or taurultam is administered to a mammalian subject suffering from or at risk to tumour growth.
Taurolidine and taurultam have the formulae given below:
TAUROL I D I NE TAURUL TAM
- 2 -
These compounds are ethylol transfer agents. 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. Such solutions are described in our European Patent Application 253662. The 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 -
It is believed that other agents known to be involved in tumour metabolism may also advantageously be co-administered in conjunction with the above combined therapy. Such agents include gamma-interferon, interleukin-1 and interleukin-2.
Cytotoxic agents such as adriamycin and actinomycin D may also be co-administered.
The 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.
The following examples are given by way of illustration only:-
Example 1
C573L/6 mice injected iv with 1.5xl06 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. When 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).
Treatment Group n Mean Pulmonary Metastases ± S.E.M
Saline 25 117.3 ± 18.5
Taurolidine (D 0-10) 16 76.4 ± 14.9 Taurolidine (D 3-10) 16 103.5 ± 14.8
In a second in vivo experiment, Balb/c mice injected sc with 1.5 x 106 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). In a third series 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).
Example 2
Taurolidine was tested against multiple cell lines (two tumours, one normal) using a range of doses.
5 -
Cell line Concentration Inhibition of tested (μg ml) cellular metabolism
(%)
Foreskin
Fibroblasts 20 31.7
LS174T (colon) 20 84.3
Jurkat (leukaemic) 20 84.6
Preferential activity against tumour lines was demonstrated at low doses with complete cellular inhibition of tumour, but not normal cells, occurring at doses > 200 μg ml
Claims
1. A method of treatment or prophylaxis of tumours in mammalian subjects wherein an effective dose of taurolidine and/or taurultam is administered to a mammalian subject suffering from or at risk to tumour growth.
2. A method as claimed in Claim 1 wherein said taurolidine and/or taurultam is administered by injection or infusion or by direct application to external tumours.
3. A method as claimed in Claim 1 or Claim 2 wherein said taurolidine and/or taurultam is administered at a dosage in the range of 150-450 mg/kg per day.
4. A method as claimed in Claim 3 wherein said taurolidine and/or taurultam is administered at a dosage in the range of 300 to 450 mg/kg per day.
5. A method as claimed in any one of Claims 1 to 4 for the treatment or prophylaxis of lymphomas, sarcomas, melanomas and carcinomas.
6. A method as claimed in any one of Claims 1 to 5 further comprising administering to said mammalian subject separately or simultaneously cytotoxic agents or agents known to be involved in tumour metabolism.
7. A method as claimed in Claim 6 comprising further administering gam a-interferon, interleukin-1, interleukin-2, adriamycin or actinomycin D. - 7 -
8. Use of taurolidine and/or taurultam for the treatment or prophylaxis of tumours in mammalian subjects.
9. Use of taurolidine and/or taurultam for the preparation of pharmaceutical compositions for the treatment or prophylaxis of tumours in mammalian subjects.
10. A pharmaceutical composition comprising taurolidine and/or taurultum and at least one agent selected from cytotoxic agents or agents involved in tumour metabolism for separate or simultaneous administration to a mammalian subject suffering from or at risk to tumour growth.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9015108.5 | 1990-07-09 | ||
| GB909015108A GB9015108D0 (en) | 1990-07-09 | 1990-07-09 | Chemical compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992000743A1 true WO1992000743A1 (en) | 1992-01-23 |
Family
ID=10678847
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1991/001269 WO1992000743A1 (en) | 1990-07-09 | 1991-07-08 | Use of taurolidine and/or taurultam for the treatment of tumours |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0491018A1 (en) |
| JP (1) | JP3465824B2 (en) |
| GB (1) | GB9015108D0 (en) |
| WO (1) | WO1992000743A1 (en) |
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19606897A1 (en) * | 1996-02-13 | 1997-08-14 | Joachim Michael Prof D Mueller | Agent inhibiting tumour cell spread and metastasis in surgery of tumours |
| WO1999006114A3 (en) * | 1997-07-31 | 1999-04-08 | Geistlich Soehne Ag | Use of taurolidine or taurultam for the manufacture of a medicament for the prevention of metastases |
| EP1201247A2 (en) | 2000-10-27 | 2002-05-02 | Ed Geistlich Söhne AG Für Chemische Industrie | Treatment of tumor metastases and cancer |
| WO2001039762A3 (en) * | 1999-12-06 | 2002-05-02 | Rhode Island Hosp Lifespan Ptr | Use of taurolidine or taurultam for the manufacture of a medicament for the treatment of tumors of the central nervous system |
| EP1247524A1 (en) | 2001-04-03 | 2002-10-09 | Ed. Geistlich Söhne Ag Für Chemische Industrie | Composition comprising taurolidine and/or taurultam for the treatment of cancer |
| EP1066830A3 (en) * | 1999-06-04 | 2002-10-16 | Ed. Geistlich Söhne Ag Für Chemische Industrie | Uses and compositions for treating primary and secondary tumors of the central nervous system (cns) |
| EP1208840A3 (en) * | 2000-11-28 | 2003-05-21 | Ed Geistlich Söhne AG Für Chemische Industrie | Combination of fluorouracil and a methylol transfer agent for the treatment of tumor metastases and cancer |
| US6641571B2 (en) | 2000-01-05 | 2003-11-04 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Reduction of postoperative complications of cardiopulmonary bypass (CPB) surgery |
| US6753328B2 (en) | 2001-10-01 | 2004-06-22 | Rhode Island Hospital | Methods of inhibiting metastases |
| 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 |
| WO2008029264A3 (en) * | 2006-09-07 | 2008-09-04 | Geistlich Soehne Ag | Method of treating bone cancer |
| RU2343924C2 (en) * | 2003-03-28 | 2009-01-20 | Эд.Гайстлих Зёне Аг Фюр Хемише Индустри | Adhesive antitumoral compositions |
| US7479505B2 (en) | 1999-12-06 | 2009-01-20 | Geistlich Phama Ag | Use of taurolidine to treat tumors |
| EP1377281A4 (en) * | 2001-03-15 | 2009-06-17 | Rhode Island Hospital | TAURINE COMPOUNDS |
| EP1797884A3 (en) * | 1999-12-06 | 2010-02-10 | Geistlich Pharma AG | Use of taurolidine or taurultam for the manufacture of a medicament for the treatment of tumors of the central nervous system |
| 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 |
| US8236794B2 (en) | 2003-09-29 | 2012-08-07 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Treatment of mesothelioma |
| 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0139534A2 (en) * | 1983-10-20 | 1985-05-02 | Ed. Geistlich Söhne Ag Für Chemische Industrie | Compositions for the prophylactic treatment of osteitis and osteomyelitis |
-
1990
- 1990-07-09 GB GB909015108A patent/GB9015108D0/en active Pending
-
1991
- 1991-07-08 EP EP91911804A patent/EP0491018A1/en not_active Withdrawn
- 1991-07-08 WO PCT/EP1991/001269 patent/WO1992000743A1/en not_active Application Discontinuation
- 1991-07-08 JP JP51135891A patent/JP3465824B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0139534A2 (en) * | 1983-10-20 | 1985-05-02 | Ed. Geistlich Söhne Ag Für Chemische Industrie | Compositions for the prophylactic treatment of osteitis and osteomyelitis |
Non-Patent Citations (3)
| Title |
|---|
| Annals of Royal College of Surgeons of England, vol. 66, No. 3, May 1984, Henry C. Umpleby et al.:"The Efficacy of Agents Employed to Prevent Anastomotic Recurrence in Colorectal Carcinoma", pages 192-194, see the whole document * |
| Annals of the Royal College of Surgeons of England, vol. 72, 1990, M.E. Lucarotti et al.:"Antiseptic Toxicity to Breast Carcinoma in Tissue Culture: An Adjuvant to Conservation Therapy?", pages 388-392, see the whole document * |
| J.E.F. Reynolds: "Martindale", The Extra Pharmacopoeia, 29th Edition, 1989, The Pharmaceutical Press, (London, GB), page 162, "Taurolidine", see the whole article * |
Cited By (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19606897C2 (en) * | 1996-02-13 | 2002-08-29 | Geistlich Soehne Ag | Means for preventing the spread of tumor cells and the development of trocar metastases in open and laparoscopic surgery of malignant tumors |
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| EP1377281A4 (en) * | 2001-03-15 | 2009-06-17 | Rhode Island Hospital | TAURINE COMPOUNDS |
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| US8236794B2 (en) | 2003-09-29 | 2012-08-07 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Treatment of mesothelioma |
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| EP3028705A1 (en) * | 2006-09-07 | 2016-06-08 | Ed. Geistlich Söhne Ag Für Chemische Industrie | Treating bone cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0491018A1 (en) | 1992-06-24 |
| GB9015108D0 (en) | 1990-08-29 |
| JPH05500973A (en) | 1993-02-25 |
| JP3465824B2 (en) | 2003-11-10 |
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