WO2003045359B1 - Combination of cimetidine and cysteine derivatives for treating cancer - Google Patents
Combination of cimetidine and cysteine derivatives for treating cancerInfo
- Publication number
- WO2003045359B1 WO2003045359B1 PCT/DK2002/000792 DK0200792W WO03045359B1 WO 2003045359 B1 WO2003045359 B1 WO 2003045359B1 DK 0200792 W DK0200792 W DK 0200792W WO 03045359 B1 WO03045359 B1 WO 03045359B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cysteine
- cimetidine
- cancer
- group
- derivative
- Prior art date
Links
- 229960001380 cimetidine Drugs 0.000 title claims abstract 42
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 title claims abstract 42
- 206010028980 Neoplasm Diseases 0.000 title claims abstract 24
- 201000011510 cancer Diseases 0.000 title claims abstract 20
- 150000001944 cysteine derivatives Chemical class 0.000 title claims abstract 20
- 239000000203 mixture Substances 0.000 claims abstract 23
- 239000000126 substance Substances 0.000 claims abstract 15
- 241000124008 Mammalia Species 0.000 claims abstract 8
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract 4
- 206010061218 Inflammation Diseases 0.000 claims abstract 3
- 230000004054 inflammatory process Effects 0.000 claims abstract 3
- 230000001629 suppression Effects 0.000 claims abstract 3
- 230000009610 hypersensitivity Effects 0.000 claims abstract 2
- 150000003839 salts Chemical class 0.000 claims 29
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 15
- 235000018417 cysteine Nutrition 0.000 claims 15
- 238000000034 method Methods 0.000 claims 15
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims 12
- IDIDJDIHTAOVLG-VKHMYHEASA-N S-methylcysteine Chemical compound CSC[C@H](N)C(O)=O IDIDJDIHTAOVLG-VKHMYHEASA-N 0.000 claims 12
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims 12
- 239000003795 chemical substances by application Substances 0.000 claims 9
- 239000003112 inhibitor Substances 0.000 claims 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 8
- 239000002246 antineoplastic agent Substances 0.000 claims 8
- 239000003814 drug Substances 0.000 claims 8
- 239000013543 active substance Substances 0.000 claims 7
- 108010024636 Glutathione Proteins 0.000 claims 6
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 claims 6
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims 6
- IDIDJDIHTAOVLG-UHFFFAOYSA-N S-methyl-L-cysteine Natural products CSCC(N)C(O)=O IDIDJDIHTAOVLG-UHFFFAOYSA-N 0.000 claims 6
- 229960003067 cystine Drugs 0.000 claims 6
- 229960003180 glutathione Drugs 0.000 claims 6
- RYGLCORNOFFGTB-YFKPBYRVSA-N (2r)-2-acetamido-3-methylsulfanylpropanoic acid Chemical compound CSC[C@@H](C(O)=O)NC(C)=O RYGLCORNOFFGTB-YFKPBYRVSA-N 0.000 claims 5
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims 5
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 claims 5
- GGLZPLKKBSSKCX-UHFFFAOYSA-N S-ethylhomocysteine Chemical compound CCSCCC(N)C(O)=O GGLZPLKKBSSKCX-UHFFFAOYSA-N 0.000 claims 5
- NOKPBJYHPHHWAN-REOHCLBHSA-N S-sulfo-L-cysteine Chemical compound OC(=O)[C@@H](N)CSS(O)(=O)=O NOKPBJYHPHHWAN-REOHCLBHSA-N 0.000 claims 5
- 229960004308 acetylcysteine Drugs 0.000 claims 5
- HSPYGHDTVQJUDE-LURJTMIESA-N dacisteine Chemical compound CC(=O)N[C@H](C(O)=O)CSC(C)=O HSPYGHDTVQJUDE-LURJTMIESA-N 0.000 claims 5
- 150000003710 vitamin D derivatives Chemical class 0.000 claims 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 4
- 102000003945 NF-kappa B Human genes 0.000 claims 4
- 108010057466 NF-kappa B Proteins 0.000 claims 4
- ULXKXLZEOGLCRJ-BYPYZUCNSA-N S-ethyl-L-cysteine zwitterion Chemical compound CCSC[C@H](N)C(O)=O ULXKXLZEOGLCRJ-BYPYZUCNSA-N 0.000 claims 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 4
- 229940072107 ascorbate Drugs 0.000 claims 4
- 235000010323 ascorbic acid Nutrition 0.000 claims 4
- 239000011668 ascorbic acid Substances 0.000 claims 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 4
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims 4
- 210000005095 gastrointestinal system Anatomy 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 0.000 claims 4
- 229940125697 hormonal agent Drugs 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 208000037819 metastatic cancer Diseases 0.000 claims 4
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 4
- 210000002784 stomach Anatomy 0.000 claims 4
- 229910021653 sulphate ion Inorganic materials 0.000 claims 4
- 206010009944 Colon cancer Diseases 0.000 claims 3
- 229930003316 Vitamin D Natural products 0.000 claims 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims 3
- 230000000340 anti-metabolite Effects 0.000 claims 3
- 239000002256 antimetabolite Substances 0.000 claims 3
- 229940100197 antimetabolite Drugs 0.000 claims 3
- 229960002433 cysteine Drugs 0.000 claims 3
- 230000002519 immonomodulatory effect Effects 0.000 claims 3
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims 3
- 230000000699 topical effect Effects 0.000 claims 3
- 235000019166 vitamin D Nutrition 0.000 claims 3
- 239000011710 vitamin D Substances 0.000 claims 3
- 229940046008 vitamin d Drugs 0.000 claims 3
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims 2
- 208000011231 Crohn disease Diseases 0.000 claims 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims 2
- 206010012442 Dermatitis contact Diseases 0.000 claims 2
- 201000005569 Gout Diseases 0.000 claims 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 2
- 208000002193 Pain Diseases 0.000 claims 2
- 201000004681 Psoriasis Diseases 0.000 claims 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims 2
- 206010039085 Rhinitis allergic Diseases 0.000 claims 2
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- 208000000728 Thymus Neoplasms Diseases 0.000 claims 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- 210000004100 adrenal gland Anatomy 0.000 claims 2
- 201000010105 allergic rhinitis Diseases 0.000 claims 2
- 125000000732 arylene group Chemical group 0.000 claims 2
- 208000006673 asthma Diseases 0.000 claims 2
- 201000008937 atopic dermatitis Diseases 0.000 claims 2
- 208000010668 atopic eczema Diseases 0.000 claims 2
- 210000004556 brain Anatomy 0.000 claims 2
- 229960002908 cimetidine hydrochloride Drugs 0.000 claims 2
- QJHCNBWLPSXHBL-UHFFFAOYSA-N cimetidine hydrochloride Chemical compound [H+].[Cl-].N#C/N=C(/NC)NCCSCC=1N=CNC=1C QJHCNBWLPSXHBL-UHFFFAOYSA-N 0.000 claims 2
- 210000001072 colon Anatomy 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 208000010247 contact dermatitis Diseases 0.000 claims 2
- 208000037765 diseases and disorders Diseases 0.000 claims 2
- 239000002552 dosage form Substances 0.000 claims 2
- 238000009472 formulation Methods 0.000 claims 2
- 230000002496 gastric effect Effects 0.000 claims 2
- 125000005549 heteroarylene group Chemical group 0.000 claims 2
- 210000004185 liver Anatomy 0.000 claims 2
- 201000007270 liver cancer Diseases 0.000 claims 2
- 208000014018 liver neoplasm Diseases 0.000 claims 2
- 210000004072 lung Anatomy 0.000 claims 2
- 230000001404 mediated effect Effects 0.000 claims 2
- 201000008482 osteoarthritis Diseases 0.000 claims 2
- 210000000496 pancreas Anatomy 0.000 claims 2
- 238000007911 parenteral administration Methods 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 210000002307 prostate Anatomy 0.000 claims 2
- 206010038038 rectal cancer Diseases 0.000 claims 2
- 201000001275 rectum cancer Diseases 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 210000003079 salivary gland Anatomy 0.000 claims 2
- 208000008742 seborrheic dermatitis Diseases 0.000 claims 2
- 210000003491 skin Anatomy 0.000 claims 2
- 208000017520 skin disease Diseases 0.000 claims 2
- 210000000813 small intestine Anatomy 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 210000000952 spleen Anatomy 0.000 claims 2
- 208000024891 symptom Diseases 0.000 claims 2
- 201000009377 thymus cancer Diseases 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- SMLNREUXXJESLR-UHFFFAOYSA-N 2-(ethylamino)-3-sulfanylpropanoic acid Chemical compound CCNC(CS)C(O)=O SMLNREUXXJESLR-UHFFFAOYSA-N 0.000 claims 1
- 206010002198 Anaphylactic reaction Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- -1 S-ethγl-homocystelne Chemical compound 0.000 claims 1
- 125000004419 alkynylene group Chemical group 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 230000036783 anaphylactic response Effects 0.000 claims 1
- 208000003455 anaphylaxis Diseases 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 208000037976 chronic inflammation Diseases 0.000 claims 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims 1
- 239000005516 coenzyme A Substances 0.000 claims 1
- 229940093530 coenzyme a Drugs 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 210000005002 female reproductive tract Anatomy 0.000 claims 1
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 1
- 210000004392 genitalia Anatomy 0.000 claims 1
- SYKWLIJQEHRDNH-CKRMAKSASA-N glutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SYKWLIJQEHRDNH-CKRMAKSASA-N 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 210000003563 lymphoid tissue Anatomy 0.000 claims 1
- 210000005001 male reproductive tract Anatomy 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 229930003231 vitamin Natural products 0.000 claims 1
- 239000011782 vitamin Substances 0.000 claims 1
- 229940088594 vitamin Drugs 0.000 claims 1
- 235000013343 vitamin Nutrition 0.000 claims 1
- 150000003722 vitamin derivatives Chemical class 0.000 claims 1
- 230000002113 chemopreventative effect Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 0 *C(CC(C(O*)=O)N*)S Chemical compound *C(CC(C(O*)=O)N*)S 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to new substances in the form of chemical complexes comprising cimetidine or a derivative thereof and a cysteine derivative and to compositions comprising said complexes or combination. The invention further relates to the therapeutic effect of such combinations in relation to treating cancer, cancer chemoprevention or the suppression of hypersensitivity and/or inflammatory reactions of a mammal.
Claims
49
AMENDED CLAIMS
[received by the International Bureau on 15 December 2003 (15.12.03); original claims 1-59 replaced by amended claims 1-51 (7 pages)]
1. A substance consisting of a chemical complex comprising: ι) a cysteine derivative selected from the group consisting of cysteine, N-acetyl-cysteine, cystine, homocysteine, cysteine methyiester, 5-ethyl-cysteine, N,S- isobuturyl -cysteine, 5- carboxymethyi-cysteine, S-ethyl-homocysteine, S-methyl-cysteine, cysteine S-sulfate, N,S-diacetyl-cysteine methyiester, N-acetyl-S-methylcystelne, glutathione, stereoisomers thereof, salts thereof and mixtures thereof; ii) cimetidine or a pharmaceutically acceptable salt thereof.
2. A substance consisting of a chemical complex comprising: i) a cysteine derivative of Formula I, stereoisomers thereof and/or salts thereof,
I wherein n Is an integer from 1 to 3; p is a whole number selected from the group consisting of 1 and 2;
R1 is a monoradicai selected from the group consisting of hydrogen, halogen, sulphate, - C8-acyleπe, Cj-Cs-alkylene, C3-C7-cycloalkylene, C2-CB-alkenylene and C2-C8-alkynylene; R2 is a monoradicai selected from the group consisting of hydrogen, halogen, sulphate, Cj- C8-alkylene, rCv-cycloalkylene, C2-Cβ-a!kenylene and C2-C8-alkynylene; and R3 is a monoradicai selected from the group consisting of hydrogen, sulphate, - - alkylene, C2-C8-alkenylene, C2-Ca-aIkynylene, arylene, heteroarylene and
ii) cimetidine or pharmaceutically acceptable salts thereof.
3. The substance according to claims 1 or 2, wherein the pharmaceutically acceptable salt of cimetidine is selected from the group consisting of cimetidine hydrochloride, cimetidine
5 hydrobromide, cimetidine acetate, cimetidine ascorbate and cimetidine benzoate.
4. The substance according to any one of claims 1 to 3, wherein the cimetidine or a salt thereof and the cysteine derivative are present in a molar ratio or a mass ratio of between about 1: 10000 to 10000: 1, preferably about 1: 1000 to 1000: 1, more preferably about
10 1: 100 to 100:1, such as about 1:10 to 10:1, about 1:5 to 5:1, or about 1:2 to 2:1.
5. The substance according to any one of claims 1 to 4, wherein the complex further comprises one or more therapeutically active agents.
15 6. The substance according to claim 5, wherein the one or more therapeutically active agent is an anticancer agent.
7. The substance according to claim 6, wherein the anticancer agent is selected from the group consisting of DNA-iπteractlve agents, antimetabolites, tubulin-interactive agents 20 hormonal agents, protease inhibitors, cyclooxygeπase inhibitors, nuclear factor kappa B inhibitors and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitors.
8. A composition comprising a substance as defined in any of the claims 1 to 7 and and one or more pharmaceutically acceptable excipient(s) or carrier(s).
25
9. A composition comprising i) a cysteine derivative selected from the group consisting of cysteine, N-acetyl-cysteine, cystine, homocysteine, cysteine methyiester, S-ethyl-cystelne, N,5-isobuturyl-cysteine, S- carboxymethyl-cysteine, S-ethγl-homocystelne, S-methyl-cysteine, cysteine S-sulfate,
30 N,S-dlacetyl~cysteine methyiester, N-acetyl-S-methylcysteine, glutathione, stereoisomers thereof, salts thereof and mixtures thereof; ii) cimetidine or pharmaceutically acceptable salts thereof; and iii) one or more acceptable excipient(s) or carrier(s).
35 10. A composition comprising: i) a cysteine derivative of Formula I, stereoisomers thereof and/or salts thereof,
wherein n is an integer from 1 to 3; p is a whole number selected from the group consisting of 1 and 2;
R1 is a monoradicai selected from the group consisting of hydrogen, halogen, sulphate, Cx-
C8-acylene, Ci- -alkylene, C3-C7-cycloa!kylene, C2-C8-alkenylenε and C2-C8-alkynylene;
R2 is a monoradicai selected from the group consisting of hydrogen, halogen, sulphate, Ci-
C8-alkylene, C3-C7-cycloalkylene, C2-C8-alkenyleπe and C2-C8-alkynylene; and
R3 is a monoradicai selected from the group consisting of hydrogen, sulphate, Cι-C8- alkylene, C2-C8-alkenylene, C2-C8~alkynylene, arylene, heteroarylene and
10
15 11. The composition according to any one of claims 8 to 10, wherein the cimetidine or a pharmaceutically acceptable salt thereof is selected from the group consisting of cimetidine hydrochloride, cimetidine hydrobromide, cimetidine acetate, cimetidine ascorbate and cimetidine benzoate.
20 12. The composition according to any one of claims 8 to 11, wherein the cimetidine or a salt thereof and the cysteine derivative are present in a moiar ratio or mass ratio of between about 1: 10000 to 10000: 1, such as about 1: 1000 to 1000: 1, preferably about 1:100 to 100:1, such as about 1: 10 to 10:1 e.g. about 1:5 to 5: 1, such as about 1:2 to 2: 1.
25
13. The composition according to any one of claims 8 to 12, further comprising one or more therapeutically active agents.
14. The composition according to claim 13, wherein the one or more therapeutically active 30 agents is an anticancer agent.
15. The composition according to claim 14, wherein the anticancer agent Is selected from the group consisting of DNA-interactive agents, antimetabolites, tubulin-interactive agents hormonal agents, protease inhibitors, cyclooxygenase inhibitors, nuclear factor kappa B
35 inhibitors, 3-hydroxy-3-methy!glutaryl-coenzyme A (HMG-CoA) inhibitors, vitamin O derivatives and vitamin D analogs.
16. The composition according to any one of claims 8 to 15, formulated in a form for peroral, oral, topical, transdermal, or parenteral administration.
52
17. The composition according to claim 16, formulated in a form for peroral or topical administration.
5 18. The composition according to any one of claims 8 to 17, formulated as a solid, a semi- solid, a suspension or an emulsion.
19. Use of a combination of cimetidine or a pharmaceutically acceptable salt thereof and a cysteine derivative selected from the group consisting of cysteine, N-acetyl-cysteine,
10 cystine, homocysteine, cysteine methyiester, S-ethyl-cysteine, N,S-isobuturyl-cysteine, S- carboxymethyl-cysteine, S-ethyl-homocysteine, S-methyl-cysteine, cysteine S-sulfate, N,S-diacetyl-cysteine methyiester, N-acetyl-S-methylcysteine, glutathione, stereoisomers thereof, salts thereof and mixtures thereof for the preparation of a medicament for the treatment of cancer in a mammal.
15
20. Use of a combination of cimetidine or a pharmaceutically acceptable salt thereof and a cysteine derivative of Formula 1 of claim 2, wherein n, p, R1, R2 and R3 is a as defined In claim 2 for the preparation of a medicament for the treatment of cancer in a mammal.
20 21. The use according to any one of claims 19 or 20, wherein the cancer is selected from the group of cancer in the gastrointestinal system, metastatic cancers and invasive cancers.
22. The use according to claim 21, wherein the cancer of the gastrointestinal system is 25 selected from the group of colon cancer, rectal cancer, colorectal cancer, pancreatic cancer, stomach (gastric) cancer, oesophageal cancer, liver cancer or bladder cancer.
23. The use according to claim 21, wherein the metastatic cancers and invasive cancers cancer is selected from the group of breast cancer, cancer of the male and female genital
30 tract, cancer of the thymus, lung, stomach, small Intestine, prostate, adrenal gland, pancreas, colon, lymphoid tissue, liver, brain, salivary gland, spleen and skin.
24. Use of a combination of cimetidine or a pharmaceutically acceptable salt thereof and a cysteine derivative selected from the group consisting of cysteine, N-acetyl-cysteine,
35 cystine, homocysteine, cysteine methyiester, S-ethyl-cysteine, N,S-isobuturyl-cysteine, S- carboxymethyl-cysteine, S-ethyl-homocysteine, S-methyl-cysteine, cysteine S-sulfate, N,S-diacetyl-cysteine methyiester, N-acetyl-S-methylcysteine, glutathione, stereoisomers thereof, salts thereof and mixtures thereof for the preparation of a medicament for immunomodulatlon of a mammal.
40
25. The use according to claim 24, wherein immunomodulating activity relates to the suppression of inflammatory reactions such as treatment of diseases and disorders, or symptoms associated therewith, selected from the group consisting of hypersensitivity skin disease, atopic eczema, contact dermatitis, seborrhoeic eczema, psoriasis, IgE mediated
allergic reactions, asthma, allergic rhinitis, anaphyiaxis, autoimmune disease, chronic inflammatory disease, Crohn's disease, ulcerative colitis, rheumatoid arthritis, gout, osteoarthritis and pain.
5 26. The use according to any one of claims 19 to 25, wherein the cimetidine or a pharmaceutically acceptable salt thereof is selected from the group consisting of cimetidine hydrochlorlde, cimetidine hydrobromide, cimetidine acetate, cimetidine ascorbate and cimetidine benzoate.
10 27. The use according to any one of claims 19 to 26, wherein the medicament comprises a substance consisting of a complex as defined in any one of claims 1 to 7.
28. The use according to any one of claims 19 to 26, wherein the medicament comprises a composition as defined in any one of claims 8 to 18.
15
29. The use according to any one of claims 19 to 28, wherein the medicament further comprises one or more therapeutically active agents.
30. The use according to claim 29, wherein the one or more therapeutically active agents 20 is an anticancer agent.
31. The use according to claim 30, wherein the anticancer agent is selected from the group consisting of DNA-interactive agents, antimetabolites, tubulin-interactive agents hormonal agents, protease inhibitors, cyclooxygenase inhibitors, nuclear factor kappa B Inhibitors, 3-
25 hydroxy-3-methylg!utaryI-coenzyme A (HMG-CoA) inhibitors, vitamin D derivatives and vitamin D analogs.
32. The use according to any one of claims 19 to 31, wherein the medicament is formulated for peroral, oral, topical, transdermal or pareπteral administration.
30
33. The use according to any one of claims 19 to 32, wherein the medicament is formulated for delivery of the composition to the gastro-intestinal tract.
34. The use according to any one of claims 19 to 24 and 28 to 33, wherein the cimetidine 35 or a salt thereof and the cysteine derivative are each individually comprised in separate dosage forms.
35. The use according to any one of claims 19 to 33, wherein the cimetidine or a salt thereof and the cysteine derivative are together comprised in a single dosage form.
40
36. A method for treating cancer in a mammal, comprising administration to a mammal an effective amount of a combination of cimetidine or a pharmaceutically acceptable salt thereof; and a cysteine derivative selected from the group consisting of cysteine, N-acetyl- cysteine, cystine, homocysteine, cysteine methyiester, S-ethyl-cysteine, N,S-isobuturyl-
cysteine, S-carboxymethyl-cysteine, S-ethyl-homocysteine, S-methyl-cysteine, cysteine.5- sulfate, N,S-diacetyl-cysteine methyiester, N-acetyl-S-methylcysteine, glutathione, stereoisomers thereof, salts thereof and mixtures thereof.
5 37. The method according to claim 36, wherein the cancer is selected from the group of cancer in the gastrointestinal system, metastatic cancers and invasive cancers.
38. The method according to claim 37, wherein the cancer of the gastrointestinal system is selected from the group of colon cancer, rectal cancer, cotorectal cancer, pancreatic
10 cancer, stomach (gastric) cancer, oesophageal cancer, liver cancer or bladder cancer.
39. The method according to claim 37, wherein the metastatic cancers and invasive cancers cancer is selected from the group of breast cancer, cancer of the male and female genital tract, cancer of the thymus, lung, stomach, small intestine, prostate, adrenal gland,
15 pancreas, colon, lymphold tissue, liver, brain, salivary gland, spleen and skin.
40. A method for immunomodulation in a mammal, comprising administration to said mammal an effective amount of a combination of cimetidine or a pharmaceutically acceptable salt thereof; and a cysteine derivative selected from the group consisting of
20 cysteine, N-acetyi-cysteine, cystine, homocysteine, cysteine methyiester, S-ethyl-cysteine, N,S-lsobuturyl-cysteine, S-carboxymethyl-cysteine, S-ethyl-homocysteine, S-methyl- cysteine, cysteine S-sulfate, N,S-diacetyl-cysteine methyiester, N-acetyl-S-methylcysteine, glutathione, stereoisomers thereof, salts thereof and mixtures thereof.
25 41. The method according to claim 40, wherein immunomodulating activity relates to the suppression of inflammatory reactions such as treatment of diseases and disorders, or symptoms associated therewith, selected from the group consisting of hyperseπsitivity skin disease, atopic eczema, contact dermatitis, seborrhoeic eczema, psoriasis, IgE mediated allergic reactions, asthma, allergic rhinitis, anaphylaxis, autoimmune disease, chronic
30 inflammatory disease, Crohn's disease, ulcerative colitis, rheumatoid arthritis, gout, osteoarthritis and pain.
42. The method according to any one of claims 36, 39 and 40, wherein the cimetidine or a pharmaceutically acceptable salt thereof is selected from the group consisting of cimetidine 35 hydrochloride, cimetidine hydrobromide, cimetidine acetate, cimetidine ascorbate and cimetidine benzoate.
44. The method according to any one of claims 36, 39 and 40, wherein the combination of cimetidine or a salt thereof and the cysteine derivative, is in the form of a substance
40 consisting of a chemical complex as defined in any one of claims 1 to 7.
45. The method according to any one of claims 36, 39 and 40, wherein the combination of cimetidine or a salt thereof and the cysteine derivative is a composition as defined in any one of claims 8 to 18.
55
46. The method according to any one of claims 36, 39 and 40, further comprising the administration of one or more therapeutically active agents.
47, The method according to claim 44, wherein the one or more therapeutically active agents is an anticancer agent,
48. The method according to claim 45, wherein the anticancer agent is selected from the group consisting of DNA-interactive agents, aπtimetabolites, tubulin-interactive agents hormonal agents, protease inhibitors, cyclooxygenase inhibitors, nuclear factor kappa B inhibitors, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitors and vitamin D derivatives and vitamin D analogs.
49 The method according to any one of claims 36, 39 and 40, wherein said combination of cimetidine or a salt thereof and the cysteine derivative is administered by peroral, oral, topical, transdermal, or parenteral administration, or combinations thereof.
50. The method according to any one of claims 36, 39 and 40, wherein the combination of cimetidine or a salt thereof and the cysteine derivative, are together comprised in a single formulation.
51. The method according to any one of claims 36, 39 and 40, wherein the combination of cimetidine or a derivative thereof and the cysteine derivative are each individually comprised in separate formulations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2002350432A AU2002350432A1 (en) | 2001-11-26 | 2002-11-26 | Combination of cimetidine and cysteine derivatives for treating cancer |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200101761 | 2001-11-26 | ||
| DKPA200101761 | 2001-11-26 | ||
| DKPA200201086 | 2002-07-10 | ||
| DKPA200201086 | 2002-07-10 | ||
| US39534402P | 2002-07-12 | 2002-07-12 | |
| US60/395,344 | 2002-07-12 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2003045359A2 WO2003045359A2 (en) | 2003-06-05 |
| WO2003045359A3 WO2003045359A3 (en) | 2003-12-18 |
| WO2003045359B1 true WO2003045359B1 (en) | 2004-02-19 |
Family
ID=27222564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/DK2002/000792 WO2003045359A2 (en) | 2001-11-26 | 2002-11-26 | Combination of cimetidine and cysteine derivatives for treating cancer |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2002350432A1 (en) |
| WO (1) | WO2003045359A2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10337638A1 (en) * | 2003-08-16 | 2005-03-24 | Kirschfeld, Kuno, Prof. Dr. | Method of treating prostatitis |
| US7829709B1 (en) | 2007-08-10 | 2010-11-09 | Marquette University | Cysteine prodrugs to treat schizophrenia and drug addiction |
| CA2714226C (en) | 2008-02-07 | 2017-03-28 | Marquette University | Cysteine and cystine prodrugs to treat schizophrenia and reduce drug cravings |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5668117A (en) * | 1991-02-22 | 1997-09-16 | Shapiro; Howard K. | Methods of treating neurological diseases and etiologically related symptomology using carbonyl trapping agents in combination with previously known medicaments |
| FR2709960B1 (en) * | 1993-09-14 | 1995-12-01 | Marthe Dehorne | Use of a composition for the preparation of a medicament intended to maintain or restore a rate of aggregation of blood platelets close to the normal value. |
| DE10004651A1 (en) * | 2000-02-03 | 2001-08-16 | Jutta Dierkes | Combination of antihypertensive agents with drugs that reduce homocysteine levels |
| US20010036924A1 (en) * | 2000-03-21 | 2001-11-01 | Weidner Morten Sloth | Chemical complex comprising a substituted pyridine carboxy derivative and a glucosaminoglycan |
| US20020137785A1 (en) * | 2001-03-26 | 2002-09-26 | George Kindness | Inflammatory mechanism modulator composition and methods with anti-asthmatic properties |
-
2002
- 2002-11-26 WO PCT/DK2002/000792 patent/WO2003045359A2/en not_active Application Discontinuation
- 2002-11-26 AU AU2002350432A patent/AU2002350432A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002350432A8 (en) | 2003-06-10 |
| WO2003045359A2 (en) | 2003-06-05 |
| AU2002350432A1 (en) | 2003-06-10 |
| WO2003045359A3 (en) | 2003-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107250149A (en) | Deuterated chenodeoxycholic acid derivatives and the pharmaceutical composition comprising the compound | |
| RU2000113729A (en) | HETEROCYCLIC COMPOUNDS FOR INHIBITING GASTRIC ACID SECRET, METHODS FOR PRODUCING THEM AND THEIR PHARMACEUTICAL COMPOSITIONS | |
| KR101986272B1 (en) | Tricyclic compounds, compositions comprising them and uses thereof | |
| JP2019515884A5 (en) | ||
| EP2124930B1 (en) | Isosorbide mononitrate derivatives for the treatment of intestinal disorders | |
| SG174272A1 (en) | Pharmaceutical combinations comprising rdea119/bay 869766 for the treatment of specific cancers | |
| CN111320635B (en) | Compounds for the treatment of osteoarthritis | |
| CN116368141A (en) | Thiadiazolone derivatives and their use as AMPK agonists for the treatment of diabetes and related diseases | |
| WO2003045359B1 (en) | Combination of cimetidine and cysteine derivatives for treating cancer | |
| US20210214310A1 (en) | Crystalline form of s-apomorphine | |
| CN103304573B (en) | Narcissine compounds is preparing the application of antitumor drug | |
| WO2005102313A1 (en) | Preventive and/or therapeutic agent for chronic sinusitis | |
| US20190282527A1 (en) | Reversibly protected thiolated electrophilic fatty acids as prodrugs | |
| CN109789121A (en) | Mediate the reversible nitrogen oxides derivative of the novel nitroolefin of nitrosation and alkylated reaction | |
| EP1685134B1 (en) | Novel chelidonine derivatives, methods for the production thereof, and use thereof for producing pharmaceutical agents | |
| US20030158118A1 (en) | Combination of cimetidine and cysteine derivatives for treating cancer | |
| WO2001000217A1 (en) | Medicinal compositions for preventing or treating diarrhea | |
| JP2009519344A (en) | Demethylpenchromedine analogues and their use as anticancer agents | |
| CN105949277B (en) | A kind of antitumoral compounds and application thereof | |
| KR20020025181A (en) | Diesters of maleic or fumaric acid | |
| WO2024026102A2 (en) | Prodrugs for delivery of testosterone to the central nervous system | |
| US7345079B2 (en) | Treatment of disorder related to low cyclic GMP levels | |
| CN117243948A (en) | Application of daphnetin-containing composition in preparation of rheumatic arthritis drugs | |
| JPH0149130B2 (en) | ||
| JPH09227529A (en) | Nitroimidazole derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| B | Later publication of amended claims |
Effective date: 20031215 |
|
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase in: |
Ref country code: JP |
|
| WWW | Wipo information: withdrawn in national office |
Country of ref document: JP |