CA1281288C - Tumor therapy - Google Patents
Tumor therapyInfo
- Publication number
- CA1281288C CA1281288C CA000493821A CA493821A CA1281288C CA 1281288 C CA1281288 C CA 1281288C CA 000493821 A CA000493821 A CA 000493821A CA 493821 A CA493821 A CA 493821A CA 1281288 C CA1281288 C CA 1281288C
- Authority
- CA
- Canada
- Prior art keywords
- proline
- amino acids
- hydroxy
- cis
- hydroxyproline
- 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.)
- Expired - Lifetime
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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
- Peptides Or Proteins (AREA)
Abstract
Abstract Tumor Therapy.
This invention relates to a new therapy for cancer, blood vessel- and viral dideases by administering Hydroxy - prolin and additional compounds.
This invention relates to a new therapy for cancer, blood vessel- and viral dideases by administering Hydroxy - prolin and additional compounds.
Description
Description:
The main subject of this application is a new therapy for cancer especially carcinomas and related tumors. The expression "related tumors" means tumors which are like carcinomas of an embryologically epithelial origin. Examples are astrocytomas, neurinomas, suprarenal (medulla) tumors and so on.
In the years 1933 - 1946 Helen M. Dyer of the United States National Cancer Institute administered a wide range of amino acids in experimen-tal tumors of the ~ . Among others she mentioned hydroxyproline, but it is known that results of experimental animal tumors are scarcely transferable to human cancer.
In the last about 20 years electronmicroscopic device have shown the existence of the so called cytoskeleton within the ce71s. Immunolo-gical methods applied on the cytoskeleton are today used to recognize the origin of a cancer in their metastases. Applicant's concept, however, goes farther and postulates that a disturbance of the cytoske-leton is an essential factor for the pathogenesis of cancer, especially carcinomas. When in cancer cells and tissues the cytoskeleton, the cell junctions, the basal laminas and the filaments of the extra-cellular matrix, the connective tissues additionally are out of order it is doubtless indicated to substitute the constituents of these filamental systems which are specific amino acids.
From this point of view one of the most important of these amino acids is hydroxyproline. Here, however, it is not sufficient to differentiate between L and D configuration as Dyer had done. The decisive act is to differentiate also between cis and trans isomers of hydroxyproline which arise of the asymmetrical nature of the hydroxyl-group bearing carbon atom (this carbon atom is preferably number 49 but also number 3 is to be considered).
: ' 1 The proof that that is so was established by tests which were performed according to applicants suggestion. These were not tests on experimental animal tumors which are scarcely trans-ferable in their results to native human cancer. They were performed in human cell culture, the cells of which were re-moved from brain tumor patient by neurosurgery. The administe-ring of L - 4 - cis - Hydroxyproline to these astrocytoma tumor cells brought about not only a considerably slowed rate of cell division but also induced morphological redifferentia-tion, that is the cells resembled no longer tumor but normal astroglial cells. On the other side the trans isomer of L - 4 -Hydroxyproline showed not at all any positive effects.
Hydroxyproline may be given alone or combined with other amino acids which are occuring in the above named filamental system as there are proline, valine, alanine, lysine, hydroxylysine, glycine, cysteine and cystine.
The administration of such compounds however is not restricted to cancer cases alone, but is also indicated in cases of viral infection and blood vessels disease. Even neurological and rheumatological indications are marking out.
The administering of amino acids in their free form is a pos-sible method. Their specific effect however can also be brought into existence by administering compounds containing these amino acids that is for examples in acetylated form or as correspon-ding peptides. That means the administering of the named amino acids can be directly or indirectly.
Amino acids are scarcely toxic at all, therefore the named com-pounds have a wide doses range. However as with all amino acids therapy the known contraindications should wherever possible be excluded, especially patients with renal diseases.
The therapeutic administering of these compounds is principally the same as with all amino acid therapy. Tabletts or dragees for oral, solutions for intravenous (or central intravenous) administering.
Dosis range for hydroxyproline 0,01 - 0,1 g/kg daily in severe cases up to 0,2 g/kg.
Dosis range for hydroxyproline combined with proline, valine, alanine, lysine, hydroxylysine and glycine is for hydroxyproline 0,006 0,06 and 0,003 - 0,03 for each of the other amino acid.
The main subject of this application is a new therapy for cancer especially carcinomas and related tumors. The expression "related tumors" means tumors which are like carcinomas of an embryologically epithelial origin. Examples are astrocytomas, neurinomas, suprarenal (medulla) tumors and so on.
In the years 1933 - 1946 Helen M. Dyer of the United States National Cancer Institute administered a wide range of amino acids in experimen-tal tumors of the ~ . Among others she mentioned hydroxyproline, but it is known that results of experimental animal tumors are scarcely transferable to human cancer.
In the last about 20 years electronmicroscopic device have shown the existence of the so called cytoskeleton within the ce71s. Immunolo-gical methods applied on the cytoskeleton are today used to recognize the origin of a cancer in their metastases. Applicant's concept, however, goes farther and postulates that a disturbance of the cytoske-leton is an essential factor for the pathogenesis of cancer, especially carcinomas. When in cancer cells and tissues the cytoskeleton, the cell junctions, the basal laminas and the filaments of the extra-cellular matrix, the connective tissues additionally are out of order it is doubtless indicated to substitute the constituents of these filamental systems which are specific amino acids.
From this point of view one of the most important of these amino acids is hydroxyproline. Here, however, it is not sufficient to differentiate between L and D configuration as Dyer had done. The decisive act is to differentiate also between cis and trans isomers of hydroxyproline which arise of the asymmetrical nature of the hydroxyl-group bearing carbon atom (this carbon atom is preferably number 49 but also number 3 is to be considered).
: ' 1 The proof that that is so was established by tests which were performed according to applicants suggestion. These were not tests on experimental animal tumors which are scarcely trans-ferable in their results to native human cancer. They were performed in human cell culture, the cells of which were re-moved from brain tumor patient by neurosurgery. The administe-ring of L - 4 - cis - Hydroxyproline to these astrocytoma tumor cells brought about not only a considerably slowed rate of cell division but also induced morphological redifferentia-tion, that is the cells resembled no longer tumor but normal astroglial cells. On the other side the trans isomer of L - 4 -Hydroxyproline showed not at all any positive effects.
Hydroxyproline may be given alone or combined with other amino acids which are occuring in the above named filamental system as there are proline, valine, alanine, lysine, hydroxylysine, glycine, cysteine and cystine.
The administration of such compounds however is not restricted to cancer cases alone, but is also indicated in cases of viral infection and blood vessels disease. Even neurological and rheumatological indications are marking out.
The administering of amino acids in their free form is a pos-sible method. Their specific effect however can also be brought into existence by administering compounds containing these amino acids that is for examples in acetylated form or as correspon-ding peptides. That means the administering of the named amino acids can be directly or indirectly.
Amino acids are scarcely toxic at all, therefore the named com-pounds have a wide doses range. However as with all amino acids therapy the known contraindications should wherever possible be excluded, especially patients with renal diseases.
The therapeutic administering of these compounds is principally the same as with all amino acid therapy. Tabletts or dragees for oral, solutions for intravenous (or central intravenous) administering.
Dosis range for hydroxyproline 0,01 - 0,1 g/kg daily in severe cases up to 0,2 g/kg.
Dosis range for hydroxyproline combined with proline, valine, alanine, lysine, hydroxylysine and glycine is for hydroxyproline 0,006 0,06 and 0,003 - 0,03 for each of the other amino acid.
Claims
Claim 1 Use of cis-4-hydroxy-L-proline in the preparation of a medicament for the treatment of carcinoma.
or related tumors.
Claim 2 Use of cis-3-hydroxy-L-proline in the preparation of a medicament for the treatment of carcinomas or related tumors.
Claim 3 Use of cis-4-hydroxy-L-proline in the preparation of a medicament according to Claim 1, the me-dicament also comprising the amino acids proline, valine, alanine, lysine, hydroxylysine, glycine, cycteine and systine.
Claim 4 Use of cis-3-hydroxy-L-proline in the preparation of a medicament, according to Claim 2, the me-dicament also comprising the amino acids proline, valine, alanine, lysine, hydroxylysine, glycine, cycteine and cystine.
or related tumors.
Claim 2 Use of cis-3-hydroxy-L-proline in the preparation of a medicament for the treatment of carcinomas or related tumors.
Claim 3 Use of cis-4-hydroxy-L-proline in the preparation of a medicament according to Claim 1, the me-dicament also comprising the amino acids proline, valine, alanine, lysine, hydroxylysine, glycine, cycteine and systine.
Claim 4 Use of cis-3-hydroxy-L-proline in the preparation of a medicament, according to Claim 2, the me-dicament also comprising the amino acids proline, valine, alanine, lysine, hydroxylysine, glycine, cycteine and cystine.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US66820084A | 1984-11-05 | 1984-11-05 | |
US06/668,200 | 1984-11-05 | ||
US72356585A | 1985-04-15 | 1985-04-15 | |
US06/723,565 | 1985-04-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1281288C true CA1281288C (en) | 1991-03-12 |
Family
ID=27099851
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000493821A Expired - Lifetime CA1281288C (en) | 1984-11-05 | 1985-10-24 | Tumor therapy |
Country Status (5)
Country | Link |
---|---|
JP (1) | JPH0723309B2 (en) |
CA (1) | CA1281288C (en) |
CH (1) | CH667591A5 (en) |
DE (1) | DE3538619C2 (en) |
GB (1) | GB2171302B (en) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1987004925A1 (en) * | 1986-02-18 | 1987-08-27 | Biota Scientific Management Pty. Ltd. | Stimulation of angiogenesis |
DE3728852C2 (en) * | 1987-08-28 | 2003-06-18 | Wilhelm Hoerrmann | Medicines for tumor therapy |
EP0307390A3 (en) * | 1987-09-04 | 1991-04-10 | Merckle Gmbh | Chemical compound consisting of cis-3-hydroxyproline for therapeutic treatment, and process for its preparation |
US5827874A (en) * | 1995-05-05 | 1998-10-27 | Meyer; Hans | Methods of treating pain and inflammation with proline |
WO1997033578A1 (en) * | 1996-03-11 | 1997-09-18 | Wilhelm Hoerrmann | Combination of cis-4-hydroxy-l-proline and n-methyl-cis-4-hydroxy-l-proline for use as a therapeutic agent, in particular in cancer treatment |
WO1997038690A1 (en) * | 1996-04-16 | 1997-10-23 | Chephasaar Chem.-Pharm. Fabrik Gmbh | Agent for inhibiting leukocyte invasion of tissues |
DE10359828A1 (en) * | 2003-12-12 | 2005-07-28 | Zoser B. Dr.Rer.Nat. Salama | CHP gemcitabine combination agents and their use as antitumor agents, in particular anti-metastatic agents |
DE10359829A1 (en) * | 2003-12-12 | 2005-07-21 | Salama, Zoser B., Dr.Rer.Nat. | Use of CHP as inhibitor of glutathione-S-transferases and collagen IV |
UA82753C2 (en) * | 2003-12-18 | 2008-05-12 | Цозер Б. Салама | Proline derivatives used as pharmaceutical active ingredients for the treatment of tumours |
RU2007101074A (en) * | 2004-06-14 | 2008-07-20 | Зозер Б. САЛАМА (DE) | PHARMACEUTICAL ANTICANCER COMPOSITION PROLINE OR ITS DERIVATIVES AND ANTITUM ANTIBODY |
WO2007059047A2 (en) | 2005-11-11 | 2007-05-24 | Chandran V Ravi | Acetylated amino acids as anti-platelet agents, nutritional and vitamin supplements |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3932638A (en) * | 1967-09-14 | 1976-01-13 | Franco-Chimie S.A.R.L. | Compositions and methods for wound healing |
FR7639M (en) * | 1967-09-14 | 1970-02-02 | ||
GB1399887A (en) * | 1971-06-10 | 1975-07-02 | Prockop D J | Composition and methods for controlling collagen synthesis |
FR2207702B1 (en) * | 1972-11-23 | 1975-11-28 | Rhone Poulenc Ind | |
JPS59164718A (en) * | 1983-03-10 | 1984-09-17 | Advance Res & Dev Co Ltd | Preventive for cancer |
-
1985
- 1985-10-24 CA CA000493821A patent/CA1281288C/en not_active Expired - Lifetime
- 1985-10-29 CH CH4616/85A patent/CH667591A5/en not_active IP Right Cessation
- 1985-10-30 DE DE3538619A patent/DE3538619C2/en not_active Expired - Lifetime
- 1985-11-04 GB GB8527159A patent/GB2171302B/en not_active Expired
- 1985-11-05 JP JP24642585A patent/JPH0723309B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
DE3538619C2 (en) | 1995-11-09 |
DE3538619A1 (en) | 1986-05-07 |
JPS61155324A (en) | 1986-07-15 |
GB8527159D0 (en) | 1985-12-11 |
GB2171302B (en) | 1989-08-23 |
JPH0723309B2 (en) | 1995-03-15 |
CH667591A5 (en) | 1988-10-31 |
GB2171302A (en) | 1986-08-28 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
MKLA | Lapsed | ||
MKEC | Expiry (correction) |
Effective date: 20121205 |