DE4208868A1 - Use of ginkgolide cpds., esp. ginkgolide B - in treatment of metastatic cancers, to enhance the effect of chemotherapeutic agents - Google Patents
Use of ginkgolide cpds., esp. ginkgolide B - in treatment of metastatic cancers, to enhance the effect of chemotherapeutic agentsInfo
- Publication number
- DE4208868A1 DE4208868A1 DE19924208868 DE4208868A DE4208868A1 DE 4208868 A1 DE4208868 A1 DE 4208868A1 DE 19924208868 DE19924208868 DE 19924208868 DE 4208868 A DE4208868 A DE 4208868A DE 4208868 A1 DE4208868 A1 DE 4208868A1
- Authority
- DE
- Germany
- Prior art keywords
- ginkgolide
- use according
- chemotherapeutic agents
- treatment
- effect
- 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- Withdrawn
Links
- 229930184727 ginkgolide Natural products 0.000 title claims abstract description 12
- 230000000694 effects Effects 0.000 title claims abstract description 7
- 208000037819 metastatic cancer Diseases 0.000 title claims abstract description 6
- 208000011575 metastatic malignant neoplasm Diseases 0.000 title claims abstract description 6
- SQOJOAFXDQDRGF-WJHVHIKBSA-N ginkgolide B Natural products O=C1[C@@H](C)[C@@]2(O)[C@@H]([C@H](O)[C@]34[C@@H]5OC(=O)[C@]23O[C@H]2OC(=O)[C@H](O)[C@@]42[C@H](C(C)(C)C)C5)O1 SQOJOAFXDQDRGF-WJHVHIKBSA-N 0.000 title claims abstract description 5
- SQOJOAFXDQDRGF-MMQTXUMRSA-N ginkgolide-b Chemical compound O[C@H]([C@]12[C@H](C(C)(C)C)C[C@H]3OC4=O)C(=O)O[C@H]2O[C@]24[C@@]13[C@@H](O)[C@@H]1OC(=O)[C@@H](C)[C@]21O SQOJOAFXDQDRGF-MMQTXUMRSA-N 0.000 title claims abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 title claims abstract 5
- 229940127089 cytotoxic agent Drugs 0.000 title claims abstract 5
- 239000000824 cytostatic agent Substances 0.000 claims abstract description 12
- 230000001085 cytostatic effect Effects 0.000 claims abstract description 11
- 235000008100 Ginkgo biloba Nutrition 0.000 claims abstract description 6
- 244000194101 Ginkgo biloba Species 0.000 claims abstract description 6
- 238000001990 intravenous administration Methods 0.000 claims abstract 2
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 229940044683 chemotherapy drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 claims 1
- 210000004881 tumor cell Anatomy 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract 1
- 238000002512 chemotherapy Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000005907 cancer growth Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- SQOJOAFXDQDRGF-NNGCZKEZSA-N ginkgolide B Chemical compound C12([C@H](C(C)(C)C)C[C@H]3OC4=O)[C@@H](O)C(=O)O[C@H]1O[C@]14C23[C@@H](O)[C@@H]2OC(=O)[C@@H](C)[C@]12O SQOJOAFXDQDRGF-NNGCZKEZSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 208000006268 Sarcoma 180 Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- MOLPUWBMSBJXER-YDGSQGCISA-N bilobalide Chemical compound O([C@H]1OC2=O)C(=O)[C@H](O)[C@@]11[C@@](C(C)(C)C)(O)C[C@H]3[C@@]21CC(=O)O3 MOLPUWBMSBJXER-YDGSQGCISA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 235000020686 ginkgo biloba extract Nutrition 0.000 description 1
- FPUXKXIZEIDQKW-MFJLLLFKSA-N ginkgolide A Natural products O=C1[C@H](C)[C@@]2(O)[C@@H](O1)C[C@]13[C@@H]4OC(=O)[C@]21O[C@@H]1OC(=O)[C@H](O)[C@]31[C@@H](C(C)(C)C)C4 FPUXKXIZEIDQKW-MFJLLLFKSA-N 0.000 description 1
- FPUXKXIZEIDQKW-VKMVSBOZSA-N ginkgolide-a Chemical compound O[C@H]([C@]12[C@H](C(C)(C)C)C[C@H]3OC4=O)C(=O)O[C@H]2O[C@]24[C@@]13C[C@@H]1OC(=O)[C@@H](C)[C@]21O FPUXKXIZEIDQKW-VKMVSBOZSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 230000001225 therapeutic effect 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
Die Erfindung betrifft die Verwendung von Ginkgoliden für eine therapeutische Anwendung bei metastatischen Krebserkrankungen.The invention relates to the use of ginkgolides for a therapeutic application in metastatic Cancer.
Präparate auf der Basis eines Trockenextraktes aus Blättern des Ginkgo biloba Baumes werden seit Jahren zur Behandlung verschiedener Formen von Durchblutungsstörungen eingesetzt. Neben oralen Darreichungsformen kommen auch parenterale Darreichungsformen zur Anwendung.Preparations based on a dry extract from leaves of the Ginkgo biloba tree have been used for years various forms of circulatory disorders. In addition to oral dosage forms, there are also parenteral ones Dosage forms for use.
Die therapeutisch eingesetzten Ginkgo biloba Extrakte, wie z. B. das Fertigarzneimittel "Tebonin forte" der Firma Dr. Willmar Schwabe, enthalten ca. 24% Flavonoide, 6% Terpenoide (Ginkgolide A, B, C, Bilobalid), organische Säuren und andere Stoffgruppen.The therapeutically used Ginkgo biloba extracts, such as e.g. B. the finished drug "Tebonin forte" from Dr. Willmar Schwabe, contain approx. 24% flavonoids, 6% Terpenoids (Ginkgolide A, B, C, Bilobalid), organic acids and other groups of substances.
Für die Ginkgolide wurde eine große Zahl pharmakologischer Effekte beschrieben (P. Braquet et al.: Ginkgolides, J.R. Prous Science Publishers, Barcelona, ISBN: 84-404-1648-2), wobei sich das Ginkgolid B als besonders potenter Antagonist des körpereigenen plättchenaktivierenden Faktors erwiesen hat.A large number became pharmacological for the ginkgolides Effects described (P. Braquet et al .: Ginkgolides, J.R. Prous Science Publishers, Barcelona, ISBN: 84-404-1648-2), the ginkgolide B being a particularly potent antagonist of the body's own platelet activating factor Has.
Die Verwendung eines derartigen Ginkgo biloba Trockenextraktes zur Behandlung metastasierender Krebserkrankungen wurde beschrieben (Offenlegungsschrift: P 38 32 056.8), wobei ein potenzierender Effekt der krebswachstumshemmenden Wirkung verschiedener Zytostatikamittel hervorgehoben wurde. Eine Zuordnung dieser Wirkungen zu einzelnen Inhaltsstoffen des Ginbkgo biloba Extraktes ist bisher jedoch nicht erfolgt. The use of such a ginkgo biloba Dry extract for the treatment of metastatic Cancer has been described (published in: P 38 32 056.8), with a potentiating effect of cancer growth-inhibiting effects of various Cytostatic agent has been highlighted. An assignment of this Effects on individual ingredients of the Ginbkgo biloba However, no extract has been made so far.
Hideji Itokawa et. al Chem. Pharm. Bul. 35(7) 3016-3020 (1987) und Chem. Pharm. Bul. 37(6) 1619-1621 (1989) beschreiben einen direkten hemmenden Effekt von langkettigen Phenolen aus Ginkgo biloba auf Sarkoma 180 ascites bei der Maus.Hideji Itokawa et. al Chem. Pharm. Bul. 35 (7) 3016-3020 (1987) and Chem. Pharm. Bul. 37 (6) 1619-1621 (1989) describe a direct inhibitory effect of long chain Phenols from Ginkgo biloba on sarcoma 180 ascites at the Mouse.
Die Erfindung besteht in der Verwendung von Ginkgoliden bzw. Ginkgolid B zur Behandlung metastatischer Krebserkrankungen. Es ist hierbei von Bedeutung, daß die Ginkgolide vor der Gabe zytostatischer Chemotherapeutika verabreicht werden. Dieses kann oral wie auch parenteral erfolgen, wobei wegen noch nicht geklärter Bioverfügbarkeit der parenteralen Verabreichung der Vorzug zu geben ist. Eine besonders große Verstärkung des krebswachstumshemmenden Effektes der zytostatischen Chemotherapie läßt sich durch mehrfache vorangehende Verabreichung von Ginkgoliden erzielen.The invention consists in the use of ginkgolides or Ginkgolid B for the treatment of metastatic cancer. It is important that the ginkgolide before the dose cytostatic chemotherapy drugs. This can be done orally and parenterally, but because of still unexplained bioavailability of parenteral Preference is given to administration. A particularly large one Enhancing the cancer growth-inhibiting effect of cytostatic chemotherapy can be done through multiple achieve previous administration of ginkgolides.
Die meisten metastasierenden Tumore sind inkurabel. Die Entstehung zytostatikaresistenter Tumorzellen limitiert die Effektivität der Chemotherapie. Bei bestehender Zytostatikaresistenz führt die vorherige Verabreichung von Ginkgolid zu einem erneuten Ansprechen auf das Zytostatikum.Most metastatic tumors are incurable. The The development of cytostatic-resistant tumor cells limits the Effectiveness of chemotherapy. With existing Cytostatic resistance leads to the previous administration of Ginkgolid to respond to the cytostatic again.
Ginkgolid B führt zu charakteristischen Formveränderungen an der Membran der menschlichen roten Blutzelle. Es ist noch nicht geklärt, ob derartige Membraneffekte auch an der Tumorzelle zu beobachten sind und ob diese für den die Chemotherapie verstärkenden Effekt verantwortlich sind.Ginkgolid B leads to characteristic shape changes the membrane of the human red blood cell. It is still not clarified whether such membrane effects on the Tumor cell can be observed and whether this for the Chemotherapy enhancing effect are responsible.
Claims (9)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19924208868 DE4208868A1 (en) | 1992-03-04 | 1992-03-04 | Use of ginkgolide cpds., esp. ginkgolide B - in treatment of metastatic cancers, to enhance the effect of chemotherapeutic agents |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19924208868 DE4208868A1 (en) | 1992-03-04 | 1992-03-04 | Use of ginkgolide cpds., esp. ginkgolide B - in treatment of metastatic cancers, to enhance the effect of chemotherapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE4208868A1 true DE4208868A1 (en) | 1993-09-09 |
Family
ID=6454487
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19924208868 Withdrawn DE4208868A1 (en) | 1992-03-04 | 1992-03-04 | Use of ginkgolide cpds., esp. ginkgolide B - in treatment of metastatic cancers, to enhance the effect of chemotherapeutic agents |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE4208868A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001012208A1 (en) * | 1999-08-12 | 2001-02-22 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Use of ginkgo extract |
| US7078434B1 (en) | 1999-08-12 | 2006-07-18 | Societe De Conseils De Recherches Et D'applications Scientifiques Sas | Use of Ginkgo extract |
| EP1865319A1 (en) * | 1999-08-12 | 2007-12-12 | Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S. | Method of testing whether a tumor is susceptible to treatment with a ginkgo biloba extract or Ginkgolide B by testing whether the cancer is characterized by an over-expression of peripheral-type benzodiazepine receptor protein |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0359951A2 (en) * | 1988-09-21 | 1990-03-28 | Scholle, Helmut, Dr. med. | Use of a ginkgo extract against metastases |
| EP0373986A1 (en) * | 1988-12-02 | 1990-06-20 | Abraxas Bio Labs S.A. | Anti-virus composition and its uses |
| EP0459432A1 (en) * | 1990-06-01 | 1991-12-04 | Korth, Ruth-Maria, Dr. med | Treatment of diseases with paf-acether antagonists and procedure for determining their efficacy |
-
1992
- 1992-03-04 DE DE19924208868 patent/DE4208868A1/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0359951A2 (en) * | 1988-09-21 | 1990-03-28 | Scholle, Helmut, Dr. med. | Use of a ginkgo extract against metastases |
| EP0373986A1 (en) * | 1988-12-02 | 1990-06-20 | Abraxas Bio Labs S.A. | Anti-virus composition and its uses |
| EP0459432A1 (en) * | 1990-06-01 | 1991-12-04 | Korth, Ruth-Maria, Dr. med | Treatment of diseases with paf-acether antagonists and procedure for determining their efficacy |
Non-Patent Citations (5)
| Title |
|---|
| CHEMICAL ABSTRACTS, Vol.112,No.17: 151356c * |
| et.al.: Antitumor Principles from Ginkgo biloba L. In: Chem.Pharm.Bull., Vol.35, 1987,pp.3016-3020 * |
| EVANS,T.W. * |
| ITOKAWA,H. * |
| u.a.: Bleomicin-Induced Lung Injury in the RAt: Effects of the Platelet-Activating Factor (PAF)Receptor Antagonist BN 52021 and Platelet Depletion. In: Environmental Health Perspectives, Vol.38,1990,pp.65-69 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001012208A1 (en) * | 1999-08-12 | 2001-02-22 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Use of ginkgo extract |
| US7078434B1 (en) | 1999-08-12 | 2006-07-18 | Societe De Conseils De Recherches Et D'applications Scientifiques Sas | Use of Ginkgo extract |
| JP2007126472A (en) * | 1999-08-12 | 2007-05-24 | Soc De Conseils De Recherches & D'applications Scientifiques Sas | Use of ginkgo biloba extract |
| EP1865319A1 (en) * | 1999-08-12 | 2007-12-12 | Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S. | Method of testing whether a tumor is susceptible to treatment with a ginkgo biloba extract or Ginkgolide B by testing whether the cancer is characterized by an over-expression of peripheral-type benzodiazepine receptor protein |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OM8 | Search report available as to paragraph 43 lit. 1 sentence 1 patent law | ||
| 8139 | Disposal/non-payment of the annual fee |