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 agents

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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
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Prior art keywords
ginkgolide
use according
chemotherapeutic agents
treatment
effect
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Withdrawn
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DE19924208868
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German (de)
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Des Erfinders Auf Nennung Verzicht
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MICHAELIS PETER DR MED
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MICHAELIS PETER DR MED
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Priority to DE19924208868 priority Critical patent/DE4208868A1/en
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Withdrawn legal-status Critical Current

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    • 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)

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  • 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

Use of ginkgolides in treatment of metastatic cancers is new. Pref. ginkgolides are A, B and C (in their natural state, as present in Ginkgo biloba tree leaves from which they are isolated) or ginkgolide B alone. USE/ADVANTAGE - The method enhances the effect of cytostatic chemotherapeutic agents while reducing side-effects. This allows the chemotherapeutic agents to be more effective against tumour cells which are resistant to cytostatics (claimed). Admin. is oral or parenteral (esp. intravenous) prior to admin. of the cytostatic chemotherapeutic agent

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)

1. Verwendung eines Arzneimittels zur Behandlung von metastatischen Krebserkrankungen, dadurch gekennzeichnet, daß das Arzneimittel als Wirkstoff Ginkgolide enthält.1. Use of a drug for the treatment of metastatic cancer, characterized in that the drug contains ginkgolide as an active ingredient. 2. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß die Ginkgolide aus Blättern des ginkgo biloba Baumes gewonnen wurden.2. Use according to claim 1, characterized, that the ginkgolide from leaves of the ginkgo biloba tree won. 3. Verwendung nach Anspruch 1 und 2, dadurch gekennzeichnet, daß die Ginkgolide A, B und C ihrem natürlichen Vorkommen in den Blättern des Ginkgo biloba Baumes entsprechend enthalten sind.3. Use according to claim 1 and 2, characterized, that the ginkgolides A, B and C occur naturally in according to the leaves of the Ginkgo biloba tree are. 4. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß ausschließlich Ginkgolid B enthalten ist.4. Use according to claim 1, characterized, that only ginkgolide B is contained. 5. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß die Verabreichung jeweils vor der Gabe zytostatischer Chemotherapeutika erfolgt. 5. Use according to claim 1, characterized, that the administration before the administration of cytostatic Chemotherapy drugs are used.   6. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß der tumorwachstumshemmende Effekt zytostatischer Chemotherapeutika verstärkt wird.6. Use according to claim 1, characterized, that the tumor growth inhibiting effect is cytostatic Chemotherapeutic agents is strengthened. 7. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß die unerwünschten Wirkungen zytostatischer Chemotherapeutika vermindert werden.7. Use according to claim 1, characterized, that the undesirable effects of cytostatic Chemotherapy drugs can be reduced. 8. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß die Verabreichung als intravenöse Gabe erfolgen kann.8. Use according to claim 1, characterized, that the administration can take place as an intravenous dose. 9. Verwendung nach Anspruch 1, dadurch gekennzeichnet, daß die Verabreichung per os erfolgen kann.9. Use according to claim 1, characterized, that the administration can take place via os.
DE19924208868 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 Withdrawn DE4208868A1 (en)

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

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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

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Cited By (3)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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

Patent Citations (3)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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 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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