WO2003045410A1 - Pharmaceutical preparation containing micro-encapsulated or nano-encapsulated ginsenosides - Google Patents

Pharmaceutical preparation containing micro-encapsulated or nano-encapsulated ginsenosides Download PDF

Info

Publication number
WO2003045410A1
WO2003045410A1 PCT/DE2002/004281 DE0204281W WO03045410A1 WO 2003045410 A1 WO2003045410 A1 WO 2003045410A1 DE 0204281 W DE0204281 W DE 0204281W WO 03045410 A1 WO03045410 A1 WO 03045410A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical preparation
preparation according
ginsenosides
therapeutic treatment
microapplication
Prior art date
Application number
PCT/DE2002/004281
Other languages
German (de)
French (fr)
Inventor
Ernes-Elme Berg
Original Assignee
Mediwirk Gmbh
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Mediwirk Gmbh filed Critical Mediwirk Gmbh
Priority to AU2002358418A priority Critical patent/AU2002358418A1/en
Publication of WO2003045410A1 publication Critical patent/WO2003045410A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • 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
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals

Definitions

  • the invention relates to a pharmaceutical preparation with an active substance enclosed in a microapplication sleeve.
  • This new carrier system can give the active ingredient completely new properties with regard to its effects and properties.
  • the active ingredients are usually in the form of tablets and capsules, which are administered orally. Such orally administered applications first pass through a liver passage before they are distributed through the bloodstream in the organism. With this route of application, the active ingredient can largely be broken down into effective secondary products before it reaches the intended site of action (cells, tissue, organ). As a result, it is not uncommon for a higher dose or multiple injections or oral administrations per day to be maintained in order to maintain a therapeutically effective concentration in the body.
  • the liposomes are generally divided into three basic types, Small Unilamellar Vesicles (SUV), Large Unilamellar Vesicles (LUV) and Multilamellar Large Vesicles (MLV). These basic types differ in their size and in their shell structure. Small unilamellar vesicles are understood to be liposomes with a diameter of up to 50 nm, while large unilamellar vesicles with a diameter of 50 nm to 3 ⁇ m and multilamellar vesicles with a diameter of 100 nm to several micrometers are attributed.
  • nanoparticles So-called solid lipid nanoparticles (SLN) viewed (Dirk Hoffmann op. cit.).
  • the object of the invention is to provide a further pharmaceutical composition with an active ingredient packaged in a microapplication shell for various new therapeutic uses with minimal stress on the organism.
  • the object is achieved by a pharmaceutical preparation having the features of claim 1.
  • the invention has the particular advantage that for the first time the therapeutic potential of active substances in the ginseng plant, ginsenosides, is tapped in the form of "drug targeting".
  • the new form of application enables a variety of new uses for pharmaceutical preparations, including medicinal products containing ginsenosides, and allows the different pharmacological effects of ginsenosides to be exploited effectively.
  • the ginseng plant is known as a medicinal plant through many homeopathic uses.
  • the ingredients of the ginseng extract are said to have very different effects. Appropriate liquid and solid preparations should strengthen the organism's natural resistance and accelerate its recovery after resilience.
  • the ginsenosides can be brought directly to the target cell by means of the application route according to the invention.
  • the ginsenosides are thus protected against the attack of body fluids and thus against decay when they enter the organism. They can develop their full effectiveness at the destination. Because of the “packaging” in microapplication casings, the pharmacological compositions containing ginsenosides can also be administered intravenously for the first time.
  • the microapplication shells are formed by liposomes or nanoparticles or the microapplication sheath has a multilayer membrane.
  • a further preferred embodiment of the invention provides that the ginsenosides from the group aglycon (20S) -protopanaxadiol with the ginsenosides Ra1, Ra2, Ra3, Rb1, Rb2, Rb3, the notoginsenosides R4, Rs1 and Rs2 and the malonylginsenosides Rb1, Rc and Rd and / or the group Aglykon (20S) -protopanaxtriol with the ginsenosides Re, Rf, Rg1 and the notoginsenoside R1 and / or the aglykon oleanolic acid with the ginsenosides Ro, also known as Chikusetsusasaponin-V, are.
  • the pharmaceutical preparation containing at least one of the ginsenosides R1, R4, Ra1, Ra2, Ra3, Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rs1, Rs2, Ro or Chikusetsusasaponin-V or on several of the ginsenosides mentioned in a mixture or in combination with other active substances linked via ligands coupled to the microapplication shell.
  • ginsenosides were isolated as individual components in an HPLC system, packaged in liposomes and used for pharmacological studies.
  • a pharmaceutical preparation can be made available whose use is suitable for the therapeutic treatment of liver tumors, cirrhosis of the liver and other chronic liver diseases.
  • compositions according to the invention containing ginsenoside Ro are suitable for the treatment of hepatitis.
  • Preparations according to the invention with a content of the ginsenosides Rb1 and Rg1 are preferably suitable for the therapy of aggressions, those with a content of the ginsenoside of the type Rb for therapy for heart diseases and preparations with a content of the ginsenosides Rb1 and Rg3 for the protection of nerve cells.
  • lipid composition to be used for the packaging in accordance with its organ-specific targeting, as is evident from the known prior art, and to pack the ginsenoside or the mixture of ginsenosides with the relevant organ-specific effect therein in accordance with the targeting strategy.
  • the ginsenosides can also be packaged according to the technical solutions resulting from DE 198 52 928 C1.
  • the solutions according to the invention offer completely new and inexpensive starting points for the therapeutic field of application of the individual ginsenosides and their compositions and the increase in the therapeutic efficiency of pharmaceutical preparations by their concentration at the site of action.

Abstract

The invention relates to a pharmaceutical preparation comprising a ginsenoside that is encased in a micro-application sheath and to the use of said preparation. The invention taps the therapeutic potential of active substances of the ginseng plant, ginsenosides, in the form of drug targeting. Ginsenosides are thus transported directly into the interior of the target cell. Said application method protects the ginsenosides against attack by bodily fluids and against disintegration during their introduction into the organism, thus achieving their full efficacy at the target site. In addition, the encasement in micro-application sheaths allows the ginsenosides to be administered intravenously for the first time.

Description

PHARMAZEUTISCHES PRÄPARAT ENTHALTEND MIKROODER NANOVERKAPSELTE GINSENOSIDE PHARMACEUTICAL PREPARATION CONTAINING MICROODER NANOVER-CAPSULED GINSENOSIDE
Die Erfindung bezieht sich auf ein pharmazeutisches Präparat mit einem in einer Mikroapplikationshülle eingeschlossenen Wirkstoff.The invention relates to a pharmaceutical preparation with an active substance enclosed in a microapplication sleeve.
Die Entwicklung auf dem Gebiet der systematischen Applikation von Wirkstoffen ist seit den 70er Jahren unter dem Einfluss der medizinischen und pharmazeutischen Herausforderungen vor allem durch die Verwendung von Liposomen und Nanopartikeln als Transportvehikel der Wirkstoffe, die unter dem Begriff des zielgerichteten „Drug Delivery Systems" beziehungsweise der „kontrollierten Arzneistoffapplikation" (controlled drug release) bekannt wurden, gekennzeichnet (CT. Moonen, MR-Temperaturmapping bei lokaler Medikamentenapplikation und Thermotherapie; Medica Mundi, Ausgabe 1. Februar 2001 ; Dirk Hoffmann, NMR-Untersuchungen an Nanokapsel- Dispersionen, Fachbereich 6 der Gerhard-Mercator-Universität Duisburg, Duisburg 2000). Allgemein wird darunter die gezielte Zuführung eines Wirkstoffes an einen gewünschten Zielort verstanden, meist in Verbindung mit einem optimierten Freigabeverhalten nach gewebespezifischer Anreicherung. Mit dieser Entwicklung verbinden sich unter dem Aspekt des therapeutischen Potentials eines Wirkstoffes im Vergleich zu herkömmlichen Darreichungformen wesentliche Vorzüge. Dieses neue Trägersystem kann dem Wirkstoff völlig neue Eigenschaften bezüglich dessen Wirkungen und dessen Eigenschaften geben. In der festen Darreichungsform liegen die Wirkstoffe meistens in Form von Tabletten und Kapseln vor, die oral verabreicht werden. Derartige oral verabreichte Applikationen machen zunächst eine Leberpassage durch, bevor sie durch den Blutstrom im Organismus verteilt werden. Bei diesem Applikationsweg kann der Wirkstoff weitgehend zu wirksamen Folgeprodukten abgebaut werden, bevor er den beabsichtigten Wirkungsort (Zellen, Gewebe, Organ) erreicht. Die Folge davon ist, dass nicht selten eine höhere Dosis oder mehrfache Injektionen oder orale Verabreichungen pro Tag erforderlich sind, um eine therapeutisch wirksame Konzentration im Körper aufrechtzuerhalten.The development in the field of the systematic application of active substances has been under the influence of the medical and pharmaceutical challenges since the 1970s, especially through the use of liposomes and nanoparticles as transport vehicles for the active substances, which are known as "drug delivery systems" or “Controlled drug release” have been known, characterized (CT. Moonen, MR temperature mapping for local drug application and thermotherapy; Medica Mundi, February 1, 2001 edition; Dirk Hoffmann, NMR investigations on nanocapsule dispersions, Department 6 of Gerhard Mercator University Duisburg, Duisburg 2000). In general, this means the targeted delivery of an active ingredient to a desired destination, usually in conjunction with an optimized release behavior after tissue-specific enrichment. This development has significant advantages in terms of the therapeutic potential of an active ingredient compared to conventional dosage forms. This new carrier system can give the active ingredient completely new properties with regard to its effects and properties. In the solid dosage form, the active ingredients are usually in the form of tablets and capsules, which are administered orally. Such orally administered applications first pass through a liver passage before they are distributed through the bloodstream in the organism. With this route of application, the active ingredient can largely be broken down into effective secondary products before it reaches the intended site of action (cells, tissue, organ). As a result, it is not uncommon for a higher dose or multiple injections or oral administrations per day to be maintained in order to maintain a therapeutically effective concentration in the body.
Die Liposome werden im allgemeinen in drei Grundtypen eingeteilt, Small Unilamellar Vesicles (SUV), Large Unilamellar Vesicles (LUV) und Multilamellar Large Vesicles (MLV). Diese Grundtypen unterscheiden sich in ihrer Größe und in ihrem Schalenaufbau. Unter kleinen unilamellaren Vesikeln werden Liposome mit einem Durchmesser bis zu 50 nm verstanden, während großen unilamellaren Vesikeln ein Durchmesser von 50 nm bis 3 μm und multilamellaren Vesikeln ein Durchmesser von 100 nm bis zu mehreren Mikrometern zugeschrieben wird Als ein alternatives Carriersystem zu Liposomen werden Nanopartikel, sogenannte Solid-Lipid-Nanoparticles (SLN) angesehen (Dirk Hoffmann a.a.O.).The liposomes are generally divided into three basic types, Small Unilamellar Vesicles (SUV), Large Unilamellar Vesicles (LUV) and Multilamellar Large Vesicles (MLV). These basic types differ in their size and in their shell structure. Small unilamellar vesicles are understood to be liposomes with a diameter of up to 50 nm, while large unilamellar vesicles with a diameter of 50 nm to 3 μm and multilamellar vesicles with a diameter of 100 nm to several micrometers are attributed. As an alternative carrier system to liposomes, nanoparticles, So-called solid lipid nanoparticles (SLN) viewed (Dirk Hoffmann op. cit.).
Aufgabe der Erfindung ist es, eine weitere pharmazeutischen Zusammensetzung mit einem in einer Mikroapplikationshülle verpackten Wirkstoff für verschiedene neue therapeutische Verwendungen bei minimaler Belastung des Organismus bereitzustellen.The object of the invention is to provide a further pharmaceutical composition with an active ingredient packaged in a microapplication shell for various new therapeutic uses with minimal stress on the organism.
Erfindungsgemäß wird die Aufgabe durch ein pharmazeutisches Präparat mit den Merkmalen des Anspruches 1 gelöst. Mit der Erfindung verbindet sich der besondere Vorzug, dass erstmals das therapeutische Potential von Wirkstoffen der Ginsengpflanze, von Ginsenosiden, in Form eines „Drug Targeting" erschlossen wird.According to the invention the object is achieved by a pharmaceutical preparation having the features of claim 1. The invention has the particular advantage that for the first time the therapeutic potential of active substances in the ginseng plant, ginsenosides, is tapped in the form of "drug targeting".
Die neue Applikationsform ermöglicht vielfältige neue Einsatzmöglichkeiten pharmazeutischer Präparate einschließlich von Arzneimitteln mit einem Gehalt an Ginsenosiden und gestattet es, die unterschiedlichen pharmakologischen Wirkungen der Ginsenoside auf effektive Weise auszuschöpfen.The new form of application enables a variety of new uses for pharmaceutical preparations, including medicinal products containing ginsenosides, and allows the different pharmacological effects of ginsenosides to be exploited effectively.
Die Ginsengpflanze ist als Heilpflanze durch viele homöopathische Anwendungen bekannt. Den Inhaltsstoffen des Ginsengextraktes werden sehr unterschiedliche Wirkungen zugesprochen. So sollen entsprechende flüssige und feste Zubereitungen die natürliche Widerstandsfähigkeit des Organismus stärken und dessen Erholung nach Belastbarkeit beschleunigen.The ginseng plant is known as a medicinal plant through many homeopathic uses. The ingredients of the ginseng extract are said to have very different effects. Appropriate liquid and solid preparations should strengthen the organism's natural resistance and accelerate its recovery after resilience.
Mit der Erfindung ist es nun möglich, das Freigabeverhalten des pharmazeutischen Präparates hinsichtlich der Ginsenoside am Zielort zu optimieren sowie deren Abgaberate zu kontrollieren und die Dauer der Wirksamkeit der Ginsenoside bei den Zielzellen zu steuern. Mittels des erfindungsgemäßen Applikationsweges können die Ginsenoside direkt zur Zielzelle gebracht werden. Die Ginsenoside sind dadurch vor dem Angriff von Körperflüssigkeiten und damit vor dem Zerfall bei Eingabe in den Organismus geschützt. Sie können am Zielort ihre volle Wirksamkeit entfalten. Durch die „Verpackung" in Mikroapplikationshüllen können die Ginsenoside enthaltenden pharmakologischen Zusammensetzungen erstmals auch intravenös verabreicht werden.With the invention it is now possible to optimize the release behavior of the pharmaceutical preparation with regard to the ginsenosides at the target site, to control their release rate and to control the duration of the effectiveness of the ginsenosides in the target cells. The ginsenosides can be brought directly to the target cell by means of the application route according to the invention. The ginsenosides are thus protected against the attack of body fluids and thus against decay when they enter the organism. They can develop their full effectiveness at the destination. Because of the “packaging” in microapplication casings, the pharmacological compositions containing ginsenosides can also be administered intravenously for the first time.
Gemäß einer bevorzugten Ausführungsform des pharmazeutischen Präparates sind die Mikroapplikationshüllen durch Liposome oder Nanopartikel gebildet oder weist die Mikroapplikationshülle eine mehrschichtige Membran auf.According to a preferred embodiment of the pharmaceutical preparation, the microapplication shells are formed by liposomes or nanoparticles or the microapplication sheath has a multilayer membrane.
Eine weitere bevorzugte Ausführungsform der Erfindung sieht vor, dass die Ginsenoside solche der Gruppe Aglykon (20S)-Protopanaxadiol mit den Ginsenosiden Ra1 , Ra2, Ra3, Rb1 , Rb2, Rb3, den Notoginsenosiden R4, Rs1 und Rs2 und den Malonylginsenosiden Rb1 , Rc und Rd und/oder der Gruppe Aglykon (20S)-Protopanaxtriol mit den Ginsenosiden Re, Rf, Rg1 und dem Notoginsenosid R1 und/oder der Aglykon Oleanolsäure mit den Ginsenosiden Ro, auch als Chikusetsusasaponin-V bezeichnet, sind.A further preferred embodiment of the invention provides that the ginsenosides from the group aglycon (20S) -protopanaxadiol with the ginsenosides Ra1, Ra2, Ra3, Rb1, Rb2, Rb3, the notoginsenosides R4, Rs1 and Rs2 and the malonylginsenosides Rb1, Rc and Rd and / or the group Aglykon (20S) -protopanaxtriol with the ginsenosides Re, Rf, Rg1 and the notoginsenoside R1 and / or the aglykon oleanolic acid with the ginsenosides Ro, also known as Chikusetsusasaponin-V, are.
Als eine besonders bevorzugte Ausführungsform der Erfindung hat sich das pharmazeutische Präparat mit einem Gehalt an mindestens einem der Ginsenoside R1 , R4, Ra1 , Ra2, Ra3, Rb1 , Rb2, Rb3, Rc, Rd, Re, Rf, Rg1 , Rs1 , Rs2, Ro oder Chikusetsusasaponin-V oder an mehreren der genannten Ginsenoside im Gemisch oder in Kombination mit über an der Mikroapplikationshülle gekoppelte Liganden verbundenen anderen Wirkstoffen erwiesen.As a particularly preferred embodiment of the invention, the pharmaceutical preparation containing at least one of the ginsenosides R1, R4, Ra1, Ra2, Ra3, Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rs1, Rs2, Ro or Chikusetsusasaponin-V or on several of the ginsenosides mentioned in a mixture or in combination with other active substances linked via ligands coupled to the microapplication shell.
Überraschend wurde gefunden, dass einzelne in Mikroapplikationshüllen verpackten Ginsenosiden eine besondere therapeutische Wirkung haben und zur Verwendung als Arzneimittel geeignet sind.Surprisingly, it was found that individual ginsenosides packaged in microapplication sleeves have a special therapeutic effect and are suitable for use as medicaments.
Hochreine Ginsenoside wurden als Einzelkomponenten in einer HPLC-Anlage isoliert, in Liposomen verpackt und für pharmakologische Studien eingesetzt. In einer derartigen Studie wurde die Wirksamkeit des Ginsenosides Rg1 , verpackt in einer Lipid-Formulierung, für die in der Literatur ein Lebertargeting beschrieben ist, an Ratten mit akuter Leberschädigung untersucht. Die Studie wurde mit einer Dosierung von 0,1 mg bis 50,0 mg reinem Ginsenosid Rg1 pro ml Liposom durchgeführt.High-purity ginsenosides were isolated as individual components in an HPLC system, packaged in liposomes and used for pharmacological studies. In such a study, the effectiveness of the ginsenoside Rg1, packaged in a lipid formulation for which liver targeting is described in the literature, was investigated in rats with acute liver damage. The study was carried out with a dosage of 0.1 mg to 50.0 mg pure ginsenoside Rg1 per ml liposome.
Bereits nach 7 Tagen war ein Wirkungseintritt festzustellen. Im Ergebnis der Studie konnte unerwartet und überraschend festgestellt werden, dass durch das Ginsenosid Rg1 eine Gewebeerneuerung an der Leber der Ratte bewirkt wurde. Erstmals kann so ein pharmazeutisches Präparat bereitgestellt werden, deren Verwendung für die therapeutische Behandlung von Lebertumoren, Leberzirrhosen und anderen chronischen Lebererkrankungen geeignet ist.The onset of effects was already evident after 7 days. As a result of the study, it was unexpectedly and surprisingly found that the ginsenoside Rg1 caused tissue renewal in the liver of the rat. For the first time, a pharmaceutical preparation can be made available whose use is suitable for the therapeutic treatment of liver tumors, cirrhosis of the liver and other chronic liver diseases.
Studien haben des weiteren ergeben, dass erfindungsgemäße pharmazeutische Präparate mit einem Gehalt an dem Ginsenosid Ro zur Therapie von Hepatitis geeignet sind. Erfindungsgemäße Präparate mit einem Gehalt an den Ginsenosiden Rb1 und Rg1 sind vorzugsweise zur Therapie von Aggressionen, solche mit einem Gehalt an dem Ginsenosid des Typs Rb zur Therapie bei Herzerkrankungen und Präparate mit einem Gehalt an den Ginsenosiden Rb1 und Rg3 zum Schutz von Nervenzellen geeignet.Studies have further shown that pharmaceutical preparations according to the invention containing ginsenoside Ro are suitable for the treatment of hepatitis. Preparations according to the invention with a content of the ginsenosides Rb1 and Rg1 are preferably suitable for the therapy of aggressions, those with a content of the ginsenoside of the type Rb for therapy for heart diseases and preparations with a content of the ginsenosides Rb1 and Rg3 for the protection of nerve cells.
Die erfindungsgemäßen Verwendungen des neuen pharmazeutischen Präparates ergeben sich aus den Merkmalen der Ansprüche 7 bis 28.The uses of the new pharmaceutical preparation according to the invention result from the features of claims 7 to 28.
Zweckmäßig ist es, die für die Verpackung einzusetzende Lipidkomposition entsprechend ihrem organspezifischen Targeting, wie es sich aus dem bekannten Stand der Technik ergibt, auszuwählen und in Übereinstimmung mit der Targetingstrategie darin das Ginsenosid oder das Gemisch an Ginsenosiden mit der betreffenden organspezifischen Wirkung zu verpacken.It is expedient to select the lipid composition to be used for the packaging in accordance with its organ-specific targeting, as is evident from the known prior art, and to pack the ginsenoside or the mixture of ginsenosides with the relevant organ-specific effect therein in accordance with the targeting strategy.
Die Verpackung der Ginsenoside kann auch nach den sich aus dem DE 198 52 928 C1 ergebenden technischen Lösungen erfolgen.The ginsenosides can also be packaged according to the technical solutions resulting from DE 198 52 928 C1.
Des weiteren ist es möglich, die Ginsenoside oder deren Mischungen nach der bekannten und in der Literatur beschriebenen Kavitator-Technologie zu verpacken.Furthermore, it is possible to package the ginsenosides or their mixtures using the known cavitator technology described in the literature.
Insgesamt bieten die erfindungsgemäßen Lösungen völlig neue und kostengünstige Ansatzpunkte für das therapeutische Anwendungsfeld der einzelnen Ginsenoside und deren Kompositionen und die Erhöhung der therapeutischen Effizienz pharmazeutischer Präparate durch deren Konzentration am Wirkungsort. Overall, the solutions according to the invention offer completely new and inexpensive starting points for the therapeutic field of application of the individual ginsenosides and their compositions and the increase in the therapeutic efficiency of pharmaceutical preparations by their concentration at the site of action.

Claims

Patentansprüche: claims:
1. Pharmazeutisches Präparat mit einem in einer Mikroapplikationshülle eingeschlossenen Wirkstoff, dadurch gekennzeichnet, dass der Wirkstoff ein Ginsenosid ist.1. Pharmaceutical preparation with an active substance enclosed in a microapplication shell, characterized in that the active substance is a ginsenoside.
2. Pharmazeutisches Präparat nach Anspruch 1 , dadurch gekennzeichnet, dass die Mikroapplikationshülle ein Liposom, oder ein Nanopartikel ist oder die Mikroapplikationshülle eine mehrschichtige Membran aufweist.2. Pharmaceutical preparation according to claim 1, characterized in that the microapplication shell is a liposome or a nanoparticle or the microapplication shell has a multilayer membrane.
3. Pharmazeutisches Präparat nach Anspruch 1 , dadurch gekennzeichnet, dass das Liposom vorzugsweise aus einer Lipidkomposition an sich bekannter Art, besonders bevorzugt aus einer Lipidkomposition mit bekanntem Targeting gebildet ist.3. Pharmaceutical preparation according to claim 1, characterized in that the liposome is preferably formed from a lipid composition known per se, particularly preferably from a lipid composition with known targeting.
4. Pharmazeutisches Präparat nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass das Präparat mindestens 1 Ginsenosid aus der Gruppe der Aglykon (20S)-Protopanaxadiole und/oder der Gruppe der Aglykon (20S)-Protopanaxtriole und/oder der Gruppe Aglykon Oleanolsäure enthält.4. Pharmaceutical preparation according to one of claims 1 to 3, characterized in that the preparation at least 1 ginsenoside from the group of aglycone (20S) -protopanaxadiols and / or the group of aglycone (20S) -protopanaxtriols and / or the group of aglyconic oleanolic acid contains.
5. Pharmazeutisches Präparat nach Anspruch 4, dadurch gekennzeichnet, dass Aglykon (20S)-Protopanaxadiol die Ginsenoside Ra, Ra2, Ra3, Rb1 , Rb2, Rb3, Notoginsenosid R4, Rs1 , Rs2 und die Malonylginsenoside Rb1 , Rc und Rd, Aglykon (20S)- Protopanaxtriol die Ginsenoside Re, Rf, Rg1 und das Notogrinsenosid R1 und Aglykon Oleanolsäure die Ginsenoside Ro und Chikusetsusasaponin-V enthält. 5. Pharmaceutical preparation according to claim 4, characterized in that aglycon (20S) -protopanaxadiol the ginsenosides Ra, Ra2, Ra3, Rb1, Rb2, Rb3, notoginsenoside R4, Rs1, Rs2 and the malonylginsenosides Rb1, Rc and Rd, aglycon (20S ) - Protopanaxtriol which contains the ginsenosides Re, Rf, Rg1 and the notogrinsenoside R1 and aglycon oleanolic acid which contains the ginsenosides Ro and Chikusetsusasaponin-V.
6. Pharmazeutisches Präparat nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass das Präparat die Ginsenoside R1 , R4, Ra1 , Ra2, Ra3, Rb1 , Rb2, Rb3, Rc, Rd, Re, Rf, Rg1 , Rs1 , Rs21 oder Ro (Chikusetsusasaponin-V) einzeln oder mehrere der genannten Ginsenoside im Gemisch oder Metaboliten der genannten Ginsenoside oder die genannten Ginsenoside in Kombination mit anderen über an die Mikroapplikationshülle gekoppelte Liganden verbundenen Wirkstoffen enthält.6. Pharmaceutical preparation according to one of claims 1 to 3, characterized in that the preparation contains the ginsenosides R1, R4, Ra1, Ra2, Ra3, Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rs1, Rs21 or Ro (Chikusetsusasaponin-V) contains individually or several of the ginsenosides mentioned in a mixture or metabolites of the said ginsenosides or the said ginsenosides in combination with other active ingredients connected to the microapplication ligand coupled to the active ingredients.
7. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur Herstellung eines Arzneimittels.7. Use of a pharmaceutical preparation according to claims 1 to 6 for the manufacture of a medicament.
8. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von Tumoren.8. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of tumors.
9. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von Lebertumoren, Leberzirrhose oder anderen Lebererkrankungen.9. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of liver tumors, liver cirrhosis or other liver diseases.
10. Verwendung nach Anspruch 9, dadurch gekennzeichnet, dass das pharmazeutische Präparat vorzugsweise das Ginsenosid Rg1 oder Ro enthält.10. Use according to claim 9, characterized in that the pharmaceutical preparation preferably contains the ginsenoside Rg1 or Ro.
11. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von Diabetes Mellitus.11. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of diabetes mellitus.
12. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von HIV- infizierten Personen.12. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of HIV-infected people.
13. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 als Infektionsprophylaktikum und zur Therapie von Infektionen, wie der von Candida albicans. 13. Use of a pharmaceutical preparation according to claims 1 to 6 as an infection prophylactic and for the therapy of infections, such as that of Candida albicans.
14. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur Stimulierung des Immunsystems, vorzugsweise bei Personen mit einer chronischen Pseudomonas aeruginosa Infektion.14. Use of a pharmaceutical preparation according to claims 1 to 6 for stimulating the immune system, preferably in people with a chronic Pseudomonas aeruginosa infection.
15. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von kurz- und längerfristiger Blutdrucksteigerung.15. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of short and long-term increase in blood pressure.
16. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur Senkung des Cholesterinspiegels.16. Use of a pharmaceutical preparation according to claims 1 to 6 for lowering the cholesterol level.
17. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur Stärkung der Leistungs-, Gedächtnis- und Konzentrationsfähigkeit.17. Use of a pharmaceutical preparation according to claims 1 to 6 for strengthening the performance, memory and ability to concentrate.
18. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von Stresssituationen.18. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of stressful situations.
19. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur Prevention und Therapie der Abhängigkeit von Morphinen, Kokain, Methamphetaminen und Alkohol.19. Use of a pharmaceutical preparation according to claims 1 to 6 for the prevention and therapy of dependence on morphine, cocaine, methamphetamines and alcohol.
20. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung erectiler Dysfunction.20. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of erectile dysfunction.
21. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 als Aphrodisiaca remedia.21. Use of a pharmaceutical preparation according to claims 1 to 6 as Aphrodisiaca remedia.
22. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung bei Herzerkrankungen. 22. Use of a pharmaceutical preparation according to claims 1 to 6 for therapeutic treatment in heart diseases.
23. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung hormonaler Effekte.23. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of hormonal effects.
24. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von Kälte- und Wärmestauung.24. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of cold and heat build-up.
25. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von Depressionen.25. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of depression.
26. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zur therapeutischen Behandlung von Aggressionen.26. Use of a pharmaceutical preparation according to claims 1 to 6 for the therapeutic treatment of aggressions.
27. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zum Schutz gegen Gamma-Strahlung.27. Use of a pharmaceutical preparation according to claims 1 to 6 for protection against gamma radiation.
28. Verwendung eines pharmazeutischen Präparates gemäß den Ansprüchen 1 bis 6 zum Schutz von Nervenzellen. 28. Use of a pharmaceutical preparation according to claims 1 to 6 for the protection of nerve cells.
PCT/DE2002/004281 2001-11-19 2002-11-18 Pharmaceutical preparation containing micro-encapsulated or nano-encapsulated ginsenosides WO2003045410A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002358418A AU2002358418A1 (en) 2001-11-19 2002-11-18 Pharmaceutical preparation containing micro-encapsulated or nano-encapsulated ginsenosides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10158281.1 2001-11-19
DE2001158281 DE10158281A1 (en) 2001-11-19 2001-11-19 Pharmaceutical preparation comprises ginsenoside enclosed in micro-shell, e.g. liposome, providing targeted and controlled delivery, useful e.g. in treatment of liver tumors, diabetes mellitus or hypertension

Publications (1)

Publication Number Publication Date
WO2003045410A1 true WO2003045410A1 (en) 2003-06-05

Family

ID=7707206

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2002/004281 WO2003045410A1 (en) 2001-11-19 2002-11-18 Pharmaceutical preparation containing micro-encapsulated or nano-encapsulated ginsenosides

Country Status (3)

Country Link
AU (1) AU2002358418A1 (en)
DE (1) DE10158281A1 (en)
WO (1) WO2003045410A1 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006026924A1 (en) * 2004-09-08 2006-03-16 Zelin Li The use of ginsenoside in the treatment of aids
KR100842070B1 (en) 2007-04-09 2008-06-30 박준원 Nano platinum ginsenoside particle and production method thereof
WO2008086739A1 (en) * 2007-01-16 2008-07-24 Chengdu Di'ao Jiuhong Pharmaceutical Factory Use of ursolic acid saponin, oleanolic acid saponin in preparation of increasing leucocyte and/or platelet medicine
EP2455084A2 (en) * 2009-07-16 2012-05-23 CJ CheilJedang Corporation Antihypertensive composition containing a ginsenoside-enriched fraction
CN106924427A (en) * 2017-03-24 2017-07-07 成都海青生物科技有限公司 It is a kind of effectively to treat Chinese medicine composition of diabete and preparation method thereof
CN108014118A (en) * 2017-12-25 2018-05-11 上海中医药大学 A kind of purposes of notoginsenoside Ft1
CN113896757A (en) * 2020-07-07 2022-01-07 中国科学院上海药物研究所 Pentacyclic triterpene carbon glycoside compounds, and preparation method and application thereof
WO2022052996A1 (en) * 2020-09-10 2022-03-17 上海交通大学 Uses of protopanaxadiol compounds in treatment of pain, and physical dependence, psychological dependence and addiction of addictive substances

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006113495A2 (en) * 2005-04-15 2006-10-26 Hui-Ling Chen Dicarboxylic acid ester derivatives of ginsenoside, pharmaceutical preparations containing the same, and preparation thereof
DE102005052005B4 (en) * 2005-10-31 2007-10-18 Infineon Technologies Ag Processor arrangement
CN100438876C (en) * 2006-06-09 2008-12-03 上海中药创新研究中心 Use of 20(S)-protopanoxadiol in preparation of antidepressant medicine
CN101264096B (en) * 2007-03-12 2011-11-09 中国医学科学院药物研究所 Use of ginsenoside Rg1 in preparing spermatogenic product
CN110200981A (en) * 2019-06-06 2019-09-06 中国药科大学 The medical usage and its pharmaceutical composition of pentacyclic triterpene saponin

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2179042A (en) * 1985-07-22 1987-02-25 Takeda Chemical Industries Ltd Ginsenoside-Rd
US5776460A (en) * 1995-06-07 1998-07-07 Man Ki Park Processed ginseng product with enhanced pharmacological effects
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
WO2000028972A2 (en) * 1998-11-17 2000-05-25 Novosom Gmbh Nanocapsules and method of production thereof
WO2000074656A1 (en) * 1999-06-07 2000-12-14 Bio Dar Ltd. Microencapsulated and controlled-release herbal formulations
EP1142903A1 (en) * 1998-12-22 2001-10-10 Japan Science and Technology Corporation BRAIN CELL OR NERVE CELL-PROTECTIVE AGENTS COMPRISING GINSENOSIDE Rb 1?
WO2002007732A2 (en) * 2000-07-26 2002-01-31 Cambridge University Technical Services Limited Use of panaxatriol for stimulation angiogenesis
WO2002069980A2 (en) * 2001-03-07 2002-09-12 Cambridge University Technical Services Limited Pharmaceutically effective ginsenosides and their use

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5646817A (en) * 1979-09-27 1981-04-28 Ryuta Ito Saponin antitumor agent
JPH09241166A (en) * 1996-03-06 1997-09-16 Kureha Chem Ind Co Ltd Synthesis suppressant containing ginsenosides for protein belonging to hsp60 family

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2179042A (en) * 1985-07-22 1987-02-25 Takeda Chemical Industries Ltd Ginsenoside-Rd
US5776460A (en) * 1995-06-07 1998-07-07 Man Ki Park Processed ginseng product with enhanced pharmacological effects
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
WO2000028972A2 (en) * 1998-11-17 2000-05-25 Novosom Gmbh Nanocapsules and method of production thereof
EP1142903A1 (en) * 1998-12-22 2001-10-10 Japan Science and Technology Corporation BRAIN CELL OR NERVE CELL-PROTECTIVE AGENTS COMPRISING GINSENOSIDE Rb 1?
WO2000074656A1 (en) * 1999-06-07 2000-12-14 Bio Dar Ltd. Microencapsulated and controlled-release herbal formulations
WO2002007732A2 (en) * 2000-07-26 2002-01-31 Cambridge University Technical Services Limited Use of panaxatriol for stimulation angiogenesis
WO2002069980A2 (en) * 2001-03-07 2002-09-12 Cambridge University Technical Services Limited Pharmaceutically effective ginsenosides and their use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WANG Z-G ET AL: "Current status and future direction of Chinese herbal medicine", TRENDS IN PHARMACOLOGICAL SCIENCES, ELSEVIER, AMSTERDAM, NL, vol. 23, no. 8, 1 August 2002 (2002-08-01), pages 347 - 348, XP004386169, ISSN: 0165-6147 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006026924A1 (en) * 2004-09-08 2006-03-16 Zelin Li The use of ginsenoside in the treatment of aids
WO2008086739A1 (en) * 2007-01-16 2008-07-24 Chengdu Di'ao Jiuhong Pharmaceutical Factory Use of ursolic acid saponin, oleanolic acid saponin in preparation of increasing leucocyte and/or platelet medicine
US8394776B2 (en) 2007-01-16 2013-03-12 Chengdu Di'ao Jiuhong Pharmaceutical Factor Use of ursolic acid saponin,oleanolic acid saponin in preparation of increasing leucocytes and/or platelet medicine
KR100842070B1 (en) 2007-04-09 2008-06-30 박준원 Nano platinum ginsenoside particle and production method thereof
EP2455084A2 (en) * 2009-07-16 2012-05-23 CJ CheilJedang Corporation Antihypertensive composition containing a ginsenoside-enriched fraction
EP2455084A4 (en) * 2009-07-16 2013-06-05 Cj Cheiljedang Corp Antihypertensive composition containing a ginsenoside-enriched fraction
CN106924427A (en) * 2017-03-24 2017-07-07 成都海青生物科技有限公司 It is a kind of effectively to treat Chinese medicine composition of diabete and preparation method thereof
CN108014118A (en) * 2017-12-25 2018-05-11 上海中医药大学 A kind of purposes of notoginsenoside Ft1
CN113896757A (en) * 2020-07-07 2022-01-07 中国科学院上海药物研究所 Pentacyclic triterpene carbon glycoside compounds, and preparation method and application thereof
WO2022052996A1 (en) * 2020-09-10 2022-03-17 上海交通大学 Uses of protopanaxadiol compounds in treatment of pain, and physical dependence, psychological dependence and addiction of addictive substances

Also Published As

Publication number Publication date
DE10158281A1 (en) 2003-05-28
AU2002358418A1 (en) 2003-06-10

Similar Documents

Publication Publication Date Title
DE69613463T3 (en) FILM-FORMING PHARMACEUTICAL COMPOSITIONS FOR TRANSDERMAL ADMINISTRATION
DE69933472T2 (en) PULMONARY DRUG DISABLING
DE60117711T2 (en) ANTINEOPLASTIC MEDICAMENT
WO2003045410A1 (en) Pharmaceutical preparation containing micro-encapsulated or nano-encapsulated ginsenosides
EP0617623A1 (en) Transdermally administered system containing acetylsalicylic acid for thrombosis therapy and cancer prophylaxis
WO2005076750A2 (en) A novel synergistic herbal formulation for diabetes cure
DE3116860C2 (en)
WO2000048445A2 (en) Pharmaceutical composition containing desoxypeganine for the treatment of nicotine dependence
WO1992004036A1 (en) Kava extract, method of preparing the extract, and its use
EP1001756B1 (en) Synergistically acting compositions for selectively combating tumor tissue
EP2136816B1 (en) Oleyl phosphocholine
DE19530708C2 (en) Pharmaceutical preparation with trypanocidal properties
EP1886694B1 (en) Peroral formulation of dienogest and ethinylestradiol for contraception
EP1212072B1 (en) Pharmaceutical composition that contains eucalyptus and orange oil
DE69724228T2 (en) COMBINATION THERAPY OF TOPOISOMERASE II TOXINES AND BIS-DIOXYPIPERAZINE DERIVATIVES
Oladimeji et al. Phytochemical and antimicrobial studies on some Nigerian medicinal plants
DE60202299T2 (en) PHARMACEUTICAL COMPOSITION CONTAINING SALMETEROL AND BUDESONIDE FOR THE TREATMENT OF RESPIRATORY DISEASES
DE3840946A1 (en) USE OF ALUMINUM POTASSIUM SULFATE AND / OR 1 OR MORE OF ITS HYDRATES
WO1998017229A2 (en) Medicament
Aderjan et al. Poisoning by diphenhydramine—forensic-toxicologic interpretation of analytic results
DE3511236C2 (en)
Aderjan et al. Vergiftungen mit Diphenhydramin—Forensisch-toxikologische Beurteilung von Analysenbefunden
DE102022115137A1 (en) Composition with hepatoprotective effect
DE60216979T2 (en) Synergistic hepatoprotective composition of trans-tetracos-15-enoic acid and apocynin and use thereof
EP4058039A1 (en) Homeopathic topical composition

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ 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 VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

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

WWE Wipo information: entry into national phase

Ref document number: 2002792600

Country of ref document: EP

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWW Wipo information: withdrawn in national office

Ref document number: 2002792600

Country of ref document: EP

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP