DE3711724A1 - System for acting on, in particular destroying, viruses - Google Patents

System for acting on, in particular destroying, viruses

Info

Publication number
DE3711724A1
DE3711724A1 DE19873711724 DE3711724A DE3711724A1 DE 3711724 A1 DE3711724 A1 DE 3711724A1 DE 19873711724 DE19873711724 DE 19873711724 DE 3711724 A DE3711724 A DE 3711724A DE 3711724 A1 DE3711724 A1 DE 3711724A1
Authority
DE
Germany
Prior art keywords
liposomes
genetic information
membrane
substance
acting
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.)
Granted
Application number
DE19873711724
Other languages
German (de)
Other versions
DE3711724C2 (en
Inventor
Harro Boerner
Joachim Giese
Peter Gerhardts
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HARRO BOERNER MEDIZINISCHE KOM
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HARRO BOERNER MEDIZINISCHE KOM
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.)
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Application filed by HARRO BOERNER MEDIZINISCHE KOM filed Critical HARRO BOERNER MEDIZINISCHE KOM
Priority to DE19873711724 priority Critical patent/DE3711724A1/en
Publication of DE3711724A1 publication Critical patent/DE3711724A1/en
Application granted granted Critical
Publication of DE3711724C2 publication Critical patent/DE3711724C2/de
Granted legal-status Critical Current

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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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6425—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
    • A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome

Abstract

A system for acting on, in particular destroying, viruses comprises liposomes in whose membranes at least one receptor which recognises and binds the virus to be acted on is incorporated, and whose interior contains at least one substance acting on the viral genetic information. A system of this type is produced by incorporating receptors into the membrane of liposomes with the aid of a detergent solubilisation.

Description

Die Theraphie von Viruserkrankungen ist bisher schwierig und teilweise überhaupt nicht möglich, da die virale Erbinformation häufig außerhalb der Zellen als Doppelstrang vorliegt und durch die Hülle gegen Einflüsse von außen her gut geschützt ist.The therapy of viral diseases has so far been difficult and partially not possible at all because of the viral genetic information often present outside the cells as a double strand and through the cover is well protected against external influences.

Der Erfindung liegt die Aufgabe zugrunde, ein System zu schaffen, mit dem in einem von pathogenen Viren befallenen Organismus auf die Viren eingewirkt und insbesondere eine Zerstörung dieser Vi­ ren erreicht werden kann, ohne dabei die Zellen des Organismusses zu gefährden.The invention has for its object to provide a system with the organism infected with pathogenic viruses the viruses acted and in particular a destruction of this Vi Ren can be achieved without losing the cells of the organism to endanger.

Diese Aufgabe löst ein System mit den Merkmalen des Anspruches 1. This problem is solved by a system with the features of the claim 1.  

Der Weg der Infektion von Zellen durch Viren geht im allgemeinen so vor sich, daß das Virus über einen in der Plasmamembran der Zelle vorhandenen Receptor erkannt und gebunden wird und danach seine freigelegte Erbinformation (DNA oder RNA) in den Innenraum der infizierten Zelle abgibt, während die Virushülle oder Be­ standteile davon auf der Außenseite der Zelle verbleiben. Die in die Zelle eingeschleuste virale Erbinformation veranlaßt die Zielzelle, das Virus und seine Bestandteile zu vermehren.Viruses generally infect cells so before that the virus over one in the plasma membrane of the Cell existing receptor is recognized and bound and afterwards its exposed genetic information (DNA or RNA) into the interior releases the infected cell while the virus envelope or Be parts of it remain on the outside of the cell. In the the cell infiltrates viral genetic information which causes the Target cell to multiply the virus and its components.

Ausgehend von der Überlegung, daß eine erfolgversprechende Bekäm­ pfung von Viren nur dann aussichtsreich ist, wenn deren Erbinfor­ mation für die Bekämpfungssubstanz gut zugänglich ist, daß aber innerhalb der infizierten Zellen die Unterscheidung zwischen der viralen Erbinformation und der zelleigenen Erbinformation schwie­ rig, wenn nicht sogar unmöglich ist, wurde mit der erfindungsge­ mäßen Lösung ein System geschaffen, das die virale Erbinformation außerhalb der Zellen des Organismus für eine Einwirkung mittels einer geeigneten Substanz zugänglich macht. Die erfindungsgemäßen Liposomen sind nämlich dank ihrer membranständigen, virusspezifi­ schen Receptoren in der Lage, die zu bekämpfenden Viren zu erken­ nen oder von dieser erkannt zu werden und sie zu binden. Dadurch werden die Viren wie bei infizierten Zellen des Organismus dazu veranlaßt, ihre Erbinformation in das Liposom einzuschleusen. Mit der im Innenraum des Liposoms vorhandenen Substanz kann dann auf die freigelegte Erbinformation des Virus eingewirkt und diese Erbinformation im Bedarfsfalle zerstört werden. Von besonderem Vorteil ist hierbei, daß es nicht zu Verwechslungen mit einer zelleigenen Erbinformation kommen kann und daß die Einwirkung oder Zerstörung der viralen Erbinformation und damit auch des Vi­ rus in dem von der Membran des Liposoms umschlossenen Komparti­ ments und damit ohne Nebenwirkung erfolgt. Based on the consideration that a promising comb Virus detection is only promising if its inheritance Mation is easily accessible for the control substance, but that within the infected cells the distinction between the viral genetic information and the cell's own genetic information are rig, if not impossible, was invented with the inventive solution created a system that contains the viral genetic information outside the cells of the organism for exposure a suitable substance. The invention Liposomes are virus-specific thanks to their membrane-bound receptors are able to detect the viruses to be controlled or to be recognized by it and to bind them. Thereby the viruses become like in infected cells of the organism causes her genetic information to enter the liposome. With the substance present in the interior of the liposome can then the exposed genetic information of the virus is affected and this If necessary, genetic information can be destroyed. Of particular The advantage here is that there is no confusion with a cell's genetic information can come and that the exposure or destruction of the viral genetic information and thus also the Vi rus in the compartment enclosed by the membrane of the liposome and therefore without side effects.  

Selbstverständlich müssen die verwendeten Liposomen eine geeigne­ te Größe, elektrische Ladung, chemische Zusammensetzung, Asymme­ trie und Lamellarität haben. Vorteilhafterweise sind die Liposo­ men so groß, daß eine Vielzahl von Receptoren in die Membran ein­ gebaut werden kann. Die elektrische Ladung ist so zu wählen, daß keine Abstossungskräfte gegen die Bindung der Viren auftreten. Die chemische Zusammensetzung der Liposomen sollte so gewählt werden, daß eine unmittelbare Annäherung von Liposom und Virus zur Wechselwirkung mit dem Receptor ermöglicht wird. Die Asymme­ trie der Liposomenmembran soll den Receptor in der für die Bin­ dung des Virus geeigneten Konformation stabilisieren. Weiterhin ist es zweckmäßig, unilamellare Liposomen vorzusehen, damit nach dem Eindringen der viralen Erbinformation ein Kontakt mit der Zerstörungs- oder Inaktivierungssubstanz gesichert ist. Diese Li­ posomen können nach bekannten Verfahren, wie zum Beispiel durch Extrusion, Detergensdialyse oder Reverse-Phase Evaporation herge­ stellt werden.Of course, the liposomes used must be suitable te size, electric charge, chemical composition, asymmetry trie and lamellarity. The liposo are advantageous so large that a large number of receptors enter the membrane can be built. The electrical charge should be chosen so that there are no repulsive forces against the binding of the viruses. The chemical composition of the liposomes should be chosen in this way be that an immediate approximation of liposome and virus to interact with the receptor. The Asymme The drive of the liposome membrane is said to be the receptor in the bin stabilize the appropriate conformation of the virus. Farther it is advisable to provide unilamellar liposomes so that after the penetration of the viral genetic information a contact with the Destructive or inactivating substance is secured. This li Posomes can be made by known methods, such as by Extrusion, detergent dialysis or reverse phase evaporation be put.

Die Receptoren lassen sich ohne Schwierigkeiten aus den Zielzel­ len des jeweiligen Virus isolieren. Für eine Reihe von Viren sind sie jedoch bekannt und zum Teil auch bereits gentechnologisch synthetisiert. Der Einbau der Receptoren in die Membran der Lipo­ somen kann beispielsweise mittels einer Detergens Solubilisierung erfolgen.The receptors can be easily removed from the target cell Isolate len of the respective virus. For a number of viruses are however, they are known and in some cases already genetically engineered synthesized. The incorporation of the receptors into the membrane of the lipo Somen can, for example, solubilize using a detergent respectively.

Der Einschluß der für das Einwirken auf die virale Erbinformation vorgesehenen Substanz in den Liposomen kann nach bekannten Ver­ fahren erfolgen oder nach dem in der deutschen Patentanmeldung P 36 35 506.2-43 vorgeschlagenen Verfahren, bei dem an vorgefertig­ ten Liposomen durch Zugabe wenigstens eines unbedenklichen Deter­ gens in niedriger Konzentration eine vorübergehende Erhöhung der Membranpermeabilität bewirkt und während dieser Phase erhöhter Membranpermeabilität der Eintritt der Substanz aus einem die Li­ posomen enthaltenen Außenmedium in den Innenraum der Liposomen herbeigeführt wird. The inclusion of those acting on the viral genetic information provided substance in the liposomes can according to known Ver drive take place or according to the in the German patent application P 36 35 506.2-43 proposed method in which to prefabricated ten liposomes by adding at least one harmless detergent gens in low concentration a temporary increase in Membrane permeability causes and increases during this phase Membrane permeability of the entry of the substance from a Li Posomen contained external medium in the interior of the liposomes is brought about.  

Als Substanzen zur Zerstörung der viralen Erbinformation kommen insbesondere DNAse, RNAse und diese abbauende Enzyme in Frage.Coming as substances to destroy viral genetic information in particular DNAse, RNAse and these degrading enzymes in question.

Da mittels der Liposomen des erfindungsgemäßen Systems die in einen Organismus eingedrungenen Viren zumindest so erheblich de­ zimiert werden können, daß die Gefahr einer Infektion der Ziel­ zellen stark reduziert ist, kann man das erfindungsgemäße System als Virenfalle bezeichnen.Since by means of the liposomes of the system according to the invention the Viruses that have invaded an organism at least as significantly can be cimated that the risk of infection is the target cells is greatly reduced, you can the system of the invention call it a virus trap.

Im folgenden ist die Erfindung anhand eines Ausführungsbeispiels - erläutert.In the following, the invention is based on an embodiment - be explained.

Für die Zerstörung von AIDS-Viren werden unilamellare Lecithin- Liposomen nach einem der üblichen Verfahren (Extrusion, Deter­ gensdialyse oder Reverse-Phase Evaporation) hergestellt. In die Membran dieser Liposomen werden für das AIDS-Virus spezifische Receptoren aus der Plasma-Membran von T-Helferzellen mit Hilfe einer Detergens Solubilisierung eingebaut. Man könnte aber auch klonierte Receptoren dieser Art verwenden. Danach wird eine für den Abbau der viralen Erbinformation geeignetes Enzym (DNAse oder RNAse) nach einem der bekannten Verfahren oder dadurch einge­ schlossen, daß durch Zugabe wenigstens eines unbedenklichen De­ tergens in niedriger Konzentration eine vorübergehende Erhöhung der Membranpermeabilität bewirkt und während dieser Phase erhöh­ ter Membranpermeabilität der Eintritt des Wirkstoffes oder der Wirkstoffe aus einem die Liposomen enthaltenden Außenmedium in den Innenraum der Liposomen herbeigeführt.Unilamellar lecithin is used to destroy AIDS viruses Liposomes using one of the usual methods (extrusion, det gene dialysis or reverse phase evaporation). In the Membranes of these liposomes become specific for the AIDS virus Receptors from the plasma membrane of T helper cells with the help a detergent solubilization. But you could also use cloned receptors of this type. After that, one for the degradation of the viral genetic information suitable enzyme (DNAse or RNAse) according to one of the known methods or thereby concluded that by adding at least one harmless De tergens in low concentration a temporary increase membrane permeability and increase during this phase ter membrane permeability the entry of the active ingredient or the Active substances from an external medium containing the liposomes in brought about the interior of the liposomes.

Die Form der Anwendung kann verschieden sein. Beispielsweise kön­ nen zunächst die Liposomen in einem physiologisch verträglichen Medium, z.B. gepufferter Kochsalzlösung, suspendiert sein. Man kann dann die Suspension intravenös, intramuskulär, subcutan oder endolymphatisch injizieren. Es kommt aber auch eine Injektion in die Hirnventrikel bei entsprechender Virusinfektion in Frage. Im Prinzip kann jedes Organ injiziert werden. Auch intraperitoneale Anwendung kommt in Frage.The form of application can be different. For example, first the liposomes in a physiologically acceptable Medium, e.g. buffered saline. Man can then the suspension intravenously, intramuscularly, or subcutaneously inject endolymphatic. But there is also an injection the brain ventricles in question with a corresponding virus infection. in the  In principle, any organ can be injected. Also intraperitoneal Application is possible.

Weiterhin kommt eine Vernebelung als Aerosol in Frage, wobei na­ sale, bronchiale oder pulmonale Anwendungen möglich sind. Auch dermale Anwendungen in Form von Salben, Pasten, Gelen usw. sind in Betracht zu ziehen.Furthermore, nebulization as an aerosol comes into question, where na sale, bronchial or pulmonary applications are possible. Also dermal applications in the form of ointments, pastes, gels, etc. to consider.

Claims (7)

1. System zum Einwirken auf, insbesondere Zerstören von Viren, gekennzeichnet durch Liposomen, in deren Membrane zumin­ dest ein das Virus, auf das die Einwirkung erfolgen soll, erken­ nender und bindender Receptor eingebaut ist und in deren Innen­ raum wenigstens eine auf die virale Erbinformation einwirkende Substanz enthalten ist.1. System for acting on, in particular destroying viruses, characterized by liposomes, in the membrane of which at least one receptor which recognizes and binds the virus on which the action is to take place, and in the interior of which at least one contains the viral genetic information acting substance is included. 2. System nach Anspruch 1, dadurch gekennnzeichnet, daß die Substanz ein die Erbinformation zerstörendes Mittel ist.2. System according to claim 1, characterized in that the substance is a means that destroys genetic information. 3. System nach Anspruch 2, dadurch gekennzeichnet, daß das die Erbinformation zerstörende Mittel ein DNA oder RNA ab­ bauendes Enzym ist.3. System according to claim 2, characterized in that the agent destroying the genetic information detects a DNA or RNA building enzyme. 4. System nach einem der Ansprüche 1 bis 3, dadurch ge­ kennzeichnet, daß die Liposomen unilamellare Lecithin-Liposomen sind.4. System according to any one of claims 1 to 3, characterized ge indicates that the liposomes are unilamellar lecithin liposomes are. 5. Verfahren zum Herstellen des Systems gemäß einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, daß klonierte Recep­ toren, gentechnologisch synthetisierte Receptoren oder Recep­ toren aus der Plasmamembran von T-Helfer Zellen mit Hilfe einer Detergens Solubilisierung in die Membran von Liposomen eingebaut werden. 5. Method of manufacturing the system according to one of the Claims 1 to 4, characterized in that cloned recep gates, genetically engineered receptors or recep gates from the plasma membrane of T-helper cells with the help of a Detergent solubilization built into the membrane of liposomes will.   6. Verfahren nach Anspruch 5, dadurch gekennzeichnet, daß der Einbau der Receptoren erfolgt, ehe in die Liposomen die auf die virale Erbinformation einwirkende Substanz eingebracht worden ist.6. The method according to claim 5, characterized in that the incorporation of the receptors takes place before the liposomes introduced substance acting on the viral genetic information has been. 7. Verfahren nach Anspruch 5 oder 6, dadurch gekenn­ zeichnet, daß zum Einschluß der auf die virale Erbinformation einwirkenden Substanz in die Liposomen an vorgefertigten Liposo­ men durch Zugabe wenistens eines unbedenklichen Detergens in niedriger Konzentration eine vorübergehende Erhöhung der Membran­ permeabilität bewirkt und während dieser Phase erhöhter Membran­ permeabilität der Eintritt der Substanz aus einem die Liposomen enthaltenden Außenmedium in den Innenraum der Liposomen herbeige­ führt wird.7. The method according to claim 5 or 6, characterized records that to include the on viral genetic information substance acting in the liposomes on pre-made liposo by adding at least one harmless detergent low concentration a temporary increase in the membrane permeability and increased membrane during this phase permeability of the entry of the substance from a liposome containing external medium in the interior of the liposomes leads.
DE19873711724 1987-04-07 1987-04-07 System for acting on, in particular destroying, viruses Granted DE3711724A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19873711724 DE3711724A1 (en) 1987-04-07 1987-04-07 System for acting on, in particular destroying, viruses

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19873711724 DE3711724A1 (en) 1987-04-07 1987-04-07 System for acting on, in particular destroying, viruses

Publications (2)

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DE3711724A1 true DE3711724A1 (en) 1988-10-20
DE3711724C2 DE3711724C2 (en) 1992-05-07

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0432693A1 (en) * 1989-12-11 1991-06-19 Sumitomo Chemical Company, Limited Liposomes cytotoxic to virus-infected cells
WO1992011846A1 (en) * 1991-01-07 1992-07-23 St George's Enterprises Limited Particulates
WO1993002709A1 (en) * 1991-07-31 1993-02-18 Microcarb Inc. Receptor conjugates for targeting drugs and other agents
WO1994016061A1 (en) * 1993-01-15 1994-07-21 Micro Vesicular Systems, Inc. Method of inhibiting viral reproduction
WO1995032734A1 (en) * 1994-05-26 1995-12-07 Innogenetics N.V. New methods and compounds for the selective modulation of antigen-specific t-cell responsiveness
WO1996022763A1 (en) * 1995-01-27 1996-08-01 PALOMINO MUÑOZ, Juan Manuel Liposome for destroying hiv and cells infected by said virus
ES2088752A1 (en) * 1995-01-27 1996-08-16 Palomino Munoz Juan Manuel Liposome for the destruction of HIV and the cells infected by it.
EP0904066A1 (en) * 1996-05-03 1999-03-31 Roger S. Cubicciotti Prodrug compositions and drug delivery methods using synthetic receptors
EP0979655A1 (en) * 1998-08-01 2000-02-16 Boehringer Mannheim Gmbh Means for treatment of infections caused by RNA-Virusses such as HIV
EP2747786A4 (en) * 2011-08-26 2015-03-04 Vecoy Nanomedicines Ltd Pathogen and substance traps

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Die Pharmazie, 33.Jahrgang, Heft 8, August 1978, S. 493-496 *
J.S.SIM and K.G.MCCULLAGH in Approaches to Antiviral Agents Ed.M.R.Harnden, VCH Weinheim, 1985, S. 16-46 *
T.Y.SHEN in Directed Drug Delivery Ed.R.T. BORCHARDT et al., Humana Press, Clifton, New Jersey 1985, S. 231-245 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0432693A1 (en) * 1989-12-11 1991-06-19 Sumitomo Chemical Company, Limited Liposomes cytotoxic to virus-infected cells
WO1992011846A1 (en) * 1991-01-07 1992-07-23 St George's Enterprises Limited Particulates
WO1993002709A1 (en) * 1991-07-31 1993-02-18 Microcarb Inc. Receptor conjugates for targeting drugs and other agents
WO1994016061A1 (en) * 1993-01-15 1994-07-21 Micro Vesicular Systems, Inc. Method of inhibiting viral reproduction
WO1995032734A1 (en) * 1994-05-26 1995-12-07 Innogenetics N.V. New methods and compounds for the selective modulation of antigen-specific t-cell responsiveness
WO1996022763A1 (en) * 1995-01-27 1996-08-01 PALOMINO MUÑOZ, Juan Manuel Liposome for destroying hiv and cells infected by said virus
ES2088752A1 (en) * 1995-01-27 1996-08-16 Palomino Munoz Juan Manuel Liposome for the destruction of HIV and the cells infected by it.
EP0904066A1 (en) * 1996-05-03 1999-03-31 Roger S. Cubicciotti Prodrug compositions and drug delivery methods using synthetic receptors
EP0904066A4 (en) * 1996-05-03 2002-04-24 Roger S Cubicciotti Prodrug compositions and drug delivery methods using synthetic receptors
EP0979655A1 (en) * 1998-08-01 2000-02-16 Boehringer Mannheim Gmbh Means for treatment of infections caused by RNA-Virusses such as HIV
EP2747786A4 (en) * 2011-08-26 2015-03-04 Vecoy Nanomedicines Ltd Pathogen and substance traps
AU2012303619B2 (en) * 2011-08-26 2017-01-19 Vecoy Nanomedicines Ltd. Pathogen and substance traps

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