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Use of lipid conjugates in the treatment of infection

a technology of conjugates and lipids, applied in the field of infection treatment with lipid conjugates, can solve the problems of difficult to distinguish viral replicative mechanisms from host replicative processes, relatively few effective pharmaceutical compositions intended or adapted for antiviral, antifungal, etc., and achieve the effect of suppressing, inhibiting, or treating

Inactive Publication Date: 2006-08-24
YISSUM RES DEV CO OF THE HEBREWUNIVERSITY OF JERUSALEM LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The lipid-conjugates demonstrate broad-spectrum efficacy in reducing infection severity, preventing relapse, and enhancing patient survival by inhibiting key enzymes and mediators involved in infection processes, as shown in various animal and cell models, including HIV, influenza, and bacterial infections.

Problems solved by technology

Although significant resources have been dedicated to identifying compounds having antimicrobial properties, microbial infections continue to present a significant human health risk
There are relatively few effective pharmaceutical compositions intended or adapted for antiviral, antifungal, or antiparasitic therapy.
A major obstacle in the development of antiviral agents is the difficulty in distinguishing viral replicative mechanisms from host replicative processes.
An additional limitation of existing antiviral drugs is that they have a narrow antiviral spectrum and are often ineffective against the latent virus.
However, in recent years the capacity to manage infectious diseases has been threatened by the emergence of bacterial strains that are no longer susceptible to currently available antimicrobial agents.
In fact, the usefulness of most existing antimicrobial treatments are limited by the development of multidrug resistance and the emergence of long-term toxicities.
Other challenges include creating a drug that is broadly applicable in combating many different types of microbial infections, which is especially important in the treatment of immunocompromised individuals.

Method used

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  • Use of lipid conjugates in the treatment of infection
  • Use of lipid conjugates in the treatment of infection
  • Use of lipid conjugates in the treatment of infection

Examples

Experimental program
Comparison scheme
Effect test

example 1

Viral Infection

[0453] The Lipid-conjugates are effective in the prophylaxis and treatment of viral infection, particularly infections due to the human immunodeficiency virus (HIV), human influenza virus and vaccinia virus. This is demonstrated for HIV in Experiments 1.1-1.3 below, for human influenza virus in Experiment 1.4-1.5, and for vaccinia in Experiment 1.6 below.

[0454] Viral infection is the cause of a number of human and animal diseases throughout the world. The process of viral infection comprises several stages, including attachment, penetration, uncoating, replication, maturation, release and reinfection. In order to assess the ability of Lipid-conjugates to prevent viral infection, human cell lines were incubated with a preparation of a viral agent, and the ability of the virus to infect cells is compared in the presence and absence of Lipid-conjugate.

[0455] Experiment 1.1: To demonstrate that the Lipid-conjugates are capable of preventing HIV infection of target cell...

example 2

Treatment of Chlamydia Infection

[0491] Intracellular bacterial parasites are one of the most prevalent forms of sexually transmitted disease and are frequently intractable to conventional antibiotic therapy. Infection of the female genital tract with chlamydia species is a salient example. Experiment 2.1 demonstrates the ability of Lipid-conjugate treatment to prevent infection of HeLa cells by Chlamydia. Human cervical adenocarcinoma cell line, HeLa 229 (ATCC, Manassas, Calif.), were cultured and incubated with the phospholipid conjugates (20 micromolar) for 30 min, then incubated with Chlamydia psittaci (an avian form of Chlamydia trachomatis) (guinea pig inclusion conjunctivitis serologically variant strains (servovars)) for 24 hr. Infected cells were detected by cytofluorometry (FACS) using FITC-conjugated anti-Chlamydia antibody (FIG. 2.1A).

[0492]FIG. 2.1B depicts the dose response of the Lipid-conjugates' inhibitory effect on infection of HeLa cells by Chlamydia. HeLa cells ...

example 3

Obstructive Respiratory Disease

[0495] In asthma, the impeded airflow is due to airway obstruction which is the result of constriction and obstruction of luminal vessels of the lungs. In order to determine the effect of Lipid-conjugates on obstructive respiratory disease, contraction of smooth muscle preparations isolated from airways was induced in the presence and absence of Lipid-conjugates. This is a widely-accepted experimental system to investigate airway constriction.

[0496] A muscle preparation (tracheal rings) was isolated from rats (Experiments 3.1-3.3) and from guinea pigs (Experiments 3.4-3.5). Muscle contraction was measured by attachment of the muscle to a pressure transducer, which works much like a spring. Administration of asthmatogenic substances such as endothelin-1 (ET) and acetylcholine (AcCh) induces muscle contraction. Endothelins are released upon vascular endothelial injury, and they activate macrophages and act as strong chemo-attractants for circulating mo...

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Abstract

This invention provides compounds and methods of use thereof in suppressing, inhibiting, preventing, or treating a pathogenic effect on a cell, including, inter alia, infection with intracellular pathogens. Also provided are compounds and methods of use thereof in suppressing, inhibiting, preventing, or treating an infection in a subject.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. application Ser. No. 10 / 952,496 filed Sep. 29, 2004, and a continuation-in-part of U.S. application Ser. No. 10 / 627,981, filed Jul. 28, 2003, which are continuation-in-part applications of U.S. application Ser. No. 09 / 756,765, filed Jan. 10, 2001, which claims priority from U.S. Provisional Application Ser. No. 60 / 174,905, filed Jan. 10, 2000, and U.S. Provisional Application Ser. No. 60 / 174,907 filed Jan. 10, 2000, which are hereby incorporated by reference.FIELD OF THE INVENTION [0002] This invention provides compounds and methods of use thereof in suppressing, inhibiting, preventing, or treating a pathogenic effect on a cell, including, inter alia, infection with intracellular pathogens. Also provided are compounds and methods of use thereof in suppressing, inhibiting, preventing, or treating an infection in a subject. BACKGROUND OF THE INVENTION [0003] Lipid-conjugates are thought t...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/739A61K31/727
CPCA61K31/727A61K31/739A61K2300/00A61K47/544A61K47/61
Inventor YEDGAR, SAUL
Owner YISSUM RES DEV CO OF THE HEBREWUNIVERSITY OF JERUSALEM LTD
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