Use of leukotriene B4 or its analogues as antiviral and antineoplastic agents

A technology for antiviral agents and analogues, applied in the field of leukotriene B4 or its analogues as antiviral agents and antitumor agents, capable of solving problems such as low activity and side effects

Inactive Publication Date: 2003-07-09
LTB4 SWEDAN AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] Although some prostaglandins have been shown to have antiviral activity, they cause unwanted side effects and show relatively low activity

Method used

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  • Use of leukotriene B4 or its analogues as antiviral and antineoplastic agents
  • Use of leukotriene B4 or its analogues as antiviral and antineoplastic agents
  • Use of leukotriene B4 or its analogues as antiviral and antineoplastic agents

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0106] Detection of EBV-induced clump formation and EBNA synthesis in peripheral blood mononuclear cells

[0107] lump formation

[0108] Dextran previously described by BoyumA. (Scand., Journal of Immunology, 1976, 5(5): 9)

[0109] Sedimentation and Ficoll-Paque TM Peripheral blood mononuclear cells were obtained from healthy donors after gradient centrifugation

[0110] cells (PBMC). At a viral titer of 10 7 In the presence of transforming units (TFU) / ml of infectious EBV strain B95-8, cells were resuspended in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum (FCS). In short, while using different concentrations of LTB 4 , that is, LTB at 0.3, 3.0 and 30 nM, respectively 4 Treatment (single addition) of EBV-infected PBMCs. Cells were cultured in 96-well-culture plates (10 6 cells / ml, 200 μl / well) for 12 days, and use an inverted microscope (100×) to evaluate the formation of clumps that can characterize cells i...

Embodiment II

[0117] Detection of HSV-1 infection in peripheral blood mononuclear cells

[0118] Detection of specific HSV-1 antigens

[0119] As described in Example 1, with TCID 50 for 10 7 / ml of HSV-1 (McIntyre strain) infected PBMC with or without different concentrations of LTB 4 Treatment (adding on days 0, 2 and 4 of culture Figure 4 LTB at indicated concentrations 4 ). After 5 days of culture, the presence of specific HSV-1-associated antigen synthesized in the cytoplasm of infected cells was assessed by immunofluorescence using a monoclonal antibody (H62) (ImmunoCorp, Montreal, Canada). LTB at 100nM 4 When present, the synthesis of viral antigens is inhibited by 60% ( Figure 4 ). Figure 4 Results shown are representative of five (5) additional experiments. Similar results (75% inhibition) were obtained by using specific antisera (obtained from chronically infected donors) in the immunofluorescence assay.

[0120] Synthesis of HSV-1 particles

[0121] To evaluate LTB ...

Embodiment III

[0132] Detection of HIV-1 infection in peripheral blood mononuclear cells

[0133] Also rated LTB 4 Antiviral properties against HIV-1 infection.

[0134] Reverse transcriptase activity in cells infected with HIV-1

[0135] to 10 6 Resuspend the PBMC in culture medium (RPMI-1640 supplemented with 10% FBS) at a density of 1 cell / ml at 37°C in 5% CO 2 Cells were cultured for 2-3 days in the presence of 3 μg / ml of PHA-P (Sigma, St. Louis, MO) and 30 U / ml of recombinant human IL-2 in an atmosphere of . Take 1×10 6 PHA-stimulated PBMCs were resuspended at a density of 3 cells / ml and incubated in the absence or presence of increasing concentrations of LTB 4 (0, 30, 100 and 200 nM), cells were infected with HIV-IIIB (various multiplicity of infection: number of infectious virus particles / target cell). Change the medium twice a week, and add an appropriate amount of LTB each time the medium is changed 4 . Cell-free culture supernatants were frozen for specific periods of time ...

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Abstract

The present invention relates to the use of leukotriene B4 (LTB4), variants and derivatives thereof as a therapeutic agent in the treatment or prophylaxis of viral infections caused by human and animal viruses. The present invention also relates to the use of LTB4, variants and derivatives thereof as an anti-neoplastic agent in the prophylaxis and treatment of cancers induced by tumor viruses and in other neoplastic diseases. The human and animal viruses are DNA viruses, such as parvoviridae, papovaviridae, adenoviridae, herpesviridae, poxviridae and hepadnaviridae; RNA viruses, such as picornaviridae, togaviridae, orthomyxoviridae, paramyxoviridae, coronaviridae, reoviridae, oncornaviridae and filoviridae in general, and Retroviridae such as HIV-1 and HIV-2.

Description

technical field [0001] The present invention relates to leukotriene B4 (LTB 4 ) antiviral activity and involves leukotriene B4 (LTB 4 ) as a therapeutic agent for the treatment of viral infections caused by human and animal viruses. Background technique [0002] Many important infectious diseases that afflict humans are caused by viruses. Some infectious diseases are important because they are often fatal; these are rabies, smallpox, polio, hepatitis, yellow fever, immunodeficiency and various encephalitis. Other communicable diseases are also important because they are highly contagious and cause acute illness, such as influenza, measles, mumps and chickenpox, as well as respiratory-gastrointestinal complaints. Other infectious diseases such as rubella and cytomegalovirus can cause congenital abnormalities. Finally, there are viruses known as oncoviruses, which can cause tumors and cancers in humans and animals. [0003] Among viruses, the herpes virus family has high ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/21A61K31/00A61K31/20A61K31/23A61K31/231A61K31/232A61K31/557A61K45/06A61P31/00A61P31/12A61P31/14A61P31/18A61P31/20A61P31/22
CPCA61K31/231A61K31/232A61K31/557A61P31/00A61P31/12A61P31/14A61P31/18A61P31/20A61P31/22A61K31/23
Inventor 琼·戈塞林皮埃尔·伯吉特
Owner LTB4 SWEDAN AB
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