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Apoptosis-mimicking synthetic entities and use thereof in medical treatment

a synthetic entity and apoptosis technology, applied in the field of synthetic and semi-synthetic compositions having biochemical activity, can solve the problems of large amount of liposomes given to a human, too large to act as immune system modifiers, and high cost and therefore undesirabl

Inactive Publication Date: 2005-06-09
VASOGEN IRELAND LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes the discovery that certain types of cells can be used to treat various diseases. Specifically, the patent describes methods for using PS-carrying bodies to treat T-cell function-mediated disorders, inflammatory disorders, endothelial function disorders, and immune system disorders characterized by inappropriate cytokine expression. The patent also describes pharmaceutical compositions containing these bodies for administration to patients. The technical effect of this invention is the discovery of a novel treatment method using modified cells to target specific receptors on immune cells, which can help in the treatment of various diseases.

Problems solved by technology

An equivalent dose of liposomes given to a human (greater than 2 grams per average individual) would be potentially toxic, expensive and therefore impractical and undesirable.
Such quantities would be active, if at all, as drugs, and would be too large to act as immune system modifiers.

Method used

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  • Apoptosis-mimicking synthetic entities and use thereof in medical treatment
  • Apoptosis-mimicking synthetic entities and use thereof in medical treatment
  • Apoptosis-mimicking synthetic entities and use thereof in medical treatment

Examples

Experimental program
Comparison scheme
Effect test

examples 1-5

[0064] These examples show the effect of injecting various phosphatidylserine-containing liposomes of various sizes and compositions, and in various concentrations, on ear swelling in the murine contact hypersensitivity (CHS) model, a Th1-mediated inflammatory reaction, an art-accepted model. For these experiments, female BALB / c mice (Jackson Laboratories) age 6-8 weeks and weighing 22-25 g were used.

example 1

PS Liposomes

[0065] Phosophatidylserine (PS) containing liposomes of size 100±20 nanometers were prepared as described above which had a phosphatidylserine content of 100% (i.e. made entirely of PS). A stock suspension of liposomes containing 4.8×1014 liposomes per ml was diluted with PBS to give an injection suspension containing 6×106 particles per ml, and each animal was injected with 50 μl of this suspension, containing 3×105 liposomes.

Protocol

[0066] Test group A which received the liposomes comprised 25 animals in number. Control group comprised 24 animals. The following experiments were run:

TABLE 1Day 7GroupDay 1Day 2Day 3Day 4Day 5Day 6(24 hours)AInjectInjectInjectInjectInjectInjectEar measured100%thenthenPSsensitizechallengepositivesensitizedchallengeEar measuredcontrol(untreatedanimals)

[0067] On Days 1-6, mice of Group A were injected with liposomes prepared from 100% PS. Liposomes were injected in 50 μl volume via intramuscular (IM) injection, i.e. 300,000 liposomes pe...

example 2

[0071] Liposomes of size 100±20 nanometers and containing different amounts of phosphatidyl serine, namely 90%; 75% and 50%, with the remainder being phosphatidylcholine (PC), were prepared as described, from starting mixtures of the appropriate relative quantities of the respective phospholipids. Using 4 different groups of animals, five mice per group, the following experiments were run.

Day 7GroupDay 1Day 2Day 3Day 4Day 5Day 6(24 hours)BInjectInjectInjectInjectInjectInjectEar measured90% PSthenthensensitizechallengeCInjectInjectInjectInjectInjectInjectEar measured75% PSthenthensensitizechallengeDInjectInjectInjectInjectInjectInjectEar measured50% PSthenthensensitizechallengepositivesensitizedchallengedEar measuredcontrol(untreatedanimals

The amounts and procedure for injection, the sensitization procedure, the challenge procedure and the results measurements were all as described in Example 1.

[0072] The results are given below, in Table 2, and are graphically presented on FIG. ...

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Abstract

Synthetic and semisynthetic bodies having a three-dimensional structure, sized and shaped to resemble apoptotic cells and apoptotic bodies, and having phosphatidyl serine (PS) molecules on the surface thereof, are administered to a patient, to alleviate a variety of disorders such as T-cell mediated disorders (autoimmune conditions). The bodies are believed to trigger an apoptosis-like mechanism in the patient.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to Canadian Application Serial Number 2,319,928 filed Sep. 18, 2000. FIELD OF THE INVENTION [0002] This invention relates to synthetic and semi-synthetic compositions having biochemical activity, and to the uses thereof in the treatment and / or prophylaxis of various disorders in mammalian patients. More particularly, it relates to preparation and use of synthetic and semi-synthetic bodies which can mimic the process of cell apoptosis after introduction into the body of a patient, to produce beneficial effects. BACKGROUND OF THE INVENTION [0003] The following documents are cited herein: [0004] 1. Kerr, J. F. R., Wyllie A. H., Currie, A. R. (1992), “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.”British Journal of Cancer 26: 239-257; [0005] 2. Fadok (1998) J. Clin. Invest., 101.890-898; [0006] 3. Fadok V. A., Voelker D. P., Campbell P. A., Cohen, J. J., Bratton,...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/127A61K9/16A61K47/48
CPCA61K9/0019A61K9/127A61K47/4823A61K9/1676A61K31/685A61K9/141A61K47/61A61P29/00A61P37/02
Inventor BOLTON, ANTHONY E.MANDEL, ARKAYD
Owner VASOGEN IRELAND LTD
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