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Compounds having anti-proliferative properties

A technology of mixtures and drugs, applied in the field of compounds with anti-proliferative properties, can solve the problems that atherosclerosis is not an effective clinical option and the results of atherosclerosis treatment are not clear

Inactive Publication Date: 2006-01-18
VITAL HEALTH SCIENCES PTY LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0025] But clinical trials of vitamin E in the treatment of atherosclerosis have mixed results
Vitamin E supplementation is therefore currently not an effective clinical option for the treatment of atherosclerosis

Method used

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  • Compounds having anti-proliferative properties
  • Compounds having anti-proliferative properties
  • Compounds having anti-proliferative properties

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] This example investigated the effects of tocopherol and tocopherol phosphate on the proliferation of rat aortic smooth muscle cells.

[0083] Rat aortic smooth muscle cells (RASMC) used for proliferation studies were taken from the intima and media of healthy, plaque-free adult rat aorta. This cell line is an acceptable model for studying atherosclerosis, because an increase in arterial smooth muscle mass is found in atherosclerotic intimal damage. The second generation cells of RASMC are cryopreserved, which can proliferate at least 16 population doublings. RASMC responds to various factors through cell proliferation and overgrowth, which is a significant sign of atherosclerosis in vascular diseases. RASMC is also suitable for the study of the growth and differentiation of large vascular smooth muscle cells and is used as an in vitro model together with live rat models.

[0084] material

[0085] · 6-well plate (cell count)

[0086] ·96-well plate (MTT analysis)

[0087] ·...

Embodiment 2

[0106] This example uses two types of cell count analysis: adhesion cell count and MTS analysis to evaluate the anti-α-tocopherol phosphate (TP), bis-tocopherol phosphate (T2P), TP / T2P mixture, and α-tocopherol. Proliferative activity.

[0107] Perform MTS proliferation analysis to further support and confirm the adhesion cell count analysis. MTS analysis is a very mature method for the evaluation of cell proliferation. This method measures the viable cells that adhere to the disc (counting the same adherent cells) and the cells that detach and float in the culture medium during the test (in the adherence). The cell count will be missed) for counting.

[0108] material

[0109] · 6-well plate (cell count)

[0110] ·96-well plate (MTS analysis)

[0111] ·DMEM / F12 medium-GIBCO / Life Technologies

[0112] ·Fetal Bovine Serum (serum)

[0113] ·Rat aortic smooth muscle cells (RASMCs) fourth generation CellApplications company

[0114] ·Gentamicin——GIBCO / Life Technologies

[0115] ·Cell ...

Embodiment 3

[0130]The purpose of this study was to compare the effects of TP / T2P mixture and tocopherol on the expression of CD36, the absorption of oxidized LDL (oxLDL) and the growth of human THP-1 monocytes in vitro.

[0131] step

[0132] Cell culture: Dissolve the tocopherol and TP / T2P mixture in ethanol, and determine the concentration of the stock solution by spectrophotometry. Monocytes (THP-1) grow in RPMI / 10% FCS.

[0133] Mark oxLDL: OxLDLs (90% to 100% oxidation rate) were purchased from Intracell. CuSO for a small amount of LDL 4 (20mmol / L) Oxidize at 37°C for 18-22 hours. The oxidation of LDL was confirmed by the characteristic tailing bands that appeared on the agarose gel. The labeling of oxLDL is basically carried out according to the above method. OxLDLs and DiO (molecular probes) were cultured in lipoprotein-deficient serum at 37°C for 15 hours. The labeled oxLDLs (oxLDL-DiO) were purified by ultracentrifugation on KBr gradient and dialyzed for multiple exchanges of sodium-...

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Abstract

Provided is a method for inhibiting one or more of the following situations: the proliferation of monocytes / phages; or the proliferation of smooth muscle cells; or the expression of CD36 receptors; or the absorption of oxidized LDL, the method comprising an effective amount of The step of administering one or more phosphate derivatives of one or more electron transfer agents.

Description

Invention field [0001] The present invention relates to the ability of a modified electron transfer agent to inhibit one or more of the following conditions: monocyte / macrophage proliferation, smooth muscle cell proliferation, scavenger receptor (scavenger receptor) expression or oxidative type LDL absorption. Background of the invention [0002] In this specification, if documents, regulations or clauses are cited or discussed, such quotation or discussion does not acknowledge that these documents, regulations or clauses or any combination of them are part of common general knowledge on the priority date; or known and attempted to resolve the issue. Any issues covered in the instructions are related. [0003] While the following discussion relates to tocopherol phosphate (TP), it should be understood that this discussion is only illustrative. This invention is not limited to TP. The discussion is similarly related to other phosphate derivatives of electron transfer reagents. Rea...

Claims

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Application Information

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IPC IPC(8): A61K31/355A61K31/661A61K31/6615A61P25/28A61P3/10A61P9/10
Inventor 西蒙・迈克尔・韦斯特埃斯拉・奥格鲁
Owner VITAL HEALTH SCIENCES PTY LTD
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