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Polycationic compounds and uses thereof

A polycation, compound technology, applied in 92,744 and 5,202,352. , another aspect involves the regulation of domains in animals or humans in need of

Inactive Publication Date: 2007-07-11
宝利麦迪克斯股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

polycation

Method used

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  • Polycationic compounds and uses thereof
  • Polycationic compounds and uses thereof
  • Polycationic compounds and uses thereof

Examples

Experimental program
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preparation example Construction

[0256] A syrup or suspension is prepared by adding the active compound to a concentrated, aqueous solution of a sugar (eg, sucrose) along with any auxiliaries. Such adjuvants may include flavourings, sugar crystallization retarding agents or agents which increase the solubility of any other ingredient, for example polyols such as glycerol or sorbitol.

[0257] Formulations for rectal administration may be presented as suppositories, with conventional carriers such as cocoa butter or Witepsol S55 (trade name of Dynamite Nobel Chemical, Germany) used as suppository base.

[0258] Alternatively, the compounds can be administered as liposomes or microspheres (or microparticles). Methods for preparing liposomes and microspheres for administration to patients are well known to those skilled in the art. US Patent No. 4,789,734 describes methods for encapsulating biological material into liposomes, the contents of which are incorporated herein by reference. In general, the material ...

Embodiment 1

[0263] The following examples illustrate the anti-angiogenic effect of exemplary polycationic compounds of the invention. Ten-day-old embryos purchased from Spafas, Inc. (Preston, CT) were incubated at 37°C and 55% relative humidity. With the aid of a light-transmitting inspection light in the dark, a hypodermic needle is inserted into the casing to form a small hole to conceal the air cell. When viewed under light transmission, a second hole is formed on the egg's wider side piercing the shell, which passes directly through the avascular portion of the embryo's membrane. A pseudo-air sac is created under the second hole by applying negative pressure to the first hole, which separates the chorioallantoic membrane (CAM) from the shell. Use a small craft wheel (Dremel, Division of Emerson Electric Company Racine, Wisconsin) to cut out approximately 1.0 cm past the dislodged CAM on the shell 2 The fenestration allows direct access to the CAM below. Discs of #1 filter paper (Wh...

Embodiment 2

[0277] The following examples illustrate the inhibition of endothelial cell tube formation by polycationic compounds of the invention. Differentiation of endothelial cells was detected using the method developed by Grant et al. (Grant et al., In Vitro Cell Dev. Biol., 27A: 327-336 (1991). Matrigel without phenol red  Matrix (commercially available from Becton Dickinson, Bedford, MA) was thawed overnight at 4°C. Using a cold pipette tip, dispense 3.0 mg / well Matrigel  Put the matrix into a cold 24-well plate. Allow Matrigel during 30 min incubation at 37 °C  Matrix polymerization.

[0278] At 37°C, 5% CO 2 Human umbilical vein endothelial cells (HUVEC) were maintained in endothelial cell growth medium with 2% fetal calf serum (EGM) and 95% humidity. Tube assays were performed in endothelial basal medium (EBM), supplemented with 0.5% bovine serum albumin (BSA) and a 1:100 dilution of insulin-transferrin-selenium-G supplement (I-T-Se, 100X) . HUVECs were trypsinized, ce...

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Abstract

Aspects of the present invention relate to compounds and methods useful in modulating angiogenesis and methods of treating or preventing diseases associated with angiogenesis by administering a polycationic compound. The present invention relates to methods of use and compositions for inhibiting angiogenesis-mediated disorders in mammals including animals and humans. Additionally, this invention relates to the combined use of polycations with other anti-angiogenesis agents for the treatment of different angiogenesis-mediated disorders. Additionally, those polycationic compounds can be used with various anti-inflammatory and cytotoxic agents as well as with radio-therapeutic agents in cancer patients to prevent and treat tumor growth and metastasis.

Description

[0001] REFERENCE TO RELATED APPLICATIONS: This application claims US Provisional Application Serial No. 60 / 579,282, entitled "Use of Polycationic Compounds to Modulate Angiogenesis," filed June 15, 2004, the entire contents of which are hereby incorporated by reference. Background of the invention [0002] Angiogenesis is the development of new blood vessels from already existing blood vessels. Physiologically, angiogenesis ensures the proper development of the mature organism, prepares the uterus for egg implantation, and plays an important role in wound healing, fracture recovery, and the establishment and maintenance of pregnancy. Angiogenesis is also associated with pathological diseases that are associated with several disease states such as cancer, inflammation, and eye disease. [0003] Angiogenesis or "neovascularization" is a multistep process controlled by the balance of pro-angiogenic and anti-angiogenic factors. A later stage of the process involves the proliferat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/05C07C275/00A61K31/17A61K31/165C07C235/20C07C235/56C07C235/60C07C237/24C07C237/42C07C243/38C07C279/12C07C279/14C07C323/42C07D239/28
CPCC07C219/06C07C279/14C07C237/44C07C237/42C07C235/62C07D239/28C07C235/60C07C237/40C07C235/56C07C323/42C07C243/38C07C235/20C07C2103/92C07C323/63A61K31/167C07C279/12C07C2101/14C07C2601/14C07C2603/92A61P1/00A61P1/04A61P15/00A61P15/08A61P17/00A61P17/02A61P17/06A61P19/02A61P25/00A61P27/00A61P27/02A61P27/06A61P27/10A61P29/00A61P31/18A61P35/00A61P35/02A61P41/00A61P43/00A61P7/00A61P7/04A61P9/00A61P9/10A61P9/14A61P3/10A61K31/166A61K31/17
Inventor 莫萨·沙克尔
Owner 宝利麦迪克斯股份有限公司
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