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Method and composition for enhancing anti-angiogenic therapy

A technology of angiogenesis inhibition and composition, which is applied in the direction of drug combination, antineoplastic drugs, pharmaceutical formulations, etc., and can solve problems such as not showing sufficient efficacy

Inactive Publication Date: 2007-11-07
TILTAN PHARMA LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, these agents do not demonstrate sufficient efficacy in cancer therapy by themselves
[0016] With few exceptions, there are no single drugs or drug combinations that are effective for most cancers

Method used

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  • Method and composition for enhancing anti-angiogenic therapy
  • Method and composition for enhancing anti-angiogenic therapy
  • Method and composition for enhancing anti-angiogenic therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] Cyclophosphamide-resistant breast cancer cells of the EMT-6 / CTX cell line were thawed, grown in tissue culture plates, and injected subcutaneously (s.c.) (10 6 cells / ml) into the rear flank of 27 g CB6F1 male mice.

[0088] The anti-angiogenic therapy (hereby defined as "4x4") consisted of periodic combinations of the drugs detailed in Table 1. The efficacy of 4x4 treatment with xylitol (group 3) or 4x4 treatment without xylitol (group 2) was compared.

[0089] The mice were divided into 3 groups, 7 in each group. Five days after tumor inoculation, the 4x4 group and the 4x4+xylitol group received intraperitoneal injections of corresponding doses (as per the mg / Kg doses shown in Table 1 for each group). The agent containing menadione, cyclophosphamide and diclofenac (= complete combination) is administered twice a week (Sunday and Wednesday) within 4 weeks after inoculation, and during the same period, during the remaining 4 days of the week (Except Saturday) A dose c...

Embodiment 2

[0094] Experiments Demonstrating the Efficacy of Adding Sulfasalazine to Tiltan Formulations

[0095] The term "Tiltan formulation" or "Tiltan" as used here and throughout is the treatment regimen described in Table 1 Group 3 ("4x4"+xylitol; complete combination+xylitol).

[0096] Experiments discussed below show that the addition of sulfasalazine to Tiltan formulations results in enhanced tumor suppression in a murine in vivo model.

[0097] program

[0098] In the following experiments, different drug combinations for inhibiting tumor growth in mice were tested in vivo. The drug combination was compared with the control group (receiving the vehicle containing only the inactive ingredients) and the Tiltan group (receiving the Tiltan drug combination).

[0099] Inoculation: subcutaneously inject 3.5 × 10 5 mouse breast cancer cells (EMT 6 / CTX). Mice were then labeled and grouped.

[0100] Tumor measurements: Tumor dimensions were measured and graphed twice a week. The ...

Embodiment 3

[0120] Case study: Ovarian cancer patient with lung and liver metastases.

[0121] The patient was a 60-year-old ovarian cancer patient with lung and liver metastases.

[0122] Time 0: Ovary with metastatic adenocarcinoma (Stage IV); TAH+BSO

[0123] Time 0+5 months: adjuvant therapy with carboplatin and taxol. Following an increase in CA-125 labeling (see Figure 4), the patient was switched to TiltAn therapy (performance status-0).

[0124] Time 0+30 months: Start TiltAn treatment (50% dose at weeks 1 and 2; 75% dose at weeks 3 and 4; full dose after week 5).

[0125] The 60% aqueous solution of xylitol of 50ml, this aqueous solution contains following reagent:

Cyclophosphamide 400mg

Diclofenac 200mg

Vitamin K 3 140mg

[0126] The 60% aqueous solution of xylitol of 50ml, this aqueous solution contains following reagent:

Vitamin K 3 →140mg

[0127] Results (see Figures 4 and 5 for details):

[0128] Tumor markers: A...

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Abstract

The present invention relates to the surprising discovery that agents that increase intracellular accumulation of NADH + H<+> enhance the anti-cancer effects of angiogenesis inhibitors. Furthermore, treatment of a mammal with a combination of at least one angiogenesis inhibitor and at least one agent that enhances intracellular accumulation of NADH + H<+> allows for the enhanced treatment and / or prevention of ,angiogenic diseases and disorders.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit under 35 U.S.C. 119(e) of US Provisional Application No. 60 / 616,348, filed October 6, 2004, which is hereby incorporated by reference in its entirety. Background technique [0003] Cancer generally refers to one of a group of more than 100 diseases caused by uncontrolled, abnormal growth of cells that can spread to adjacent tissues or other parts of the body. Cancer cells can form solid tumors, where the cancer cells are clustered together, or exist as scattered cells, such as in leukemia. Normal cells divide until they reach maturity and then only when needed to replace damaged or dead cells. Cancer cells are often called "malignant" because they divide endlessly, eventually crowding out nearby cells and spreading to other parts of the body. The propensity of cancer cells to spread from one organ to other organs, or from one part of the body to other parts, distinguishes them from b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K47/00
CPCA61K45/06A61P17/06A61P19/02A61P27/02A61P3/00A61P35/00
Inventor 什姆埃尔·A·本-萨松
Owner TILTAN PHARMA LTD
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