Anti-tumoral therapy agent containing a contrast agent

Details Anti-tumoral therapy agent containing a contrast agent Anti-tumoral therapy agent containing a contrast agent

2000-06-06

2001-03-27

Hollinden, Gary E. (Department: 1619)

Drug, bio-affecting and body treating compositions

In vivo diagnosis or in vivo testing

Magnetic imaging agent

C424S009400, C424S009430, C424S009450, C424S450000

Reexamination Certificate

active

06207133

ABSTRACT:

This application is a 371 of PCT/DE98/01514 Jun. 4, 1998.
BACKGROUND OF THE INVENTION
The invention relates to a new anti-tumoral therapy agent based on liposome-encapsulated cytostatic agents and/or the metabolites thereof. Fields of application of the invention are pharmaceutical industry and medicine.
A few agents for anti-tumoral therapy are known. In DE 43 41 478 an agent was described which, in particular, may be used for the therapy of non-resectable primary and secondary liver tumours. This agent contains lyophylized starch particles which are combined with one or a few cytostatic agents and dissolved in contrast agents containing iodine, gadolinium and magnetite. A preferred cytostatic agent for this agent is Carboplatin.
SUMMARY OF THE INVENTION
According to 43 41 478 by means of this agent a high concentration of the cytostatic agent used is reached in the tumour to be treated. However, a disadvantage consists in the fact that the residence time in the tumour totals only approx. 4-6 hours which, in general, is not sufficient for a successful therapy.
The aim of the invention is to build up drug targeting to combat cancer through suitable carrier systems. The invention is based on the task to increase distinctly the concentration of cytostatic agents and the residence time in tumours. At the same time, toxic side-effects on the remaining organs are to be reduced.
An essential aspect of the invention is the encapsulation of the cytostatic agents used and/or the metabolites thereof, preferably with PEG liposomes. Furthermore, the use of degradable starch particles resulting in retarding the flow and thus the contact time is of great importance.
The encapsulation of the cytostatic agents is implemented in a way known as such, e.g. by preparing a mixture of hydrogenated phosphatidylcboline, cholesterol, dicetyl phosphate and additionally polyethylene glycol in chloroform and diisopropyl ether.
Object of the invention are also the pharmaceutical preparations of the first component of the agent according to the invention consisting of
a) natural, semisynthetic of fully synthetic amphipathic such as lipid, surface-active agent, emulsifier or polyethylene glycol (PEG) or lipid-PEG,
b) a steroid,
c) a charged lipid component,
d) the cytostatic agent soluble in water or lipid and
e) a carrier liquid and, if necessary, additional auxiliary agents such as e.g. nanoparticles.
The natural, semisynthetic or fully synthetic amphipathic has preferably the general formula I
wherein R
1
, and R
2
=C
10
-C20-alcanoyl, alkenoyl, alkyl, alkenyl.
The steroid has preferably the general formula II
Wherein R=H (cholesterol) or =CH
2
—CH
2
—O—CH
2
—OH (dicholesterol). The charged lipid component is preferably the anion of dicetyl phosphate, palmitic acid, stearic acid, the anion of a phospholipid such as phosphatidylserine, phosphatidic acid or the anion of a sphingolipid such as sulphatide or polyethylene glycol such as MPES-DSPE. Preferred cytostatic agents are Carboplatin, 5-fluorouracil and 5-fluorouridine. The quantity ratios of the components are preferably a:b:c in a molar ratio 1:0.3:0.1 up to 1:1:0.1 or up to 1:1:0.5 and c:d in a molar ration 2:1 up to 10:1.
The advantages of the new agent become visible in application. Compared to the known agents they consist in the essentially higher efficiency which is due to the fact that a higher quantity of the cytostatic agent may be brought into the tumour, staying there for a longer time. The so-called AUC value (“area under the curve”), the residence time and the quantity of the therapeutic agent collected in the tumour are decisive for the therapeutic effect. When applying the agent according to the instant invention this value is distinctly higher than in the case of the agents known, e.g. in the agent according to DE 43 41 478.
FIG. 12
shows e.g. that the AUC of encapsulated 5-fluorouridine has been increased by 417 times as compared with the free compound (when adding degradable starch particles by 4.4 times).
The application regime of the agent according to the instant invention is also of importance. The intra-arterial application results mostly in a strong increase of the AUC. A further advantage essential for the practical application consists in the fact that the agent may be also applied orally.
The invention is explained in greater detail by examples of execution and the following
FIGS. 1
to
13
.


REFERENCES:
patent: 4590060 (1986-05-01), Ehrenfeld
patent: 5213788 (1993-05-01), Ranney
patent: 5213804 (1993-05-01), Martin et al.
patent: 5215680 (1993-06-01), D'Arrigo
patent: 5312617 (1994-05-01), Unger et al.
patent: 5387410 (1995-02-01), Bosworth et al.
patent: 5512294 (1996-04-01), Li et al.
patent: 5582172 (1996-12-01), Papisov et al.
patent: 5620703 (1997-04-01), Reszka et al.
patent: 5705187 (1998-01-01), Unger
patent: 4341478 (1995-06-01), None
patent: 98/44910 (1998-10-01), None

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