DE2619686C2 - Use of a lysolecithin for tumor treatment - Google Patents

Description

for the treatment of tumors.

The invention relates to the use of a compound of the lysolecithin type for the treatment of tumors.

The use of of synthetic lysolecithin compounds to increase the resistance of the organism and as a 25 immunological adjuvants are described.

It is also known that lysophosphatides, as the lysolecithin analogs can also be called, increase phagocytosis of peritoneal macrophages. It also occurs after injection of lysophosphatides for the formation of activated cells, which are able to increase the body's resistance to harmful influences.

30 It has now surprisingly been found that the lysolecithin compound of the general formula I is a special one Effectiveness on the growth of tumors.

The invention therefore relates to the use of the compound

- O— (CH ₂ ), 7 — CH ₃ (I)

35 I.

HC-O-CH ₃

⁴⁰ H ₂ CO-P-O-CH ₂ -CH ₂ -N (CH ₃ ) ₃

Ο ^θ

45 for the treatment of tumors.

This compound is called ET-18-OCH ₃ .

The compound of the formula I can be prepared in one of the ways described in the literature, for example after:

so Arnold, D., Weitzien, H. U. and O. Westphal:

"About the synthesis of lysolecithins and their ether analogues". Liebigs Ann. Chem. 709, 234-239 (1967);

Weitzien, H. U. and O. Westphal:

"O-Methylated and O-Acetylated Lysolecithins" Liebigs Ann. Chem. 709: 240-243 (1967);
55 Eibl, H. and O. Westphal:

»Palmitoyl-propanediol- (1,3) -phosphorylcholine (2-deoxylysolecithin) - and oxy-alkanediol analogues« Liebigs Ann. Chem. 709: 244-247 (1967).

The effectiveness of the compound of general formula I on the growth of tumors is expedient 60 demonstrated on tumors in test animals. Various experimental tumors are used for this, for example Ehrlich's ascites tumor, a methylcholanthrene-induced tumor and a myeloma tumor in mice, as well as a chemically induced rat tumor.

The antitumor substance is administered parenterally into the tumor-bearing test animals. Is preferred intra-venous and intra- or subcutaneous application. Oral applicability is also corresponding 65 higher dosage of the anti-tumor agent and with a physiologically compatible preparation, e.g. B. in capsules not excluded.

In the case of parenteral administration, the dosage has proven to be expedient, about 0.05 to 5 mg / kg To use body weight.

In a low concentration, the compound according to the invention leads to a reduction in the rate of growth of the tumors. In medium concentrations, the tumors often come to regression. To Regression of the tumors, the test animals show a specific resistance to the test Re-implant tumor of the same type. The tumor no longer grows. About the anti-tumor drugs To let it persist in the circulatory system for a long time, it often makes sense to use the remedy daily or every 2-3 days To apply distances.

The following test examples show the effectiveness of the use according to the invention of ET-18-OCH:

Experimental example 1

Mice with Ehrlich Ascites Carcinoma cells (see Tab. 1) were infected on the 7th day after tumor inoculation the anti-tumor binding ET-I8-OCH3 treated intravenously.

The survival rate of the mice was determined, originally with a different number of Tumor cells were inoculated intraperitoneally. Table 1 shows the test result and the dependency the efficacy of the anti-Tiimormittel ET-I8-OCH3 from the daily intravenous dose as a ratio of surviving animals to the total number.

Table 1

Daily doses Number of tumor cells applied to inoculate the tumor

of ET-I8-OCH3 per mouse

per 20 g mouse, _χ , _n3 1 χ ίο ⁴ 5 X 10 "1 χ ΙΟ ⁵ 5 χ 10 ^s

1 μg

100 µg

control

(without ET-I8-OC3)

0/5 *)

0/5

0/5

0/5

3/5 1/5 3/5

0/5

*) Survivors / total number of test animals.

3/5 1/5 2/5

0/5

3/5
1/5
3/5

0/5

1/5
1/5
1/5

0/5

Comparative example 2

By intravenous injection of ET-18-OH (see formula II, in which OCH _{3 is} replaced by OH), the growth of methylcholanthrene-induced tumor cells in (Balb / c X C57bl / 6) _{F |} Mice are controlled. The following table shows the possibility of varying the start of treatment over several days after tumor inoculation. With an appropriate dose of the anti-tumor agent, the ratio of the surviving number of test animals to the total number is always more favorable than in the case of the untreated control animals, none of which survived.

Table 2 shows the survival rate of the animals at the start of treatment in stages. The intravenous application of the anti-tumor agent was done daily for 14 days.

Table 2

begin the
treatment
during the day

Dose of ET-18-OH / 20g mouse

1 µg 10 µg 100 µg

+ 1 2/5 *) 3/5 4/5 +3 3/5 3/5 2/5 +5 3/5 4/5 3/5 +7 2/5 1/5 3/5 +9 3/5 2/5 4/5 Control 0/5 *) Survivors / total number of Laboratory animals.

A comparable test result is obtained if ET-I8-OCH3 was injected intracutaneously.

Comparative example 3

5 X 10 ⁴ myeloma tumor cells (Potter x 5563) were inoculated subcutaneously into C3H mice. The mice were then treated with the anti-tumor agent ET-I8-OCH3 by applying 10 μg / 20 g mouse

5 26 19 686 Survivors /
Total number
of the laboratory animals 10
15th carried out intracutaneously at a location remote from the tumor for 14 days. Table 3 below shows the results
Benefit rate of the test animals as a function of the start of treatment with the anti-tumor agent. 4/5
3/5
3/5
1/5
0/5 20th Table 3 25th Deginned the treatment on the table 30th + 1
+ 7
+11
+ 15
Control (without ET-18-OCHj) 35 I. 40 I. 45 50 55 60

Claims (1)

Claim:
Using the connection 5 H ₂ CO- (CH ₂ ) H-CH ₃ _ (1) HCO-CH ₃
O 10 Il H ₂ COPO-CH ₂ -CH ₂ -N (CHj) ₃
Ο ^θ