DE1237730B - Process for the manufacture of an anti-cancer agent - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

Int. Cl .:

A 61k -

GERMAN

PATENT OFFICE

EDITORIAL

German KL: 30 h-2/36

Number. 1237 730

File number: L 47339IV a / 30 h

Filing date: March 19, 1964

Carcassing day: March 30, 1967

The known treatment of malignant growth is essentially limited to Surgery, radiation and the use of chemotherapeutic agents. The operation brings Successes mostly only in the early stages of the disease. The treatment results of radiation therapy are largely unsatisfactory because the healthy tissue is also damaged and the cancerous tissue are partly radiation-resistant. The cytostatic substances, on the other hand, are also cytotoxic, which primarily results in damage to blood formation.

It is known that heparin inhibits the growth of sarcoma cells in vitro. It is further known that heparinoids (mucopolysaccharide polysulfuric acid ester) with simultaneous administration of dextran im Animal experiments inhibit benzopyrene sarcomas and even cause a regression, but only with intratumoral ones Use. However, the heparinoids are liver-damaging and inhibit blood clots tion (see Klinische Wochenschrift, 40th year [1962], p. 542).

It has now been found that you can make a new anti-cancer agent if you Connective tissue cells in the form of fresh cells, cells obtained in tissue culture, frozen or Freeze-dried cells resuspended in isotonic solution and resuspended with heparin and converts dextran.

With the product produced according to the invention, not only cancer-inhibiting, but also cancer-inhibiting ones are achieved cancer-healing effects.

The claimed process creates a new product, which is evident from the fact that the reaction product by conventional methods such as ultracentrifugation, treatment with organic solvents or column chromatography, not separated again into its starting components can be. Another indication of the emergence of a new product is the potentiation of the thera- ♦ <> therapeutic effect. The effect of the product produced according to the invention is namely greater than the sum of the effects of the starting products. For example, if you give the three in animal experiments Starting compounds of the same animal at the same time, but separately, it becomes a considerably lower anti-cancer one and has no cancer-curing effect at all.

In particular, fetal connective tissue cells, preferably from the above, are used as connective tissue cells Umbilical cord, into consideration. The production of connective tissue cells is known. Heparin is a commercially available one

Method of making a
Anticancer agent

Applicant:

Dr. med. Albert Landsberger,

Heidelberg, Görrestr. 67;

Dr. med. Joachim Stein, Heidelberg, Bergstr. 55

Named as inventor:

Dr. med. Albert Landsberger,

Dr. med. Joachim Stein, Heidelberg

accessible product. The polysaccharide dextran is also commercially available.

The process conditions are not critical. If you use freeze-dried connective tissue cells If cells are used, the suspension time in isotonic solution is for rewetting about 10 minutes before adding the heparin and polysaccharide. Generally will both the floating of the connective tissue cells and the mixing of the cells with the rest both components made at about room temperature.

The starting products are preferably in a ratio of 0.04 to 0.07 g, especially 0.05 g, des Polysaccharides to 400 to 1000, in particular 500 to 800, international units of heparin 3 to 8 mg, in particular 3 to 5 mg, of the fresh cells (calculated as dry matter) are used.

20 rats with benzpyrene sarcomas were treated according to the invention from fetal connective tissue cells, Heparin and Dextran manufactured product treated as follows:

The product of 3 to 5 mg of connective tissue cells, 500 IU of heparin and 0.05 g dextran, suspended in isotonic solution. This product was total for every animal injected subcutaneously twelve times at an interval of 14 days each time.

The associated 20 control animals died up to the 179th day after the benzopyrene injection. All Animals had tumors the size of a walnut to lemon; in 40% of the cases it was also metastatic Watch growth.

Of the 20 treated animals, they were still alive on the 179th day after the benzopyrene injection

709 547/370

10 animals (= 50%). Of these 10, 7 animals were tumor-free, 3 animals only had the size of a hazelnut Tumors. On the 790th day (the lifespan of laboratory rats is around 750 to 850 days) 5 tumor-free animals lived (= 25 · / »). Of the 7 rats that showed no tumor on the 179th day, Two died of a relapse between the 580th and 600th days.

To check these results, the tests were repeated with the slight change, that the 20 animals received not 12, but 14 injections at an interval of about 8 days. The dose stayed the same. The associated control animals died in this experiment up to 198th day. Of the 20 rats treated, 14 animals (= 70%) were still alive. On the 480th day after the Benzpyrene injection, 7 animals (= 35 * / o) still lived tumor-free. 7 animals had previously relapsed died.

In both experiments it was shown that - both in those animals in which the tumor in its growth was strongly inhibited, as well as in the rats, in which tumor inhibition did not occur - no metastases were found by dissection.

The products produced according to the invention are harmless. Neither in living animals nor in histological ones Investigations revealed any changes in parenchymal organs in the Toxic damage can be observed.

The successes in animal experiments described after using commercially available cytostatics

mice and rats are limited to vaccine tumors. With experimentally generated Irritable tumors, e.g. B. by dimethyl nitrosamine, butter yellow, methyl cholanthrene + 3,4-benzopyrene, a cure could not be achieved in a single case with known cystostatics. Inhibitions to growth could not be proven with certainty either.

example

50 mg of lyophilized connective tissue cells are taken from the umbilical cord of the sheep, washed in 10 ml Tyrode solution (see. Pschyrembel, Clinical Dictionary, 61st to 84th edition, p. 747) on and promotes rewetting of the dry cells by gently swirling for 10 minutes. Afterward add 5000 international units of heparin, shake again and then add 5 g of T. Add 10% dextran solution.

All work processes are carried out under sterile conditions.

The product produced in this way is intended as a single dose for ten animals suffering from tumors.

Claims (1)

Claim: Process for the production of an anti-cancer agent, characterized in that that connective tissue cells in the form of fresh cells, cells obtained in tissue culture, are frozen or freeze-dried cells in isotonic solution and the suspension reacts with heparin and dextran.