DE2343809A1 - MEDICINAL PRODUCTS WITH ANTIGOTUS EFFECT - Google Patents

Description

MEDICINAL PRODUCTS WITH ANTI-GAY EFFECT Priority dated November 17, 1972 USSR No. 1848995

The present invention relates to a medicament - with an antigenic swelling effect, v / elches for treatment various types of "malignant neoplasms, for example chronic leukosis, polyaythaemias, lymphogranuldmatoses, Larynx cancer etc. is determined.

For the treatment of some forms of malignant tumors, remedies are known whose anti-tumoral effects are caused by ß -bromopropionyl residues -pipobroman (Verzyts) or by ß-haloacyl (alkyl) amine groups -sarcolysine, smbichin, novoembichin.

These preparations have a low selectivity of the effect and exert a toxic effect on the organism off, among other things, they strongly suppress blood formation.

The purpose of the present invention is to provide the specified

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To eliminate the disadvantage by developing a remedy that has a selective effect on the tumor tissue and a smaller toxic effect on the organism. In connection with this, a remedy with a

Anti-tumor effect created, according to the invention ^a l ^ß therapeutically effective amount of the active base - 1,2-di (ß - bromopropionylamine) ethane * of the formula BrCH ₂ CH ₂ COHHH ₂ C- -CH ₂ KHCOCH ₂ CH ₂ Br and a pharmaceutical carrier for it contains. -

The a ⁿ given preparation is called indication "Prodimin ¹ *. The active ingredient of the formula given is a white crystalline powder that is insoluble in water.

For ingestion (per os) the preparation is in the form of Tablets are recommended, in which the carrier substance is a pharmaceutical filler, for example sucrose, lactose, sodium chloride, calcium stearate, liagnesium stearate, talc, Represents starch or another suitable filler. In terms of quantity, the content of the active base in the ! Tablets 25 to 100 mg.

The proposed preparation can be taken as a powder, in which the carrier substance is a pharmaceutical one Fillers, for example sodium chloride, lactose and any other suitable filler for powders. The content of the active base in the powder can be in the range from 25 mg to 100 mg.

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For ingestion, a preparation is also recommended in which

the

the carrier substance is the pharmaceutical solvent Represents mixture consisting of twin 80 and castor oil. Included the content of the active base is 25 to 100 ng

The anti-tumor activity of prodimine is found in rats and mice with over-vaccinated tumors were examined. The following tumor strains were used:

Eat ten sarcoma 45, Jansen's sarcoma, sarcoma M-I, sarcoma 556 »Alveolar Cell Carcinoma FiS-I;

on mouse sarcoma 180, sarcoma AEC, carcinoma HK, Garding-Passy - melanoma.

Data on the influence of prodimine on the growth of vaccinated rat and lice neoplasms after injections are given in the table.

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Animal species Tumor-
tribe. Beginning
d.Handl. Dose,
mg / kg number
tions 6th Change of the
Animal weight:
Vers. Contr. 8th 1 CVJ 3 4th 5 98 7th +16 Bat te Jenson's sarcoma 24 hours 85 6th 77 +16 +16 ditto ditto 24 hours 43 6th 97 +12 +12 ditto ditto 5 days 125 7th 91 +17 -4 ditto ■ ditto 5 days 90 6th 68 +7 +2 ditto Sarcoma M-I 5 days 80 6th -14

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Aas the table it is apparent that the Prod imines inn ah 'me a significant anti-tumor effect in relation to a series of rat tumors causes. The use of the preparation in the maximum tolerable dose (125 to 85 mg / kg /) causes a significant slowdown in the growth of Jensen's sarcoma (by 98%) and alveolar cell carcinoma R3-1 (by 92%) .

A moderate growth rate is acceptable when using the? Dose observed in rats with the sarcoma MI (around 68%), the sarcoma 45 (around 41%); In maximally tolerated doses (119 to 75 μg / kg), the preparation brought about a slowdown in the growth of sarcoma 180 (by 72%), sarcoma AK (by 62%) and carcinoma HK (by 51%).

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In a comparative study of the proposed

Preparation with the well-known Pipobroman, it has been shown that

the latter in the therapeutic dose has the same size as the antigenic tumor activity as the proposed preparation. The new drug is less toxic but, its average death dose (LD ™) is for mice with a single injection 544 mg / kg, while / kg for Pipobroman LDc ₀ ^ ^ei single injection for mice 225 mg.

The proposed according to the invention: suppressed preparation in tolerable doses the leukopoiesis with predominant ver. termination of granulocytopoiesis.

In this way, the proposed preparation has a small toxicity, has a wide range of Aotigesch «uls> effect, suppresses leukopoiesis in tolerable doses with a predominant effect on granulocytopoiesis. All of that is there The reason for it is in malignant neoplasms, including chronic leukosis, polycythemia, lymphogranulomatosis and cancer of the larynx to try

Prodimin is recommended in clinical settings for ingestion (per os) in tablets; treatment must begin with the daily intake of the preparation at a dose of 25 mg / kg, then the dose can be gradually increased to 50.75.100 mg and more if well tolerated . A total of 750 to 1000 mg (O _f 75 to 1 g) of the preparation is recommended for one treatment.

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The proposed preparation is supplied in capsules of 0.025 and 0.05 g each. It should be kept in a cool place.

One of the advantages of the proposed preparation is there in that it is easy to obtain and is produced in the following way

A mixture of 40 ml of methylene chloride, 16.7% of sodium hydrogen carbonate and 4.27 g of 70% 1,2-ethylenedlamine are used a solution of 25 * 7 g ß-bromopropionyl chloride with vigorous stirring in 50 ml of methylene chloride at such a rate, that the mixture temperature does not exceed 15 ° C. At this temperature, the reaction mixture obtained is in the course of Mixed for 8 hours. The precipitate that has separated out is filtered, cleaned of inorganic salts with water and dried to constant weight.

11.5 g (70%) of 1,2-di (β-bromopropionylamine) ethane, melting point 181 to 185 ° (from alcohol) are obtained. Is composition, ^ C 29, J4; H 4.35; Ν 8.61; Br 48.41. C ₈

Target composition,% C 29 »H; H 4 ·, 25; N 8.48; Br 48.45

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Claims (1)

- 9 PATENT CLAIMS: 1. Medicines with an anti-tumor effect, thereby. characterized as being a therapeutically effective amount of an active basis l, 2-Di (ß-b * ompropionylamin) ethane of the formula Bi ^ H ₂ CH ₂ COMCH ₂ -CH ₂ NHGOCH ₂ CH ₂ Br and a pharmaceutical carrier substance for it contains « 2 «Medicament according to claim 1, characterized in that it is a carrier substance contains pharmaceutical filler for tablets 3 «Medicament according to claim 1 or 2, characterized labeled that it contains sucrose as a filler, Lactose, sodium chloride, calcium stearate, magnesium stearate, Contains talc, or starch. 4. Medicament according to claim 1 ^ 3 »characterized in that that it contains 25 to 100 mg of active basis « 5 · Medicament according to claim 1, characterized thereby It is believed to contain a pharmaceutical filler for powder. 6. Medicament according to claim 1 and 5, characterized known that it contains lactose as a filler, Contains sucrose or sodium chloride. 409823/1097 7. Medicament according to claim. l _t 5 and 6, characterized geJcennze without i t that it contains 25 to 100 mg of active basis. 8. Medicament according to claim 1, characterized in that that it contains a pharmaceutical solvent as a carrier substance 9 · A pharmaceutical composition according to claim 1 and 8 characterized gekennze _t iohnet that it contains solvent consisting of twin-80 and castor oil. 10. Medicines. Claim . 1,8 and 9 _t aaduroh indicated that it contains 25 to 100 mg of active foundation. 409823/1097 \