Antitumoral terpenoid pharmaceutical composition 'ABISILIN' exhibiting angiogenesis-inhibiting action

An angiogenesis and composition technology, which can be used in anti-tumor drugs, drug combinations, cardiovascular system diseases, etc., and can solve problems such as toxicity, loss of multiple activities of drugs, and low efficacy.

Inactive Publication Date: 2011-04-27
伊尼蒂雅姆-医药有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] The above-mentioned compounds prepared by the methods described above have the following disadvantages: a certain degree of toxicity, which is inherent to all drugs (causing neutropenia, fibrous neutropenia, infection, vomiting, diarrhea, stomatitis, weakness , neurological (motor) and blood complications, etc.) and low efficacy, these shortcomings force oncologists to look for combinations of these angiogenesis inhibitors with other active agents to provide more effective treatment
[0018] These disadvantages of prior art anti-angiogenic terpenoid drugs may originate from the multi-step protocols proposed for their preparation aimed at the individual active substances in isolated pure form based on partial or complete synthesis, which favors various types of toxicity reveal, and deprive the drug of essential multiple activities

Method used

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  • Antitumoral terpenoid pharmaceutical composition 'ABISILIN' exhibiting angiogenesis-inhibiting action
  • Antitumoral terpenoid pharmaceutical composition 'ABISILIN' exhibiting angiogenesis-inhibiting action
  • Antitumoral terpenoid pharmaceutical composition 'ABISILIN' exhibiting angiogenesis-inhibiting action

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] In the determination of acute toxicity, no deaths of animals were observed at the maximum possible dose of 10000 mg / kg, which makes it possible to classify the drug in substance hazard category IV according to Russian state standard (GOST) 12.1.007-76 .

[0055] Subchronic experiments were performed on non-pedigree male and female rats with mean body weights of 165±3 grams and 163±3 grams, respectively. The study drugs were administered intragastrically once daily for 14 days at doses of 100, 500 or 1000 mg / kg for male rats and 100 and 1000 mg / kg for female rats.

[0056] According to the experimental results, the studied doses of Abisilin have significant effects on the overall indicators of experimental animals (weight gain, behavioral response, food and water intake); peripheral blood cell composition; liver excretion, absorption, protein synthesis and carbohydrate function; serum Cholesterol levels; and cardiovascular, excretory, and neurological functional status ...

Embodiment 2

[0060] Cytotoxic and programmed cell death-inducing activities of Abisilin on tumor cells

[0061] In vitro studies were performed on the following tumor cell lines: Jurkat (T-cell lymphocytic leukemia), Raji (B-cell leukemia), K562 (chronic myeloid leukemia), U937 (myeloid leukemia), Mel P (melanoma) , T 47 D (breast cancer), SKOV-3 (ovarian cancer) and PC-3 (prostate cancer).

[0062] Incubate the above cell lines at 37°C and CO 2 Grow in complete RPMI-1640 medium containing 10% fetal bovine serum, 2 mM / mL glutamine, 0.1 mg / mL gentamicin, vitamins, sodium pyruvate, and amino acids in atmosphere.

[0063] In the study, Abisilin was used at the following concentrations: 300 μg / mL, 500 μg / mL, 800 μg / mL and 1000 μg / mL. 1% DMSO (dimethylsulfoxide) was used as diluent.

[0064] The cytotoxic activity of Abisilin was determined colorimetrically using the MTT assay. will be 5×10 4 Tumor cells at a concentration of 3 cells / ml were inoculated on a Saarsted flat-bottom 96-well pla...

Embodiment 3

[0083] Antitumor activity of oral pharmaceutical composition Abisilin in transplantable tumors

[0084] The antitumor activity of Abisilin was studied on mouse transplantable tumors included in the list of mandatory animal tumor models for screening new antitumor substances, namely: melanoma B-16, epidermoid Lewis lung cancer (LLC), breast cancer Ca-755, stage 5 cervical cancer CC-5, colon adenocarcinoma (CAC) and pleomorphic cell sarcoma M-1.

[0085] The experimental animals were BDF (C BI / 6×DBA / 2) and F (C D1 / 6 and CBA / 2) first-generation hybrid mice; CBA / 2, BALB / c and DBA / 2 strain mice (male and female), the body weight of each animal is 20-25 grams; and non-purebred pedigree female rats, the body weight of each animal is 200-250 grams. Mice and rats were purchased from the Experimental Animal Division of the Blokhin Russian Oncologic Center, the Russian Academy of Medicinal Sciences, and fed normal food rations.

[0086] Abisilin was administered orally (orally) as an o...

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Abstract

The invention relates to medicine and the chemical and pharmaceutical industry and to agents for treating diseases caused by angiogenesis regulation disorders, in particular to a method for treating oncological diseases of different genesis by inducing angiogenesis inhibition which is secondary to the direct antitumoral, anti-reccurant and anti-metastatic action as well as by the associated activation of the apoptosis endogenous system. The invention uses a novel peroral medicinal form 'Abisilin', comprising ingredients relating to the class of natural terpene compounds (isoprenoids), produced from coniferous threes of a Pinaceae family, which medicinal form contains: sesquiterpenoids (3-6%), neutral diterpenoids (11-15%), diterpene acids (22-28%), triterpene acids (8-16%), unsaturated and saturated fatty acids (0.1-0.3%), phenolic compounds (0.1-0.2%), monoterpenoids being the rest, wherein the bornyl acetate content is equal to not less that 10.0% of the total terpene composition. It is expected that the use of the novel peroral medicinal form 'Abisilin', the substance of which exhibits immunomodulating, antibacterial, antiinflammatory, anesthetic, wound-healing and other pharmacologically-significant actions, is free of contra-indications and toxic effects and can be used together with different agents, provides a novel therapeutic approach and enhances the efficiency of treatment of oncological and many other diseases caused by angiogenesis process disorders.

Description

technical field [0001] The present invention relates to the medical, chemical and pharmaceutical industries, and in particular to the development of antineoplastic agents for the treatment of neoplastic diseases of various origins by inducing a cascade of antineoplastic processes, including through the use of non-toxic multiple active agents that induce these processes, i.e. based on Abisilin, a pharmaceutical composition for oral administration of terpenes (isoprenoids) of coniferous trees, inhibits angiogenesis, induces endogenous programmed cell death, slows down tumor cell proliferation, and activates anti-relapse and anti-metastasis effects, so The composition comprises the following components: monoterpenoids, sesquiterpenoids, neutral diterpenoids, diterpene acids, triterpene acids, phenolic compounds and unsaturated and saturated fatty acids. [0002] Furthermore, the present invention can be used in the treatment of various diseases associated with disorders of angiog...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K36/15A61P35/00A61K31/125
CPCA61K36/15A61K31/125A61P35/00A61P35/04A61P43/00A61P9/14
Inventor N·M·皮尼吉娜L·A·莱特瑟鲁斯A·U·巴利辛尼科夫F·I·马加诺娃A·M·科兹洛夫Z·S·斯米尔诺夫娜
Owner 伊尼蒂雅姆-医药有限责任公司
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