RU2311917C2 - Composition for treatment and prophylaxis of oncological disease - Google Patents

Abstract

FIELD: medicine, oncology, phytotherapy, chemical-pharmaceutical industry.

SUBSTANCE: invention relates to an agent used for strengthening the immune system of body and prophylaxis of oncological diseases. The composition comprises spotted milk thistle fruits extract (Sylibum marianum (L.) Gaerth), purple coneflower roots and herb extract (Echinacea purpurea L.) and/or oblique sponk extract (Inonotus obliquus (Pers) Pil.) and accessory substances taken in the definite ratio. The composition can be prepared in form of tablet, solid or soft gelatin capsule, liquid infusion and liposomal forms. The composition can comprise starch, aqueous-alcoholic syrup, lactose, magnesium stearate, lecithin, phospholipids in form of liposomes as accessory substances. After intake dosing the composition shows the positive effect on enhancing resistance to unfavorable factors of environment, treatment and prophylaxis of oncological diseases.

EFFECT: valuable medicinal properties of composition.

2 cl, 5 tbl, 3 ex

Description

The invention relates to food industry and medicine, and more specifically relates to a means for the treatment and prevention of cancer, strengthening the body's immune system.

Known means for the prevention of diseases of the oncological and non-oncological profile and for the correction of disorders of homeostasis caused by oxidative stress (US Pat. RF No. 2208446). The product is a dry water-alcohol extract of individual plants selected from the group consisting of geranium, plantain, calendula, shrubby cinquefoil (Kuril tea) and angelica (angelica), or mixtures thereof.

Known means based on plant materials (US Pat. RF No. 2164146) for the rehabilitation of patients with cancer, as well as for the restoration of body functions after surgery, for the prevention and correction of functional disorders and diseases associated with exposure to stress and exhausting external factors environment, ionizing and radiation radiation. The tool is divided into 2 doses for a single dose (morning and evening), containing Rhodiola rosea, licorice and peony in various combinations, while the morning and evening doses are tabletted separately.

A biologically active food supplement is also known to strengthen the body's immune system (US Pat. RF No. 2176895). The dietary supplement contains water-alcohol extracts of marigold flowers, dill seeds, blackcurrant leaves, sage, noble laurel, tarragon grass, hyssop, hairy hawks, lycopodium spores, blood-red geranium root, and the supplement may also contain menthol alcohol and rose oil.

A known composition of ingredients for producing an elixir containing aronia chokeberry, rose hips, linden flowers, wormwood grass, chaga, black pepper, nutmeg, nettle leaves, prune fruits, propolis, aloe juice, bee honey, ginseng roots, echinacea grass , marjoram grass, hawthorn fruit, incense rhizomes, St. John's wort grass, dried grapes, sugar, ethyl alcohol. The elixir has an adaptogenic and restorative effect during intense and prolonged neuropsychological and physical exertion. The elixir is also indicated for prophylactic purposes at the first sign of colds (US Pat. RF 2233168).

The closest invention to the proposed technical solution relates to a tool having a radioprotective effect based on plant materials, containing the seeds of milk thistle and a mixture of medicinal plants, namely the seeds of flax and oats, chitosan. In addition, the tool contains auxiliary substances (US Pat. RF 2187325). The drug has a restorative, tonic effect. It contributes to the successful treatment and prevention of a number of chronic diseases: ulcer, cholecystitis, is a preventive measure in conditions of environmental distress in industrial areas

The disadvantages of the above funds and dietary supplements include their complexity and multicomponent nature, which may be a risk factor for side effects when using the drug, as well as differences in the composition of the funds for administration at different times of the day.

The objective of the present invention is to provide a comprehensive, cheap, characterized by simplicity and manufacturability of obtaining funds for the treatment and prevention of cancer based on a small number of components of natural raw materials.

The problem is solved through the use of a composition comprising an extract of the fruits of milk thistle (Silybum marianum (L.) Gaertn) with extracts of medicinal plants with immunomodulating and antitumor effects. As such additional extracts, it is proposed to use the extract of roots and grass of Echinacea purpurea (Echinacea purpurea L.) and / or chaga extract (oblique tinder, Inonotus obliquus (Pers.) Pil.) Taken in the following ratios, wt.%:

Milk thistle extract 20-56 Echinacea Extract 30-70 Chaga extract 10-70 Excipients The rest is up to 100%

The proposed composition can be made in the form of tablets, hard or soft gelatin capsules, liquid infusions, liposome forms. The composition may contain as auxiliary substances, for example, starch, water-alcohol syrup, milk sugar, magnesium stearate, lecithin, phospholipids in the form of liposomes.

Milk thistle fruit extract contains silymarin - a mixture of flavonoids silibinin, silidianin and silicristine. This drug is distinguished by its availability, lack of toxicity and high antitumor activity. Recently, experimental data have appeared that indicate the high antioxidant activity of silymarin, which makes the thistle flavonoids spotted very attractive from the point of view of creating drugs not only for the treatment of cancer, but also for their prevention.

Echinacea purpurea extract contains a large number of biologically active substances - flavonoids, glucosides, rutin, anthocyanins, tannins of the pyrocatechol group and organic acids (coffee, quinic and tartaric), lectins, betaine, glycine, alkaloids. The main active substances with immunostimulating activity are Echinacea polysaccharides, as well as essential oils.

Chaga extract also contains substances with antioxidant, immunostimulating and antitumor activity polyphenols, triterpenoids, resins, agarcinic acid, flavonoid inotodion, alkaloids, polysaccharides, sterols - as well as a large number of trace elements.

The proposed composition has a high antioxidant activity, detoxifying and anticarcinogenic effects due to the unique composition of biologically active substances with a wide spectrum of action, which makes it possible to use it as an effective tool for the prevention of cancer and other pathologies associated with a weakening of the functional state of the immune system caused by chronic inflammatory diseases exposure to ionizing radiation, ultraviolet rays, chemotherapists toxic drugs, long-term antibiotic therapy.

The invention is confirmed by the following examples.

Example 1. Preventive effect of the composition against tumor growth.

Extract 1 - extract of the fruits of milk thistle.

Extract 2 - extract of the roots and herbs of Echinacea purpurea.

Extract 3 - chaga extract.

Test mixes.

Extract 1 (45%) + Extract 2 (45%) + auxiliary things. (10%).

Extract 1 (45%) + Extract 3 (45%) + auxiliary things. (10%).

Extract 1 (45%) + Extract 2 (30%) + Extract 3 (15%) + auxiliary things. (10%).

Pharmaceutical compositions with a different combination of components taken in equal proportions were administered orally to intact C57BI / 6 mice for 2 months. Physical animals were given to control animals daily. solution according to the same scheme. 1 month after the start of taking the drugs, the mice were injected subcutaneously with tumor cells of B16 melanoma. At the end of the course of taking the drugs, the prophylactic and antitumor effects were evaluated, using the frequency of cases of tumors and the death of experimental animals as evaluation criteria. The experimental results are shown in table 1.

Table 1 No. Composition The number of animals in the group The number of cases of tumors The number of deaths 2 months after the start of the experiment one Fiz. solution (control) 10 10 10 2 Extract 1 10 7 5 3 Extract 2 10 10 8 four Extract 3 10 8 5 5 Extract 1 + Extract 2 10 6 2 6 Extract 1 + Extract 3 10 5 3 7 Extract 1 + Extract 2 + Extract 3 10 3 one

Thus, as a result of the studies, the high prophylactic activity of the proposed compositions (columns 5-7 of the table) with respect to the risk of the onset and development of the tumor, as well as the synergy of the action of correctly selected components of the composition, is shown.

Example 2. The antioxidant effect of the claimed composition.

The synergy effect of the antioxidant effect of the extracts of medicinal plants that make up the composition was determined by the influence of the composition and its individual components on the process of initiated oxidation of the hydrocarbon [Ipatova OM and others, Biomedical chemistry, 2003, No. 2, S. 165-176]. The inhibitory effect of the studied drugs was evaluated by their effect on the duration of the induction period of the oxidation chain reaction. The results of the study are given in table.2.

table 2 A drug The induction period (T), seconds The degree of synergism,% Extract 1 970 - Extract 2 590 - Extract 3 380 - Extract 1 + Extract 2 2640 41 Extract 1 + Extract 3 2380 43 Extract 1 + Extract 2 + Extract 3 3970 51

The degree of synergism was calculated by the formula:

Thus, the combination in the composition of the extract of milk thistle with extracts of echinacea and chaga leads to the manifestation of the biological synergy of the components of the composition.

Example 3. Antitumor activity of the claimed composition

The therapeutic efficacy of the claimed composition was investigated on a model of transplantable subcutaneous mouse Lewis lung carcinoma (3LL). In the experiment, C57BL / 6 mice were used. The tumor was transplanted by subcutaneous injection of 10 ⁶ cells into the armpit. The composition was administered starting from 2 days after tumor inoculation for 10 consecutive days intragastrically through a probe. As an additional control used the individual components of the composition, introduced according to the same scheme.

Tumor growth inhibition (TPO) was evaluated by the following formula:

where V _k and V _o are the average volume of tumors (in mm ³ ) in the control and experimental groups, which was determined for each solid tumor as the product of three mutually perpendicular diameters of the tumor node.

The increase in animal longevity (LLL) was evaluated by the following formula:

where P _about and P _to - the average life expectancy in the experimental and control groups of animals.

The degree of synergism of the action of the components of the composition with respect to increasing the life expectancy of experimental animals was calculated by the formula:

The experimental results are shown in table.3.

Table 3 No. Animal Group / Drug SRW,% UPZH,% The degree of synergism,% 12 day 20 day one Extract 1 23 12 eighteen - 2 Extract 2 6 3 2 - 3 Extract 3 eleven 6 5 - four Extract 1 + Extract 2 32 24 28 28.6 5 Extract 1 + Extract 3 thirty 23 26 11.5 6 Extract 1 + Extract 2 + Extract 3 48 39 41 39.0

From table 3 it is seen that, in contrast to the use of individual extracts of medicinal plants for the treatment of model tumors, their use in the composition of the claimed composition leads to a significant antitumor effect, which is manifested both in terms of inhibiting tumor growth and increasing the life expectancy of treated animals. In addition, the synergism of the action of the components of the composition with respect to increasing the life expectancy of experimental animals has been demonstrated.

The therapeutic efficacy of the claimed composition was investigated on a model of transplantable subcutaneous mouse Lewis lung carcinoma (3LL). In the experiment, C57BL / 6 mice were used. The tumor was transplanted by subcutaneous injection of 10 ⁶ cells into the armpit. The composition was administered starting from 2 days after tumor inoculation for 10 consecutive days intragastrically through a probe. As an additional control used the individual components of the composition, introduced according to the same scheme.

Tumor growth inhibition (TPO) was evaluated by the following formula:

where V _k and V _o are the average volume of tumors (in mm ³ ) in the control and experimental groups, which was determined for each solid tumor as the product of three mutually perpendicular diameters of the tumor node.

The increase in animal longevity (LLL) was evaluated by the following formula:

where P _about and P _to - the average life expectancy in the experimental and control groups of animals.

The experimental results are shown in table 4.

Table 4 No. Animal Group / Drug SRW,% UPZH,% 12 day 20 day one Extract 1 23 12 eighteen 2 Extract 2 6 3 2 3 Extract 3 eleven 6 5 four Extract 1 + Extract 2 32 24 28 5 Extract 1 + Extract 3 thirty 23 26 6 Extract 1 + Extract 2 + Extract 3 48 39 41

From table 4 it is seen that, in contrast to the use of individual extracts of medicinal plants for the treatment of model tumors, their use in the composition of the claimed composition leads to a significant antitumor effect, which is manifested both in terms of inhibiting tumor growth and increasing the life expectancy of treated animals.

Example 4. The protective effect of the composition, reducing toxicity

A study of the specific hepatoprotective activity of the composition was carried out on a model of acute toxic hepatitis in mice. In experiments, white outbred mice were used in adulthood.

The composition was administered intragastrically using a probe in the form of a suspension. A solution of carbon tetrachloride was used as a hepatotropic agent. The composition was administered to animals daily for 6 days before hepatotoxin was administered, and then three more times with an interval of 2 days. As a comparison drug used the composition of the prototype (see table 5). Control animals were administered only hepatotoxin (carbon tetrachloride) and a solvent in equivalent volumes. One day after the last injection, the animals were decapitated and an autopsy and a study of biochemical blood parameters were performed. The activity of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) was determined by the method of Reitman-Frenkel. Total protein was determined using a biuret reagent. The results of the study are given in table.5.

Table 5 No. Animal Group / Drug Relative liver mass * ALAT activity ** ACAT activity ** Total protein ** one Extract 1 130.3 ± 3.9 292.3 ± 9.3 85.1 ± 2.6 75.2 ± 4.8 2 Extract 2 152.6 ± 2.9 460.8 ± 12.3 216.1 ± 11.7 57.0 ± 6.3 3 Extract 3 159.4 ± 8.3 482.0 ± 21.8 223.8 ± 13.2 61.2 ± 7.9 four Extract 1 + Extract 2 118.6 ± 3.2 227.9 ± 13.4 71.3 ± 5.0 84.2 ± 8.8 5 Extract 1 + Extract 3 121.7 ± 4.9 244.6 ± 9.6 76.4 ± 7.3 82.2 ± 7.5 6 Extract 1 + Extract 2 + Extract 3 109.6 ± 2.8 197.3 ± 9.7 64.8 ± 2.3 92.3 ± 5.7 7 Prototype (milk thistle + oats + flax + chitosan + auxiliary things.) 126.1 ± 4.0 264.3 ± 10.9 80.5 ± 3.8 78.9 ± 5.3 * -% of the liver mass of healthy intact animals
** -% of indicators in healthy intact animals

Thus, the use of the proposed composition positively affects the metabolic, metabolic, choleretic and detoxification functions of the liver in case of acute toxic hepatitis. Moreover, although the separately used extracts 2 and 3 have a slightly pronounced activity with respect to the normalization of the studied parameters, their use together with the extract 1 significantly enhances the prophylactic effect of the latter (synergistic action of the components of the composition). In addition, the effect of the use of the composition in all cases exceeds the effect of the composition of the prototype.

Similarly, the compositions shown in table 6 were tested.

Table 6 №№ Milk thistle extract, wt.% Echinacea extract wt.% Chaga extract wt.% Aux. wt.% one twenty 70 10 2 56 10 34 3 40 thirty 25 5 four 25 70 5 5 twenty 40 thirty 10

The results of the study showed that the use of all the studied compositions had a positive effect on increasing the body's resistance to adverse environmental factors, treatment and prevention of cancer. In this case, a small amount of components of natural raw materials was used. The inventive composition is simple and manufacturable.

Claims (2)

1. Composition for the treatment and prevention of cancer, comprising a mixture of the extract of the fruit of Milk Thistle (Silybum marianum (L.) Gaertn) with extracts of medicinal plants and excipients, characterized in that the composition contains an extract of the roots and herbs of Echinacea purpurea as an extract of medicinal plants (Echinacea purpurea L.) and / or chaga extract (oblique tinder, Inonotus obliquus (Pers.) Pil.) In the following ratio, wt.%: milk thistle extract 20-56 echinacea extract 30-70 chaga extract 10-70 Excipients rest 2. The composition according to claim 1, characterized in that it is made in the form of tablets, hard or soft gelatin capsules, liquid infusions, liposome forms.