RU2116798C1 - Agent "fucus" for cancer prophylaxis - Google Patents

Abstract

FIELD: medicine, oncology. SUBSTANCE: proposed agent has an extract of plant bladder wrack (Fucus) obtained by alkaline hydrolysis of plant biomass at concentration from 0.2 to 100%, acceptable additional agents and inert vehicles. Agent "Fucus" suppresses effectively onset and development of breast and large bowel cancer. EFFECT: enhanced effectiveness of an agent proposed. 1 cl, 6 ex, 4 tbl

Description

 The invention relates to medicine, namely to preventive oncology.

 It is known to use beta-carotene obtained from plant materials as an oncological prophylaxis, which is able to inhibit the development of malignant tumors of certain localizations (Mathews-Roth MM Beta-carotene, canthaxanthin, and phytoene // In: Nutrition and Cancer Prevention. Ed by TE Moon, MS Micozzi. - New York and Basel: M. Dekker, Inc. 1989, P. 273-290). Known means for the prevention of malignant neoplasms "Fitolon" and "Fitolon-M" based on chlorophyll derivatives obtained from brown seaweed saccharose kelp (patent N 2031654, class A 61 K 35/80, 31/40, from 05/18/93, publ. BI N 9 of 03/27/95).

 The closest in its action to the present invention is the "Means for the prevention of cancer" Klamin ", obtained on the basis of brown seaweed kelp sugary (patent N 2034560, class A 61 K 35/80, from 05/18/93, publ. BI from 10.05 .95).

 However, preventive oncology needs new oncological prophylactics. In addition, the amount of produced Klamin tablet dietary supplement is constrained by the capacity of the algal plant producing the substance, as a result, the amount of Klamin produced is clearly not enough.

 The aim of the invention is to expand the range of products and food additives from seaweed with oncological prophylactic effect.

 This goal is achieved in that the agent for the prevention of cancer "Fucus" contains a fucus extract (EF) obtained from vesiculus fucus (Fucus vesiculosus), as well as, if necessary, physiologically acceptable excipients and excipients used for the preparation of dosage forms.

 As is known, bubbly fucus is one of the varieties of edible brown algae that is widely used in homeopathic practice. It is used in homeopathy for iodine deficiency, hypothyroidism, obesity, constipation, and also for the treatment of nodular goiter (Keller G. Homeopathy, trans. With it., 5th edition / Freiburg 1983). In modern medicine, the possibilities of using biologically active substances of the Fucus algae for the prevention and treatment of various diseases are being studied. For example, polysaccharides and polyphenols of Fucus vesiculus revealed antiviral activity against the AIDS virus (Beress A., Wassermann O., Bruhn T., Beress L. A new procedure for the isolation of anti-HIV compounds (polysaccharides and polyphenols) from the marine alga Fucus vesiculosus // J. Nat. Prod., 1993, Vol. 56, P. 478 - 488). The use of Fucus vesiculus or EF for a new purpose - as an oncoprophylactic agent is not known and is new.

EF is obtained from Fucus vesiculata White Sea by water-soda extraction at the Arkhangelsk algae plant. The extraction of air-dried algae is carried out with hot water at a temperature of 60 ± 5 ^o C in a ratio of 1: 20 (to the mass of algae), soda ash in an amount of 1.0 to 1.5 wt. %, after which algae is boiled in this solution for 4 - 5 hours, the solution is filtered, evaporated and dried. Dried under pressure of 0.19 ± 0.01 MPa or 1.9 ± 0.1 ct / kg. Mass fraction of water in dried EF should be no more than 18%. The dried EF film is crushed to powder. Alkaline hydrolysis of algae is possible.

 The resulting product contains TU 15-02-009-08-94 "Fucus extract", intended for use as a bioactive additive in the perfumery and cosmetics industry.

 Appearance: EF is a dark brown powder, highly soluble in water. Composition: water content - not more than 18%, ash to dry product - not more than 30%, when 1% solution is dissolved in water - pH 8 - 12. Fucus extract has a hygienic certificate N 43 dated 09.09.94 of the Arkhangelsk regional center State Sanitary and Epidemiological Surveillance.

 EF contains substances such as polysaccharides, fucosterols, amino acids, carbohydrates, lipids, minerals, including iodine, B vitamins, vitamin C. The rich mineral composition of fucus algae differs from other brown algae in its high zinc content, since these algae are capable of extract and store zinc from water. The composition Fucus includes a number of natural anticarcinogenic substances, such as, for example, fucoidan polysaccharide, fucosterols, omega-3 polyunsaturated fatty acids, and trace elements. Fucosterols, which are part of the product, have antioxidant activity, that is, they inhibit the formation of free radicals, in particular superoxide, in the body. Presumably due to the complex of bioactive substances, the adaptogenic, oncoprophylactic and radioprotective effect of the Fucus agent is manifested. An additional effect is created by alginic acids, which make up from 18 to 28% (on a.s.) of EF, and have the ability to remove heavy metal salts, toxins, radionuclides from the body, as well as inhibit the absorption of radioactive elements.

 Unlike the original brown algae, EF contains the entire complex of bioactive substances from the fucus vesiculosum, but in a more digestible form for the animal organism due to alkaline hydrolysis of the algae and the conversion of lipid fractions to the bound state in the form of calcium and sodium salts.

 The following are examples of the preparation and use of Fucus. The oncological prophylactic "Fucus" can be used in the form of a powder, granules, tablets, an aqueous solution, syrup, as well as an ointment.

 Example 1

The recipe funds "Fucus" in the form of syrup, wt.%:
EF - 2.0 - 4.0
Sugar - 55.0 - 70.0
Citric acid - 0.2 - 0.8
Ethyl alcohol - 0 - 10.0
Food flavoring - 0 - 0.5
Boiled water - Other - Up to 100.0
To prepare the Fucus syrup, 20 g of EF powder are loaded into a separate container and 160 ml of warm boiled water (1/2 of the prescription amount of water) are poured into it for swelling and dissolution (like gelatin). The container is placed in a water bath at a temperature of 50 - 70 ^o C. Dissolution is carried out with periodic stirring for 1 hour. After complete swelling and dissolution, the EF is drained and filtered through a nylon or gauze filter in an additional container. 600 g of granulated sugar is loaded into the cooking container, and the remaining amount of water is poured. Boil the syrup by boiling over low heat for 30 minutes, after which it is filtered. A 50% aqueous solution of citric acid is added to the syrup (based on 8 g of acid per 16 ml of water) and the mixture is kept at a temperature of 70 ^o C for 2 hours with periodic stirring until invert sugar is formed, after which the syrup is cooled to 30 - 40 ^o C and poured with constant stirring, an aqueous solution of EF. The mixture is stirred for 15 to 20 minutes and 144 ml of water, 50 g of ethyl alcohol and 2 g of food flavoring, for example, cherry, are added. The syrup is well mixed and served for bottling and packaging. You can use other sugars: mannitol, xylitol, sorbitol, glucose for the preparation of syrup.

Example 2. To prepare an aqueous solution of Fucus, dissolve 2 g of EF powder in 1 l of warm boiled water in a water bath at a temperature of 50 - 70 ^o C. The solution is carried out with periodic stirring for 1 h until the EF is completely dissolved, then the solution is filtered through a gauze or nylon filter. The resulting aqueous solution is a dark brown jelly-like product. This solution was given to animals in experiments.

 Example 3. Means "Fucus" can be prepared in the form of ointments for topical application.

The recipe funds "Fucus" in the form of ointments, wt.%:
EF - 1.0 - 4.0
Emulsion wax - 2.0 - 3.0
Glycerol Monostearate - 0.6 - 1.2
Cotton vegetable oil, deodorized - 6.0 - 10.0
Chicken Fat - 1.0 - 2.0
Methyl paraoxybenzoic acid (preservative) - 0.2 - 0.3
Fragrance - 0.1 - 0.3
Boiled water - Other - Up to 100.0
In the manufacture of Fucus ointment, 20 g of emulsion wax, 6 g of glycerol monostearate, 80 g of vegetable oil, 10 g of chicken fat and 2 g of preservative are loaded into a water jacketed reactor. The mixture is fused when heated and at a temperature of 60 - 70 ^o C to a homogeneous liquid mass (fat base). 10 g of EF in powder form and 870 ml of water are charged into a separate container. The mixture is heated in a water bath until the components swell and dissolve completely for 1 to 2 hours, after which the resulting gelled EF solution is filtered through a nylon sieve. The fat base in the reactor is cooled to 50-60 ^° C and an aqueous solution of EF is introduced therein with constant stirring. Emulsification of the mixture is carried out for 1 h until the mixture is cooled to 30 - 35 ^o C, after which perfume is introduced. The resulting ointment (cream) is sent to the bottling line and packaging.

 Example 4. Use the tool "Fucus" in the form of a powder, 1 teaspoon 3 times a day, washed down with water.

 The proposed tool for the prevention of cancer "Fucus" was tested on the basis of the Oncology Research Institute. prof. N.N. Petrova of the Ministry of Health of the Russian Federation (St. Petersburg). The anticarcinogenic effect of Fucus was studied on models of breast and colon cancer. The means "Fucus" also found the ability to stimulate blood formation. At the same time, Fukus did not show acute toxicity and locally irritating effects (see Conclusion of the N.N. Petrov Oncology Research Institute).

 Oncoprophylactic properties of Fucus are confirmed by the following examples.

 Example 5. On a model of breast cancer.

 In female rats, LIO wiring of the Research Institute of Oncology named after N.N. Petrov with an initial body weight of 200 - 230 g induced breast tumors by a single intramammary injection of N-methyl-N-nitrosourea (MNM) into the tissue of all 12 mammary glands, 1 mg of MNM per gland (week 1 of the experiment). In the experimental group, rats were orally given EF until the end of the experiment with drinking water at a concentration of 2 g / l (see Example 2), which corresponds to a daily intake of 200 mg / kg of animal body weight. EF was given starting from the 6th week of the experiment, i.e., in the phase of promotion / progression of carcinogenesis. In the experiments, there were also 2 groups of intact animals that did not receive a carcinogen: intact control, intact animals + EF. After 12 months, the rats were sacrificed, and the frequency and multiplicity of the development of breast tumors were evaluated. Histological processing of organs and tissues of all animal groups was carried out according to a standard method with hematoxylin / eosin staining. Under light microscopy, a pathomorphological analysis of the material was performed. Tumors were classified according to the requirements of the International Agency for Research on Cancer (Pathology of Tumours in Laboratory Animals, Second Edition, Vol. 1, Tumours of the Rat / Ed. By VS Turusov and U. Mohr. - IARC Sci., Publ. N 99 Lyon: IARC, 1990). The experimental results were processed by methods of variation statistics using the criteria t (Student) and chi-square.

 The effect of Fucus on the development of MNM-induced breast tumors in rats is presented in Table. 1. As can be seen from the data table. 1, the Fucus agent statistically significantly reduced the incidence of breast tumors by 27%, and their multiplicity by 51%. In groups of rats treated with carcinogen, most breast tumors were malignant, less often benign.

 Example 6. On a model of colon cancer.

 In female rats, LIO wiring of the Research Institute of Oncology named after N.N. Petrov with an initial body weight of 200 - 230 g induced colon tumors by means of intrectal instillations of MNM. From the 2nd to the 5th week of the experiment, rats underwent 4 intrarectal instillations of CMA of 4 mg in 0.5 ml of physiological saline per rat, i.e. Once a week for 4 weeks. In the experimental group, rats were orally given EF until the end of the experiment with drinking water at a concentration of 2 g / l (see Example 2), which corresponds to a daily intake of 200 mg / kg of animal body weight. EF was given starting from the 6th week of the experiment, i.e. in the phase of promotion / progression of carcinogenesis. In the experiments, there were also 2 groups of intact animals that did not receive a carcinogen: intact control, intact animals + EF. After 12 months, the rats were sacrificed, and the frequency and multiplicity of development of colon tumors was evaluated. Histological processing of organs and tissues of all animal groups was carried out according to a standard method with hematoxylin / eosin staining. Under light microscopy, a pathomorphological analysis of the material was performed. Tumors were classified according to the requirements of the International Agency for Research on Cancer.

 The effect of EF on the development of colon tumors induced by MNM in rats is presented in Table 2.

 As can be seen from the data table. 2, the Fucus agent statistically significantly reduced the frequency of colon neoplasms by 28%, and their multiplicity by 45%. Most colon tumors were malignant.

 The test results indicate that the Fucus agent effectively inhibits the development of breast and colon cancer induced by MNM in rats, that is, it has anticarcinogenic activity against the 2 most common malignant tumors in humans.

 On the same tumor models, experiments were conducted with beta-carotene and Clamin, a cancer prevention drug (see Tables 3 and 4). The following were used in the experiments: the water-soluble form of beta-carotene Aquiton-U (St. Petersburg) and the tablet food supplement Klamin (St. Petersburg).

 When comparing the data of 2 oncological prophylactics with the proposed Fucus agent, it follows that in the model of breast cancer, clamin and fucus showed approximately the same anticarcinogenic effects, while beta-carotene did not inhibit breast carcinogenesis in this model. In the model of colon cancer, all three compared drugs reduced the multiplicity of tumors of a given localization to approximately the same degree, on average, by 45-50%, while the frequency of colon tumors reduced Fucus by 28%, i.e. more pronounced than beta-carotene - by 16%, and clamin - by 18%.

 The use of the proposed Fucus means for cancer prevention allows us to expand the range and quality of oncological prophylactics from natural raw materials.

Claims (1)

 An agent for the prevention of cancer based on brown seaweed, characterized in that it contains a fucus extract obtained by alkaline hydrolysis from vesiculos fucus (Fucus veculosus) in a concentration of 0.2-100%, physiologically acceptable excipients and inert fillers.

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