Bioactive complex additive to anticancer drugs to prevent secondary brain tumor metastasis (brain metastasis) using plant bioactives rosavin and granin in combination with gallic acid and (HPMC)

Abstract

The invention of "Bioactive complex additive to anticancer drugs to prevent secondary metastasis of brain tumor (brain metastasis) using plant bioactives rosavin and granin in combination with gallic acid and (HPMC)" as a drug of plant origin and using compounds that inhibit defective and hyperactive cancer cells consisting of free radicals and reactive (active) damaged nucleic acids (which have a high tendency to react with healthy nucleic acids and cause defects in them), and can prevent in the bloodstream and lymphatic parts The destructive activity of these compounds is slow, so the brain tissue will be protected from its damage. Unlike conventional chemotherapy drugs, the present drug does not have any side effects or damage to healthy tissue cells of the body and can be mass-produced using raw materials available in the country and be made available to cancer patients safely and at an affordable price before and after surgery, and it prevents secondary brain metastasis.

Description

Description of the invention Title of the invention Bioactive complex additive to anticancer drugs to prevent secondary brain tumor metastasis (brain metastasis) using plant bioactives rosavin and granin in combination with gallic acid and (HPMC) Technical background of the relevant invention The present invention relates to the fields of medicine, pharmacy and chemistry and also relates to a bioactive complex additive to anticancer drugs and also relates to the prevention of secondary metastasis of brain tumors and also relates to the use of plant bioactives rosavin and granin in combination with gallic acid and (HPMC) Technical problem and stating the objectives of the invention One of the most deadly and common diseases that many people around the world are dealing with is cancer. This disease can progress silently in the body and affect the normal course of a person's life by involving various organs. In general, the cells of the human body reproduce and create new cells in a natural activity with a normal lifespan, and when this balance is disrupted by environmental or genetic factors and the cells begin to reproduce abnormally, cancer occurs. There are different types of cancer that can differ depending on the tissue of origin, such as skin cancer, leukemia, colon cancer, breast cancer, and . . . In each of these cancers, there is the possibility of forming a cancerous tumor and abnormal proliferation of a part of the tissue cells.At the same time, some of the cancer cells may separate from the primary cancer mass (origin) and travel to different parts of the body through the lymphatic system or blood, causing the spread of cancer to other parts of the body, which is called cancer metastasis. In this way, cancer cells spread from the organ where the cancer started to other parts of the body, causing the spread and development of cancer in other tissues of the patient's body. At this stage, the cancer is called (metastatic cancer), (secondary cancer), or (advanced cancer). One of the most common and dangerous types of metastasis in cancer patients is secondary brain metastasis, in which cancer cells from other organs in the body migrate from their original location to the brain and form a brain tumor. As metastatic brain tumors grow, they put pressure on brain tissue and cause changes in the area, eventually causing a decrease in brain function and then brain death. Therefore, one of the most important concerns and concerns in all types of cancer is the rapid treatment of the primary cancer and the prevention of cancer tumor metastasis, especially metastasis to the brain and brain damage. Currently, many methods are used to treat cancer, such as chemotherapy, radiation therapy, immunotherapy, or surgery. However, in the case of metastasis of cancer cells and the formation of a brain tumor, due to the presence of the blood-brain barrier (BBB), which is the barrier that separates the intercellular fluid and blood in the nervous tissue and brain, the pores of the blood capillaries of the brain tissue, unlike the body's natural capillaries, are unable to absorb some drugs. Therefore, in brain tumor patients, due to the presence of this blood-brain barrier and the inability of drugs to pass through this barrier and as a result, some conventional drugs are ineffective in treating cancer, its treatment is much more difficult and the life expectancy of patients with it is also lower. Therefore, it is better to prevent secondary metastasis and brain metastasis in the early stages of any type of cancer by taking drugs to treat it, because as mentioned, it is not easy to treat it. The role of free radicals in cancer: Free radicals are highly reactive and unstable molecules that are naturally produced in the body as a byproduct of metabolism (oxidation) or as a result of exposure to environmental toxins such as tobacco smoke and ultraviolet light. These free radicals, such as (.NO), have a high tendency to react with nucleic acid molecules in DNA, proteins, and intracellular and extracellular structures, so the reaction of these compounds with these parts can cause mutations and problems in the normal activity of the cell, and as a result, cause abnormal proliferation and cancer. Metastatic cells from primary cancer, due to unbalanced proliferation and more intense reactions, usually have many free radicals attached to them, so secondary or metastatic cancer usually occurs more quickly. Due to the molecular structure of compounds such as rosavin, granin and gallic acid, which have many active polyorganic groups, they have very good antioxidant and inhibitory effects, and this anti-radical effect of theirs is considered a good anti-proliferative effect because each free radical itself will initiate a series of abnormal cellular reactions. However, the use of these compounds in a specific structure under a drug that can be placed in all parts of the patient's blood with appropriate dispersion in the blood and balanced density and at any time has the possibility of repelling and inhibiting independent free radicals resulting from the abnormal metabolism of the primary tumor or the carriers of these free radicals (such as cells isolated from the primary tumor) is vital. Cell Cycle Cell proliferation: Briefly, cell proliferation occurs in a specific cycle and has different phases, so that in the first phase (interphase) the cell grows and replicates DNA, in the mitotic phase the cytoplasmic content of the cell is separated and the entire cell is divided into two other cells. The interphase phase itself has different stages: The first stage of interphase is the G1 or GAP1 stage, during which the cell grows and organelles begin to divide. In G1 or (GAP1), the cell condenses chromosomal units, produces and prepares proteins related to it. Given that the enzyme activity in tumors and cancer cells (high-active) is much higher, if substances can be used that inhibit the enzymes active in the G1 stage of interphase, it is possible to control excessive cell proliferation. The structure of this complex contains the plant bioactives rosavin and granin with active terpenoids to control and inhibit G1 stage enzymes in interphase and reduce the activity and speed of this cycle, which has the property of preventing rapid and abnormal cell proliferation. Therefore, the bioactive complex added to anticancer drugs to prevent secondary brain tumor metastasis (brain metastasis) using the plant bioactives rosavin and granin in combination with gallic acid and hydroxypropyl methylcellulose, as an effective complex, can be used simultaneously with chemotherapy drugs for patients with various types of cancer. This complex, with the anticancer effects of the compounds rosavin, granin and gallic acid as antioxidants and free radical inhibitors, prevents secondary cancer metastasis and prevents brain metastasis. Also, the presence of plant bioactives rosavin and granin and gallic acid as (anti-proliferative) and reducing the enzymatic speed of the G1 phase and as a result reducing the speed of cell proliferation in tumors released from the primary cancer tumor to a large extent prevents the activity of these cells after separation from the mother tumor and nutrient metastasis. A description of the state of the prior art and the history of developments related to the claimed invention. Cancer, as the largest cause of death among all types of diseases, has always been of interest to the scientific community for timely diagnosis and appropriate treatment with minimal side effects. In many years, according to global statistics, an average of 362 people out of every 100,000 people are diagnosed with cancer. There are many different types of cancer, the most common of which are skin, stomach, intestinal, lung, blood, prostate, breast, etc. In all types of diseases, timely diagnosis and treatment with various methods such as chemotherapy, radiotherapy, immunotherapy, etc. are important. In research conducted on cancer in the past, the emphasis has been on treating cancer or slowing its progression.But what has worried oncologists in most patients is the possibility of the spread of cancer and its so-called metastasis, especially to the brain, because cancer or brain tumors are less likely to be effective and dangerous due to the existence of the blood-brain barrier and the high sensitivity of blood capillaries. Therefore, in the treatment of any type of cancer, the concern about metastasis is sometimes greater than the treatment of primary cancer. Therefore, preventing metastasis and preventing the spread of primary cancer tumors, especially metastasis to the brain, has been vital, and its importance is sometimes even greater than the treatment of primary cancer. In this suspension complex, an additive to anticancer drugs using compounds effective in scavenging free radicals (as one of the main factors aggravating cancer) and preventing inappropriate cell proliferation (inhibiting G1-activating enzymes) can significantly prevent secondary cancer metastasis. This additive complex has differences and advantages compared to common anticancer drugs. - Previously developed drugs emphasize the treatment of cancer, but as mentioned, after cancer cells metastasize and the patient develops brain cancer, treatment is much more difficult due to the reduced ability of conventional drugs to cross the blood-brain barrier. Therefore, the emphasis of this drug complex is on preventing metastasis, and the patient can use this complex along with conventional chemotherapy drugs. - The side and negative effects of chemotherapy drugs, such as rapid weakening of physical strength, hair loss, reduction of muscle mass, etc., have been evident for years. Therefore, it is not possible to increase the dose of chemotherapy drugs or enhance radiation in radiation therapy methods due to the many side effects. Therefore, it is necessary for the patient to use a drug that can flow in the blood without side effects (or very few side effects) and has the ability to fight cancer cells before they reach the brain tissue (and other tissues) with its bioactive and anti-cancer properties. This therapeutic complex, due to its herbal base, provides this possibility with the least side effects. - One of the biggest problems with anticancer drugs is their improper dispersion in different parts of the body, as the accumulation of anticancer drugs in parts of the body causes irreversible complications such as serious tissue damage and blood clotting, etc. In this complex, the presence of cellulose compounds hydroxypropyl methylcellulose and the intermediate surfactant tween as a double-ended intermediate for the proper mixing of the main active ingredients (herbal bioactives rosavin and granin and gallic acid) in the aqueous mixture of the complex, as well as its proper dispersion in the blood and lymphatic fluid circulation system, enables the elimination of cancer cells separated from the primary tumor uniformly in all parts of the blood and lymph, and secondary metastasis to the brain and other organs of the body is greatly reduced. This proper dispersion also means that there is no accumulation of substances in one tissue and its adverse effects. - Patent application number 139750140003002456, registered in 2018 by Ms. Soheila Rahgozar, Narges Abrouy, and Elnaz Pourabutaleb, concerns the production of a multidrug-resistant T-cell subtype of childhood acute lymphoblastic leukemia, which is completely different from my drug due to the use of herbal bioactives in my invention and the complementary effects. - Patent application number 139750140003000526, registered in 2018 by Mr. Mostafa Zahedifar, Mr. Ehsan Sadeghi, and Mr. Marat Karimi, is about the production of gamma alumina quantum dots with silver impurities for the treatment of various types of cancer, which is completely different due to my use of plant-extracted bioactive compounds as a complex and the lack of use of metal impurities and radiation dots such as gamma. - The invention with application number 139850140003002566, which was registered in 2019 by Mr. Masoumeh Mohammad Pourdashtabi, is a preventive and therapeutic complex of capsules and tablets formulated for ovarian cancer patients. Considering that the focus of this invention is on ovarian cancer and is based on iron surfactants, the active ingredients in my medicine are completely different and the goal is to eliminate metastasized cancer cells and prevent brain tumors. Therefore, the present medicine is completely different from the medicine invented in 2019. - The invention with application number 139250140003000791, registered in 2013 by Ms. Mahboobeh Eslami Moghadam and Adeleh Diosalar, is the synthesis of an anti-cancer pharmaceutical compound based on palladium tessellation, which is completely different from the present invention in terms of its purpose, which is cancer treatment, and the type of materials used in it. The present invention does not correspond to any of the above and registered on the patent registration site and the scientific article search site, as well as global patents in terms of formulation and ingredients used, and in terms of the new formulation, the herbal ingredients used in it, and the therapeutic purpose, it is unique and is presented for the first time in the world. Providing a solution to an existing technical problem along with an accurate, sufficient, and integrated description of the invention According to studies, the plant bioactive compounds rosavin, granin, and gallic acid extracted from the plants Rhodiola rosea (rosavin) and geranium (granin) are effective in preventing secondary brain metastasis with two basic functions. 1) These plant compounds, with their appropriate structures and the presence of hydroxyl groups, absorb free radicals such as NO, O, and . . . They are effective because these radicals are by-products of the unbalanced proliferation of primary cancer cells. After entering the bloodstream, they can quickly react with intracellular and extracellular proteins of cells and nucleic acids of the cell's DNA structure, causing cell mutations and, as a result, the formation of new cancerous tumors. Also, due to the small diameter of the cerebral blood capillaries, the possibility of accumulation and interaction of these compounds in the brain is greater, and as a result, the probability of brain metastasis increases. Therefore, the bioactive compounds of the drug (rosavin, granin, and gallic acid) are extracted by Soxhlet in a water / ethanol solvent and oven-centrifuge fermentation, and 10-10-5 grams of them are used in the complex structure, respectively.2) Also, in cancer cells, due to excessive proliferation, the presence of enzymes that facilitate proliferation increases. Therefore, if cancer cells are separated from the primary tissue and go to other parts, in addition to the free radicals with them, there is a possibility of excessive cell cycle proliferation enzymes. Therefore, the plant bioactives rosavin and granin contain active terpenoids to control and inhibit these active enzymes, and in the G1 stage of the interphase phase, by inhibiting these enzymes and preventing them from binding to their respective receptors (cell receptors), they reduce cell activity and reduce the speed of cell proliferation in this stage. This cycle has the property of preventing rapid and abnormal cell proliferation. And it prevents the spread of cancer. Also, this complex has the ability to be produced industrially and can be provided to cancer patients as a complementary product. Manufacturing method: First step: First, separate 200 grams of Rhodiola rosea and Geranium plants and place them in powder form in a 19 cm semi-permeable paper with dimensions of 15 x 15 cm, close it and place it in a Soxhlet condenser, then connect the condenser to the flask and fill the flask with a water-ethanol mixture in a ratio of 30 to 70 and place it on a heater at a temperature of 80 to 90 degrees Celsius and connect the water outlet to perform Soxhlet. After 40 minutes, remove the extract liquid inside the flask and place it in an oven at a temperature of 100 degrees Celsius and perform solvent removal. Purify the obtained paste again with ethanol, in such a way that (wash twice with 5 cc of 90% ethanol and place it again in the oven at a temperature of 80 degrees). Until the desired extract crystallizes and is obtained. Then, from the extract, HPLC, CNMR, and HNMR were used to identify the effective compounds rosavin and granin as plant bioactives. Second step: Pour 50 cc of deionized water into a three-necked flask and place it on a heater stirrer or hot water bath (bain-marie) until its temperature reaches 40 degrees Celsius, then add 5 cc of gallic acid dropwise and under neutral nitrogen gas conditions and stir the mixture until the pH of the solution is 5.5. Finally, remove this mixture from the heater and place it at room temperature. Step 3: Place the mixture from Step 2 in an ultrasonic device with a voltage of 70 V and a temperature of 45 °C, add 5 grams of each of the plant extracts of rosavin and granin prepared in Step 1, and maintain this mixture for 10 minutes under ultrasonic conditions at a temperature of 60 °C and a frequency of 2000. Step Four: Place the mixture obtained from step three on a heater stirrer at a temperature of 40°C and add 2 cc of fatty tail hydroxypropyl methylcellulose (HPMC) to the mixture. Stir for 15 minutes at this temperature with a stirrer. While stirring, add 4 cc of the desired surfactant (Tween 80) dropwise to the mixture until the desired suspension is formed. Step 5: To stabilize the suspension, reduce the temperature to 35°C and stir the suspension on a stirrer with a 2 cm magnet for 30 minutes until the desired suspension is obtained. The active ingredient of each ingredient: The active ingredient rosavin is able to inhibit osteoclast cells (which are multinucleated cells that feed by absorbing minerals and organic substances from the bone surface, causing bone destruction and abnormalities in bone tissue, thereby increasing the likelihood and proliferation of cancer) by inhibiting nuclear factor, thereby preventing further cancer growth in the patient and reducing the likelihood of metastasis to the brain. One of the main functional activities of granin is the inhibition of the CCND1 gene in humans and the prevention of the activity of the CDK4 / CyclinD1 and CDK2 / CyclinE complexes, which are two proteins that, after binding to the aforementioned gene, CCND1, increase cell proliferation, as well as increase resistance to chemotherapy and increase the strength of cancer cells and increase their ability to survive longer in the blood. As a result, there is a possibility of them reaching the brain tissue through the blood and brain metastasis. Therefore, this active substance prevents the operation of these cyclin complexes by inhibiting this cycle. Physicochemical properties examination: Macroscopic examinations: Morphological examination: The product was exposed to different atmospheric temperatures for a period of 6 months, and its morphological characteristics such as shape (light green color), smell, and taste were evaluated visually. During this period, the product remained unchanged. Viscosity: The viscosity of the product was measured using a VR3000 device, the results of which are reported below. PH: The pH of the suspension was measured using a PL-7000 PC model PH meter, and the acidity of the final suspension was 6.78. Monotomy and uniformity: The product was exposed to direct sunlight, indirect sunlight, and various ambient temperatures for 6 months, and the uniformity of the product remained stable without any change, and no biphasizing or separation occurred. Structural and chemical studies: HPLC: High-performance liquid chromatography CNMR: Carbon Nuclear Magnetic Resonance Analysis HNMR: Hydrogen Nuclear Magnetic Resonance Analysis A bioactive complex additive to anticancer drugs for the prevention of secondary brain tumor metastasis (brain metastasis) using the plant bioactives rosavin and granin in combination with gallic acid and hydroxypropyl methylcellulose. It is prepared by an ultrasonic device using Soxhlet extraction and extraction and includes the following components: Ethanol Deionized water Rhodiola rosea root (rosavin extract) Geranium root (Geranium extract) Gallic acid Hydroxypropyl methylcellulose (HPMC) Surfactant (Tween 80) (Polysorbate 80) This bioactive complex, an additive to anticancer drugs for the prevention of secondary brain tumor metastasis (brain metastasis), is prepared with a liquid viscosity of CP 1300 using a hot water bath, heater stirrer, and ultrasonics. 50 cc of deionized water is placed on a heater stirrer at a temperature of 40°C in a three-necked flask, and 5 cc of gallic acid is slowly added dropwise under neutral environmental conditions, and the mixture is stirred for 2 minutes to obtain an initial acidic solution with a pH of 5.5.Then, 5 grams of Rosavin plant extract and Granin plant extract were added to the mixture as two effective bioactives, and the mixture was stirred using an ultrasonic device with a voltage of 70 and a temperature of 45°C for 10 minutes. Then, the resulting mixture was placed on a heater stirrer at a temperature of 40°C. Then, 2 cc of hydroxypropyl methylcellulose (HPMC) was added to the mixture and stirred for 15 minutes at this temperature with a stirrer. Then, 4 cc of surfactant was added dropwise to the mixture while stirring until the desired suspension was formed. Then, the temperature was adjusted to 35°C and stirring was repeated for 30 minutes to prepare the final desired suspension. The extract obtained from Rhodiola rosea (rosavin) and Geranium (granin) was obtained by Soxhlet method with water-ethanol solvent in ratio 30 / 70 and evaporation of its solvent in viscous liquid form is carried out in oven at 90°C to obtain hydroalcoholic extract. Gallic acid used in neutral environment (under nitrogen gas) is added to the mixture and oxidation and destruction of gallic acid as bioactive does not occur in it. The edible surfactant (Tween 80) present in the suspension prevents oxidation of plant extracts by establishing hydrogen bonds of ether groups on its surface and by hydrogen bonds of this compound with extracts and water and gallic acid provides uniform dispersion of the extract in the suspension. Hydroxypropyl methyl cellulose (HPMC), with its cyclic structure and ether hydrogen bonds, provides better consistency and viscosity of the suspension, which reduces the speed of movement of the suspension in the digestive and plasma systems, providing the opportunity for the suspension to be absorbed by the absorbent tissue of the digestive tract.Bioactive complex additive to anticancer drugs to prevent secondary metastasis of brain tumors (brain metastasis) using plant bioactives rosavin and granin in combination with gallic acid and (HPMC) can be used during the course of cancer along with chemotherapy drugs and circulate in the digestive tract and then the blood and react with them in the form of dispersion and metastasis of cancer cells from the cancerous tissue of origin. Explanation of shapes, maps and diagrams Figure 1: Molecular structure of the components of the complex Figure 2: Mechanism of complex formation Figure 3: Complex viscosity at different shear rates of the VR3000 device Figure 4: HPLC (High Performance Liquid Chromatography) Figure 5: HNMR (Hydrogen Nuclear Magnetic Resonance Analysis) A clear and precise statement of the advantages of the claimed invention over prior inventions. 1. Much fewer side effects (due to the use of effective herbal bioactives, which have far fewer side effects compared to chemotherapy drugs, reducing the need for increased chemotherapy drugs and, consequently, the increase in side effects caused by them) 2. Economical (use of effective herbal compounds and cost-effective materials and no need to increase the dosage of expensive chemotherapy drugs) 3. Possibility of easy industrial production and manufacturing (no need for complex equipment to manufacture this product) 4. Safe raw materials (unlike radiotherapy methods and chemotherapy drugs, these drugs use completely safe and side-effect-free raw materials in the preparation of this suspension) 5. Possibility of adjusting the dosage to the desired amount (unlike oral or injectable chemotherapy drugs, this suspension can be used in the desired amount) 6. Longer duration and effectiveness of the drug in the body (unlike chemotherapy drugs, which have an immediate effect, this drug works over a longer period of time and with better effectiveness) 7. Easy preparation of raw materials (the raw materials for this suspension are available domestically and are easily accessible) 8. Its complementary role (this drug has a complementary role alongside other anti-cancer drugs and reduces the need to use higher and unconventional doses of drugs with high side effects, such as chemotherapy and . . .) 9. Easy to use (unlike conventional cancer treatments such as phototherapy, immunotherapy, and some chemotherapy drugs, this drug can be used by the patient anywhere and does not require special hospital equipment) 10. High product durability 11. Avoid using harmful chemical preservatives such as parabens and... Description of at least one implementation method for implementing the invention Bioactive complex is an additive to anticancer drugs for the prevention of secondary brain tumor metastasis (brain metastasis) using the herbal bioactives rosavin and granin in combination with gallic acid and (HPMC) in the form of an oral suspension that can be used orally in different amounts and doses during the treatment of a person with cancer, along with other drugs and therapeutic methods of the breast to prevent primary cancer metastasis to the brain, so that the suspension is first stirred several times and then its lid is opened and, like other oral medicinal liquids, poured into a graduated cup (in cc) in the prescribed amount and consumed orally. The amount of consumption can vary from 5 to 10 cc per day, depending on the prescription. Explicit mention of the industrial application of the invention In all types of cancer, a person with cancer is always at risk of metastasis of the primary cancer to the brain and developing a metastatic brain tumor, so in most cases, treatment of primary cancer in different parts of the body (lungs, intestines, stomach, skin, etc.)) is possible, but the separation of a part of this primary tumor, which is accompanied by various free radicals and is prone to the spread of cancer, and its transfer through the blood to the brain tissue and the development of a brain tumor can make it much more difficult to treat and save the affected person, because when a cancerous tumor reaches the brain and spreads there, due to the existence of the blood-brain barrier, it is not possible to receive and exchange some conventional chemotherapy drugs. Also, a number of treatments such as surgery and phototherapy are associated with high risk. Therefore, the use of this bioactive complex as an additive to anticancer drugs to prevent secondary metastasis of brain tumors (brain metastasis) using the herbal bioactives rosavin and granin in combination with gallic acid and (HPMC) along with other cancer treatments such as the use of chemotherapy drugs with antioxidant therapeutic properties and the ability to reduce the process of the abnormal cell cycle prevents the cancer cells separated from the primary cancerous tissue from reaching and affecting the brain through the blood and greatly reduces the possibility of brain metastasis.

Claims

Claim What is claimed: Claim 1) The invention of "Bioactive complex additive to anticancer drugs for preventing secondary metastasis of brain tumor (brain metastasis) using plant bioactives rosavin and granin in combination with gallic acid and (HPMC)" is a bioactive complex additive to anticancer drugs for preventing secondary metastasis of brain tumor (brain metastasis) using plant bioactives rosavin and granin in combination with gallic acid and hydroxypropyl methyl cellulose. Which is prepared by an ultrasonic device using extraction and extraction by the Soxhlet method and includes the following components: Ethanol Deionized water Rhodiola rosea root (Rosavin extract) Geranium root (Granin extract) Gallic acid Hydroxypropyl methyl cellulose (HPMC) Surfactant (Tween 80) (Polysorbate 80) Claim 2) According to claim 1, this bioactive complex, an additive to anticancer drugs for preventing secondary brain tumor metastasis (brain metastasis), is prepared with a liquid viscosity of CP 1300 using a hot water bath, heater stirrer and ultrasonics, by placing 50 cc of deionized water on a heater stirrer at a temperature of 40°C in a three-necked flask, and slowly adding 5 cc of gallic acid dropwise under neutral environmental conditions, and stirring the mixture for 2 minutes to obtain an initial acidic solution with a pH of 5.5.Then, 5 grams of Rosavin plant extract and Granin plant extract were added to the mixture as two effective bioactives, and the mixture was stirred using an ultrasonic device with a voltage of 70 and a temperature of 45°C for 10 minutes. Then, the resulting mixture was placed on a heater stirrer at a temperature of 40°C. Then, 2 cc of hydroxypropyl methylcellulose (HPMC) was added to the mixture and stirred for 15 minutes at this temperature with a stirrer. Then, 4 cc of surfactant was added dropwise to the mixture while stirring until the desired suspension was formed. Then, the temperature was adjusted to 35°C and stirring was repeated for 30 minutes to prepare the final desired suspension. Claim 3) According to claim 2, the extract obtained from the Rhodiola rosea plant (rosavin) and Geranium (granin) is obtained by the Soxhlet method with a water-ethanol solvent in a ratio of 30 / 70, and the solvent is evaporated in the form of a viscous liquid in an oven at a temperature of 90 degrees Celsius to obtain a hydroalcoholic extract. Claim 4) According to claim 2, the gallic acid used is added to the composition in a neutral environment (under nitrogen gas), and oxidation and degradation of the bioactive gallic acid does not occur in it. Claim 5) According to claim 2, the oral surfactant (Tween 80) present in the suspension prevents the oxidation of plant extracts by establishing hydrogen bonds between its surface ether groups, and by hydrogen bonding this compound with the extracts, water, and gallic acid provides uniform dispersion of the extract in the suspension. Claim 6) According to claim number 2, hydroxypropyl methylcellulose (HPMC), having a cyclic structure and ether hydrogen bonds, provides better consistency and viscosity of the suspension, which provides the opportunity for the suspension to be absorbed by the absorbent tissue of the digestive tract by reducing the speed of movement of the suspension in the digestive and plasma systems. Claim 7) According to claim number 1, the bioactive complex, an additive to anticancer drugs for the prevention of secondary metastasis of brain tumors (brain metastasis), using the plant bioactives rosavin and granin in combination with gallic acid and (HPMC), can be used during the course of cancer along with chemotherapy drugs and circulate in the digestive tract and then the blood, and react with them in the form of dispersion and metastasis of cancer cells from the cancerous tissue of origin.

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