KR101708278B1 - Kit for preventing or treating cancer comprising descurainia sophia extracts or fraction thereof and platinum anticancer drugs - Google Patents

Abstract

The present invention relates to a kit for preventing or treating cancer and a method of preventing or treating cancer. More specifically, the present invention relates to a composition comprising: a) a first composition comprising as an active ingredient, an extract of Zygomagosa japonica or Bacillus subtilis or a fraction thereof; And b) a second composition comprising a platinum-based anticancer agent as an active ingredient, and a kit for preventing or treating cancer using the kit. The present invention also relates to a method for preventing or treating cancer by administering the first composition and the second composition in combination.
According to the present invention, when the first composition and the second composition are administered in combination, they exhibit synergistic effects of anti-cancer, mitigate cancer cachexia, and reduce the platinum-based anticancer drug-induced toxicity.

Description

KIT FOR PREVENTING OR TREATING CANCER COMPRISING DESCURANIA SOPHIA EXTRACTS OR FRACTION THEREOF AND PLATINUM ANTICANCER DRUGS <br> <br> <br> Patents - stay tuned to the technology KIT FOR PREVENTING OR TREATING CANCER COMPRISING DESCURANIA SOPHIA EXTRACTS OR FRACTION THEREOF AND PLATINUM ANTICANCER DRUGS

The present invention relates to a kit for preventing or treating cancer and a method of preventing or treating cancer. More specifically, the present invention relates to a composition comprising: a) a first composition comprising as an active ingredient, an extract of Zygomagosa japonica or Bacillus subtilis or a fraction thereof; And b) a second composition comprising a platinum-based anticancer agent as an active ingredient, and a kit for preventing or treating cancer using the kit. The present invention also relates to a method for preventing or treating cancer by administering the first composition and the second composition in combination.

Cancer is one of the world's most deadly diseases, with the cancer age gradually decreasing, while the average life expectancy is increasing, and cancer incidence is expected to increase further. According to the 2013 statistics provided by the National Cancer Center (Non-Patent Document 1), 202,053 cancer patients in Korea registered in the Cancer Registration Statistics Section in 2010 are 202,053, and about 270,000 in 2015 Of the total.

Platinum-based anticancer drugs containing platinum as anticancer drugs conventionally used in chemotherapy are widely used. Cisplatin, Carboplatin, Nedaplatin, etc. are representative preparations of such platinum-based anticancer drugs.

These conventional anticancer drugs are chemically synthesized anticancer drugs. When they are administered to an individual in an excessive amount for a long period of time, serious irritation is induced in the body to decrease the body weight of the subject, and hepatotoxicity, nephrotoxicity, neurotoxicity, , And toxicity (ototoxicity). Studies on the serious side effects caused by such conventional anticancer drugs have been constantly being announced, and studies for reducing side effects due to chemotherapy have been continuing (Non-Patent Document 2).

Under these circumstances, the inventors of the present invention have conducted studies on an anticancer treatment method which is excellent in anticancer efficacy but does not cause or reduce side effects. In case of using the extract of Jemugus or Bacillus subtilis in combination with a conventional platinum-based anticancer agent, The present inventors have found that even when the dose of the anticancer drug conventionally used is reduced to less than half, the survival period is increased and the side effects caused by the platinum-based anticancer drug are significantly suppressed and decreased. In addition, To complete a kit for the prevention or treatment of cancer.

[Prior Art Literature]

[Non-Patent Document]

(Non-Patent Document 1) National Cancer Center Cancer Facts & Figures 2013, p 18, 2013

(Non-Patent Document 2) Dong Wang and Stephen J. Lippard, Nature Reviews Drug Discovery, Vol. 4, 307-320 (April 2005)

The present invention aims to prevent, ameliorate, or treat cancer by using an extract of Zymugrus japonica or Bacillus subtilis or a fraction thereof, and a platinum-based anticancer agent.

Specifically, one object of the present invention is to provide a composition comprising: a) a first composition containing, as an active ingredient, an extract or a fraction thereof of Zymoglossia or Bleach; And a second composition comprising a platinum-based anticancer agent as an active ingredient, and b) a kit for preventing or treating cancer.

It is another object of the present invention to provide a method for preventing or treating cancer using the kit.

It is still another object of the present invention to provide a method of preventing or treating cancer, comprising co-administering the first composition and the second composition to an individual.

According to one aspect of the present invention for achieving the above object, the present invention provides a composition comprising: a) a first composition comprising as an active ingredient, an extract of Zugchuprodia or Bacillus subtilis or a fraction thereof; And b) a second composition comprising a platinum-based anticancer agent as an active ingredient.

The Descurainia sophia of the present invention is a biennial plant, also called energetic, belonging to the family Brassicaceae, Descurainia, and is a plant native to the country.

The Peucedanum praeruptorum Dunn of the present invention is a plant belonging to the genus Umbelliferae and is a plant different from Anthriscus sylvetris HOFFMANN having the same name as herb medicine and herb medicine.

The term "extract " used in the present invention refers to an extract obtained by extracting a natural product, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, an adjusted product or a purified product of the extracted solution, And extracts of all formulations that can be formed using an extract.

In the present invention, there is no particular limitation on the method for extracting japonica or white mugwort, and extraction can be carried out according to a method commonly used in the art. Non-limiting examples of the extraction method include an ultrasonic extraction method, a filtration method, and a reflux extraction method.

In the present invention, the kind of the solvent used for extracting the zelgugis or white mugwort is not particularly limited, and any solvent known in the art can be used. Examples of the extraction solvent include water, alcohols and mixed solvents thereof. These solvents may be used alone or in admixture of two or more. When alcohol is used as a solvent, C1 to C4 alcohols (methanol, ethanol, propanol, butanol) may be more preferably used, and ethanol is more preferably used.

The extract of Zymugrus japonica or Bacillus subtilis according to the present invention can be extracted from various organs of natural, hybrid, and variant plants of the above-mentioned Zymugrus or Bacillus subtilis, and can be extracted from various organs such as roots, ground parts, stems, leaves, flowers, It can be extracted not only from the bark of the fruit but also from the plant tissue culture.

The term "fraction " as used herein means a product obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.

The fractionation method for obtaining the fraction in the present invention is not particularly limited and may be carried out according to a method commonly used in the art. In one embodiment of the present invention, a method of obtaining a fraction from the extract by treating a predetermined solvent with an extract obtained by extracting the extracts of white flour was used.

The kind of the solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the fraction solvent include polar solvents such as water and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of two or more. When alcohols are used in the fraction solvent, C ₁ to C ₄ alcohols can be preferably used.

The extract or fraction thereof of the present invention exhibits excellent anticancer efficacy. Specifically, the extract or fraction thereof of Zygomugosa suppresses tumor growth, inhibits metastasis of cancer cells, and inhibits neovascularization. Also, since it is a substance derived from natural materials, there is no toxicity, and it is highly utilizable because it does not cause side effects when applied to human body.

When the extract of Z. japonica or Bacillus subtilis or a fraction thereof and a platinum-based anticancer agent such as cisplatin are administered in combination, synergistic effects are more excellent in anticancer effects. Specifically, in the case of administering the extract or its fraction of cisplatin and cisplatin in combination, it is possible to increase the survival time of the cancer disease individual even when a considerably small amount (for example, less than half) of the cisplatin extract or cisplatin is administered Effect. The survival rate of Bacillus subtilis extract was higher than that of the control group. In addition, there is an advantage that side effects due to chemotherapy can be reduced by reducing the dose of the platinum-based anticancer drug, which has been a problem due to serious side effects.

In a specific embodiment of the present invention, when the japonica extract of the present invention and cisplatin were co-administered to a cancer-induced mouse, the dose of the japonica extract and cisplatin alone was reduced by half, (Example 1). In addition, it was confirmed that when the extract of Bacillus subtilis of the present invention was administered to a cancer-induced mouse, the survival rate was higher than that of the control group (Example 2). Furthermore, when the extract alone was administered to a cancer-induced mouse, it maintained a normal body weight and exhibited cancer cachectic relief (Example 2-3). In addition, Baishin Bulletin also confirmed the effect of reducing cisplatin-induced toxicity (Example 4).

In another embodiment of the present invention, the first composition may contain an extract or fraction thereof of both zymogrand and white moth.

In the present invention, when the first composition contains both the extract of Zygomycetus japonica and the extract of Bacillus totalianum, they may be present in the form of a mixed extract of Zygomycetes and Bacillus subtilis.

The mixed extract of Zygomiris japonica and Y. japonica according to the present invention may be prepared by extracting each of the above-mentioned Z. japonica and Y. chrysanthemum and then mixing them with each other, or extracting the Z. japonica and Y. japonica together.

When the first composition of the present invention contains a mixed extract of Zygomagos and Bacillus subtilis, the above-mentioned mixed extract shows synergistic effects on anticancer efficacy as compared with the case of using the Zygomycetum extract or Bacillus subtilis extract alone. In particular, in the case of white pox, it has excellent anticancer efficacy as well as a side effect (for example, decrease in body weight of patient, decrease of organ weight, increase of toxicity of organ, etc.) as well as anticancer drugs that cause side effects such as cisplatin When used in combination, side effects are significantly mitigated.

The weight ratio of the extract of Zykthoxylum or its fraction contained in the first composition of the present invention and the fraction thereof or the fraction thereof or the fraction thereof is not particularly limited, but may be preferably contained in a weight ratio of about 1: 1. When contained in the above-mentioned range, it can effectively inhibit the growth of cancer cells and the metastasis of cancer cells, and can effectively inhibit neovascularization.

The platinum-based anticancer agent of the second composition of the present invention means an anticancer agent containing platinum, and the kind thereof is not particularly limited, and a platinum-based anticancer agent conventionally used in the art can be used. Non-limiting examples of the platinum-based anticancer agent include cisplatin, carboplatin, and nedaplatin. These may be used alone or in combination of two or more.

The present invention is based on the discovery that adverse effects such as weight loss, long term weight loss, organs toxicity, and pain due to excessive dose and frequency of frequent administration, And / or the combination of the extracts of Bacillus subtilis and the combination of Bacillus subtilis and Bacillus subtilis in combination. This technical feature was first described by the present inventors.

The first composition and the second composition of the present invention may further comprise a pharmaceutically acceptable carrier. The first composition and the second composition of the present invention may be formulated together with the carrier to provide a food, a medicine, a feed additive, a drinking water additive, or the like.

As used herein, the term "pharmaceutically acceptable carrier" means a carrier or diluent that does not interfere with the biological activity and properties of the compound being administered, without stimulating the organism.

The type of the carrier that can be used in the present invention is not particularly limited, and any carrier conventionally used in the art and pharmaceutically acceptable may be used. Non-limiting examples of the carrier include saline, sterilized water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and the like. These may be used alone or in combination of two or more.

In addition, if necessary, other conventional additives such as an antioxidant, a buffer and / or a bacteriostatic agent can be added to the composition, and a diluent, a dispersant, a surfactant, a binder and / or a lubricant may be additionally added thereto to form an aqueous solution, a suspension, Capsules, granules, tablets or the like.

The first composition and the second composition of the present invention may be manufactured into various formulations depending on whether the desired administration mode is oral administration or parenteral administration.

Non-limiting examples of formulations for oral administration include troches, lozenges, tablets, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups, .

Such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose, or gelatin, for formulation into oral dosage forms such as tablets, capsules and the like. Binder; Excipients such as dicalcium phosphate and the like; Disintegrating agents such as corn starch or sweet potato starch; Lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax, and the like. Furthermore, in the case of a capsule formulation, in addition to the above-mentioned substances, a liquid carrier such as a fatty oil may be further contained.

Formulations for parenteral administration include, for example, injectable forms such as subcutaneous, intravenous, or intramuscular injections; Suppository injection system; Or an aerosol formulation that allows for inhalation through the respiratory tract, but is not limited thereto. In order to formulate the injectable preparation, the composition of the present invention may be mixed with a stabilizer or a buffer in water to prepare a solution or suspension, which may be formulated for unit administration of an ampoule or a vial. When formulated for spraying with an aerosol or the like, a propellant or the like may be blended with the additive such that the water-dispersed concentrate or the wet powder is dispersed.

The kind of the kit of the present invention is not particularly limited, and a kit of a type commonly used in the art can be used.

The kit of the present invention may be packaged in the form that the first composition and the second composition are each contained in a separate container or contained in one container divided into one or more compartments and the first composition and the second composition May be packaged in the form of a unit dose of one dose each.

The first composition and the second composition in the kit may be separately administered at appropriate times depending on the health condition of the subject to be administered.

The weight ratio of the first composition and the second composition in the kit of the present invention can be preferably 5: 1 to 15: 1, more preferably about 10: 1.

The kit of the present invention may further include instructions for describing the dosage, administration method and frequency of administration of each of the first composition and the second composition.

According to another aspect of the present invention, there is provided a method of preventing or treating cancer using the kit.

The method for preventing or treating cancer using the kit includes administering the first composition and the second composition contained in the kit to a subject.

As used herein, the term "individual" refers to all animals, including humans, who have developed or are at risk of developing cancer.

The preventive or therapeutic method of the present invention specifically includes a first composition containing an extract of Z. japonica or Y. japonica or a mixed extract of Z. japonica or Y. japonica or fractions thereof in a subject who has developed or is at risk of developing cancer And a second composition containing the platinum-based anticancer agent in a pharmaceutically effective amount. The appropriate single and / or single daily usage of the first and second compositions may be suitably determined by those skilled in the art within the scope of sound medical judgment.

The specific pharmaceutically effective amount of the composition for a particular animal will depend upon a variety of factors, including the type and degree of response to be achieved, the age, weight, general health status, sex or diet of the individual, as well as the administration time, Rate of administration, duration of treatment, etc., and may be varied according to various factors, including drugs and other compositions used concurrently or simultaneously, and similar factors well known in the medical arts.

The preferred daily dose of the first composition of the present invention may be from 100 mg / kg / day to 400 mg / kg / day, more preferably from 200 mg / kg / day to 300 mg / kg / day. The preferred dosage frequency of the first composition of the present invention may be once per day.

The preferred first weekly dosage of the second composition of the present invention may be from 1 mg / kg / week to 10 mg / kg / week, more preferably from 1 mg / kg / week to 5 mg / kg / week , More preferably from 2 mg / kg / week to 3 mg / kg / week. The preferred dosage frequency of the second composition of the present invention may be once a week.

When the first composition and the second composition of the present invention are administered at the above-mentioned frequency and dose, synergistic effect is produced between the two compositions, thereby exerting excellent anticancer efficacy. In addition, excessive use of the platinum-based anticancer drug is prevented, And the first composition and the second composition work together in an appropriate amount in the body to advantageously inhibit and / or reduce the side effects caused by the platinum-based anticancer agent alone.

The route of administration and the mode of administration of the first composition and the second composition of the present invention may be independent of each other, and the method is not particularly limited, and the first composition and the second composition may be And any route of administration and mode of administration may be used. The first composition and the second composition may be administered orally or parenterally.

The parenteral administration may be, for example, intravenous administration, intraperitoneal administration, intramuscular administration, subcutaneous administration or local administration, and the method of applying, spraying or inhalation the composition to a diseased site may also be used But are not limited to.

The first composition of the present invention can be preferably orally administered, and the second composition can preferably be administered by injection, more preferably by intraperitoneal administration.

The appropriate application, spray or dose of the first composition and the second composition of the present invention may be appropriately selected depending on the formulation method, administration mode, administration time and / or administration route of the first composition and the second composition, May be varied by factors such as age, weight, sex, severity of disease symptoms, food intake, rate of excretion, etc. Those of ordinary skill in the art will readily be able to administer dosages effective for the desired treatment You can decide and prescribe.

As used herein, the term "cancer" refers to a disease associated with the control of death of a cell, which refers to a disease caused by excessive cell proliferation when the normal balance of apoptosis is broken. These abnormal hyperproliferative cells invade surrounding tissues and organs in some cases to form masses (masses), and they may cause destruction or deformation of normal structures in the body. Such conditions are collectively referred to as cancer.

In general, a tumor refers to a mass abnormally grown by autonomous overgrowth of the body tissue. The tumor can be divided into benign tumor and malignant tumor. Malignant tumors have a much faster growth rate than benign tumors, and they invade the surrounding tissues, causing metastasis and endangering life. These malignant tumors are commonly referred to as 'cancer'.

In the present invention, the type of cancer is not particularly limited. Non-limiting examples of such cancers include cerebrospinal tumors, head and neck cancer, lung cancer, breast cancer, thymoma, mesothelioma, esophageal cancer, cervical cancer, colon cancer, liver cancer, gastric cancer, pancreatic cancer, biliary cancer, kidney cancer, bladder cancer, prostate cancer, , Ovarian cancer, cervical cancer, endometrial cancer, colon cancer, lymphoma, acute leukemia, chronic leukemia, multiple myeloma, sarcoma, malignant melanoma and the like.

The first composition and the second composition of the present invention exhibit an effective anticancer efficacy even in cancer other than the above-mentioned kind of cancer, but are more effective for preventing, improving or treating lung cancer, colon cancer, stomach cancer, blood cancer and lymphoma .

As used herein, the term "prevention" refers to any act that inhibits or delays the onset of cancer by administering the first and second compositions of the invention to an individual.

The term "treatment" as used in the present invention means all the actions that cause the symptom of cancer to be improved or benefited by administering the first composition and the second composition of the present invention to the individual.

When the first composition and the second composition of the present invention are administered to an individual to prevent or treat cancer, the dose of the extract of Zymuglus or Chrysanthemum vulgaris, or fractions thereof, and the platinum-based anticancer agent, Even when administered in a relatively small amount, similar tumor growth inhibitory effect is exhibited, and further, in case of survival day, the effect is increased, and the synergistic effect on anticancer efficacy is exerted. In addition, the present invention alleviates the side effects such as weight loss and long-term weight reduction caused by the use of the platinum-based anticancer agent alone, and exhibits an effect of suppressing and reducing it to a considerable extent.

In view of the above results, the first and second compositions of the present invention can be used as an anticancer agent which is difficult to use an anticancer agent which causes a side effect of the prior art, an individual of low age or old age, and a constitution sensitive to stimuli applied outside the body It can be used more usefully in individuals and so on.

The kit comprising the first composition containing the extract of Zymugrus japonica or Bacillus subtilis or fractions thereof and the second composition containing the platinum-based anti-cancer agent according to the present invention is characterized by comprising an extract of Zymuglus or Bacillus subtilis or a fraction thereof and a platinum- The present invention provides a synergistic effect that not only shows a similar degree of anticancer efficacy in inhibiting the proliferation of cancer cells but also prolongs the survival period of the cancer disease individual even when administered in a significantly smaller amount than when each of them is administered.

The kit comprising the first and second compositions of the present invention or the first and second compositions of the present invention is more effective than the platinum-based anticancer drug alone in suppressing or reducing adverse effects caused by the individual It is safe to perform chemotherapy.

FIG. 1 is a graph showing the survival days of mice according to the combined use of japonica extract and a platinum-based anticancer agent, which are one embodiment of the present invention.
FIG. 2 is a graph showing changes in body weight of a mouse according to an embodiment of the present invention, which is a combination of a japonica extract and a platinum-based anticancer agent.
FIG. 3 is a graph showing a change in body weight of a mouse by administering the extract of Bacillus subtilis, an embodiment of the present invention.
FIG. 4 is a graph showing a change in body weight of a mouse according to an embodiment of the present invention, in combination with an extract of Bokwangjiae extract and a platinum-based anticancer agent.
FIG. 5 is a graph showing a decrease in the cisplatin-induced toxicity of the extract of Bacillus subtilis and its ethyl acetate fraction, which is an embodiment of the present invention.
FIG. 6A shows the effect of inhibiting the tumor volume increase in combination with the combined extract of Zymugrus japonica and Bacillus subtilis, which is an embodiment of the present invention, and the platinum-based anticancer agent.
FIG. 6B is a graph showing a change in the volume of a tumor according to the combined use of a mixed extract of Zymugrus japonica and Bacillus subtilis, and a platinum-based anticancer agent according to an embodiment of the present invention. In this data, '% ctrl' means the percentage of the mean tumor volume at the time of vehicle administration.
FIG. 6C shows the effect of inhibiting the tumor weight increase by the combination of the mixed extract of Zymugrus japonica and Bacillus subtilis, which is an embodiment of the present invention, and the platinum-based anticancer agent.
FIG. 7 is a graph showing a change in body weight of a mouse according to an embodiment of the present invention, which is a combination of a mixed extract of japonica japonica and Bacillus subtilis, and a platinum-based anticancer agent.
FIG. 8A is a graph showing changes in the liver weight according to the combined use of the mixed extract of japonica japonica and Bacillus subtilis, and the platinum-based anticancer agent of the present invention.
FIG. 8B is a graph showing changes in weight of kidneys according to the combined use of the mixed extract of Zymugrus japonica and Bacillus subtilis, and the platinum-based anticancer agent of the present invention.
FIG. 9 is a graph showing the cancer cell killing activity according to the combined use of the mixed extract of Zymugrus japonica and Bacillus subtilis, and the platinum-based anticancer agent according to one embodiment of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for illustrating the present invention, and thus the scope of the present invention is not construed as being limited by these embodiments.

Production Example 1: Preparation of Extracts of Zykthoxylum and White Radix

(1) Extract of Zymax

The seeds of Zygomyrthouse japonica were obtained, dried and ground, and then extracted at room temperature with 40 L of 80% ethanol per 9 kg of Seagrass seeds. The extraction was carried out by changing the solvent every time, and was repeated three times in total for 24 hours at a time. After the extraction, the extract was concentrated under reduced pressure to remove the oil component in the upper layer, and then the extract of the lower layer was dried and homogenized to obtain an extract of Zykthoxin. The obtained extract was dissolved in 0.5% carboxymethyl cellulose (CMC) aqueous solution containing 2% ethanol at a concentration of 125 mg / ml to 500 mg / ml and stored in a frozen state.

(2) Extract of Baekhwa

The roots of Korean white pine needles were obtained, dried and pulverized, and sonicated in 70% ethanol. The ultrasonic extraction was performed by exchanging the solvent every time, and was repeated twice for 60 minutes at a time. After the ultrasonic extraction, the extract was concentrated under reduced pressure and homogenized to obtain an extract of Bacillus subtilis. The obtained extract was dissolved in a 0.5% aqueous solution of carboxymethylcellulose containing 2% ethanol at a concentration of 125 mg / ml to 500 mg / ml and stored in a frozen state.

(3) Mixed extract of japonica and white mulberry

The above-prepared extracts of Zymoglass and Baishin can be prepared by mixing, or may be prepared by extracting the Zygomus japonica and Baisho extract together according to one of the methods described above in the raw material state.

In this example, the above-prepared extracts of Zymoguramis japonica and Bacillus subtilis were mixed and used.

Preparation Example 2: Preparation of fractions of Zykthoxylum and Scutellaria baicalensis

Distilled water was added to each of the japonica extracts obtained in Preparation Example 1 and the extracts of Bacillus chrysanthemum, respectively, and the suspension was suspended. Then, an equal amount of n-hexane was added and mixed. Then, the n-hexane-soluble fraction and the water-soluble fraction were separated, and this was repeated three times. The mixture was filtered and concentrated under reduced pressure to obtain a hexane fraction Respectively. Then, the hexane fraction was removed and ethyl acetate was added in the same amount to the remaining water layer, and an ethyl acetate fraction was obtained in the same manner as above. Then, the ethylacetate fraction was removed and an equal amount of butanol was added to the remaining water layer to obtain a butanol fraction in the same manner as described above. The butanol fraction was then removed and the remaining water layer was concentrated to obtain a water fraction.

The obtained hexane fraction, ethyl acetate fraction, butanol fraction and water fraction were respectively dried under reduced pressure and stored in a frozen state.

Example 1: Validation of survival day and weight loss of mice according to the combination administration of japonica extract and platinum-based anticancer agent

The japonica extract prepared in Preparation Example 1 and the platinum-based anticancer drug cisplatin, which were obtained in the market, were administered to an animal test group to determine survival days and weight loss of the animals.

Specifically, a 6-week-old Balb / c ^{nu / nu} mouse lacking immunity (obtained from a central laboratory animal) was purified for 1 week, and the A549 human lung cancer cell line of the logarithmic growth phase was diluted in RPMI medium without serum, 2 × 10 ⁵ cells per animal were injected into the lungs to create an ischemic lung cancer model.

One day after the injection of the lung cancer cells, each mouse was administered to each mouse according to the composition of the following Table 1, and the survival day and weight loss were measured.

[Table 1]

As a result, the survival rate and survival rate were significantly increased in the groups treated with japonica extract, cisplatin, japonica extract and cisplatin compared with the vehicle treated group. In particular, in the case of the japonica extract and cisplatin combination treatment group, the best survival days were increased even though each dose of japonica extract and cisplatin was reduced by half as compared with each single treatment group (Fig. 1).

In addition, in the weight change due to progression of lung cancer, the delayed effect of weight loss was superior to that of cisplatin treatment group in the case of the japonica extract alone, but the weight gradually decreased with progression of lung cancer. On the contrary, in the case of administration of japonica extract and cisplatin, body weight was decreased due to administration of cisplatin at the beginning, but the body weight was recovered over time, and it was confirmed that the side effect of cisplatin could be alleviated ).

Example 2: Effect of Cancer Cachexia Mitigation on the Cancer Animal Model by Administration of White Radish Extract

The development of cachexia in cancer progression and chemotherapy is inevitable, and cachexia, which is a major symptom of sudden weight loss (more than 5%), occurs in 90% or more of terminal cancer. In order to examine the effect of the extract of Bacillus subtilis on cancer, the A549 human lung cancer cell line was injected into the left lung of an immunodeficient mouse to prepare an ischemic lung cancer model, and the weight change of the mouse was measured according to the growth of the cancer 1 and the same model).

[Table 2]

As a result, as shown in Table 2, in the case of vehicle-administered group, rapid weight loss was observed after 50 days of tumor induction. However, mice administered with 250 mg / kg / d of Bombyx mori extract showed relatively normal weight until 80 days Respectively.

In addition, it was confirmed that the median survival time increase and the survival rate increase effect were shown compared to the vehicle administration group (FIG. 3).

Example 3: Evaluation of the efficacy of platinum-based anticancer drug induced chelating dentifrice extract

The white algae extract and cisplatin prepared in Preparation Example 1 were administered to each mouse grown in Example 1 according to the composition shown in the following Table 3 and the weight loss was measured

[Table 3]

As a result of the above experiment, when a high dose of cisplatin was administered, all the mice showed a rapid decrease in body weight. On the other hand, when cisplatin was administered in combination with cisplatin, the weight loss rate was significantly decreased, Also, it was confirmed that Bacillus chrysanthemum extract significantly alleviated adverse effects of chemotherapy (FIG. 4).

Example 4: Reduction of Cisplatin-Induced Toxicity of Bacillus licheniformis Extract and Ethyl Acetate Fraction

Cisplatin, widely used as an anticancer drug, causes death in experimental animals due to rapid weight loss, hepatotoxicity and hematopoietic toxicity when administered at a high dose. Bacillus thuringiensis extract and its ethyl acetate fraction have the effect of reducing the mortality due to the cisplatin toxicity and at the same time alleviating various hematopoietic toxicities and showing superior efficacy to megastrol acetate which is currently used as a cancer cachexia remover.

Thus, each mouse grown in Example 1 was administered according to the composition shown in the following Table 4, and the effect of reducing cisplatin-induced toxicity was confirmed. The results are shown in Table 5 and FIG.

[Table 4]

[Table 5]

As a result, as shown in Table 5, it was confirmed that the cisplatin-induced toxicity was reduced when cisplatin, Cisplatin and Eisaceafil EA fraction were used together. In addition, it was confirmed that the combined use of Bacillus chrysanthemum extract or Bacillus cholerae EA fraction showed better toxicity reduction effects than the case of using megestrol acetate currently used as a cancer cachexia remover (Table 5 and Fig. 5).

Example 5: Inhibition of tumor growth inhibition by the combined administration of the mixed extract of Zymugrus japonica and Bacillus subtilis and the platinum-based anticancer drug

In each of the mice raised in Example 1, the mixed extracts of Zymugoropsis and Bryophyta, prepared in Preparation Example 1, and cisplatin, a platinum-based anticancer agent obtained in the market, were administered in combination with the composition shown in the following Table 6 to inhibit tumor growth Were measured.

[Table 6]

In the administration of each of the above substances, the japonica extract, Bombyx mori extract, or the mixed extract of Zymugrus and Brycepia japonica were orally administered once a day, and the cisplatin was administered by intraperitoneal injection once a week. After the administration, each mouse was fed with water and feed, and tumor size (volume) and weight of each mouse were measured twice a week. The volume of the tumor was measured by calculating the long axis and short axis length (mm) of the tumor using calipers, and then calculating the short axis ² × long axis × 0.52.

As a result of the above-mentioned experiment, excellent synergistic effect was exhibited when the combined extracts of Zyklomus and White Radix and the combination of cisplatin and 2.5 mg / kg were administered in combination, respectively, as compared with the case where the japonica extract and Brassica officinalis extract were administered alone Showed excellent tumor growth inhibitory effect, showing similar tumor growth inhibitory effect as in the case of 5.0 mg / kg of cisplatin alone, showing that the same effect is obtained even when the dose of cisplatin with high toxicity is reduced (FIGS. 6A and 6B) .

In addition, in the case of increasing the tumor weight, when the combination of cisplatin and cisplatin in combination with the extract of Zymoglossia and Bacillus subtilis was also administered, excellent synergistic effects were exhibited, and the extracts of Zymugrus and Bacillus subtilis, as well as the test group administered with cisplatin alone (Fig. 6C).

Example 6: Verification of weight loss according to the combination administration of the mixed extract of Zykthoxylum japonica and Bacillus subtilis and a platinum-based anticancer drug

The weight loss of each of the mice raised in Example 1 was measured.

As a result, the cisplatin alone showed serious weight loss after about 6 weeks. As a result, it was found that side effects were caused by the use of cisplatin. On the other hand, when cisplatin and cisplatin were administered in combination, Was not observed.

In light of the above results, it was confirmed that a synergistic effect is positively generated when cisplatin is used in combination with Zygomycetes japonica and Bacillus subtilis extract, thereby suppressing or reducing adverse effects caused by cisplatin (FIG. 7).

Example 7: Evaluation of abnormality of organs according to the combination administration of the mixed extract of Zykthoxylum and Bacillus subtilis and a platinum-based anticancer drug

The weight loss and toxicity index changes of liver and kidney of each mouse that were grown in Example 1 were measured.

The liver and kidney weights of liver and kidney were reduced (Table 7 below). In the case of cisplatin alone, liver and kidney weights were reduced to a considerable extent and abnormalities were observed in the organs, while the mixed extracts of cisplatin and cisplatin (Fig. 8A and Fig. 8B), there was no significant difference compared to the control group in which the cancer cells were not injected.

[Table 7]

In addition, the results of measurement of hepatotoxicity and renal toxicity (Table 8 below) showed that hepatotoxicity index and kidney toxicity index increased significantly in the case of cisplatin alone group, whereas mixed extracts of cisplatin and cisplatin, When administered concomitantly, it was observed that the toxicity index was rather lower than the vehicle control.

[Table 8]

When the results of Examples 5 to 7 are summarized, the combination of cisplatin and cisplatin combined with the extract of Zymugrus japonica and Bacillus subtilis showed superior tumor growth inhibitory effect compared with the case of the conventional anticancer agent cisplatin alone And it could be used as an excellent anticancer agent.

In addition, when cisplatin is administered alone, there is a serious increase in liver toxicity and kidney toxicity index as well as serious weight loss of body weight and organs, resulting in serious side effects. In the present invention, When the cisplatin is administered in combination, the side effects caused by the cisplatin are not significantly or significantly inhibited or reduced by the positive synergy effect between the mixed extract and the cisplatin. Therefore, It is a high and valuable invention.

Example 8: Evaluation of cancer cell death by the combined administration of the mixed extract of Zygomugosa japonica and Bacillus subtilis and the platinum-based anticancer drug

5000 A549 human lung cancer cell lines per well were seeded in 96-well plates in 100 ml RPMI + 10% FBS culture medium for 24 hours. The medium was treated with cisplatin alone or in combination with cisplatin alone (5 mM, 20 mM, 40 mM), and a mixed extract of Zymoglossia and Bacillus subtilis, respectively.

Cell viability in each well was measured using EZ-Cytox solution 48 hours after the treatment. The experimental results were calculated as the relative survival rate to the mean value of cell viability in negative control (PBS) (Fig. 9).

As a result of the above experiment, it was confirmed that when the cisplatin 5 mM and the mixed extract of Zymugrus and Bacillus subtilis were administered in combination, the cancer cell killing effect was almost the same as that of the cisplatin 40 mM alone, showing strong synergistic effect.

It is to be understood that both the foregoing general description and the following detailed description of the present invention are exemplary and explanatory and are intended to provide further explanation of the invention as claimed. More variations are possible within a range that does not. Accordingly, the present invention may be embodied in other ways than those specifically described and illustrated herein, and will be understood by those skilled in the art.

Claims (13)

a) a first composition containing, as an active ingredient, an extract of Descurainia sophia and Peucedanum praeruptorum Dunn or a fraction thereof; And
b) a second composition comprising a platinum-based anticancer agent as an active ingredient;
A kit for preventing or treating cancer,
Wherein the platinum-based anticancer agent is at least one selected from the group consisting of cisplatin, carboplatin, and nedaplatin. The kit according to claim 1, wherein the first composition comprises the japonica extract or a fraction thereof and the Bacillus subtilis extract or a fraction thereof in a weight ratio of 1: 1. The kit according to claim 1, wherein the extract of the first composition is extracted with at least one solvent selected from the group consisting of water and C ₁ to C ₄ alcohols. The kit according to claim 1, wherein the fraction of the first composition is fractionated with at least one solvent selected from the group consisting of water, alcohol, chloroform, ethyl acetate and hexane. 2. The kit of claim 1, wherein the kit comprises the first composition and the second composition in a weight ratio of 5: 1 to 15: 1. The kit according to claim 1, wherein the kit shows a synergistic effect of anti-cancer when the first composition and the second composition are administered to an individual, mitigates cancer cachexia, and reduces platinum-based anticancer drug-induced toxicity Features a kit. 2. The kit according to claim 1, wherein the kit is different in administration route or administration frequency of the first composition and the second composition. a) an agent for promoting the efficacy of a platinum-based anticancer agent comprising an extract of Descurainia sophia and Peucedanum praeruptorum Dunn or a fraction thereof as an active ingredient, wherein the platinum-based anticancer agent is selected from the group consisting of cisplatin, &Lt; / RTI &gt; and latin. 9. The agent according to claim 8, wherein the agent enhances tumor growth inhibitory effect or cancer cell killing effect. A pharmaceutical composition for suppressing side effects of a platinum-based anticancer drug comprising an extract of Peucedanum praeruptorum Dunn or a fraction thereof as an active ingredient,
Wherein the platinum-based anticancer agent is at least one selected from the group consisting of cisplatin, carboplatin, and nedaplatin. 11. The formulation according to claim 10, wherein the side effect is selected from the group consisting of weight loss of the individual, loss of organ weight, increased toxicity of the organ, and pain due to overdose and frequent dosing frequency.
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