JP6947521B2 - Cell proliferation inhibitor - Google Patents

Description

The present invention relates to a cell proliferation inhibitor, a cancer preventive / therapeutic agent, and a food and drink composition for cell proliferation inhibition.

Currently, cancer is the leading cause of death, and the number of patients is increasing year by year. Among them, an extract derived from a natural product having an effect of suppressing cancer cell growth has been found, and is highly safe as compared with conventional anticancer agents. Therefore, it is expected to provide a cell proliferation inhibitor having few side effects, an antitumor agent containing these components (also called an anticancer agent or an anticancer agent), and a health food for preventing cancer.

For example, Patent Document 1 describes an extract of Tamarix gallica, which is a halophyte derived from arid land and has an inhibitory effect on tumor cell proliferation.

Japanese Unexamined Patent Publication No. 2013-75852

An object of the present invention is to provide a novel cell proliferation inhibitor (cancer preventive / therapeutic agent) that can replace a conventionally known antitumor agent.

As a result of diligent research to solve the above problems, the present inventors have found that the sweet basil extract exhibits an excellent cell proliferation inhibitory effect, and have completed the present invention.

The first form of the present invention is a cell proliferation inhibitor containing a sweet basil extract.

A second form of the present invention is a food and drink composition for suppressing cell proliferation, which comprises a sweet basil extract.

According to the present invention, a novel cell proliferation inhibitor (cancer preventive / therapeutic agent) that can replace the conventionally known cell proliferation inhibitor (cancer preventive / therapeutic agent) is provided.

Hereinafter, embodiments of the present invention will be described. The present invention is not limited to the following embodiments. In the present specification, "X to Y" indicating a range means "X or more and Y or less", and "weight" and "mass", "weight%" and "mass%", and "parts by weight" and "parts by mass". Is treated as a synonym. Unless otherwise specified, the operation and physical properties are measured under the conditions of room temperature (20 to 25 ° C.) / relative humidity of 40 to 50%.

<Cell proliferation inhibitor>
The first form of the present invention is a cell proliferation inhibitor containing a sweet basil extract.

The sweet basil extract, which is the active ingredient of the cell growth inhibitor of the present invention, can be obtained by extracting all or a part of sweet basil (Ocimum basil) with a suitable solvent.

Here, the portion of sweet basil to be extracted is not particularly limited, and may be the whole sweet basil or a portion (leaves, seeds, roots, etc.). Of these, it is preferable to extract leaves in consideration of the cell proliferation inhibitory effect.

In addition, the whole sweet basil to be extracted or a part thereof (hereinafter, also simply referred to as "sweet basil raw material") may be subjected to extraction as it is, but it is dried in advance before being subjected to extraction. And / or preferably ground. This makes it possible to more efficiently extract the desired active ingredient from sweet basil.

Here, the drying conditions for pre-drying the sweet basil raw material are not particularly limited. Considering the ease of pulverization and the like, the drying temperature is preferably 20 to 60 ° C, more preferably 20 to 40 ° C. The drying time is preferably 24-120 hours, more preferably 48-96 hours. Alternatively, the sweet basil raw material may be dried by a method such as a freeze-drying powder method, a high-pressure method, or an ultra-high pressure method. Of these, the high-pressure method is a method in which cells in a sweet basil raw material are pressure-crushed by, for example, high-pressure heat treatment at 100 to 150 ° C. for 2 to 10 hours (for example, 120 ° C. for 4 hours).

Further, the crushing conditions when the sweet basil raw material is crushed in advance are also not particularly limited.
The size of the sweet basil raw material after pulverization is preferably about 0.5 to 10 mm, more preferably about 1 to 5 mm in consideration of extraction efficiency and the like. Examples of the crushing method include a method of slicing with a cutting machine, a slicer, a cutter, a peeler, a jaw crusher, a jet mill, a blender and the like.

The sweet basil raw material, which has been pre-dried and / or ground if necessary, is then extracted with a suitable solvent. The solvent that can be used here is not particularly limited as long as it can extract the active ingredient from the sweet basil raw material, and is appropriately selected. Specifically, water (including tap water, industrial water, distilled water, back-penetration membrane water, filtered water, sterilized water, purified water, etc.); methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, Alcohols such as 2-butanol, propylene glycol and 1,3-butylene glycol; esters such as methyl acetate and ethyl acetate; ketones such as acetone; diethyl ether, formaldehyde, dimethyl sulfoxide and the like. The solvent may be used alone or in the form of a mixed solvent of two or more kinds. Of these, the solvent is preferably water or a mixed solution of water and at least one alcohol selected from the group consisting of methanol, ethanol and isopropanol in consideration of extraction efficiency, safety and the like. That is, in a preferred embodiment of the present invention, the sweet basil extract is an extract of water or a mixture of water and at least one alcohol selected from the group consisting of methanol, ethanol and isopropanol.

If necessary, the sweet basil raw material may be extracted under acidic or alkaline conditions. That is, an acidic or alkaline solvent may be used. Here, the acid that can be used when preparing the acidic solvent is not particularly limited, but is not particularly limited, but is not limited to inorganic acids such as hydrochloric acid, sulfuric acid, nitrate and phosphoric acid, acetic acid, citric acid, oxalic acid, succinic acid, formic acid, propionic acid and the like. Organic acids and the like. The alkalinity is not particularly limited as the alkali that can be used when preparing the solvent, and examples thereof include potassium hydroxide, sodium hydroxide, and sodium carbonate. The pH of the solvent when extracting the sweet basil raw material under acidic or alkaline conditions is appropriately selected in consideration of the extraction conditions and the like. When an acidic solvent or an alkaline solvent is used, it is preferable to neutralize the extract so that it becomes neutral (pH = about 7 ± 1) after extraction.

The amount of the solvent added is not particularly limited as long as the active ingredient can be extracted from the sweet basil raw material. Specifically, it is preferable to add the solvent in an amount of 1 to 100 ml, more preferably 5 to 50 ml, with respect to 1 g of the sweet basil raw material.

The extraction conditions are not particularly limited as long as the active ingredient can be extracted from the sweet basil raw material. Specifically, the extraction temperature is preferably 40 to 200 ° C, more preferably 60 to 150 ° C. The extraction time is preferably 30 minutes to 6 hours, more preferably 1 to 4 hours. Under such conditions, the active ingredient can be efficiently extracted from the sweet basil raw material.

After the above extraction step, the solid matter (sweet basil raw material residue) is removed from the mixed solution of the sweet basil raw material and the solvent, and the extract is separated. Here, the separation method is not particularly limited, and examples thereof include filtration and centrifugation. Further, this extract may be used as it is, but if necessary, a diluted form by a diluted solution, an extract by concentration, a paste or solid form, a frozen product form by freezing, a dried powder form by freeze-drying, etc. It may be converted into various forms (extracts). Here, the conversion method may be applied alone or in combination of two or more. Preferably, a method of concentrating the extract to an appropriate concentration (for example, concentration under reduced pressure) is preferably used.

The extract or extract may be further purified. Here, the purification method is not particularly limited, and a known purification method can be used. Specifically, a method of adding a quaternary ammonium salt such as cetylpyridinium chloride to obtain a precipitate, and washing the precipitate with an appropriate solvent (for example, water or alcohol), anion exchange ion exchange chromatography, Cation exchange Ion exchange chromatography, phosphocellulose chromatography, chromatography by hydrophobic reaction, affinity chromatography, method using chromatography using hydroxyapatite chromatography, lectin chromatography and the like, recrystallization method and the like can be mentioned.

The sweet basil extract according to the present invention obtained above has a cell proliferation inhibitory effect. Therefore, the sweet basil extract according to the present invention can be suitably used as a cell proliferation inhibitor.

Here, the target of use of the cell proliferation inhibitor is not particularly limited, but is a mammal and a bird, preferably a mammal and a bird suffering from cancer. Here, mammals include primates such as humans, monkeys, gorillas, chimpanzees and orangutans, as well as non-humans such as mice, rats, hamsters, guinea pigs, rabbits, dogs, cats, pigs, cows, horses, sheep, camels and goats. Includes both human mammals. Birds include chickens, quails, and pigeons. Of these, humans, hamsters, guinea pigs, rabbits, dogs, cats and pigs are preferred. The target of use is, other than humans, more preferably pet animals such as rabbits, dogs, and cats.

The cell proliferation inhibitor of the present invention is effective in preventing and / or treating cancer. Therefore, one embodiment of the present invention relates to a prophylactic and / or therapeutic agent for cancer, which comprises the cell proliferation inhibitor of the present invention. As used herein, "prevention and / or treatment of cancer" means suppressing the progression of cancer in a patient suffering from cancer, eliminating the cancer or tumor, suppressing the growth of cancer or tumor, or cancer. It means satisfying at least one of preventing the onset of cancer and preventing the recurrence of cancer. Therefore, as used herein, the term "cancer prophylactic and / or therapeutic agent" means an agent that exhibits the above prophylactic and / or therapeutic effect when used in the treatment of cancer.

Here, the type of cancer that is the target of a cancer preventive and / or therapeutic agent is not particularly limited. For example, cancer of the nervous system (eg, brain tumor, cervical cancer); cancer of the digestive system (eg, oral cancer, pharyngeal cancer, esophageal cancer, gastric cancer, liver cancer, bile sac cancer, biliary tract cancer, spleen cancer, colon cancer, small bowel cancer) , Duodenal cancer, colon cancer, colon adenocarcinoma, rectal cancer, pancreatic cancer, liver cancer); musculoskeletal cancer (eg, sarcoma, osteosarcoma, myeloma); urinary cancer (eg, bladder cancer, renal cancer) ); Reproductive system cancer (eg, breast cancer, uterine cancer, ovarian cancer, testis cancer, prostate cancer); Respiratory system cancer (eg, lung cancer); Hematopoietic cancer (eg, acute or chronic myeloid leukemia,) Leukemia such as acute premyelogenous leukemia, acute or chronic lymphocytic leukemia, malignant lymphoma (lymphosarcoma), angiosarcoma, multiple myeloma, myelodystrophy syndrome, primary myelopathy, epithelial cytoma); Examples thereof include cancer, parathyroid cancer, tongue cancer, malignant melanoma, obesity cell tumor, cutaneous histiocytoma, lipoma, hair follicle tumor, cutaneous papilloma, sebaceous adenoma, and basal cell cancer. Of these, the cancer prophylactic and / or therapeutic agent according to the present invention has a higher effect on leukemia and gastrointestinal cancer.

Thus, preferred embodiments of the present invention relate to prophylactic and / or therapeutic agents for leukemia, including the cell proliferation inhibitors of the present invention. Among leukemias, the prophylactic and / or therapeutic agent for cancer according to the present invention has a higher effect on chronic myelogenous leukemia.

Also, preferred embodiments of the present invention relate to prophylactic and / or therapeutic agents for gastrointestinal cancers, including the cell proliferation inhibitors of the present invention. Among the cancers of the digestive system, the prophylactic and / or therapeutic agent for the cancer according to the present invention has a higher effect on colon adenocarcinoma.

The cancer prophylactic and / or therapeutic agent of the present invention can be used in the same dosage form as before, except that the sweet basil extract according to the present invention is contained as an active ingredient. That is, the cancer prophylactic and / or therapeutic agent of the present invention is a drug, quasi-drug, suitable for parenteral administration, oral administration or external administration, mixed with a pharmaceutically acceptable additive such as an excipient. It can be used in the form of food and cosmetics. In foods, it can be added to fats and oils products, emulsified products, soft drinks and the like. In pharmaceutical products, it can be added to oral preparations, external preparations, injections, inhalants, nasal drops / eye drops, etc., and depending on the method of use, tablets, solutions, injections, ointments, creams, lotions, aerosols, etc. , A desired dosage form such as a suppository can be obtained. Further, if necessary, excipients, bases, emulsifiers, stabilizers, solubilizing agents, flavoring agents, preservatives, fragrances, colorants, coating agents and the like can be appropriately added. Quasi-drugs and cosmetics can be added to lotions, emulsions, creams, etc., and if necessary, oils, moisturizers, UV absorbers, water-soluble polymers, antioxidants, surfactants, metals. Ion sequestering agents, antibacterial preservatives, etc. can be blended.

The dosage of the prophylactic and / or therapeutic agent for the cancer of the present invention depends on the route of administration; the nature of the patient's disease; the size, weight, surface area, age and gender of the patient; other agents administered; and the judgment of the attending physician. different. A suitable dose (dry weight equivalent of sweet basil extract) is 10-100 mg / kg body weight per day. Given the different available compositions and the different efficacy of different routes of administration, it is expected that the required doses can vary widely. These dose level variations can be adjusted using standard empirical procedures for optimality known in the art. Especially for oral delivery, encapsulation of the composition in a suitable delivery vehicle (eg, polymer microparticles or implantable device) increases delivery efficiency. Moreover, the said dose may be divided into once a day or a plurality of times. Alternatively, in some cases, it may be administered at a lower frequency (eg, weekly or monthly). In addition, even in the same patient, the dose may vary depending on the patient's symptoms and severity.

In cancer prophylaxis and / or therapeutic agents, therapeutically effective amounts of sweet basil extract may be formulated with one or more pharmaceutically acceptable carriers (additives) and / or diluents. That is, the cancer prophylactic and / or therapeutic agents of the present invention may also be provided in the form of drug compositions containing pharmaceutically acceptable additives (eg, excipients, carriers, etc.). Prophylactic and / or therapeutic agents for such forms of cancer can be specifically formulated for administration in solid or liquid form, as described in detail below. For oral administration, for example, liquid medicine (aqueous solution or non-aqueous solution or suspension), tablets, giant pills, powdered medicine, granules, and pastes for application to the tongue can be exemplified. For parenteral administration, for example, as a sterile solution or suspension, for example, a formulation for subcutaneous, intramuscular or intravenous injection, or for topical use, for example, as a cream, ointment or spray applied to the skin, or. It can be formulated intravaginally or in the rectum, for example as a vaginal suppository, cream or effervescent agent.

As used herein, a "therapeutically effective amount" as used herein is effective in producing any desired therapeutic effect at a reasonable benefit / risk ratio applicable to any medical treatment. Means the amount of active agent or composition. For example, the dose of the prophylactic and / or therapeutic agent for the cancer of the present invention varies depending on the target disease, the administration target, the administration route, etc., but the prevention and / or treatment of the cancer of the present invention for the purpose of prevention and / or treatment. When the drug is orally administered, the dose can be easily varied depending on conditions such as the weight of the subject, and thus can be appropriately selected by those skilled in the art. Finally, the attending physician makes an appropriate selection in consideration of the patient's symptoms and severity.

As used herein, "pharmaceutically acceptable" means, within the scope of correct medical judgment, in proportion to a reasonable benefit / risk ratio, without problems or complications such as excessive toxicity, irritation, allergic reactions, etc. It is used to refer to compounds, materials, compositions, and / or dosage forms that are suitable for use in contact with the tissue of the subject of treatment (humans, mammals, etc.).

A pharmaceutically acceptable carrier is a liquid or solid filling that is involved in transporting or transporting a prophylactic and / or therapeutic agent for the cancer of the invention from one organ or part of the body to another organ or part of the body. Means a pharmaceutically acceptable material, composition or excipient, such as an agent, diluent, prosthesis, solvent or encapsulating material. Each carrier must be "acceptable" in the sense that it is compatible with the other components of the dosage form and is not harmful to the patient. Pharmaceutically acceptable carriers include, but are not limited to, sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and derivatives thereof such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; Powdered tragacanth; malt; gelatin; starch; complementary agents such as cocoa butter and suppository wax; oils such as peanut oil, cottonseed oil, benivana oil, sesame oil, olive oil, corn oil and soybean oil; glycols such as propylene glycol; Polycarbonates such as glycerin, sorbitol, mannitol and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline Ringer solution; ethyl alcohol; starch buffer solution; as well as other non-toxic compatible substances used in drug formulation. In some embodiments, the drug formulation is non-feverish. That is, it is desirable that the patient's body temperature is not raised. Other wetting agents, emulsifiers and lubricants such as sodium lauryl sulfate and magnesium stearate, as well as colorants, release agents, coatings, sweeteners, flavors and flavors, preservatives and antioxidants can prevent and / or prevent cancer. Alternatively, it may be contained in a therapeutic agent.

Pharmaceutically acceptable antioxidants include, but are not limited to, water-soluble antioxidants such as ascorbic acid, cysteine hydrochloride, sodium hydrogensulfate, sodium disulfate, sodium sulfite, etc .; ascorbyl palmitate, butylhydroxyanisole ( Oil-soluble antioxidants such as BHA), butylhydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, etc .; as well as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, etc. Examples include metal chelating agents.

The cancer prophylactic and / or therapeutic agents of the present invention can be used in various dosage forms such as oral, nasal, topical (including oral and sublingual), rectal, vaginal and / or parenteral administration. Dosage forms may be conveniently presented in unit dosage forms and may be prepared by any method well known in the pharmaceutical art. The amount of active ingredient that can be combined with the carrier material to create a single dosage form will vary depending on the host being treated and the particular mode of administration. The amount of active ingredient that can be combined with the carrier material to create a single dosage form is generally the amount of compound that produces a therapeutic effect, whereas the amount of active ingredient (sweet basil extract) is generally the amount of cancer prevention. And / or about 0.1 parts by weight to about 99 parts by weight, preferably about 1 part by weight to about 70 parts by weight, more preferably about 5 parts by weight to about 50 parts by weight, based on 100 parts by weight of the therapeutic agent. It is a part by weight.

The method of preparing these dosage forms or compositions comprises the step of combining the sweet basil extract according to the present invention with optionally one or more sub-ingredients. Generally, the dosage form is prepared by uniformly and tightly binding the sweet basil extract according to the invention to a liquid carrier, a micronized solid carrier, or both, and shaping the product if necessary.

For example, the dosage forms of the invention suitable for oral administration are in the form of capsules, sachets, pills, tablets, lozenges (using seasoned base ingredients, usually syrup and gum arabic or tragacant), powders, granules. May be, or as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil or water-in-oil liquid emulsion, or as an elixir or syrup, or as a scented tablet (such as gelatin and glycerin, or sucrose and arabic rubber). (Use an inactive base) and / or a gargle and the like, each containing a predetermined amount of the sweet basil extract according to the present invention as an active ingredient. The cancer prophylactic and / or therapeutic agents of the present invention may be administered as giant pills, licks, or pastes.

In solid dosage forms for oral administration (capsules, tablets, pills, sugar-coated tablets, powders, granules, etc.), the active ingredient (sweet basil extract) is one such as sodium citrate or dicalcium phosphate or Mixed with multiple pharmaceutically acceptable carriers and / or any of the following: fillers or bulking agents such as starch, lactose, sucrose, glucose, mannitol, and / or silicic acid; eg, carboxymethyl cellulose, alginate. Caking agents such as gelatin, polyvinylpyrrolidone, sucrose and / or gum arabic; moisturizers such as glycerol; such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate. Disintegrant; Dissolution retarder such as paraffin; Absorption enhancer such as quaternary ammonium compound; Wetting agent such as cetyl alcohol and glycerol monostearate; Absorbent such as kaolin and bentonite clay; Talk, calcium stearate Lubricators such as magnesium stearate, solid polyethylene glycol, sodium lauryl sulphate, and mixtures thereof; and colorants. In the case of capsules, tablets and pills, the cancer prophylactic and / or therapeutic agents of the present invention may include buffers. Similar types of solid compositions can also be used as fillers in soft and hard filled gelatin capsules with complementary agents such as lactose or lactose and high molecular weight polyethylene glycol or the like.

Also, tablets can optionally be made by compression or molding, with one or more sub-ingredients. Compressed tablets include binders (eg gelatin or hydroxypropylmethyl cellulose), lubricants, inert diluents, preservatives, disintegrants (eg sodium glycolate or crosslinked sodium carboxymethyl cellulose), surface activators. Alternatively, it can be prepared using a dispersant. Molded tablets can be made by molding a mixture of powdered compounds moistened with an inert liquid diluent on a suitable machine.

Solid dosage forms such as tablets, such as dragees, capsules, pills and granules, may optionally be knurled or prepared using coatings and shells such as enteric coatings well known in the field of drug dispensing. good. They were used, for example, in various proportions of hydroxypropyl methylcellulose, other polymer matrices, liposomes and / or microspheres to provide the desired release profile, and the internal active ingredients were sustained release or controlled. It may be dispensed to provide release. They may be sterilized, for example, by filtration through a bacterial retention filter or by incorporating a sterile agent in the form of a sterile solid composition that can be dissolved in a sterile injectable medium such as sterile water immediately prior to use. .. These compositions may optionally contain a milky whitening agent, in a composition that releases one or more active ingredients only in certain parts of the gastrointestinal tract, or preferentially there, in an optionally delayed manner. There may be. Examples of implantable compositions that can be used are polymeric substances and waxes. The active ingredient may be in microencapsulated form with one or more of the above-mentioned prostheses, if appropriate.

Liquid dosage forms for oral administration of the cancer prophylaxis and / or therapeutic agents of the present invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, liquid dosage forms include inert diluents commonly used in the art such as water and other solvents, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzoic acid. Like fatty acid esters of benzyl, propylene glycol, 1,3-butadiene glycol, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofuryl alcohols, polyethylene glycol and sorbitan. Solubilizers and emulsifiers, and mixtures thereof. In addition to the Inactive Diluent, the oral composition may also include adjuncts such as wetting agents, emulsifying and suspending agents, sweeteners, flavoring agents, coloring agents, flavoring agents and preservatives. Suspensions, in addition to active compounds, such as, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar and tragacant, and mixtures thereof. It may contain a turbid agent.

Dosage forms of the cancer prophylaxis and / or therapeutic agents of the invention for rectal or vaginal administration can be presented as suppositories. The suppository is a mixture of one or more suitable non-irritating prostheses or carriers, including, for example, cocoa butter, polyethylene glycol, suppository wax or salicylate, and one or more agents of the invention. Because it is solid at room temperature but liquid at body temperature, it will melt in the rectum or vaginal cavity and release the active compound. Suitable dosage forms for vaginal administration also include pessaries, tampons, creams, gels, pastes, effervescent or spray dosage forms containing carriers as known to be suitable in the art.

Dosing forms of topical or transdermal administration of the cancer prophylactic and / or therapeutic agents of the present invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active ingredient (sweet basil extract) may be mixed under sterile conditions with a pharmaceutically acceptable substrate and, if desired, a preservative, buffer, or propellant. Ointments, pastes, creams and gels, in addition to the active ingredient (sweet basil extract), are animal fats or vegetable fats, oils, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acids, May include salves such as talc and zinc oxide, or mixtures thereof.

In addition to the active ingredient (sweet basil extract), powders and sprays may also contain prostheses such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder, or mixtures of these substances. good. The spray may further comprise fluorinated hydrocarbons and conventional high pressure gases such as volatile unsubstituted hydrocarbons such as butane and propane.

Percutaneous patches have the additional advantage of controlling and delivering the prophylactic and / or therapeutic agents of the cancer of the invention to the body. Such a dosage form can be made by dissolving or dispersing the cell proliferation inhibitor of the present invention in a suitable medium. Absorption enhancers can also be used to increase the flux of substances containing the prophylactic and / or therapeutic agents of the cancer of the invention across the skin. The speed of such a flux can be controlled either by providing a speed control membrane or by dispersing the compound in a polymer matrix or gel.

The cancer prophylactic and / or therapeutic agents of the invention suitable for parenteral administration include one or more pharmaceutically acceptable sterile isotonic or non-aqueous solutions, dispersants, suspensions, along with the sweet basil extracts according to the invention. Containing turbid liquids or emulsions, or sterile powders that can be reconstituted in sterile injectable solutions or dispersants just prior to use, such as antioxidants, buffers, bacteriostats, preparations with the target recipient's blood, etc. It may contain a solute to stretch, or a suspending or concentrating agent.

Examples of suitable aqueous and non-aqueous carriers that can be used in the cancer prophylactic and / or therapeutic agents of the present invention are water, ethanol, polyols (eg, glycerol, propylene glycol, polyethylene glycol, etc.), and suitable ones thereof. There are mixtures, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. The inherent fluidity can be maintained, for example, by the use of a coating material such as lecithin, by the maintenance of the required particle size in the case of dispersants, and by the use of surfactants.

The cancer prophylactic and / or therapeutic agents of the present invention may include adjuvants such as preservatives, wetting agents, emulsifying agents and dispersants. Prevention of microbial activity can be ensured, for example, by the inclusion of various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol sorbate. It may be desirable to include isotonic agents such as sugar, sodium chloride, etc. in the composition. In addition, sustained absorption of the injectable drug form can be caused by the inclusion of absorption-delaying agents such as aluminum monostearate and gelatin.

One embodiment of the present invention relates to a method for suppressing cancer cell metastasis, which comprises administering the cancer cell metastasis inhibitor according to the present invention to a patient who needs to suppress cancer metastasis. Furthermore, one embodiment of the present invention comprises administering the cancer cell metastasis inhibitor according to the present invention to a patient who needs to suppress or prevent cancer metastasis after cancer removal, thereby suppressing cancer metastasis after cancer removal. Or about preventive measures.

<Food and drink composition for cell proliferation suppression>
In the second aspect of the present invention, a food and drink composition for suppressing cell proliferation, which comprises a sweet basil extract, is provided.

The form of the food or drink composition for suppressing cell growth is not particularly limited, and liquid, gel-like or solid foods (for example, juice, soft drink, tea, soybean milk, salad oil, dressing, yogurt, jelly, pudding, sprinkle) , Baby milk powder, cake mix, powdered or liquid dairy products, bread, cookies, etc.), and if necessary, pellets, tablets, along with excipients such as dextrin, lactose, starch, fragrances, pigments, etc. It may be processed into granules or the like. Further, the sweet basil extract can be coated with gelatin or the like and molded into capsules to be used as a health food, a dietary supplement, or the like. The amount of sweet basil extract contained in the food or drink composition for cell proliferation suppression is difficult to uniformly specify depending on the type and condition of the food or composition, but is 0.01 with respect to the total weight of the food. ~ 90% by weight, more preferably 0.1 to 80% by weight. With such a blending amount, the effect of the sweet basil extract can be fully exhibited without impairing the flavor. In addition, food can be easily prepared.

Here, the "food and drink composition" means a composition intended to be ingested by mammals (including pets) such as humans. For example, a pet food composition is a food or drink composition intended to be ingested by a pet. Food and beverage compositions are widely known in the art. Pet food compositions may or may not be nutritionally balanced and, in addition to supplements (eg, food), are nutritionally balanced compositions suitable for daily diets. You may. Here, "nutritionally balanced" means that the composition of the present invention has known nutrients necessary for sustaining life in an appropriate amount and proportion in the field of pet nutrition. do.

In a preferred embodiment of the present invention, the food or drink composition for suppressing cell proliferation is a health food for humans or a pet food composition.

Here, when the sweet basil extract according to the present invention is added / used to human health foods (human health foods) and pet foods, the amount (content) of the sweet basil extract added is not particularly limited. However, the amount is preferably about 0.01 to 30% by weight, more preferably about 0.05 to 20% by weight, based on health foods and pet foods (in terms of solid content). Alternatively, the sweet basil extract is administered in a total daily weight of preferably about 0.1 to 1000 mg / kg body weight, more preferably about 1 to 500 mg / kg body weight. With such an amount, a sufficient cancer preventive effect can be achieved. In addition, if the amount is as described above, the pet's taste is not impaired, and the pet consumes the entire amount of the given pet food.

The pet food contains the same ingredients as before except that it contains the sweet basil extract according to the present invention. For example, in pet food, in addition to the sweet basil extract according to the present invention, monosaccharides, oligosaccharides, polysaccharides, dietary fiber, starches (for example, waxy corn starch, corn starch, wheat starch, rice starch, rice starch) , Marin 薯 starch, sweet dew starch, tapioca starch, sago starch, chemically treated or chemically modified processed starch) and grains (eg, corn, barley, wheat, rye, sorghum, rice, hie, foxtail millet, Carbohydrate sources such as Amarasansus, Kinua); Livestock and meat such as cows, pigs, sheep, rabbits and kangaroos, their by-products and processed products, chickens, turkeys, starches such as quail, their by-products and household products, Animal protein sources such as fish meat such as fish and white fish, its by-products and processed products, and the lettering of the above raw materials such as meat meal, meat bone, chicken meal, portary meal, fish meal; soybean protein, wheat protein. , Wheat gluten, corn starch, and other vegetable protein sources; α-sitosterol, β-sitosterol, stigmasterol, campesterol, α-sitstanol, β-sitstanol, stigmasterol, campestanol, cycloartenol Free forms such as starches such as these fatty acid esters, ferulic acid esters, cinnamon acid esters and other plant starches; rice starch, bran and other starches, soybean starch and other lees, vegetable extracts and other vegetables, vitamin A, Examples thereof include vitamins such as B1, B2, D, E, niacin, pantothenic acid and carotene. In addition to the above, other additives such as gelling agents, shape-retaining agents, pH adjusters, seasonings, preservatives, and nutritional supplements generally used in pet food may be contained. In addition to or in place of the above other additives, antioxidants such as butylhydroxyanisole (BHA), dibutylhydroxytoluene (BHT), ethoxyquin, tert-butylhydroquinone (TBHQ), propyl gallate, etc. It can also be used together. The addition amount (content) of each of the above-mentioned components is not particularly limited, and the same amount as before can be applied.

Pet food is produced by a conventionally known method. For example, it can be produced by mixing the sweet basil extract according to the present invention and the above-mentioned necessary components into a desired form. As an example, citric acid or citrate, if necessary, mixed with sweet basil extract, grain, meat meal and mineral components such as iron and copper, mixed well and then hydrated with water or steam. Extrusion molding is performed with an extruder. After that, the pet food is produced by drying with hot air, preferably until the water content is 10% or less. When pet food contains fats and oils having fatty acids having two or more double bonds, it is desirable to coat them after drying them with hot air.

The pet food may be in any form such as dry type, wet type, semi-moist type, jerky type, biscuit type, gum type, granular, powdery, soup-like, etc., but the dry type is convenient for storage. It is preferable from the viewpoint of sex. Examples of the dry type pet food include a kibble shape, a flat plate shape, and a bone shape. From the viewpoint of obtaining a shape that is easy to chew and handle for pets, the bulk density is 100 kg / m ³ or more, preferably 300 kg / m ³ or more, and 900 kg / m ³ or less, preferably 700 kg / m ³ or less. Yes, or preferably 100-900 kg / m ³ , especially 300-700 kg / m ³ . Pet food may also be provided in bagged, boxed, packed, canned or retort pouched forms.

The effects of the present invention will be described with reference to the following examples and comparative examples. However, the technical scope of the present invention is not limited to the following examples. In the following examples, the operation was performed at room temperature (25 ° C.) unless otherwise specified. Unless otherwise specified, "%" and "parts" mean "% by weight" and "parts by weight", respectively.

(Preparation of sweet basil extract)
The dried sweet basil was cut into about 1 to 5 mm with a blender, 50 ml of a 70 v / v% ethanol aqueous solution was added to 3.0 g thereof, and the mixture was heated at 90 ° C. for 2 hours for extraction. After that, filtration was performed to remove solids to obtain an extract. The obtained extract was concentrated under reduced pressure to obtain 0.54 g of an extract.

[Anti-cancer activity evaluation]
(Cell proliferation inhibitory effect on leukemia-derived cells)
The extract obtained above was dissolved in dimethyl sulfoxide (DMSO) to a concentration of 10 mg / ml to prepare an extract solution (sample).

Human chronic myelogenous leukemia-derived K562 cells were cultured in RPMI1640 medium containing 10% FBS at 37 ° C. under _{5% by volume CO 2.} ^{The cultured cells were seeded on a 24-well plate so as to have 5 × 10 4} cells per well, and then 1 μl of the extract solution prepared above was added so that the final concentration of the extract was 10 μg / ml. .. As a control, 1 μl of DMSO as a solvent was added. For 48 hours after adding the extract solution or DMSO, K562 cells were _{cultured under 5% by volume CO 2} at 37 ° C. After culturing for a predetermined time, the number of viable cells was measured by the trypan blue staining method, and the cell growth inhibition rate (%) of each sample was calculated by the following formula (1). The results are shown in Table 1. In the following formula (1), the "number of viable cells of the sample" indicates the number of viable cells of K562 cells when the extract solution (sample) was added and cultured, and the "number of viable cells of the control" is DMSO. The number of viable cells of K562 cells when the above-mentioned cells were added and cultured is shown.

(Cell proliferation inhibitory effect on colon adenocarcinoma-derived cells)
The extract obtained above was dissolved in dimethyl sulfoxide (DMSO) to a concentration of 10 mg / ml to prepare an extract solution (sample).

Human colon adenocarcinoma-derived DLD-1 cells were cultured in RPMI1640 medium containing 10% FBS at 37 ° C. under _{5% by volume CO 2.} ^{The cultured cells were seeded on a 12-well plate so as to have 1 × 10 4} cells per well, and then 1 μl of the extract solution prepared above was added so that the final concentration of the extract was 10 μg / ml. .. As a control, 1 μl of DMSO as a solvent was added. For 48 hours after adding the extract solution or DMSO, DLD-1 cells were _{cultured under 5% by volume CO 2} at 37 ° C. After culturing for a predetermined time, the number of viable cells was measured by the trypan blue staining method, and the cell growth inhibition rate (%) of each sample was calculated by the following formula (2). The results are shown in Table 1. In the following formula (2), the "number of viable cells of the sample" indicates the number of viable cells of DLD-1 cells when the extract solution (sample) was added and cultured, and the "number of viable cells of the control" is The number of surviving DLD-1 cells when DMSO was added and cultured is shown.

As shown in Table 1, it can be seen that the sweet basil extract has a growth inhibitory effect on leukemia cells and colon adenocarcinoma cells.

Claims (4)

Contains sweet basil extract,
The extract is an extract of the sweet basil with a mixture of water and at least one alcohol selected from the group consisting of methanol, ethanol and isopropanol.
A cell proliferation inhibitor for use in the prevention and / or treatment of colon adenocarcinoma. The cell proliferation inhibitor according to claim 1, wherein the extract is an extract of a mixture of water and ethanol of sweet basil. A food or drink composition for suppressing cell proliferation of colon adenocarcinoma , which comprises the cell proliferation inhibitor according to claim 1 or 2. The food or drink composition for suppressing colon adenocarcinoma cell proliferation according to claim 3 , which is a health food or pet food composition for humans.