KR102254338B1 - Anti-malaria composition comprising natural botanical product-derived compound - Google Patents

Abstract

The present invention relates to the antimalarial activity of compounds isolated from extracts of Yeongyo, Injinho, Gosam, Baek Duong, or casualty, and the compounds isolated from the extract have a growth inhibitory effect on both chloroquine sensitive/resistant tropical feverworms. It can be usefully utilized as a composition or a pharmaceutical composition for preventing or treating malaria disease.

Description

Antimalarial composition containing compounds derived from natural herbal extracts {ANTI-MALARIA COMPOSITION COMPRISING NATURAL BOTANICAL PRODUCT-DERIVED COMPOUND}

The present invention relates to the antimalarial activity of compounds derived from natural herbal extracts, and specifically, to the antimalarial activity of compounds isolated from Yeongyo, Injinho, Gosam, Baek Duong or casualty extracts.

Malaria is a protozoan belonging to Apicomplexa . It is an acute febrile disease caused by infection with Plasmodium spp. It is mediated by mosquitoes and is the most important infectious disease among the six infectious diseases designated by the World Health Organization (WHO). to be. Malaria is prevalent in more than 90 countries, where more than 2.5 billion people, or about 40% of the world's population, live in areas at risk of malaria infection, and 1-3 billion people are infected every year, of which 600,000 to 1 million. It is an infectious disease with the highest prevalence as a single disease in which people die (Guerra et al., 2010). Malaria-prone countries and regions are gradually expanding around the world due to environmental degradation and climate warming, and re-emergence of malaria has been steadily reported in many temperate regions. Systematic countermeasures against malaria began only after it was discovered by Ronald Ross in 1897 that mosquitoes were the carrier of protozoa. As a necessity emerged, pramaquine (1924), mepracrine (1930), chloroquine (1934), proquanil (1944), primaquine (1950), and pyrimethamine (1952) were developed.

Plasmodium is a parasitic in the red blood cells of animals, growth, reproduction and gajina many types of host cell, the five kinds of Plasmodium [P. falciparum (P. falciparum), protozoa vivax (P. vivax), egg-shaped heat protozoa (P. ovale), four days ten falciparum (P. malariae) and monkeys has been reported that the disease was infecting people ten falciparum (P. knowlesi)] (Sinden, 2002).

Currently, the optimal treatment for malaria is Artemisinin-based combination therapy (ACT), but it is also resistant to artemisinin in four countries in the Mekong River basin: Cambodia, Myanmar, Thailand, and Vietnam. If the artemisinin-resistant strain is spreading to a wide area because resistant strains showing the disease are rapidly appearing, serious public health problems may occur as there is no alternative antimalarial treatment for at least 5 years.

In addition, as a strategy to combat mosquitoes, which is a vector of malaria, the concept of malaria eradication was introduced by the application of the pesticide DDT, and from 1955 to 1969, WHO conducted a global malaria eradication project. Practically, through the quarantine project spraying pesticides in the house, it has stopped the transmission of malaria in most parts of North America, Southern Europe, Russia, and parts of Asia, including South America and Sri Lanka, and has had a significant effect in eradicating malaria. However, after problems such as resistance to DDT and the safety of DDT itself occurred, funds from outside began to decline, and public support for DDT spray was also shaken, resulting in a sluggish antimalarial project, the outbreak of a widespread malaria epidemic, and the malaria drug. The development of resistant bacteria to chloroquine has entered a new phase.

On the other hand, in recent years, in order to overcome the limitations of modern medicines, a lot of development of new medicines, natural medicines, which are researched and developed using natural ingredients and natural product fractions to overcome chronic intractable diseases, are being made. Accordingly, studies are being conducted to develop malaria treatments derived from natural products with a low risk of toxicity.

It is an object of the present invention to provide a pharmaceutical composition for antiprotozoal.

In addition, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating malaria disease.

In addition, it is an object of the present invention to provide an external preparation for skin for the treatment and prevention of malaria diseases.

In addition, it is an object of the present invention to provide a food composition for preventing or improving malaria disease.

In order to solve the above problems, the present invention provides a pharmaceutical composition containing as an active ingredient a compound isolated from Yeongyo, Injinho, Gosam, Baek Duong or casualty extract, a fraction thereof, or a compound isolated therefrom.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of malaria disease, containing as an active ingredient the extract of Yeongyo, Injinho, Gosam, Baek Duong or casualties, a fraction thereof, or a compound isolated therefrom.

In addition, the present invention provides a skin external preparation for the treatment and prevention of malaria diseases comprising the composition of the present invention.

In addition, the present invention provides a food composition for the prevention or improvement of malaria disease containing Yeongyo, Injinho, Gosam, Baek Duong or casualty extract, a fraction thereof, or a compound isolated therefrom.

According to the present invention, since the compounds isolated from the extracts of Yeongyo, Injinho, Gosam, Baek Duong or casualty have a growth inhibitory effect on both chloroquine sensitive/resistant tropical fever protozoa, it is an antigen-filling composition or a pharmaceutical composition for preventing or treating malaria disease. It can be used usefully.

1 is a diagram confirming the cytotoxicity of 28 points of compounds isolated from extracts of Yeongyo, Injinho, Gosam, Baek Duong, or casualties as hemolytic properties for red blood cells.
Figure 2 is a diagram confirming the protozoal growth inhibitory effect of 28 points of compounds isolated from Yeongyo, Injinho, Gosam, Baek Duong, or casualty extracts against chloroquine-sensitive tropical fissures (ATCC30932) by pLDH analysis.
Figure 3 is a diagram confirming the protozoal growth inhibitory effect on the chloroquine-resistance tropical thermoprotozoa (ATCC50005) of 28 points of compounds isolated from Yeongyo, Injinho, Gosam, Baek Duong or casualty extracts by pLDH analysis.

Hereinafter, the present invention will be described in detail as an embodiment of the present invention with reference to the accompanying drawings. However, the following embodiments are presented as examples of the present invention, and if it is determined that a detailed description of a technique or configuration well known to those skilled in the art may unnecessarily obscure the subject matter of the present invention, the detailed description may be omitted. However, the present invention is not limited thereby. The present invention is capable of various modifications and applications within the scope of equality interpreted from the description of the claims to be described later and therefrom.

In addition, terms used in the present specification are terms used to properly express preferred embodiments of the present invention, which may vary depending on the intention of users or operators, or customs in the field to which the present invention belongs. Therefore, definitions of these terms should be made based on the contents throughout the present specification. Throughout the specification, when a part "includes" a certain component, it means that other components may be further included rather than excluding other components unless specifically stated to the contrary.

Throughout this specification,'%' used to indicate the concentration of a specific substance is (w/w)% for solids/solids, (w/v)% for solids/liquids, and Liquid/liquid is (v/v) %.

All technical terms used in the present invention, unless otherwise defined, are used in the same meaning as those of ordinary skill in the art generally understand in the related field of the present invention. In addition, although preferred methods or samples are described in the present specification, those similar or equivalent are included in the scope of the present invention. The contents of all publications referred to herein by reference are incorporated into the present invention.

In one aspect, the present invention contains any one or more extracts selected from the group consisting of Yeongyo (ForsythiasuspensaVahl ), Injinho ( Artemisiacapillaris ), Gosam (Sophoraflavescens), Baek Duong (PulsatillachinensisRegel ) and casualties (Torilisjaponica) as an active ingredient. It relates to an antiprotozoal pharmaceutical composition.

In one embodiment, the extract or a fraction thereof is anemoside B4 (Anemoside B4), chlorogenic acid (Chlorogenic acid), adoxosidic acid (Adoxosidic acid), (-)-Macchiain ((-)-Maackiain), To Torilolone, Methyl rosmarinate, Torilin, Phylgenin, (2S)-3ß,7,4-trihydroxy-5-methoxy-8-(γ, From the group consisting of γ-methylaryl)-flavanone ((2S)-3ß,7,4-Trihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone) and Forsythoside A It may contain any one or more compounds selected, and (-)-machiain and (2S)-3ß,7,4-trihydroxy-5-methoxy-8-(γ,γ-methylaryl)-pla Banon is a compound derived from Gosam, anemoside B4 and methyl rosemarinate are compounds derived from Baekduong, torillin and torrilolone are compounds derived from casualties, chlorogenic acid is a compound derived from Injinho, adoxosidic acid, forsytoside A and Piligenin is a compound derived from Yeongyo.

In one embodiment, (-)-machiaine may be a compound of Formula 1 below:

In one embodiment, (2S)-3ß,7,4-trihydroxy-5-methoxy-8-(γ,γ-methylaryl)-flavanone may be a compound of Formula 2 below:

In one embodiment, anemoside B4 may be a compound of Formula 3:

In one embodiment, methyl rosmarinate may be a compound of Formula 4:

In one embodiment, torillin may be a compound of Formula 5:

In one embodiment, torylorone may be a compound of Formula 6:

In one embodiment, the chlorogenic acid may be a compound of Formula 7:

In one embodiment, the adoxosidic acid may be a compound of Formula 8 below:

In one embodiment, forcitoside A may be a compound of Formula 9:

In one embodiment, filigenin may be a compound of Formula 10 below:

In one embodiment, (-)-machiaine, torrilolone, methyl rosemarinate, torillin, piligenin, (2S)-3ß,7,4-trihydroxy-5-methoxy-8-(γ, Any one or more compounds selected from the group consisting of γ-methylaryl)-flavanone and forsytoside A can inhibit the growth of chloroquine-resistant lobes, and (-)-machiaine or torilolone is chloroquine-sensitive lobes. It can inhibit growth.

The present invention is anemoside B4 represented by Chemical Formulas 1 to 10, chlorogenic acid), adoxosidic acid, (-)-machiaine, torylorone, methyl rosemarinate, torillin, filigenin, (2S)-3ß, 7,4-trihydroxy-5-methoxy-8-(γ,γ-methylaryl)-flavanone and forsytoside A, as well as pharmaceutically acceptable salts thereof, possible solvents that may be prepared therefrom Cargoes, hydrates, racemates or stereoisomers are all included.

Anemoside B4 represented by Formulas 1 to 10 of the present invention, chlorogenic acid), adoxosidic acid, (-)-machiaine, torrilolone, methyl rosemarinate, torillin, filigenin, (2S)-3ß, 7,4-trihydroxy-5-methoxy-8-(γ,γ-methylaryl)-flavanone and forsytoside A can be used in the form of pharmaceutically acceptable salts. Acid addition salts formed with acceptable free acids are useful. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, and aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. It is obtained from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids. Such pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, diadrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, ioda Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate , Sebacate, fumarate, maleate, butine-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methyl benzoate, dinitro benzoate, hydroxybenzoate, me Toxibenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, hydroxybutyrate, glycolate, Maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate or mandelate.

The acid addition salt according to the present invention can be obtained by a conventional method, for example, anemoside B4 represented by the formulas 1 to 10 of the present invention, chlorogenic acid), adoxosidic acid, (-)-machiaine, torrilolone, Excess methyl rosmarinate, torillin, filigenin, (2S)-3ß,7,4-trihydroxy-5-methoxy-8-(γ,γ-methylaryl)-flavanone or forcytoside A It can be prepared by dissolving in an aqueous acid solution and precipitating this salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. In addition, the mixture may be dried by evaporating a solvent or an excess of acid, or may be prepared by suction filtration of the precipitated salt.

In addition, a pharmaceutically acceptable metal salt can be made using a base. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. In this case, as the metal salt, it is pharmaceutically suitable to prepare sodium, sulfite, or calcium salt. In addition, the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable negative salt (eg, silver nitrate).

In one embodiment, the composition of the present invention can inhibit the protozoa of the genus Plasmodium (P. falciparum ), and it is more preferable to inhibit the protozoan (P. falciparum).

In one embodiment, the extract may be one or more extracted from the group consisting of leaves, branches, stems, flowers, roots, fruits, above and below.

In one embodiment, the extract is extracted with at least one extraction solvent selected from the group consisting of water, anhydrous or hydrous alcohol having 1 to 4 carbon atoms, ethyl acetate, acetone, glycerin, ethylene glycol, propylene glycol, and butylene glycol. The fraction may be a water fraction, an n-hexane fraction, a chloroform fraction, an ethyl acetate or a butanol fraction.

In one embodiment, the extract may be an HPLC fraction.

The term "extract" as used in the present invention means an active ingredient separated from a natural product, that is, a substance exhibiting a desired activity. The extract may be obtained by an extraction process using water, an organic solvent, or a mixed solvent thereof, but is not limited thereto, but the extract obtained by the extraction treatment, the dilution or concentrate of the extract, the dried product obtained by drying the extract, It includes a modulated product or a purified product, or any form formulated using the same. The extract can be prepared using a general extraction method, separation and purification method known in the art. The extraction method is not particularly limited, and may be extracted by a method such as stirring extraction, shaking extraction, hot water extraction, cold needle extraction, reflux cooling extraction, or ultrasonic extraction, and a hot water reflux extraction method may be used.

The extract of the present invention can be prepared by extracting with an extraction solvent or by adding a fractionation solvent to an extract prepared by extraction with an extraction solvent and fractionating. The extraction solvent is not limited thereto, but water, an organic solvent, or a mixed solvent thereof may be used, and the organic solvent is an alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, hexane or dichloro. It is possible to use a non-polar solvent of methane or a mixed solvent thereof. Further, preferably, water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof may be used.

The extract of the present invention includes not only the extract by the above-described extraction solvent, but also extracts obtained through other conventional extraction methods, or extracts that have undergone purification and fermentation processes. Decompression by carbon dioxide, extraction by supercritical extraction by high temperature, extraction by extraction by ultrasonic wave, separation by using an ultrafiltration membrane with a certain molecular weight cut-off value, separation by various chromatography, natural state or various microorganisms Active fractions obtained through various purification and extraction methods, such as an extract from the fermentation product used, are also included in the extract of the present invention.

The fraction of the present invention may be prepared by additional extraction with water, n-hexane, butanol, chloroform, or ethyl acetate, but is not limited thereto.

The fraction of the present invention includes not only the fraction by the solvent described above, but also the active fraction obtained through various fractionation methods, such as separation using an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography, and the like.

The composition of the present invention may contain one or more active ingredients exhibiting the same or similar functions in addition to the extract or fraction. For administration, it may be prepared by including one or more pharmaceutically acceptable carriers in addition. Pharmaceutically acceptable carriers can be used by mixing saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components, and if necessary, antioxidants, buffers, Other conventional additives such as bacteriostatic agents may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, etc., powders, tablets, capsules, pills, granules, or injection solutions. Further, it may be preferably formulated according to each disease or ingredient by an appropriate method in the art or by using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 19th, 1990).

In one aspect, the present invention relates to a pharmaceutical composition for the prevention or treatment of malaria disease containing as an active ingredient any one or more extracts selected from the group consisting of Yeongyo, Injinho, Gosam, Baek Duong, and casualties.

In one embodiment, the extract or a fraction thereof is anemoside B4, chlorogenic acid), adoxosidic acid, (-)-machiaine, torrilolone, methyl rosemarinate, torillin, filigenin, (2S)-3ß ,7,4-trihydroxy-5-methoxy-8-(γ,γ-methylaryl)-flavanone and forcytoside A may contain any one or more compounds selected from the group consisting of, (- )-Machiaine and (2S)-3ß,7,4-trihydroxy-5-methoxy-8-(γ,γ-methylaryl)-flavanone is a compound derived from Gosam, anemoside B4 and methyl rosemary Nate is a compound derived from Baek Duong, torillin and torylorone are compounds derived from casualties, chlorogenic acid is a compound derived from Injinho, and adoxidic acid, forsytoside A, and filigenin are compounds derived from Yeongyo.

The term "treatment" as used in the present invention refers to any act of improving or beneficially altering symptoms of an inflammatory disease or complication thereof by administration of an extract of the present invention, a fraction thereof, or a composition comprising the same. Those of ordinary skill in the art to which the present invention pertains will be able to know the exact criteria of the disease in which the composition of the present application is effective, and determine the degree of improvement, improvement, and treatment with reference to data presented by the Korean Medical Association. will be.

In the present invention, the term "prevention" refers to all actions of inhibiting or delaying the occurrence, spread, and recurrence of inflammation by administration of the pharmaceutical composition according to the present invention.

In one embodiment, the pharmaceutical composition may be one or more dosage forms selected from the group including oral dosage forms, external preparations, suppositories, sterile injectable solutions and sprays.

The therapeutically effective amount of the composition of the present invention may vary depending on various factors, for example, the method of administration, the site of interest, the condition of the patient, and the like. Therefore, when used in the human body, the dosage should be determined as an appropriate amount in consideration of safety and efficiency. It is also possible to estimate the amount used in humans from the effective amount determined through animal experiments. These considerations when determining the effective amount are described, for example, in Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; And E.W. Martin ed., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" refers to an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not cause side effects, and the effective dose level is the patient's Health status, type of malaria, severity, drug activity, sensitivity to drugs, method of administration, time of administration, route of administration and rate of excretion, duration of treatment, factors including drugs used in combination or concurrently, and other factors well known in the medical field. It can be determined according to. The composition of the present invention may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. In consideration of all the above factors, it is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects, which can be easily determined by a person skilled in the art.

The compositions of the present invention may also contain carriers, diluents, excipients or combinations of two or more commonly used in biological preparations. The pharmaceutically acceptable carrier is not particularly limited as long as it is suitable for delivery of the composition in vivo, and, for example, Merck Index, 13th ed., Merck & Co. Inc. Compounds described in, saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components can be mixed and used, and other antioxidants, buffers, bacteriostatic agents, etc. Conventional additives can be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets. Further, it may be preferably formulated according to each disease or component by an appropriate method in the art or by using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).

The term "pharmaceutically acceptable" used in the present invention means exhibiting properties that are not toxic to cells or humans exposed to the composition.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, and calcium hydrogen phosphate. , Lactose, mannitol, syrup, arabic rubber, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, lead carnauba, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, Calcium stearate, sucrose, dextrose, sorbitol, talc, and the like can be used. The pharmaceutically acceptable additive according to the present invention is preferably included in an amount of 0.1 to 90 parts by weight based on the composition, but is not limited thereto.

The term "administration" used in the present invention means providing a predetermined substance to a patient by any suitable method, and parenteral administration (for example, intravenous, subcutaneous, intraperitoneal or topical administration) according to the desired method. It can be applied as an injection formulation) or can be administered orally, and the dosage range varies depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease.

The composition of the present invention may be parenterally administered (for example, intravenously, subcutaneously, intraperitoneally or topically applied) or orally according to a desired method, and the dosage may be the patient's weight, age, sex, health status, The range varies depending on diet, administration time, administration method, excretion rate, and severity of disease. The daily dosage of the composition according to the present invention is 0.0001 to 10 mg/ml, preferably 0.0001 to 5 mg/ml, and it is more preferable to administer it in divided doses from once to several times a day.

Liquid formulations for oral administration of the composition of the present invention include suspensions, liquid solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, sweeteners, fragrances, preservatives, in addition to water and liquid paraffin, which are commonly used simple diluents. Etc. may be included together. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories, and the like.

In one aspect, the present invention relates to a skin external preparation or cosmetic composition for the treatment and prevention of malaria disease comprising the composition of the present invention.

The external preparation for skin or cosmetic composition of the present invention may be formulated by a conventional method. Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can refer to the content disclosed in the formulation of external preparations for skin, and the International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance in the formulation of cosmetic compositions. Association, Inc., Washington, 1995. Specifically, the cosmetic composition can be prepared in the form of a general emulsion formulation and solubilization formulation. For example, a lotion such as a flexible lotion or a nutritional lotion; Emulsions such as facial lotion and body lotion; Creams such as nourishing cream, moisture cream, and eye cream; essence; Cosmetic ointment; spray; Gel; pack; Sunscreen; Makeup base; Foundations such as liquid type, solid type or spray type; powder; Makeup removers such as cleansing cream, cleansing lotion, and cleansing oil; Alternatively, it may be formulated with a detergent such as a cleansing foam, soap, or body wash, but is not limited thereto. In addition, the external preparation for skin may be formulated as an ointment, patch, gel, cream, or spray, but is not limited thereto.

In each formulation, the external preparation for skin or cosmetic composition of the present invention may be appropriately blended with other components within a range that does not impair the object according to the present invention depending on the type of formulation or purpose of use, in addition to the essential components in each formulation.

The external preparation for skin or cosmetic composition of the present invention may include a generally acceptable carrier, and for example, oil, water, surfactant, moisturizer, lower alcohol, thickener, chelating agent, pigment, preservative, fragrance, etc. may be appropriately blended. , But is not limited thereto. The acceptable carrier may vary depending on the formulation. For example, when formulated as an ointment, paste, cream or gel, as a carrier component, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or these Mixtures can be used.

When the skin external preparation or cosmetic composition is formulated as a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or a mixture thereof may be used as a carrier component, and in the case of a spray, chloro Propellants such as fluorohydrocarbon, propane, butane or dimethyl ether may be further included.

When the skin external preparation or cosmetic composition is formulated as a solution or emulsion, a solvent, a solubilizing agent, or an emulsifying agent may be used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, Propylene glycol, 1,3-butylglycol oil can be used, and in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan can be used. I can.

When the skin external preparation or cosmetic composition is formulated as a suspension, a liquid diluent such as water, ethanol or propylene glycol as a carrier component, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester. Suspension agents, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth, and the like may be used.

When the cosmetic composition is formulated with soap, as a carrier component, an alkali metal salt of a fatty acid, a fatty acid hemiester salt, a fatty acid protein hydrolyzate, isethionate, a lanolin derivative, an aliphatic alcohol, vegetable oil, glycerol, sugar, etc. Can be used.

The external preparations for skin or cosmetic compositions are fatty substances, organic solvents, solubilizers, thickeners, gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents commonly used in the industry depending on the quality or function of the final product. ), fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic activators, common in cosmetics It may additionally contain adjuvants commonly used in the field of cosmetics or dermatology, such as any other ingredients used as. However, the adjuvant and its mixing ratio may be appropriately selected so as not to affect the desirable properties of the cosmetic composition according to the present invention.

In one aspect, the present invention relates to a food composition for preventing or improving malaria disease comprising the composition of the present invention.

When the composition of the present invention is used as a food composition, the extract or a fraction thereof may be added as it is, or may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method. In addition to the active ingredient, the composition may contain a food additive acceptable for food, and the amount of the active ingredient mixed may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).

The term "food supplementary additive" used in the present invention refers to a component that can be added auxiliary to food, and is added to the manufacture of health functional foods of each formulation, and can be appropriately selected and used by those skilled in the art. Examples of food additives include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavors and natural flavoring agents, coloring agents and fillers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners. , pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, etc. are included, but the types of food additives of the present invention are not limited by the above examples.

The food composition of the present invention may contain a health functional food. The term "health functional food" used in the present invention refers to a food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and pills using raw materials or ingredients having useful functions for the human body. Here, "functionality" means obtaining useful effects for health purposes such as controlling nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be prepared by a method commonly used in the general technical field, and at the time of manufacture, it can be prepared by adding raw materials and ingredients commonly added in the general technical field. In addition, the formulation of the health functional food may be prepared without limitation as long as it is a formulation recognized as a health functional food. The food composition of the present invention can be prepared in various forms of formulation, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using food as a raw material, and is excellent in portability, and the present invention Health functional food of can be consumed as a supplement to enhance the effect of antimalarial.

In addition, there is no limitation on the kind of health food in which the composition of the present invention can be used. In addition, the composition comprising the extract of the present invention or a fraction thereof as an active ingredient can be prepared by mixing suitable other auxiliary ingredients and known additives that may be contained in the health functional food according to the choice of a person skilled in the art. Examples of foods that can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and There are vitamin complexes and the like, and can be prepared by adding the extract according to the present invention as a main component, such as juice, tea, jelly, and juice.

Since the extract of the present invention or its fractions are made of natural plants, even when used as a pharmaceutical composition or food composition, side effects may be less than that of general synthetic compounds, so it can be safely included in pharmaceutical compositions and health functional foods and used usefully. have.

The present invention will be described in more detail through the following examples. However, the following examples are only for embodiing the contents of the present invention, and the present invention is not limited thereto.

Example 1. Cytotoxicity confirmation of herbal extract-derived compounds

The concentrations of hemoglobin (hemoglobin) for the cytotoxicity of each of the compounds in Table 1 below isolated from Sophoraflavescens, Atractylodesjaponica, PulsatillachinensisRegel, Torilisjaponica, Artemisiacapillaris, and ForsythiasuspensaVahl. It was measured and confirmed through Hemolytic assay to confirm the hemolytic properties of red blood cells. Each compound was dissolved using DMSO and the concentration was adjusted to 100 ug/ml.

As a result, all of the compounds showed hemolysis at a level similar to that of chloroquine (CQ) and artesunate (AS), which are conventional antimalarial treatments, and all of the compounds do not cause severe hemolysis of red blood cells. It was confirmed that it can be used for growth inhibition analysis (Fig. 1).

Example 2. Analysis of the effect of inhibiting the growth of chloroquine-sensitive tropical fibroblasts

The growth inhibitory effect of each of the compounds in Table 1 on the chloroquine-sensitive tropical thermophilic strain (ATCC30932) purchased from ATCC was confirmed through pLDH analysis. Specifically, the protozoan culture was diluted by 1/2, and 100 µl (50 µl of protozoan culture + 50 µl of wash buffer) was added and incubated at 37°C for 30 minutes. After washing four times with a wash buffer, 100 μl of Plasmodium Lactate Dehydrogenase (HRP)-conjugated pLDH antibody is added to each well, incubated at 37° C. for 30 minutes, and washed four times with a wash buffer. 50 µl of the substrate was added to each well and allowed to stand at room temperature for 15 minutes. Thereafter, 50 µl of the stop solution was added to each well to stop the reaction, and absorbance was measured at 450 nm.

As a result, 7 out of 28 compounds showed a growth inhibitory effect against chloroquine-sensitive protozoa, and 2 of them (C1 and C17) had an inhibitory effect similar to AS (12%) (10-15%). Is shown (Fig. 2).

Example 3. Analysis of the effect of inhibiting the growth of chloroquine-resistant tropical parasites

As a result of confirming the growth inhibitory effect of protozoa by treating the 28 compounds in Table 1 with ATCC50005, which is a chloroquine-resistant supplement, it was confirmed that 9 out of 28 single substances had the protozoan growth inhibitory effect, and 7 out of 9 Fractions were found to have a similar degree (8 to 16%) of growth inhibition as AS (8%), and the three fractions were found to be inhibited to about 25 to 32% (Fig. 3).

In the above examples, 11 of the total 28 compounds exhibited an inhibitory effect on the growth of tropical fever protozoa, and in particular, compounds C1 ((-)-Maackiain) and C17 (Torilolone) were used in both chloroquine sensitive and resistant chungju. The inhibitory effect was shown to be similar to that of AS. In addition, C13, C16 and C26, which were slightly weaker in sensitive chungju, showed similar degree of inhibitory effect to AS in resistive chungju. In addition, it was found that C2 and C23 had a growth inhibitory effect only in resistance Chungju.

Claims (14)

delete delete Chloroquine-resistant tropical fever protozoa (Plasmodium falciparum ) containing (-)- macchiain as an active ingredient, a pharmaceutical composition for antiprotozoal. The method of claim 3,
The (-)-macchiain is represented by Formula 1, a pharmaceutical composition for antiprotozoal against chloroquine-resistant tropical fever protozoa
[Formula 1]

. The method of claim 3,
The (-)-macchiain is isolated from Sophora flavescens , a pharmaceutical composition for antigens against chloroquine-resistant tropical fever protozoa. The method of claim 3,
The (-)-macchiain is characterized in that it has an antiprotozoal effect even against chloroquine-sensitive tropical fever protozoa, a pharmaceutical composition for antiprotozoal against chloroquine-resistant tropical fever protozoa.
delete delete delete (-)- A pharmaceutical composition for the prevention or treatment of malaria diseases caused by chloroquine-resistant tropical fever protozoa ( Plasmodium falciparum ) containing macchiain as an active ingredient.
delete delete A skin external preparation for the prevention or treatment of malaria diseases caused by chloroquine-resistant tropical fever protozoa ( Plasmodium falciparum ) comprising the composition of claim 10 as an active ingredient. (-)- A health functional food composition for preventing or improving malaria diseases caused by chloroquine-resistant tropical fever protozoa ( Plasmodium falciparum ) containing macchiain as an active ingredient.

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