KR102598042B1 - Composition having centipeda minima extracts for anti-inflammatory, preventing and curing autoimmune disease and manufacturing method thereof - Google Patents

Abstract

A composition for preventing and treating anti-inflammatory and autoimmune diseases is disclosed. A composition for preventing and treating anti-inflammatory and autoimmune diseases according to an embodiment of the present invention is a composition for preventing and treating anti-inflammatory and autoimmune diseases containing an extract obtained by extracting Centipeda minima with less than 30% alcohol. A plant containing as an active ingredient at least one selected from the group consisting of Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C. (Centipeda minima) extract, which has the advantage of being effective in the prevention and treatment of anti-inflammatory and autoimmune diseases and having significantly lower cytotoxicity and side effects as it contains an extract of Chinese cauliflower extracted with less than 30% alcohol.

Description

Composition for preventing and treating anti-inflammatory and autoimmune diseases containing extracts of the plant and method for producing the same

The present invention relates to a composition for preventing and treating anti-inflammatory and autoimmune diseases, and more specifically, to a composition for preventing and treating anti-inflammatory and autoimmune diseases comprising an extract obtained by extracting Centipeda minima with less than 30% alcohol. It's about.

Anti-inflammatory refers to the efficacy of preventing, suppressing, inhibiting, improving or/and treating inflammation or/and inflammation-related diseases. Inflammation refers to edema caused by increased body fluid between tissue cells, hyperemia due to vasodilation, heat-generating substances and It appears as symptoms or signs such as fever due to vasodilation and pain due to arachidonic acid metabolites, and can be classified into acute, subacute, and chronic inflammatory diseases depending on time, and depending on the pathophysiology, infectious, allergic, autoimmune, It can be classified into toxic, metabolic, and traumatic inflammatory diseases.

For example, the inflammation may include respiratory inflammatory diseases such as rhinitis, sinusitis, otitis media, nasopharyngitis, laryngitis, bronchitis, asthma, chronic obstructive pulmonary disease, bronchiectasis, bronchiolitis, pneumonia, and pulmonary fibrosis; Inflammatory diseases of the digestive system such as stomatitis, esophagitis, gastritis, peptic ulcer, irritable bowel syndrome, inflammatory bowel disease, cholecystitis, cholangitis, pancreatitis, and hepatitis; Skin inflammatory diseases such as acne, contact dermatitis, seborrheic dermatitis, atopic dermatitis, and psoriasis; Cardiovascular inflammatory diseases such as endocarditis, myocarditis, pericarditis, vasculitis, arteriosclerosis, and sepsis; Endocrine inflammatory diseases such as thyroiditis, parathyroiditis, and diabetes; Genitourinary inflammatory diseases such as glomerulonephritis, nephropathy, interstitial kidney disease, orchitis, oophoritis, endometritis, and vaginitis; Musculoskeletal inflammatory diseases such as rheumatoid arthritis, spondyloarthropathy, osteoarthritis, gout, systemic lupus erythematosus, systemic sclerosis, myopathy, Sjogren's syndrome, Behcet's disease, and antiphospholipid syndrome; It may be a neuropsychiatric inflammatory disease such as vascular dementia, Alzheimer's disease, degenerative brain disease, depression, or schizophrenia.

Autoimmune disease is a disease that occurs when immune cells attack the body's own organs or tissues, and is caused by immune imbalance or loss of tolerance to self-antigens. Autoimmune diseases are those that cause damage to cells or tissues due to humoral immunity, cellular immunity, or both. This inappropriate response to autoantigens of the immune system is called autoimmunity. Autoimmune diseases are related to numerous molecules, cells, and tissues targeted by the autoimmune response, and can be systemic or specific to certain organs depending on the distribution of the target antigen. For example, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are systemic autoimmune diseases. In addition, alopecia areata is an autoimmune disease that causes uneven hair loss regardless of gender, age, and hair color worldwide. Alopecia areata has a prevalence of about 0.1 to 0.2% worldwide.

Tofacitinib is widely used as an immunosuppressant for autoimmune diseases.

Tofacitinib {3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl) -3-oxopropanenitrile} is a compound represented by the following chemical formula. The tofacitinib was first disclosed in International Patent Publication No. 2001/042246.

Tofacitinib is a synthetic JAK (janus kinase) inhibitor, and Janus kinase (JAK) is a type of enzyme that catalyzes the transfer of phosphate groups. Cytokines, proteins secreted by immune cells, bind to cytokine receptors to transmit signals into cells. Cytokine receptors bind to Janus phosphatases such as TYK2, JAK1, JAK2, and JAK3.

When a cytokine binds to a cytokine receptor, a phosphorylation reaction occurs at JAK, activating STAT (signal transducer and activator of transcription), and signaling continues to produce hematopoiesis, inflammatory response, and immune response. Hyperimmune response due to excessive production of cytokines. In this autoimmune disease, a JAK inhibitor inhibits the phosphorylation enzyme of the cytokine receptor to which the cytokine binds.

However, tofacitinib, as well as JAKI and JAK inhibitors of the same class, are synthetic drugs and cannot guarantee safety due to the numerous side effects confirmed by the raw materials. They were developed as prescription drugs, so patient accessibility is low, and they are limited to pharmaceutical use only and are administered orally. When taken for a long period of time, serious infections (nasopharyngitis, gastroenteritis, upper respiratory tract infection) and intestinal perforation occur due to decreased immunity, and there are problems such as increased cholesterol levels, headaches, rashes, shingles, and anemia. In addition, tofacitinib has a high cost of approximately 6 million won per month if domestic health insurance does not cover the prescription dose of 10 mg/day.

Centipeda minima (Centipeda minima) is an annual herb belonging to the Asteraceae family. In China, it is used in the private sector to treat chronic rhinitis, nose and eye diseases, and headaches. Also, rubbing the leaves and stems and putting them in the nostrils overnight is effective in treating chronic malaria. In India, it is used for eye diseases, nose diseases, and toothaches. Distributed in Korea, Japan, China, India, Australia, eastern Siberia, and North America. There is no known effect on the anti-inflammatory, autoimmune disease, and non-alcoholic fatty liver disease using Chinese cauliflower as a raw material, and research is needed.

Natural active ingredients are extracted and selected from natural raw materials. As a general extraction method, if the raw material is solid, a solid-liquid extraction method is used, and if the raw material is liquid, a liquid-liquid extraction method is used. Liquid-liquid extraction (LLE) is a method of separating specific components in a mixture from other components by applying a solvent to a liquid mixture containing a solute.

Generally, a liquid-liquid extraction method is used, and non-polar solvents such as hexane, chloroform (methane dichloride), and ethyl acetate are highly toxic during liquid-liquid extraction, and require several repetitive extraction processes and Due to the drying process to remove the non-polar solvent, the extraction process is very inefficient and complicated, and the process is long. There is a problem in that the extraction efficiency is low and the production cost is high as the process becomes longer.

For example, the process for extracting Brevilin A from Centipeda minima involves extracting the raw material with methanol multiple times, mixing the extract with hexane for fractionation multiple times, mixing with chloroform for fractionation multiple times, It is extracted through multiple fractions by mixing with ethyl acetate, and through multiple fractions by mixing with butyl alcohol. During extraction, about 25 mg of Brevilin A is extracted from 300 g of dry weight of medium-sized cauliflower, and the extraction amount is extremely low, so the efficiency is very low (non-patent). Document 1).

Accordingly, an optimal extraction method that can maximize the extraction amount of a trace amount of the active ingredient is required, which can be extracted by the extraction method of Korean Patent Publication No. 10-2020-0085024, filed by the present applicant.

Accordingly, while researching compositions for the prevention and treatment of anti-inflammatory and autoimmune diseases, the present inventor discovered that an extract obtained by extracting the Chinese herbaceous plant with less than 30% alcohol was effective in treating anti-inflammatory and autoimmune diseases with fewer side effects, and thus the invention was made. Completed.

Patent Document 1: Republic of Korea Patent Publication No. 10-2020-0085024

Non-patent Document 1: Arch Pharm Res Vol 29, No 1, 64-66, 2006.

The present invention seeks to provide a composition for preventing and treating anti-inflammatory and autoimmune diseases, comprising an extract obtained by extracting Centipeda minima with less than 30% alcohol.

However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

A composition for preventing and treating anti-inflammatory and autoimmune diseases according to an embodiment of the present invention contains less than 30% of an alcohol extract of Centipeda minima.

In the present invention, the extract of the Chinese herbaceous plant may be a composition for preventing and treating anti-inflammatory and autoimmune diseases that is extracted with 5 to 25% alcohol.

In the present invention, the alcohol is any selected from the group consisting of methanol, ethanol, propanol, butanol, benzyl alcohol, isopropyl alcohol, cetearyl alcohol, cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol and behenyl alcohol. It may be a composition for preventing and treating one or more anti-inflammatory and autoimmune diseases.

In the present invention, the extract of the Chinese apricot grass is prepared by extracting the raw material of the Chinese apricot with less than 30% alcohol to prepare a primary extract, and mixing the primary extract with a phase separation composition containing a lipophilic solubilizer and water to produce a secondary extract. It may be a composition for preventing and treating anti-inflammatory and autoimmune diseases, characterized in that it is extracted according to an extraction method that includes extracting and separating the upper layer of the phase-separated solution to obtain a non-polar natural substance.

In the present invention, the lipophilic solubilizer is BRIJ 010-SS-(RB), Capryol 90, Capryol PGMC, Gantrez ES-435, Gantrez S-97 BF, Gelucire 43/01, Gelucire 44/14, Gelucire 50/13, Gelucire 48/16, Labrafac CC, Labrafac Lipophile WL1349, Labrafac PG, Medium-chain triglycerides, Labrafil M 1944 CS, Labrafil M 2125 CS, Labrafil M 2130 CS, Lauroglycol 90, Lauroglycol FCC, Monosteol, Peceol, Pharmasolve, Plurol Oleique CC497 , Span 20-LQ-(SG), Span 60-PA-(SG), upper Refined Oleic Acid-LQ-(JP), Super Refined Tween 80A-LQ-(MH), Surfadone LP-300, Transcutol HP, Transcutol Containing any one or more selected from the group consisting of P, TWEEN 60-SS-(SG), TWEEN 80 HP-LQ-(MH), TWEEN 80-LQ-(SG), Vitamin E TPGS, Miglyol 812 and captax 355 It may be a composition for preventing and treating anti-inflammatory and autoimmune diseases.

In the present invention, the extract of the Chinese herbaceous plant is any selected from the group consisting of Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C. It may be a composition for preventing and treating anti-inflammatory and autoimmune diseases containing one or more active ingredients.

In the present invention, the brevilin A inhibits or suppresses the JAK-STAT signaling process, and the arnicolide D, the arnicolide C, and the microhelenin C interact with a cytokine-cytokine receptor. receptor interaction), MAPK signaling pathway, and PI3K-AKT signaling pathway. It may be a composition for preventing and treating anti-inflammatory and autoimmune diseases, which is characterized by controlling.

In the present invention, the content of brevilin A may be a composition for preventing and treating anti-inflammatory and autoimmune diseases, characterized in that the total content of arnicolide D, arnicolide C, and microhelenin C is 1.5 times or more. there is.

In the present invention, the extract of the Chinese herbaceous plant contains 30 to 90% by weight of the brevilin A; 0 to 40% by weight of the above arnicolide D; 0 to 20% by weight of the above arnicolide C; and 0 to 15% by weight of the microhelenin C. It may be a composition for preventing and treating anti-inflammatory and autoimmune diseases.

In the present invention, the autoimmune diseases include alopecia, alopecia areata, rheumatoid arthritis, psoriasis, atopy, eczema, seborrheic dermatitis, scleroderma, hypersensitivity to the skin, multiple sclerosis, lupus, Behcet's disease, ankylosing spondylitis, Sjögren's syndrome, Crohn's disease and inflammatory diseases. It may be a composition for preventing and treating anti-inflammatory and autoimmune diseases, characterized in that it contains one or more selected from the group consisting of intestinal diseases.

Embodiments of the present invention relate to compositions for preventing and treating anti-inflammatory and autoimmune diseases. By using natural extracts compared to tofacitinib, an existing synthetic drug for the treatment of autoimmune diseases, not only can the safety of the raw materials be guaranteed, but the existing Compared to the single treatment of brevilin A, known as an extract of the Chinese herbaceous plant, it shows greater effectiveness in anti-inflammatory and autoimmune diseases without any side effects.

In addition, existing synthetic drugs are limited to oral administration, but embodiments of the present invention using natural compositions have fewer or almost no side effects compared to synthetic drugs, and are easy to apply not only to drugs, but also to cosmetics and foods.

1 to 6 are images of the results of adverse skin reactions according to Experimental Example 1.
Figures 7 and 8 are graphs showing skin toxicity and hair growth effects according to Experimental Example 2-1.
Figures 9 and 10 are graphs showing the cytotoxic and anti-inflammatory effects according to Experimental Example 2-2.
Figures 11 to 14 are graphs showing cytotoxicity and protein expression according to Experimental Example 2-3.
Figures 15 to 22 are images of the extract according to Experimental Example 3.
Figures 23 to 30 show the results of impurity analysis of the extract according to Experimental Example 3.

Hereinafter, the extraction method of non-polar natural substances according to embodiments of the present invention, the natural substances extracted thereby, and their uses will be described.

Prior to this, terminology used in this specification is only for referring to specific embodiments and is not intended to limit the present invention. And, as used herein, singular forms include plural forms unless phrases clearly indicate the contrary. Additionally, as used herein, the meaning of 'include' or 'contains' specifies a specific characteristic, area, integer, step, operation, element or component, and refers to another specific characteristic, area, integer, step, operation, element, or This does not exclude the addition of ingredients.

In the present invention, terms such as first, second, etc. are used to describe various components, and the terms are used only for the purpose of distinguishing one component from another component.

Additionally, the terminology used herein is only used to describe exemplary embodiments and is not intended to limit the invention. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, terms such as “comprise,” “comprise,” or “have” are intended to designate the presence of implemented features, numbers, steps, components, or a combination thereof, and are intended to indicate the presence of one or more other features or It should be understood that this does not exclude in advance the possibility of the presence or addition of numbers, steps, components, or combinations thereof.

Since the present invention can be subject to various changes and can take various forms, specific embodiments will be illustrated and described in detail below. However, this is not intended to limit the present invention to a specific disclosed form, and should be understood to include all changes, equivalents, and substitutes included in the spirit and technical scope of the present invention.

Hereinafter, the present invention will be described in more detail.

A composition for preventing and treating autoimmune diseases according to an embodiment of the present invention includes an extract obtained by extracting Centipeda minima with less than 30% alcohol.

The ' Centipeda minima ' is an angiosperm and belongs to the order Campanula, a dicotyledonous plant, and grows near roadsides, fields, or rice fields in Korea, Japan, China, India, Australia, eastern Siberia, and North America. In other words, it is also called abul vinegar, and the whole plant is collected when flowers bloom in the summer, washed in water, and dried in the sun. It is known to be effective for corneal cloudiness, scabies, and bruises.

In the present invention, the extract of the Chinese herbaceous plant can be extracted with 5 to 25% alcohol.

For example, when the extract of Siberia chinensis is extracted with alcohol at a concentration of less than 5%, Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C A problem may occur in which the active ingredient consisting of (Microhelenin C) is not extracted in the desired amount. In addition, when extracted with alcohol at a concentration exceeding 25%, problems such as skin abnormalities such as cracking or exfoliation of the skin may occur.

In the present invention, the alcohol may be selected from the group consisting of methanol, ethanol, propanol, butanol, benzyl alcohol, isopropyl alcohol, cetearyl alcohol, cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol, and behenyl alcohol. ethanol can be used, and ethanol can be suitably used.

In the present invention, the term "extracted material" or "extract" refers to an extract obtained by extraction treatment, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a crude product or purified product of the extract, or a mixture thereof. etc., includes the extract itself and all formulations of the extract that can be formed using the extract.

In addition, drying of the extract can be done by a known method as long as useful components from the collected natural materials are not destroyed, for example, by natural drying in the shade. In addition, crushing or pulverization can be performed to a degree that the useful components of the plant can be sufficiently extracted during the subsequent extraction process. The drying and crushing or pulverizing processes can be performed in reverse order or repeatedly as needed.

Additionally, the extraction method is not particularly limited and can be extracted according to methods commonly used in the art. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, and reflux extraction, which may be performed alone or in combination of two or more methods, but are preferably used to dissolve non-polar natural substances. - It is referred to as Dissolution-Emulsion Extract (DEE). According to the dissolution-emulsion extraction method, non-polar natural substances in natural raw materials are extracted, mixed with a phase separation composition to dissolve and emulsify, and then non-polar natural substances are extracted through phase separation. do.

In the present invention, the extract of the Chinese apricot grass is prepared by extracting the raw material of the Chinese apricot with less than 30% alcohol to prepare a primary extract, and mixing the primary extract with a phase separation composition containing a lipophilic solubilizer and water to produce a secondary extract. It can be extracted according to an extraction method that includes extracting and separating the upper layer of the phase-separated solution to obtain a non-polar natural material.

Specifically, the primary extract is prepared by extracting natural substances from the raw material of the Chinese herbaceous plant, and alcohol is used. Ethanol can be used suitably.

For example, extraction can be performed by selecting any one of the following methods: hot water extraction, cold needle extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, and dissolution. In addition, a normal fractionation process can be performed. .

For example, natural raw materials can be extracted by soaking them in cold alcohol.

For example, the natural raw material can be used as a plant itself, or its crushed powder can be used.

이상의 온도에서 약 3시간 정도 열수 추출할 수 있으며, 알코올은 약 5% 내지 29%의 알코올을 사용할 수 있다. More specifically, the extraction is performed by soaking the raw material of Chinese cauliflower in alcohol for 60 minutes.

Hot water extraction can be performed for about 3 hours at the above temperature, and alcohol of about 5% to 29% can be used.

Next, the phase separation composition is added to the primary extract and mixed.

The phase separation composition may further include a lipophilic solubilizer and water, and may further include a surfactant or a nonionic surfactant. For example, the phase separation composition includes 10 to 50 times the amount of lipophilic solubilizer compared to the total amount of indicator substance (Brevilin-A) contained in the primary extract; and the remainder of water, may contain 40% by weight or less of a nonionic surfactant, and may completely remove the nonionic surfactant through a separate process, thereby containing an indicator substance at the desired concentration. can do.

In addition, when the primary extract is mixed with the phase separation composition, brevilin A, arnicolide D, arnicolide C, and microhelenin C, that is, non-polar natural substances, are extracted and dissolved in the nonionic surfactant or lipophilic solubilizer. At this time, when additional high-speed mixing is performed, the surface area of the surfactant and solubilizer in the mixture increases, and most of the non-polar natural substances that have not been extracted or dissolved are dissolved, resulting in an instantaneous critical micelle concentration (CMC) state. At this time, as the temperature of the mixed solution increases and the cloud point is reached, unlike ionic surfactants, the solubility of nonionic surfactants decreases with increasing temperature, so the phase separation of the mixed solution may appear more clearly. there is.

의 온도를 유지하면서 5 내지 20분간 교반할 수 있으며, 적합하게는 35 내지 45

의 온도를 유지하면서 7 내지 13분간 교반할 수 있다.In addition, when the phase separation composition includes a nonionic surfactant, a clearer phase separation can be achieved by including a process of raising the temperature in the step of mixing the phase separation composition. For example, the mixture of the primary extract and the phase separation composition is 30 to 50

It can be stirred for 5 to 20 minutes while maintaining the temperature, suitably 35 to 45 minutes.

It can be stirred for 7 to 13 minutes while maintaining the temperature.

As the primary extract is mixed with the phase separation composition as described above, the non-polar natural substances brevilin A, arnicolide D, arnicolide C, and microhelenin C contained in the raw material of the Chinese herb are combined with a lipophilic solubilizer. Phase separation may occur in one layer, and the remaining water and other components may be contained in other layers.

In addition, there is no difference in achieving the purpose of the present invention even if you proceed directly to the next step by using a mixture of adding a phase separation composition to the first extract according to the hot water extraction, but in terms of clearer phase separation and efficient extraction, the hot water extraction It is appropriate to remove unnecessary alcohol components by selectively proceeding with the step of removing the alcohol component by concentrating the mixture in which the phase separation composition is added to the primary extract according to . For example, by removing a specific layer or using a specific alcohol composition, the top and bottom of the separation layer can be adjusted by changing the specific gravity, and in order to extract trace components to the maximum, the alcohol component is removed to reduce moisture to create lipophilic properties. Only the indicator components can be salted out in the solubilizer layer. Afterwards, the phase-separated supernatant can be used as a secondary extraction liquid.

Next, the primary extract mixed with the phase separation composition can be used as a secondary extract after further including a filter step to remove impurities including hexane.

The impurities may be phenol derivatives or flavonoid series. For example, the phenol derivative may be benzoic acid, sinapic acid, syringic acid, or tetracosanoic acid, and may cause dermatitis or burns due to the proteolytic effect of the phenol derivative. Side effects may occur. Additionally, the flavonoid series may be Nicotiflorin, Luteolin, Apigenin, Hispidulin, or Quercetin-3-methyl ether. It may cause side effects such as respiratory irritation and acute toxicity.

Therefore, if the step of removing the impurities is further included, the side effects of the composition for preventing and treating anti-inflammatory and autoimmune diseases of the present invention can be minimized.

Next, the secondary extract can be phase separated to obtain a non-polar natural material.

In addition, the phase separation layer containing the brevilin A, the arnicolide D, the arnicolide C, and the microhelenin C extracted according to the above extraction method is in the microemulsion range, outside the range of the phase separation composition. The emulsified composition can be further mixed to prepare an emulsified product.

In addition, products such as natural substances extracted according to embodiments of the present invention and compositions containing the same do not use a liquid-liquid extraction method using toxic solvents, so steps such as step-by-step repetitive drying can be omitted. Since the solvent is harmless to the human body, the extract containing natural substances can be separated and immediately used as a product without any other steps. The absorption rate of the product can be increased due to micro emulsion or critical micelle concentration (CMC).

In general, the use of surfactants increases the absorption rate by increasing the solubility of the compound using the CMC of the surfactant. Microemulsions can also increase the absorption rate at the absorption site by not only increasing solubility but also reducing the size of the substance to be absorbed. there is.

In the present invention, the lipophilic solubilizer is BRIJ 010-SS-(RB), Capryol 90, Capryol PGMC, Gantrez ES-435, Gantrez S-97 BF, Gelucire 43/01, Gelucire 44/14, Gelucire 50/13, Gelucire 48/16, Labrafac CC, Labrafac Lipophile WL1349, Labrafac PG, Medium-chain triglycerides, Labrafil M 1944 CS, Labrafil M 2125 CS, Labrafil M 2130 CS, Lauroglycol 90, Lauroglycol FCC, Monosteol, Peceol, Pharmasolve, Plurol Oleique CC497 , Span 20-LQ-(SG), Span 60-PA-(SG), upper Refined Oleic Acid-LQ-(JP), Super Refined Tween 80A-LQ-(MH), Surfadone LP-300, Transcutol HP, Transcutol P, TWEEN 60-SS-(SG), TWEEN 80 HP-LQ-(MH), TWEEN 80-LQ-(SG), Vitamin E TPGS, Miglyol 812 and captax 355. You can.

In addition, the surfactant is a nonionic surfactant and is a group consisting of Labrasol, Crodex A-PA-(RB), Geleol, Gelot 64, Suppocire AS2X, Suppocire BML, Synperonic PE/F 127, Synperonic PE/L 44, and Tefose 63. It may include one or more selected from .

In the present invention, the extract of the sedge is any one selected from the group consisting of Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C. Includes the above as active ingredients.

Brevilin A is expressed by the following chemical formula:

Brevilin A has CAS number 16503-32-5, molecular formula of C20H26O5, molecular weight is 346.42, and is derived from Arnica sp., Centipeda sp., and Helenium sp. do.

Many literatures have been found that Centipeda minima contains Brevilin A, and some literature reports that Shampoo tree (Litsea glutinous) also contains Brevilin A. In addition, plants of the Arnica genus (Arnica longifolia, Arctium lappa, Arnica chamissonis subsp. Foliosa, Arnica chamissonis Less.) and Helenium genus (Helenium autumnale L, Helenium alternifolium, Helenium pinnatifidum, Helenium vernale, Helenium brevifolium, and Helenium flexuosum) Literature has been found to contain some Brevilin A.

Arnicolide D is expressed by the following chemical formula:

Arnicolide D has CAS number 34532-68-8, molecular formula of C19H24O5, and molecular weight of 332.40, and is derived from Arnica sp. and Centipeda sp.

Arnicolide C is expressed by the following chemical formula:

Arnicolide C has CAS number 34532-68-7, molecular formula of C16H26O5, and molecular weight of 334.41, and is derived from Arnica sp. and Centipeda sp.

Microhelenin C is expressed by the following chemical formula:

Microhelenin C has CAS number 63569-07-3, molecular formula of C20H26O5, and molecular weight of 346.4, and is derived from Centipeda sp. and Helenium sp.

For example, the extract of brevilin A, arnicolide D, arnicolide C, and microhelenin C includes one or more of brevilin A, arnicolide D, and microhelenin C. nicolide C, microhelenin C alone, a combination of brevilin A and arnicolide D, a combination of brevilin A and arnicolide C, a combination of brevilin A and microhelenin C, arnicolide Combination of D and arnicolide C, Combination of arnicolide D and microhelenin C, Combination of arnicolide C and microhelenin C, Combination of brevilin A, Arnicolide D and Arnicolide C, Breviline A Combination of villin A, arnicolide C and microhelenin C, combination of brevilin A, arnicolide D and microhelenin C, combination of arnicolide D, arnicolide C and microhelenin C, brevilin It may include a combination of A, arnicolide D, arnicolide C, and microhelenin C.

In the present invention, the brevilin A inhibits or suppresses the JAK-STAT signaling process, and the arnicolide D, the arnicolide C, and the microhelenin C interact with a cytokine-cytokine receptor. receptor interaction), MAPK signaling pathway, and PI3K-AKT signaling pathway. It can be adjusted.

Looking at the mechanism of action of each of the brevilin A, the arnicolide D, the arnicolide C, and the microhelenin C,

The brevilin A inhibits or inhibits the JAK-STAT signaling pathway. Specifically, brevilin A, a natural substance, inhibits JAK (janus kinase activity) in cancer cells, It is widely known to inhibit STAT3 signaling (PLoS One 8 (5) (2013) e63697). In addition, it is effective in treating alopecia areata, a type of autoimmune disease, by suppressing a strong inflammatory response and various inflammation-related targets through inhibition of the JAK-STAT (signal transducers and activators of transcription) pathway.

The arnicolide D, the arnicolide C, and the microhelenin C are involved in cytokine-cytokine receptor interaction, MAPK signaling pathway (mitogen-activated protein kinase) signaling pathway, and It is possible to inhibit or inhibit the PI3K-AKT signaling pathway (PI3K (phosphatidylinositol-3-kinase)-AKT signaling pathway).

In addition, the extract containing the brevilin A, the arnicolide D, the arnicolide C or the microhelenin C can regulate the WNT signaling pathway (WNT/β-catenin pathway). The WNT signaling pathway (WNT/β-catenin pathway) is essential for the early development or morphogenesis of animals. Specifically, Wnt is a secretory protein with a molecular weight of about 40,000, and 19 types of Wnt form a subfamily, each of which has a single transmembrane type LRP5/6 (low-density LRP5/6) in which the 7-time transmembrane receptor Frizzled of the cell membrane is a conjugative receptor. Binds to lipoprotein receptor-related protein 5/6). There are three types of intracellular signaling pathways activated by the binding of Wnt and receptors: the β-catenin pathway, the planar cell polarity pathway, and the Ca2+ pathway. The β-catenin pathway regulates the stability of β-catenin and regulates the expression of various target genes. This pathway regulates cell proliferation or differentiation, so if something goes wrong in this part, cancer can occur. When cells were not stimulated by Wnt, casein kinase I and GSK3β phosphorylated cytoplasmic β-catenin within the Axin and APC protein complex, and β-TrCP E3 ubiquitin ligase recognized the phosphorylated β-catenin and entered the uniquitination/proteasome pathway. It is decomposed through Through this process, the level of β-catenin in the cytoplasm is maintained low. When stimulation of Wnt occurs, Axin escapes from the complex, the activity of GSK3β is inhibited, and phosphorylation of β-catenin is suppressed. As a result, the level of β-catenin in the cytoplasm increases, and β-catenin moves into the nucleus, causing T cell factor Or combined with Lymphoid Enhancer-Binding factor. Through this combination, gene expression is regulated. Therefore, if there is an abnormality in the regulation of the Wnt/β-catenin pathway, cancer may be induced.

Accordingly, as in the present invention, an extract of Chinese apricot plant containing Brevilin A, Arnicolide D, Arnicolide C, or Microhelenin C is used. When used, it is possible to prevent and treat anti-inflammatory and autoimmune diseases by regulating the WNT signaling pathway (WNT/β-catenin pathway).

In the present invention, the content of brevilin A may be 1.5 times or more than the total content of arnicolide D, arnicolide C, and microhelenin C.

The brevilin A is the most important component against autoimmune diseases, such as hair growth and hair loss, and anti-inflammation, and contains the total content of other derivatives such as arnicolide D, arnicolide C, and microhelenin C. More is preferable, and the main non-polar natural substance of the raw material, the brevilin A, is the main non-polar natural substance.

The brevilin A is most related to the JAK-STAT signaling process, which is the main mechanism of action in autoimmune diseases, and when it acts together with other derivatives such as the arnicolide D, the arnicolide C, and the microhelenin C, It has a synergistic effect on immune diseases and is more effective in preventing autoimmune diseases, such as hair loss prevention and anti-inflammatory, than when each ingredient is contained alone.

In the present invention, the extract of Siberia brevillin is 30 to 90% by weight of brevilin A, 0 to 40% by weight of arnicolide D, 0 to 20% by weight of arnicolide C, and 0 to 15% by weight of arnicolide C. % of the microhelenin C.

The brevilin A is contained in an amount of 30 to 90% by weight, and if it is less than 30% by weight or more than 90% by weight, the component most related to the JAK-STAT signaling process is small, and the anti-inflammatory effect is reduced and it may interfere with other components. There is a problem in that it is difficult to sufficiently prevent and treat autoimmune diseases due to reduced synergy.

The arnicolide D is contained in an amount of 0 to 40% by weight, and when it is more than 40% by weight, the synergistic effect with other ingredients such as brevilin A, arnicolide C, and microhelenin C is reduced to sufficiently prevent autoimmune diseases. And there are problems that are difficult to treat. Preferably, the arnicolide D is included in an amount of 15 to 30% by weight.

The arnicolide C is contained in an amount of 0 to 20% by weight, and when it is more than 20% by weight, the synergistic effect with the other ingredients, brevilin A, arnicolide D, and microhelenin C, is reduced to sufficiently prevent autoimmune diseases. And there are problems that are difficult to treat. Preferably, the arnicolide C is contained in an amount of 2 to 20% by weight.

The microhelenin C is contained in an amount of 0 to 15% by weight, and when it is more than 15% by weight, the synergistic effect with other components such as brevilin A, arnicolide D and arnicolide C is reduced to sufficiently prevent autoimmune diseases. And there are problems that are difficult to treat. Preferably, the microhelenin C is contained in an amount of 1 to 15% by weight.

Therefore, if the content of each component of brevilin A, arnicolide D, arnicolide C, and microhelenin C is outside the range, anti-inflammatory efficacy cannot be achieved.

In the present invention, the autoimmune diseases include alopecia, alopecia areata, rheumatoid arthritis, psoriasis, atopy, eczema, seborrheic dermatitis, scleroderma, hypersensitivity to the skin, multiple sclerosis, lupus, Behçet's disease, ankylosing spondylitis, Sjögren's syndrome, Crohn's disease and inflammatory disease. It may be characterized as including one or more selected from the group consisting of intestinal diseases.

The composition for preventing and treating anti-inflammatory and autoimmune diseases according to the present invention can be used as hair tonic, hair conditioner, hair lotion, hair nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nutrition cream, hair moisture cream, hair Massage cream, hair wax, hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair dryer, hair preservation treatment, hair dye, hair wave agent, hair bleach, hair gel, hair glaze, hair dresser. , products such as hair lacquer, hair moisturizer, hair mousse, hair spray, etc., external skin products in the form of creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents, and cataplasma agents. It can be manufactured and appropriately utilized in liquid, solid, and gas phases.

Additionally, in the group consisting of alopecia, alopecia areata, rheumatoid arthritis, psoriasis, atopy, eczema, seborrheic dermatitis, scleroderma, skin hypersensitivity, multiple sclerosis, lupus, Behcet's disease, ankylosing spondylitis, Sjögren's syndrome, Crohn's disease and inflammatory bowel disease. It can be provided as a pharmaceutical composition for the prevention and treatment of anti-inflammatory and autoimmune diseases to prevent or treat the selected disease, and can be administered orally or parenterally, respectively, as powder, granule, tablet, or capsule according to conventional methods. , can be formulated and used in the form of oral dosage forms such as suspension, emulsion, syrup, and aerosol, external preparations, suppositories, and sterile injectable solutions.

Hereinafter, for a more detailed explanation, examples will be given in detail.

Example

Manufacturing Example 1.

The natural raw material is Chinese apricot herb, and the extract of Chinese apricot was obtained by purchasing domestic Abul vinegar (Jungan apricot, Yeongcheon) from the Goesan Medicinal Herb Organic Products Cooperative (https://natural-herb.co.kr).

Specifically, 100 mg of hay was precipitated in 10 mL of alcohol for 48 hours and then subjected to alcohol extraction to obtain the primary extract. At this time, in order to evaluate the extraction rate of Chinese apricots according to the extract quality, isopropyl alcohol, ethanol, and butyl alcohol were used as types of alcohol, and distilled water was used.

Next, the content of the indicator component (Brevilin-A) of the primary extract was determined and the measured values for evaluating the extraction rate for each extraction solvent are shown in Table 1 below. (The content of the indicator ingredient (Brevilin-A) is 3mg/mL.)

extract Extraction rate (%) isopropyl alcohol 95 ethanol 96 Butyl alcohol 75 Distilled water 5

Referring to Table 1 above. It can be seen that the extraction is most excellent when the Chinese apricot plant is extracted with ethanol, and accordingly, it was decided to use the ethanol extract in the following experimental examples.

Manufacturing example 2.

A primary extract was obtained by precipitating 1,000 g of hay from Siberia chinensis in 10 L of ethanol with a concentration according to Table 2 below for 48 hours and subjecting it to alcohol extraction. Afterwards, the content of the indicator component contained in the primary extract was checked, Labrafac was mixed as a lipophilic solubilizer at a ratio of 20 times that of the indicator material (Brevilin-A), and then concentrated under reduced pressure to reduce the alcohol composition and salt out the indicator component. (salting out) was induced. Next, after leaving it in the separation funnel for 60 minutes, the secondary extract, which is the phase-separated supernatant, was separated and used.

The phase-separated extract was tested for the content of indicator components by maintaining the contents of brevilin A, arnicolide D, arnicolide C, and microhelenin C under the same conditions.

The extract from the above was named CMX (CM-2019-001) and stored in the herbarium of Kyungsung University, and the International Nomenclature Cosmetic Ingredient (INCI) raw material number is 33,849.

division Ethanol concentration (%) Example 1 5 Example 2 25 Comparative Example 1 30 Comparative Example 2 50 Comparative Example 3 75 Comparative Example 4 95

Experimental Example 1. Skin toxicity test

A skin toxicity evaluation was conducted on the Chinese cauliflower extract (CMX) according to the ethanol concentration in Table 2 above.

Specifically, two C57BL/6 female mice were used in each group, acclimated for 7 days at a temperature of 23 ± 3°C, relative humidity of 50 ± 10%, and 12-hour lighting cycle, and hair removal agent (Nicrine, Ildong Pharmaceutical) was used. The skin from which the hair on the back had been removed was used. In addition, the extract according to Table 2 above was prepared to contain indicator ingredients at a concentration of 1 to 3 mg/mL, and 50 ul was applied twice daily for 5 days to the skin of the back, and skin changes were observed with the naked eye on the 5th day.

As a result of observation, it was found that when the extracts according to Examples 1 and 2 were used, a significantly faster hair growth effect was observed compared to the control group without causing toxicity to the skin. Compared to Example 1, Example 2 showed a slightly more effective hair growth effect. It was found that an excellent hair growth effect was observed. In contrast, referring to Figure 1, which shows an observation using DMSO as a control, and Figure 2, which shows an observation using the extract according to Example 2, it was observed that no adverse reactions appeared on the skin.

Figures 3 to 6 show observations using extracts according to Comparative Examples 1 to 4. As the ethanol concentration of the primary extract (raw material) increases, the amount of absorbed extract into the skin decreases, and the side effects of itching and dead skin cells decrease. An increase was observed, and when extracts were made using raw materials with an ethanol concentration of 75% or more, cracks occurred on the skin and wounds were observed.

Therefore, it was found that when first extracting the Chinese herbaceous plant with less than 30% alcohol according to the present invention, no adverse reaction occurred on the skin and no side effects occurred.

Experimental Example 2. Effect depending on concentration

2-1. Hair growth effect

The skin toxicity and hair growth effects of the extracts (CMX) of Example 2 and Comparative Example 4 according to the concentration of the indicator component (Brevilin-A) were evaluated using the therapeutic window technique and are shown in Figures 7 and 8.

Specifically, two C57BL/6 female mice were used at each concentration, acclimated for 7 days at a temperature of 23 ± 3°C, relative humidity of 50 ± 10%, and 12-hour lighting cycle, and hair removal agents (Nicrine, Ildong Pharmaceutical) were used. The skin from which the hair on the back was removed was used. In addition, the indicator component (Brevilin-A) of the extract (CMX) according to Example 2 and Comparative Example 4 was applied at a concentration of 0 to 4 mg/g, and toxicity evaluation was performed by observing skin adverse reactions, scoring them, and expressing them as a percentage. The hair growth effect was expressed as a percentage of the number of hair growths compared to the control group (0 mg/g). The control group used DMSO (skin adverse reaction scores were measured as dryness: 0.5, dead skin: 1, itchiness: 2, and poor skin absorption: 3, and was calculated based on a scale of 6.5).

Referring to Figures 7 and 8, both Example 2 and Comparative Example 4 showed a hair growth effect from the time the indicator ingredient (Brevilin-A) was applied at a concentration of 0.4 mg/g, and when more than 2 mg/g was applied, the hair growth effect was 50%. It was confirmed that more than % appeared.

Regarding skin toxicity, referring to FIG. 7 using the extract (CMX25) according to Example 2, toxicity to the skin began to occur upon application at a concentration of 3 mg/g of the indicator component (Brevilin-A), and Comparative Example 4 Referring to FIG. 8 using the extract (CMX95) according to , it was confirmed that toxicity to the skin occurred from the time of application at a concentration of 1.2 mg/g of the indicator component (Brevilin-A).

Therefore, it was found that the extract according to Example 2 had an excellent hair growth effect without causing adverse reactions or toxicity to the skin when applied at a concentration of 0.4 mg/g to 3 mg/g of the indicator component (Brevilin-A). , When using the extract according to Comparative Example 4, no adverse skin reactions or toxicity occurred at a concentration of the indicator component (Brevilin-A) of 0.4 mg/g to 1.2 mg/g, so Example 2 is compared to Comparative Example 4. Therefore, it was found that the indicator ingredient (Brevilin-A) can be used in high concentration and has a significantly excellent hair growth effect.

2-2. Anti-inflammatory effect

The anti-inflammatory effect through inhibition of TNF-α expression is effectively used in the treatment of psoriasis.

In order to determine the psoriasis treatment effect according to the concentration of the indicator component (Brevilin-A) in the extract (CMX) of Example 2 and Comparative Example 4, the cytotoxic and anti-inflammatory effects were evaluated using Raw 264.7 cells (mouse macrophages). The results are shown in Figures 9 and 10 using the therapeutic window technique.

Specifically, RAW 264.7 cells were dispensed on a 60 mm plate at a density of 2Х10 ⁶ cells/dish and adhered to the plate for 24 hours, and then treated with LPS (100 ng/ml), and then the extracts according to Example 2 and Comparative Example 4 were treated. The indicator component (Brevilin-A) was treated at a concentration of 0 to 96ug/ml, and then cytotoxicity and anti-inflammatory effects were evaluated after 24 hours of incubation. Cytotoxicity was evaluated through Cytotoxicity assay, anti-inflammatory effect was evaluated by inhibition of TNF-α expression, and the reduction rate of TNF-α expression compared to the control group was calculated as a percentage. The control group used a placebo at a concentration of 0ug/ml.

Referring to Figures 9 and 10, both Example 2 and Comparative Example 4 showed an effect of suppressing TNF-α expression at a concentration of 0.5ug/ml of the indicator component (Brevilin-A), and TNF-α expression was observed at a concentration of 2ug/ml or more. It was confirmed that the inhibition effect was over 90%.

Regarding cytotoxicity, referring to FIG. 9 using the extract (CMX25) according to Example 2, cell toxicity began to occur when the concentration of the indicator component (Brevilin-A) was treated at 12ug/ml, and Comparative Example 4 ( Referring to Figure 10 using the extract according to CMX95), it was confirmed that cell toxicity occurred when the concentration of the indicator component (Brevilin-A) was treated at 1.5ug/ml.

Therefore, it can be seen that the extract according to Example 2, when treated at a concentration of the indicator component (Brevilin-A) of 0.5ug/ml to 12ug/ml, has an excellent effect of inhibiting TNF-α expression without causing toxicity to cells. However, when using the extract according to Comparative Example 4, cytotoxicity did not occur at a concentration of the indicator component (Brevilin-A) of 0.5ug/ml to 1.5ug/ml, so Example 2 was compared to Comparative Example 4. It was found that the indicator ingredient (Brevilin-A) can be used in high concentrations and has a significantly excellent anti-inflammatory effect, and thus it was found to be effective in treating psoriasis.

2-3. Arthritis treatment effect

Regulation of the wnt/β-catenin signaling system and expression of cell growth factors are effective in treating arthritis.

In order to determine the arthritis treatment effect according to the concentration of the indicator component (Brevilin-A) in the extract (CMX) of Example 2 and Comparative Example 4, human-derived Dermal Papilla (DCP) cells were used to determine cytotoxicity and wnt/ We analyzed whether the β-catenin signaling system was activated and whether the expression of cell growth factors was promoted.

Specifically, DCP cells were dispensed on a 60 mm plate at a density of 2Х10 ⁶ cells/dish and adhered to the plate for 24 hours, and then treated with LPS (100 ng/ml), followed by extracts according to Example 2 and Comparative Example 4 ( CMX) indicator component (Brevilin-A) was treated at a concentration of 0 to 50ug/ml, and then after 12 hours of incubation, cytotoxicity, activation of the wnt/β-catenin signaling system, and expression level of cell growth factors were evaluated.

First, cytotoxicity was evaluated through Cytotoxicity assay and is shown in Figures 11 and 12, and DMSO without CMX was used as the control.

Referring to FIG. 11 using the extract (CMX25) according to Example 2, cell toxicity began to occur when the concentration of the indicator component (Brevilin-A) was treated at 25ug/ml. On the other hand, referring to FIG. 12 using the extract (CMX95) according to Comparative Example 4, it was confirmed that cytotoxicity of about 20% or more occurred when the concentration of the indicator component (Brevilin-A) was treated at 6.25ug/ml. In addition, it was confirmed that about 60% cytotoxicity occurred in Comparative Example 4 at 25ug/ml, which is the concentration point of the indicator component (Brevilin-A) where cytotoxicity began to occur in Example 2.

Therefore, it can be seen that the extract according to Example 2 does not cause toxicity to cells when treated with a concentration of the indicator component (Brevilin-A) of 3.13ug/ml to 12.5ug/ml, but the extract according to Comparative Example 4 When using the extract, cytotoxicity does not occur only when the concentration of the indicator component (Brevilin-A) is less than 6.25ug/ml, so Example 2 contains a high concentration of the indicator component (Brevilin-A) compared to Comparative Example 4. It was found that it could be used.

Next, the activation of the wnt/β-catenin signaling system and the expression level of cell growth factors were determined by analyzing the protein expression levels of β-Catenin and the growth factor VEGF according to the concentration of the extract (CMX25) of Example 2 by Western blotting. It is shown in Table 3 and Figures 13 and 14.

Classification (kDa) 0μg/mL 1.56μg/mL 3.13μg/mL 6.25μg/mL 12.5μg/mL 25μg/mL 35μg/mL 40μg/mL 45μg/mL 50μg/mL β-Catenin One 0 1.1 1.2 1.5 2 2.5 3 4 5 VEGF One 2 3 6 13 25 35 40 45 50

Referring to Table 3 and Figures 13 and 14, it was confirmed that the expression of β-Catenin and VEGF increased depending on the concentration of the indicator component (Brevilin-A) in the extract (CMX25) according to Example 2.

Therefore, the extract (CMX25) according to Example 2 can increase the protein expression level of β-Catenin and VEGF as the concentration of the indicator component (Brevilin-A) increases, and as the amount of Wnt/catenin signaling system protein increases, It was found that as the phosphorylation (activation) of ERK, which is involved in differentiation, increased, the phosphorylation of p38, a protein activated by stress, was suppressed.

Accordingly, when the concentration of the indicator component (Brevilin-A) of the extract (CMX25) according to Example 2 is used at 3.13ug/ml to 12.5ug/ml, it does not cause toxicity to cells and regulates the wnt/β-catenin signaling system. It was found to be effective in treating arthritis as it can promote the expression of cell growth factors. In addition, it was found that it is effective when used at an appropriate concentration depending on the treatment target.

3. Evaluation of toxic substances according to concentration

Hexane was mixed with the extracts according to Example 2 and Comparative Examples 1 to 4 according to Table 2 at a ratio of 1:1, stirred and extracted for 3 hours, and then the supernatant was separated and analyzed for impurities by HPLC analysis at 480 nm. An experiment was conducted to see if this was detected.

The impurities to be detected include phenol derivatives or a type of flavonoids, which have a protein decomposition effect and can corrode the skin or mucous membranes, resulting in dermatitis or burns. It also has side effects that can irritate the respiratory tract and produce acute toxic substances. These impurities cause stickiness and bad odor.

Referring to Figures 15 to 18, the extracts according to Example 2 and Comparative Examples 2 to 4 before adding hexane, it was confirmed that as the concentration of ethanol increases, the color becomes cloudy and an unpleasant odor occurs. Accordingly, the extract In terms of properties, differences in color and strong odor, including poorly soluble or insoluble substances, could be confirmed.

Referring to Figures 19 to 22, it can be seen that the supernatant becomes cloudy as the concentration of ethanol increases after adding hexane to the extracts according to Example 2 and Comparative Examples 2 to 4.

In addition, the extract according to Example 2 was evaluated to be easy to filter in the concentration step because it was clear in color, had no odor, and did not have a stinging smell when dried.

However, in the case of the extracts according to Comparative Examples 3 and 4, it was evaluated that filtering in the concentration step was difficult because the extracts had a lot of green color, had a bad odor, and were very sticky when dried.

Figures 23 to 26 show analysis of impurities in the extracts according to Example 2 and Comparative Examples 1, 3 and 4, and Figures 27 to 30 show the addition of hexane in the extracts according to Example 2 and Comparative Examples 1, 3 and 4. After that, the impurities contained in the supernatant of the extract were analyzed.

Specifically, referring to FIGS. 23 and 27 for Example 2, it can be seen that no impurities appear at all, and referring to FIGS. 25 and 29 for Comparative Example 3 and FIGS. 26 and 30 for Comparative Example 4, it can be seen that impurities are significantly present. I was able to confirm many things.

In addition, referring to Figures 23 to 30, it was found that when the process of filtering the extract of CMX includes the step of adding hexane, impurities can be additionally removed from the extract.

Therefore, when Centipeda minima was extracted with less than 30% ethanol according to the present invention, it was confirmed that not only was there no toxicity to the skin or cells, but no impurities were detected in the extract. In addition, it was confirmed that it has an inhibitory or anti-inflammatory effect on TNF-α expression, regulates or activates the wnt/β-catenin signaling system, and has a hair growth effect as well as an effect of promoting cell growth factor expression, thereby preventing anti-inflammatory and autoimmune diseases. Or, it was known that treatment was possible. In addition, since it can be used in high concentrations, it was found that the effectiveness of anti-inflammatory and autoimmune disease prevention or treatment can be improved by using it at an appropriate concentration depending on the treatment target.

In the foregoing, exemplary embodiments of the present invention have been described, but the present invention is not limited thereto, and those skilled in the art will understand the scope without departing from the concept and scope of the following claims. You will be able to understand that various changes and modifications are possible.

Claims (10)

A composition for preventing and treating anti-inflammatory and autoimmune diseases comprising an extract of Centipeda minima with less than 30% alcohol. According to paragraph 1,
A composition for preventing and treating anti-inflammatory and autoimmune diseases, wherein the extract of the Chinese herb is extracted with 5 to 25% alcohol. According to paragraph 1,
The alcohol is an anti-inflammatory agent selected from the group consisting of methanol, ethanol, propanol, butanol, benzyl alcohol, isopropyl alcohol, cetearyl alcohol, cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol, and behenyl alcohol. and compositions for preventing and treating autoimmune diseases. According to paragraph 1,
The extract of the above-mentioned apricot weed is prepared by extracting the asparagus raw material with less than 30% alcohol to prepare a primary extract, followed by secondary extraction by mixing the primary extract with a phase separation composition containing a lipophilic solubilizer and water, A composition for preventing and treating anti-inflammatory and autoimmune diseases, characterized in that it is extracted according to an extraction method comprising the step of separating the upper layer of the phase-separated solution to obtain a non-polar natural substance. According to paragraph 4,
The lipophilic solubilizers include BRIJ 010-SS-(RB), Capryol 90, Capryol PGMC, Gantrez ES-435, Gantrez S-97 BF, Gelucire 43/01, Gelucire 44/14, Gelucire 50/13, Gelucire 48/ 16, Labrafac CC, Labrafac Lipophile WL1349, Labrafac PG, Medium-chain triglycerides, Labrafil M 1944 CS, Labrafil M 2125 CS, Labrafil M 2130 CS, Lauroglycol 90, Lauroglycol FCC, Monosteol, Peceol, Pharmasolve, Plurol Oleique CC497, Span 20 -LQ-(SG), Span 60-PA-(SG), upper Refined Oleic Acid-LQ-(JP), Super Refined Tween 80A-LQ-(MH), Surfadone LP-300, Transcutol HP, Transcutol P, TWEEN Characterized by comprising one or more selected from the group consisting of 60-SS-(SG), TWEEN 80 HP-LQ-(MH), TWEEN 80-LQ-(SG), Vitamin E TPGS, Miglyol 812, and captax 355. A composition for preventing and treating anti-inflammatory and autoimmune diseases. According to paragraph 1,
The extract of the Chinese cauliflower contains at least one selected from the group consisting of Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C. A composition for preventing and treating anti-inflammatory and autoimmune diseases containing it as an active ingredient. According to clause 6,
The brevilin A inhibits or suppresses the JAK-STAT signaling process, and the arnicolide D, the arnicolide C, and the microhelenin C interact with a cytokine-cytokine receptor. , inhibits or inhibits the MAPK signaling pathway and the PI3K-AKT signaling pathway, and the extract from the Chinese eucalyptus regulates the WNT signaling pathway (WNT/β-catenin pathway). A composition for preventing and treating anti-inflammatory and autoimmune diseases. According to clause 6,
A composition for preventing and treating anti-inflammatory and autoimmune diseases, wherein the content of brevilin A is 1.5 times or more than the total content of arnicolide D, arnicolide C, and microhelenin C. According to clause 6,
The extract of Chinese cauliflower is,
30 to 90% by weight of said brevilin A;
0 to 40% by weight of the above arnicolide D; 0 to 20% by weight of the above arnicolide C; And a composition for preventing and treating anti-inflammatory and autoimmune diseases, comprising 0 to 15% by weight of the microhelenin C. According to paragraph 1,
The autoimmune diseases include hair loss, alopecia areata, rheumatoid arthritis, psoriasis, atopy, eczema, seborrheic dermatitis, scleroderma, hypersensitivity to the skin, multiple sclerosis, lupus, Behcet's disease, ankylosing spondylitis, Sjögren's syndrome, Crohn's disease, and inflammatory bowel disease. A composition for preventing and treating anti-inflammatory and autoimmune diseases, comprising at least one selected from the group consisting of: