Health functional food, comprising siberian chrysanthemum extract, for pain relief or antioxidation

Abstract

To provide a health functional food having pain relief or antioxidation effect.SOLUTION: Provided is a health functional food for alleviating pain of the peripheral nervous system, comprising a Siberian chrysanthemum extract which is a hot-water extract or an organic-solvent extract, the pain being selected from the group consisting of somatic pain, visceral pain, superficial pain, and deep pain.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a health functional food for pain relief or antioxidant purposes. [Background technology]

[0002] Synovial cells are cells of the synovial membrane that line the inner surface of the joint capsule. They are connective tissue cells rather than epithelial cells, and are divided into two types: type A and type B. Type A cells are macrophage-like cells that have phagocytic activity and produce many filopodia on their surface, while type B cells are fibroblasts with a relatively smooth cell surface and many rough endoplasmic reticulum within the cytoplasm.

[0003] Reactive oxygen species (ROS), including oxygen-derived superoxide anions, hydrogen peroxide, and hydroxyl radicals, are required for general functions associated with regulating intracellular signaling and redox reactions. However, excessive ROS are known to cause oxidative stress, accelerating tumor development and aging.

[0004] The Korean daisy is a perennial plant of the Asteraceae family that grows wild in foothills, riverbanks, and fields throughout Korea, and is found in Korea, northern China, Manchuria, Siberia, and other areas. The Korean daisy has a warm nature and strong analgesic and anti-inflammatory properties. In traditional Chinese medicine and among the general public, the whole plant with flowers is picked, dried in the shade, and used as a home remedy for women with cold hands and feet or postpartum chills. It is also known to be effective in treating high blood pressure and gastrointestinal disorders. Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention aims to provide a health functional food containing a Korean chrysanthemum extract, which has pain-relieving or antioxidant effects.

[0006] The present invention aims to provide a pharmaceutical composition containing an extract of Datura chinensis, which has a pain-relieving or antioxidant effect. [Means for solving the problem]

[0007] 1. A health functional food containing chrysanthemum extract for pain relief or antioxidant purposes. 2. A health functional food according to item 1, wherein the antioxidant improves oxidative damage to synovial cells.

[0008] 3. The health functional food according to item 2, wherein the oxidative damage is damage in patients with degenerative arthritis.

[0009] 4. In the above item 1, the following conditions are excluded: Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, obesity, hyperglycemia, dyslipidemia, hypertension, diabetes, heart failure, cardiovascular ischemia, cerebral ischemic injury, stroke, myocardial infarction, systemic lupus erythematosus, COPD, asthma, acute kidney injury, chronic kidney disease, diabetic nephropathy, end-stage renal disease, viral hepatitis, liver cirrhosis, inflammatory bowel disease, viral infectious diseases, solid tumors, blood cancers, sepsis, relapsing polychondritis, Kienböck's disease in adults, osteochondrosis of the carpal lunate bone, Complex regional pain syndrome, Paget's disease, fibrodysplasia ossificans progressiva, Weber-Christian disease, multifocal fibrosclerosis, diffuse fasciitis, polymyalgia rheumatica, Behçet's disease, mixed connective tissue disease, Sjögren's syndrome, sicca syndrome, systemic sclerosis, crest syndrome, polymyositis, dermatomyositis, systemic lupus erythematosus, aortic arch syndrome, Wegener's granulomatosis, lethal midline granuloma, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, Goodpasture's syndrome, polyarteritis nodosa, polyarthritis, young A health functional food for preventing or improving a disease selected from the group consisting of juvenile arthritis, juvenile ankylosing spondylitis, rheumatoid arthritis, and adult-onset Still's disease.

[0010] 5. The health functional food according to item 1, wherein the Korean chrysanthemum extract is a hot water extract or an organic solvent extract.

[0011] 6. A health functional food according to item 1, wherein the pain is selected from the group consisting of somatic pain, visceral pain, inflammatory pain, dysfunctional pain, idiopathic pain, neuropathic pain, superficial pain, deep pain, itch, migraine, and cancer pain.

[0012] 7. Pain relief with Chinese herb extract, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, obesity, hyperglycemia, dyslipidemia, hypertension, diabetes, heart failure, cardiovascular ischemia, cerebral ischemic injury, stroke, myocardial infarction, systemic lupus erythematosus, COPD, asthma, acute kidney injury, chronic kidney disease, diabetic nephropathy, end-stage renal disease, viral hepatitis, liver cirrhosis, inflammatory bowel disease, viral infectious diseases, solid tumors, blood cancers, sepsis, relapsing polychondritis, Kienböck's disease in adults, carpal lunate osteochondrosis, complex regional pain syndrome, Paget's disease, and fibrodysplasia ossificans progressiva. a pharmaceutical composition for the treatment or prevention of a disease selected from the group consisting of rheumatoid arthritis, Weber-Christian disease, multifocal fibrosclerosis, diffuse fasciitis, polymyalgia rheumatica, Behcet's disease, mixed connective tissue disease, Sjogren's syndrome, sicca syndrome, systemic sclerosis, CREST syndrome, polymyositis, dermatomyositis, systemic lupus erythematosus, aortic arch syndrome, Wegener's granulomatosis, lethal midline granulomatosis, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, Goodpasture's syndrome, polyarteritis nodosa, polyarthritis, juvenile arthritis, juvenile ankylosing spondylitis, rheumatoid arthritis, and adult-onset Still's disease.

[0013] 8. The pharmaceutical composition according to item 7, wherein the pain is selected from the group consisting of somatic pain, visceral pain, inflammatory pain, dysfunctional pain, idiopathic pain, neuropathic pain, superficial pain, deep pain, itch, migraine, and cancer pain.

[0014] 9. A pharmaceutical composition according to the above item 7, which acts as an antioxidant by reducing TBARS (thiobarbituric acid reactive substances).

[0015] 10. The pharmaceutical composition according to item 9, wherein the antioxidant is an anti-oxidant that ameliorates oxidative damage to synovial cells.

[0016] 11. The pharmaceutical composition according to item 7, wherein the Korean chrysanthemum extract is a hot water extract or an organic solvent extract. [Effects of the Invention]

[0017] The health functional food of the present invention contains an extract of Korean chrysanthemum, and thus has pain-relieving or antioxidant effects.

[0018] The pharmaceutical composition of the present invention contains an extract of Datura chinensis, and is effective in treating pain and diseases caused by oxidative damage. [Brief explanation of the drawings]

[0019] [Figure 1] Figure 1 illustrates the human testing timeline. [Figure 2] FIG. 2 shows the analgesic effect confirmed by comparing the reaction time after administration of various doses of the Dactylis glomerata extract in a hot plate mouse analgesia model. [Figure 3] Figure 3 illustrates the timeline of the acetic acid-induced analgesia study. [Figure 4] FIG. 4 is a graph showing the number of occurrences of twisting syndrome after administration of various doses of Datura chinensis extract. DETAILED DESCRIPTION OF THE INVENTION

[0020] The present invention will be described in detail below. The present invention relates to a health functional food for pain relief or antioxidant properties, which contains an extract of Datura chinensis.

[0021] "Korean daisy" refers to the Korean daisy, a resource plant of the Asteraceae family that grows wild in Korea, and specifically refers to the Korean daisy or its related plant, Pocheon daisy. The daisy may be, but is not limited to, a daisy tree, a Halla daisy tree, a Nakdong daisy tree, a Rocky dendranthema, etc. Any part of the daisy tree, including flowers, leaves, stems, and roots, may be used.

[0022] In the present invention, the term "extract" refers to an active ingredient isolated from a natural product, and includes all forms of extracts prepared by an extraction process using water, an organic solvent, or a mixture thereof, such as an extract in water, an organic solvent, or a mixture thereof, a dried powder thereof, or a formulation using the same. The extract also includes fractions of the extract obtained by the extraction process.

[0023] The Korean chrysanthemum extract may be extracted by a method known in the art, for example, a hot water extract or an ultrasonic extract.

[0024] The hot water extract may be extracted with hot water at, for example, 40 to 120°C, but is not limited thereto.

[0025] During hot water extraction, the amount of water added may be, for example, 2 to 20 times the weight of the chrysanthemum, but is not limited to this.

[0026] The heating time during hot water extraction may be, for example, 1 to 10 hours, specifically 2 to 5 hours, more specifically 2 to 4 hours, and most specifically 2 to 3 hours, but is not limited to these.

[0027] The hot water extract may be obtained by filtering to obtain a supernatant, and then further concentrating, freeze-drying, or the like.

[0028] The ultrasonic extract may be obtained by immersing the chrysanthemum in 10 to 95% ethanol and extracting it with an ultrasonic extractor. The ultrasonic waves may be, for example, 10 to 100 kHz, specifically 20 to 80 kHz, more specifically 20 to 70 kHz, but are not limited thereto.

[0029] The solvent used in producing the extract may be water, an organic solvent, or a mixture thereof, specifically, one or more selected from the group consisting of water, a lower alcohol having 1 to 4 carbon atoms, acetone, petroleum ether, ethyl acetate, butyl acetate, trichloromethane, dichloromethane, chloroform, hexane, and 1,3-butylene glycol, more specifically, ethanol, but is not limited thereto.

[0030] In the present invention, "antioxidant" may be something that improves oxidative damage to synovial cells. "Synovial cells" refers to cells of the synovial membrane that lines the inner surface of the joint capsule. Ming's health functional food can improve oxidative damage to synovial cells that can occur due to oxidative stress caused by reactive oxygen species.

[0031] The oxidative damage to synovial cells may be, for example, but not limited to, oxidative damage to synovial cells in patients with degenerative arthritis.

[0032] Furthermore, the health functional food of the present invention exhibits excellent antioxidant effects and can prevent or improve various diseases related to oxidation, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, obesity, hyperglycemia, dyslipidemia, hypertension, diabetes, heart failure, cardiovascular ischemia, cerebral ischemic injury, stroke, myocardial infarction, systemic lupus erythematosus, COPD, asthma, acute kidney injury, chronic kidney disease, diabetic nephropathy, end-stage renal disease, viral hepatitis, liver cirrhosis, inflammatory bowel disease, viral infectious diseases, solid cancer, blood cancer, sepsis, relapsing polychondritis, adult kidney disease, and the like. Rohnböck's disease, osteochondrosis of the carpal lunate, complex regional pain syndrome, Paget's disease of bone unspecified, Paget's disease of other bones, Paget's disease of the skull, fibrodysplasia ossificans progressiva, Weber-Christian disease, multifocal fibrosclerosis, diffuse fasciitis, polymyalgia rheumatica, Behçet's disease, mixed connective tissue disease, Sjögren's syndrome with myopathy, sicca syndrome, Sjögren's syndrome with keratoconjunctivitis, Sjögren's syndrome with pulmonary involvement Ren's syndrome, Sjögren's syndrome with renal tubulointerstitial disorder, systemic sclerosis with pulmonary invasion, systemic sclerosis with myopathy, CREST syndrome, combination of calcinosis-Raynaud's phenomenon-esophageal dysfunction-digital sclerosis-telangiectasia, progressive systemic sclerosis, polymyositis, other dermatomyositis, juvenile dermatomyositis, systemic lupus erythematosus with organ or system invasion, microscopic polyarteritis, aortic arch syndrome, Wegener's granulomatosis, fatal midline fibrosis The compound or compound of the present invention can exhibit the ability to prevent or improve a disease selected from the group consisting of juvenile polyarteritis, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, Goodpasture's syndrome, juvenile polyarteritis, polyarteritis with pulmonary invasion, polyarteritis nodosa, juvenile polyarthritis, chronic juvenile polyarthritis, systemically onset juvenile arthritis, juvenile ankylosing spondylitis, juvenile rheumatoid arthritis with / without rheumatoid factor, juvenile rheumatoid arthritis, and adult-onset Still's disease.

[0033] The Paget's disease may be, for example, but is not limited to, Paget's disease of unspecified bone, Paget's disease of other bone, or Paget's disease of the skull.

[0034] Sjogren's syndrome may be, for example, Sjogren's syndrome with myopathy, Sjogren's syndrome with keratoconjunctivitis, Sjogren's syndrome with pulmonary involvement, or Sjogren's syndrome with renal tubulointerstitial disorder, but is not limited to these.

[0035] The systemic sclerosis may be, for example, but not limited to, systemic sclerosis with pulmonary involvement, systemic sclerosis with myopathy, or progressive systemic sclerosis.

[0036] CREST syndrome may be, for example, but not limited to, a combination of calcinosis, Raynaud's phenomenon, esophageal dysfunction, digital sclerosis, and telangiectasia.

[0037] The dermatomyositis may be, but is not limited to, other dermatomyositis or juvenile dermatomyositis.

[0038] The systemic lupus erythematosus may be, for example, but is not limited to, systemic lupus erythematosus with organ or system invasion.

[0039] The polyarteritis may be, but is not limited to, microscopic polyarteritis, juvenile polyarteritis, polyarteritis with pulmonary involvement, or polyarteritis nodosa.

[0040] The polyarthritis may be, but is not limited to, juvenile polyarthritis or chronic juvenile polyarthritis.

[0041] Juvenile arthritis may be, but is not limited to, systemic onset juvenile arthritis.

[0042] The rheumatoid arthritis may be, but is not limited to, juvenile rheumatoid arthritis or juvenile rheumatoid arthritis with or without rheumatoid factor.

[0043] Among these diseases are relapsing polychondritis, Kienböck's disease in adults, osteochondrosis of the lunate bone of the carpals, complex regional pain syndrome, Paget's disease of bone unspecified, Paget's disease of other bones, Paget's disease of the skull, fibrodysplasia ossificans progressiva, Weber-Christian disease, multifocal fibrosclerosis, diffuse fasciitis, polymyalgia rheumatica, Behçet's disease, mixed connective tissue disease, Sjögren's syndrome with myopathy, sicca syndrome, Sjögren's syndrome with keratoconjunctivitis, Sjögren's syndrome with pulmonary involvement, Sjögren's syndrome with renal tubulointerstitial disorder, systemic sclerosis with pulmonary involvement, systemic sclerosis with myopathy, CREST syndrome, combination of calcinosis-Raynaud's phenomenon-esophageal dysfunction-digital sclerosis-telangiectasia, progressive systemic sclerosis. Non-limiting examples of rare diseases designated by the Korea Centers for Disease Control and Prevention include, but are not limited to, juvenile polyarteritis, polymyositis, other dermatomyositis, juvenile dermatomyositis, systemic lupus erythematosus with organ or system invasion, microscopic polyarteritis, aortic arch syndrome, Wegener's granulomatosis, fatal midline granuloma, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, Goodpasture's syndrome, juvenile polyarteritis, polyarteritis with pulmonary invasion, polyarteritis nodosa, juvenile polyarthritis, chronic juvenile polyarthritis, systemic-onset juvenile arthritis, juvenile ankylosing spondylitis, juvenile rheumatoid arthritis with or without rheumatoid factor, juvenile rheumatoid arthritis, and adult-onset Still's disease.

[0044] The aforementioned diseases refer to diseases caused by oxidative damage, and may include, in addition to the aforementioned diseases, diseases generally known to be caused by oxidative damage, such as, but not limited to, neurodegenerative diseases, metabolic syndrome, cardiovascular disorders, autoimmune diseases, inflammatory lung diseases, kidney diseases, liver diseases, digestive diseases, viral infectious diseases, cancer, and inflammatory diseases.

[0045] Antioxidation is achieved, for example, by reducing TBARS (thiobarbituric acid reactive substances) or matrix metalloproteinases (MMPs). It's okay to have it.

[0046] The value of TBARS (Thiobarbituric acid reactive substance) is used to judge the improvement of oxidative damage, and is a substance produced by the reaction of MDA (malondialdehyde), which is produced by peroxidation of various biological membranes, with TBA (2-thiobarbituric acid). It is an index of cell damage caused by free radicals, and the higher the TBARS value, the greater the oxidative damage.

[0047] In addition, to assess the improvement of oxidative damage, the value of matrix metalloproteinase (MMP) can be checked. When oxygen increases, the expression of MMP is activated, so if the value of MMP decreases, it can be determined that oxidative damage has been improved, and specifically, MMP-3 may be used.

[0048] In the present invention, "pain" refers to somatic pain, visceral pain, inflammatory pain, Pain, dysfunctional pain, idiopathic pain, neuropathic pain, superficial pain, deep pain The pain may be, but is not limited to, deep pain, itching, migraine and cancer pain. It is not something that can be done.

[0049] The present invention also relates to a pharmaceutical composition containing an extract of Aster japonicus for treating or preventing a disease selected from the group consisting of pain, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, obesity, hyperglycemia, dyslipidemia, hypertension, diabetes, heart failure, cardiovascular ischemia, cerebral ischemic injury, stroke, myocardial infarction, systemic lupus erythematosus, COPD, asthma, acute kidney injury, chronic kidney disease, diabetic nephropathy, end-stage renal disease, viral hepatitis, liver cirrhosis, inflammatory bowel disease, viral infectious diseases, solid cancer, blood cancer, and sepsis.

[0050] The pain may be, but is not limited to, pain within the ranges mentioned above. Antioxidation may be due to a reduction in TBARS (thiobarbituric acid reactive substances) or matrix metalloproteinases (MMPs). good.

[0051] The value of TBARS (Thiobarbituric acid reactive substance) is used to judge the improvement of oxidative damage, and is a substance produced by the reaction of MDA (malondialdehyde), which is produced by peroxidation of various biological membranes, with TBA (2-thiobarbituric acid). It is an index of cell damage caused by free radicals, and the higher the TBARS value, the greater the oxidative damage.

[0052] In addition, to assess the improvement of oxidative damage, the value of matrix metalloproteinase (MMP) can be checked. When oxygen increases, the expression of MMP is activated, so if the value of MMP decreases, it can be determined that oxidative damage has been improved, and specifically, MMP-3 may be used.

[0053] The pharmaceutical composition of the present invention may be used to improve oxidative damage to synovial cells, and the improvement of oxidative damage to synovial cells may be within the scope of the above-mentioned examples, but is not limited thereto.

[0054] The extract of Datura chinensis contained in the pharmaceutical composition of the present invention may be, but is not limited to, a hot water extract, an organic solvent extract, or an ultrasonic extract.

[0055] The health functional food or pharmaceutical composition of the present invention may contain stramonium extract granules, which are prepared by mixing and granulating a stramonium extract and a dextrin-based compound.

[0056] The dextrin-based compound basically serves to make the Korean chrysanthemum extract, which has a high viscosity (e.g., a starch syrup-like form), into a granule-like form. The amount of the granules may be 50 to 70 wt %, preferably 55 to 65 wt %, and more preferably about 60 wt % based on the total weight of the chrysanthemum extract granules. As used herein, "granules" may include fine powder, specifically a mixture of granule particles and fine powder particles, or an aggregate of fine powder particles. The size of the granule particles may be the same as that of pharmaceuticals commonly produced in the art, and is not particularly limited as long as the objective of the present invention, i.e., improved stability, is achieved.

[0057] If the content of the dextrin-based compound is less than 50% by weight of the total weight of the Korean chrysanthemum extract granules, the raw material is produced in the form of moist granules or powder (containing a lot of moisture) compared to conventional products. When the raw material is used to manufacture a finished drug, the binding property of the raw material increases, the deliquescence prevention effect of the natural product extract decreases, and the disintegration time is delayed. In addition, if the content of the dextrin-based compound exceeds 70 wt % of the total weight of the Korean chrysanthemum extract granules, the proportion of the Korean chrysanthemum extract will be relatively reduced, and a large amount of the mixture (Korean chrysanthemum extract + dextrin-based compound) will have to be used during formulation testing, which may result in problems such as reduced tabletability and changes in disintegration time during the manufacturing of finished pharmaceutical products.

[0058] Examples of such dextrin-based compounds include maltodextrin, cyclodextrin, dextrin-based compounds having similar or identical physical properties and characteristics to these, and mixtures of these, and from an economical point of view, it is preferable to use maltodextrin.

[0059] The health functional food of the present invention may contain common food additives in addition to the above-mentioned Korean chrysanthemum extract or granules thereof. The suitability of a food additive is determined in accordance with the specifications and standards for the relevant item based on the general provisions and general test methods of the Food Additives Code approved by the Ministry of Food and Drug Safety, Korea, unless otherwise specified.

[0060] Examples of items listed in the Food Additives Code include, but are not limited to, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon color, licorice extract, crystalline cellulose, sorghum color, and guar gum; and mixed preparations such as sodium L-glutamate preparations, noodle additive alkalinity agents, preservative preparations, and tar color preparations.

[0061] For example, the tablet-type health functional food can be prepared by granulating the mixture of the extract with excipients, binders, disintegrants and other additives in a conventional manner, and then adding lubricants and compressing the mixture, or by directly compressing the mixture. The tablet-type health functional food can also contain flavoring agents, if necessary.

[0062] In the case of capsule-type health functional foods, hard capsules can be prepared by filling a mixture of the extract with additives such as excipients into a conventional hard capsule, while soft capsules can be prepared by filling a mixture of the extract with additives such as excipients into a capsule base such as gelatin. The soft capsules can contain plasticizers such as glycerin or sorbitol, colorants, preservatives, etc., as needed.

[0063] The round health functional food can be produced by molding a mixture of the extract with excipients, binders, disintegrants, etc., using a conventionally known method, and if necessary, the product may be shelled with white sugar or other shell-forming agents, or the surface may be coated with materials such as starch or talc.

[0064] Granular health functional foods can be prepared by mixing the extract with excipients, binders, disintegrants, etc., and manufacturing the mixture into granules by a conventionally known method, and can contain flavoring agents, flavoring agents, etc. as needed.

[0065] The health functional foods may be beverages, meats, chocolates, meals, confectioneries, pizza, ramen, other noodles, gums, candies, ice creams, alcoholic beverages, vitamin complexes, and dietary supplements.

[0066] Health functional foods can be orally administered as a nutritional supplement, and the application form is not particularly limited. For example, in the case of oral administration, the daily intake is preferably 5000 mg or less, more preferably 2000 mg or less, and most preferably 1000 mg or less. When formulated as capsules or tablets, one tablet can be administered once a day with water.

[0067] The pharmaceutical composition of the present invention may further contain crystalline cellulose in addition to the aforementioned Korean chrysanthemum extract granules (Korean chrysanthemum extract and dextrin-based compound). The crystalline cellulose is a component that can ensure moisture stability when used in combination with a lubricant, as described below. Therefore, the tablet coating used when formulating the Korean chrysanthemum extract of the present invention corresponds to a general coating rather than a moisture-proof coating. The crystalline cellulose may be used in an amount of 50 to 70 wt %, preferably 50 to 65 wt %, and more preferably 50 to less than 60 wt %, based on the total weight of the pharmaceutical composition of the present invention. If the total weight of the initial completed composition is somewhat high due to factors such as tablet size, the amount or weight of the crystalline cellulose and the lubricant, as described below, may be reduced. In other words, the proportion of additives may be adjusted taking into account the tablet size.

[0068] If the content of the crystalline cellulose is less than 50 wt% based on the total weight of the pharmaceutical composition of the present invention, the disintegration time may be delayed compared to conventional compositions, and the anti-deliquescent effect may be reduced, resulting in changes in stability due to increased water content. Furthermore, if the content of the crystalline cellulose exceeds 70 wt% based on the total weight of the pharmaceutical composition of the present invention, the increased content of crystalline cellulose may relatively reduce the proportion of active ingredient in the same weight of the mixture, requiring tablets to be made with an excess of the mixture, which may result in changes in tablet size. Furthermore, to maintain tablet size under these conditions, increased tableting pressure may be required, increasing hardness and affecting disintegration. Furthermore, if the tablet surface is not smooth during compression, binding strength may decrease and friability may increase, ultimately resulting in problems with tableting and coating.

[0069] The pharmaceutical composition with improved stability comprising the natural product extract according to the present invention may further comprise a pharmaceutically acceptable excipient, but does not comprise a solubilizer or disintegrant.

[0070] The excipient may be a lubricant. Examples of the lubricant include lubricants commonly used in the art, such as silicon dioxide, magnesium stearate, and mixtures thereof. Preferably, silicon dioxide and magnesium stearate are used together. The lubricant may be used in an amount of 2 to 4 wt. % based on the total weight of the pharmaceutical composition of the present invention.

[0071] Meanwhile, the pharmaceutical composition with improved stability containing the natural product extract according to the present invention can be formulated in a form selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, oral liquids, emulsions, syrups, and freeze-dried preparations, but in view of the purpose of the present invention, it is most preferable to formulate it in tablet form.

[0072] When the pharmaceutical composition is formulated into a tablet, the tablet may include a coating layer, which may contain only an aqueous coating agent. That is, as described above, the present invention does not include a conventional moisture-proof coating agent by applying specific amounts of crystalline cellulose and lubricant, etc., to ensure stability against moisture (i.e., the pharmaceutical composition has a moisture-proof effect even without a moisture-proof coating agent, and the moisture-proof effect may be exerted by one or more of a dextrin-based compound, crystalline cellulose, and a lubricant).

[0073] The water-based coating agent may contain, for example, hydroxypropyl methylcellulose (HPMC), glycerin fatty acid ester, titanium dioxide, lac pigment, and substances having similar or identical physical properties and characteristics. The hydroxypropyl methylcellulose may be replaced with methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, or cellulose-based compounds having similar properties. In addition, the aqueous coating agent may further contain one or more of a solubilizer, a plasticizer, a binder, a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifier, a suspending agent, and a diluent, if necessary.

[0074] The pharmaceutical composition of the present invention, which contains the above-mentioned components, has various advantages in addition to those mentioned above. First, unlike conventional pharmaceutical compositions, the pharmaceutical composition of the present invention does not use a solubilizer, disintegrant, or moisture-proof coating agent, thereby allowing the drug content to be reduced. Furthermore, while conventional tablets tend to increase in hardness as the moisture content decreases, and therefore the disintegration time also tends to be longer, tablets made using the pharmaceutical composition of the present invention do not increase in hardness because the moisture content is maintained, thereby offering the advantage of a consistent disintegration time of within 30 minutes without the use of a disintegrant (without affecting storage temperature or period).

[0075] The present invention will be specifically described below with reference to examples. Manufacturing example: Manufacturing of Korean chrysanthemum extract To obtain the Korean chrysanthemum extract, the Korean chrysanthemum extract was prepared using hot water and organic solvent extraction methods.

[0076] 1. Hot water extraction method To prepare the hot water extract of Korean chrysanthemum, Korean chrysanthemum was washed with distilled water, crushed finely in a crusher, and then heated in hot water to obtain the Korean chrysanthemum extract.

[0077] To this end, 1.0 L of water was added to each 100 g of stramonium raw material, and the mixture was extracted by heating in hot water at 100-120°C for approximately 2-3 hours. A condenser was installed to maintain a constant temperature and prevent loss of steam. The resulting stramonium extract was filtered to obtain a supernatant, which was then concentrated using a concentrator. The stramonium concentrate was frozen and freeze-dried at -80°C to produce stramonium extract powder. As for drying methods, vacuum drying or hot air drying can be used in addition to freeze-drying.

[0078] 2. Organic solvent extraction method To prepare the organic solvent extract (ultrasonic extract) of stramonium serrata, stramonium serrata was immersed in 70% ethanol and extracted using an ultrasonic extractor for approximately 2-3 weeks to obtain the extract. The supernatant was then separated and filtered through gauze to remove impurities. The alcohol extract obtained from this process was concentrated using a concentrator, frozen, and freeze-dried at -80°C to produce stramonium serrata extract powder. In this method, an ultrasonic extractor was used for the purpose of rapid extraction in a short time, but the ultrasonic extraction step is not necessary for mass production. As with the hot water extraction method, vacuum drying or hot air drying can be used instead of freeze-drying.

[0079] Example 1. Human application test and results by ingestion of tablets containing Korean chrysanthemum extract 1. Human application test method (1) The subjects for the human trial were individuals with mild symptoms of degenerative knee arthritis, and their suitability for the inclusion or exclusion criteria was assessed through a home visit evaluation. Only those subjects who met the "suitable" criteria were randomly assigned to either the test group or the control group, and they were asked to consume the human trial food (test food or control food) for 12 weeks. An overview of the human trial is shown in Figure 1.

[0080] (2) The composition of the test food is as shown in Table 1 below, and the composition of the control food is as shown in Table 2 below. The Korean chrysanthemum extract in Table 1 was an ultrasonic extract obtained by the organic solvent extraction method in the above Preparation Example.

[0081] [Table 1]

[0082] [Table 2]

[0083] (3) Before starting the human application test, the past medical history and drug administration history were confirmed through a review of past medical records and interviews.

[0084] (4) The experimental group and the control group took one tablet of the test food (250 mg / day of Asteria sieboldii extract) and the control food, respectively, once a day for 12 weeks (84 days).

[0085] 2. Experimental Results (1) Comparison of TBARS values

[0086] [Table 3]

[0087] As shown in Table 3 above, analysis of the change in TBARS revealed that after 12 weeks of intake, the test group had a decrease of 0.21 μM, while the control group had an increase of 0.26 μM.

[0088] From these findings, it can be said that oxidative damage to synovial cells improved in the test group where TBARS values ​​decreased, while oxidative damage to synovial cells did not improve in the control group where TBARS values ​​increased.

[0089] (2) Measurement of MMP-3 levels Table 4 shows the results of analyzing the change in MMP-3 levels in the PP set, after 12 weeks of intake. A decrease of 0.76 ng / ml was observed in the test group, while an increase of 1.20 ng / ml was observed in the control group.

[0090] [Table 4]

[0091] Table 5 shows the results of analyzing the change in MMP-3 levels using the FA set. A decrease of 0.76 ng / ml was observed in the later test group, while an increase of 1.20 ng / ml was observed in the control group.

[0092] [Table 5]

[0093] Since MMP-3 in the test group decreased, while MMP-3 in the control group increased, it can be concluded that oxidative damage was improved in the test group that ingested the test food (containing the chrysanthemum extract).

[0094] Example 2. Evaluation of the analgesic effect of Korean chrysanthemum extract (70% ethanol extract of Korean chrysanthemum) 1. Experimental Method (1) Standards The test method used in this example is the "hot plate test" described in the "Guidelines for Efficacy Testing of Herbal Medicine Preparations - General Efficacy Tests for Pain Disorders" issued by the Korea Food and Drug Administration. The central nervous system analgesic efficacy test is conducted on mice using the reaction time to a heat stimulus source on a hot plate as an index. The reaction time to the heat stimulus source is measured as the time it takes the experimental animal to lick its paw or jump.

[0095] (2) Drug administration 1) Celebrex (celecoxib, Pfizer, 200 mg), Saline (JW Pharmaceutical Corporation), and Korean chrysanthemum extract (GREEN CROSS HS) in males. ICR mice (6 weeks old, weighing 30-35 g, Orient Bio) were prepared. The stramonium chloride extract in this example was extracted using the organic solvent extraction method in the above Preparation Example, using 70% ethanol.

[0096] 2) Celebrex 60mg / kg and Korean daisy extract were prepared at 50, 100, and 200mg / kg and orally administered to ICR mice. Celebrex was converted to the administration concentration and suspended in saline by vortexing. The extract of Soragonia pinnatifida was suspended in 0.5% CMC and sonicated at 20-25°C for about 10 minutes.

[0097] 2. Evaluation and Results (1) Evaluation method The hot plate test was performed using 5-week-old male ICR mice, which were purchased and allowed to acclimate for one week before the experiment. The hot plate was maintained at 55°C, and drug administration was performed 30 minutes before the experiment. The central pain response to heat sensation was measured as the time from contact with the hot plate to licking or jumping of the hind paws.

[0098] (2) Classification of study groups (n=8)

[0099] [Table 6]

[0100] (3) Experimental results The Korean chrysanthemum extract was administered at various concentrations as shown in Table 6. After 20 minutes, the mice were placed on a hot plate maintained at 55°C, and the thermal pain response was measured based on the reaction time from touching the hot plate to licking or jumping on the hind paws. The results are shown in Figure 2 and Table 7.

[0101] [Table 7]

[0102] In the case of the control group, the reaction time was 20.1 seconds, and the reaction time of the Korean chrysanthemum extract was 1. The groups administered 50, 100, and 200 mg / kg of celecoxib showed significant increases in reaction time compared to the control group, with increases of 38.4%, 47.2%, and 80.3%, respectively. The group administered Celebrex (containing celecoxib), the positive control drug, also showed an increase of 53.9% in hot plate reaction time.

[0103] As shown above, reaction times were significantly increased in all dose groups administered with Korean chrysanthemum extract compared to the control group. In particular, reaction times were significantly increased in the 200mg / kg group compared to the Celebrex group. These results suggest that Korean chrysanthemum extract can alleviate pain in patients by exerting a strong central nervous system pain inhibitory effect.

[0104] Example 3. Evaluation of the analgesic effect of a Korean chrysanthemum extract (70% ethanol extract of Korean chrysanthemum) in an acetic acid-induced analgesic test model 1. Experimental Method (1) Standards The test method used in this example is the "Acetic Acid Writhing Test" described in the "Guidelines for Efficacy Tests of Herbal Preparations - General Efficacy Tests for Pain Disorders" issued by the Ministry of Food and Drug Safety of Korea. The test method is an acetic acid writhing test, which is performed by administering acetic acid intraperitoneally to mice. Intraperitoneal capillary damage and pain were induced, and the analgesic efficacy of peripheral nerves was tested using abdominal contraction response as an index.

[0105] (2) Drug administration 1) Celebrex (celecoxib, Pfizer, 200 mg), acetic acid (Daejung Chemicals & Metals Co., Ltd.), saline (JW Pharmaceutical Corporation) and The chrysanthemum extract in this example was extracted using the organic solvent extraction method described in the Preparation Example above, using 70% ethanol.

[0106] 2) Celebrex 60mg / kg and Korean daisy extract were prepared at 50, 100, and 200mg / kg and orally administered to ICR mice. Celebrex was converted to the administration concentration and suspended in saline by vortexing. The extract of Soragonia pinnatifida was suspended in 0.5% CMC and sonicated at 20-25°C for about 10 minutes.

[0107] 2. Evaluation and Results (1) Evaluation method The acetic acid-induced analgesic efficacy test was conducted using 4-week-old male ICR mice purchased as experimental animals and allowed to acclimate for one week before the experiment. The mice were orally administered with the Aster sieboldii extract and control drug at different doses, and 30 minutes after administration, acetic acid (0.7% acetic acid-physiological saline (0.1 ml / 10 g BW)) was intraperitoneally injected. The mice were then monitored for writhing for 10 minutes starting from 5 minutes after the injection. The number of live births was measured (Figure 3).

[0108] (2) Classification of test groups (n=6)

[0109] [Table 8]

[0110] (3) Experimental results The concentrations of the Korean chrysanthemum extract were administered as shown in Table 8. After 30 minutes, 0.7% acetic acid-saline solution was administered intraperitoneally to induce pain, and the number of writhing syndromes was counted for 10 minutes starting from 5 minutes after the intraperitoneal administration. The results are shown in Figure 4 and Table 9. That's right.

[0111] [Table 9]

[0112] In the control group, the incidence of twisting syndrome was 28.33 / 10 min. The incidence of twisting syndrome was reduced by 50.1% and 61.3% in the 100 and 200mg / kg groups, respectively, except for the low-dose group of 50mg / kg administered with Korean daisy extract. The group administered Celebrex (containing celecoxib), which was administered as a positive control, also significantly reduced the incidence of twisting syndrome induced by acetic acid, with an inhibition rate of 48.9%.

[0113] These results confirmed that the number of writhing episodes was significantly reduced in all dose groups administered with Korean chrysanthemum extract compared to the control group, and that the number of writhing episodes was more significantly reduced in the 100mg / kg and 200mg / kg groups compared to the Celebrex group. Therefore, it can be said that Korean chrysanthemum extract can alleviate pain in patients by exerting a strong pain-suppressing effect on the peripheral nervous system.

Claims

1. A health functional food containing chrysanthemum extract for pain relief or antioxidant purposes.

2. The health functional food according to claim 1, wherein the antioxidant improves oxidative damage to synovial cells.

3. The health functional food according to claim 2, wherein the oxidative damage is damage in patients with degenerative arthritis.

4. Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, obesity, hyperglycemia, dyslipidemia, hypertension, diabetes, heart failure, cardiovascular ischemia, cerebral ischemic injury, stroke, myocardial infarction, systemic lupus erythematosus, COPD, asthma, acute kidney injury, chronic kidney disease, diabetic nephropathy, end-stage renal disease, viral hepatitis, liver cirrhosis, inflammatory bowel disease, viral infectious diseases, solid tumors, blood cancers, sepsis, relapsing polychondritis, Kienböck's disease in adults, carpal lunate osteochondrosis, complex regional pain syndrome, Paget's disease, fibrodysplasia ossificans progressiva, Weber-Christian syndrome 2. The health functional food according to claim 1, which is for the prevention or amelioration of a disease selected from the group consisting of rheumatic disease, multifocal fibrosclerosis, diffuse fasciitis, polymyalgia rheumatica, Behcet's disease, mixed connective tissue disease, Sjogren's syndrome, sicca syndrome, systemic sclerosis, crest syndrome, polymyositis, dermatomyositis, systemic lupus erythematosus, aortic arch syndrome, Wegener's granulomatosis, lethal midline granuloma, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, Goodpasture's syndrome, polyarteritis nodosa, polyarthritis, juvenile arthritis, juvenile ankylosing spondylitis, rheumatoid arthritis, and adult-onset Still's disease.

5. The health functional food according to claim 1, wherein the extract of Korean chrysanthemum is a hot water extract or an organic solvent extract.

6. The pain includes somatic pain, visceral pain, inflammatory pain, and functional pain. Pathogenic pain, idiopathic pain, neuropathic pain, superficial pain, deep pain 2. The method of claim 1, wherein the pain is selected from the group consisting of itch, migraine, and cancer pain. Health functional food.

7. Pain with Chinese cabbage extract, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, obesity, hyperglycemia, dyslipidemia, hypertension, diabetes, heart failure, cardiovascular ischemia, cerebral ischemic injury, stroke, myocardial infarction, systemic lupus erythematosus, COPD, asthma, acute kidney injury, chronic kidney disease, diabetic nephropathy, end-stage renal disease, viral hepatitis, liver cirrhosis, inflammatory bowel disease, viral infectious diseases, solid tumors, blood cancers, sepsis, relapsing polychondritis, Kienböck's disease in adults, carpal lunate osteochondrosis, complex regional pain syndrome, Paget's disease, and fibrous ossificans progressiva A pharmaceutical composition for the treatment or prevention of a disease selected from the group consisting of adult-onset rheumatoid arthritis, Weber-Christian disease, multifocal fibrosclerosis, diffuse fasciitis, polymyalgia rheumatica, Behcet's disease, mixed connective tissue disease, Sjogren's syndrome, sicca syndrome, systemic sclerosis, CREST syndrome, polymyositis, dermatomyositis, systemic lupus erythematosus, aortic arch syndrome, Wegener's granulomatosis, lethal midline granulomatosis, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, Goodpasture's syndrome, polyarteritis nodosa, polyarthritis, juvenile arthritis, juvenile ankylosing spondylitis, rheumatoid arthritis, and adult-onset Still's disease.

8. The pain includes somatic pain, visceral pain, inflammatory pain, and functional pain. Pathogenic pain, idiopathic pain, neuropathic pain, superficial pain, deep pain 8. The method of claim 7, wherein the pain is selected from the group consisting of pain, itch, migraine, and cancer pain. Pharmaceutical compositions.

9. The pharmaceutical composition according to claim 7, which is an antioxidant that reduces TBARS (thiobarbituric acid reactive substances).

10. The pharmaceutical composition according to claim 9, wherein the antioxidant is an improvement in oxidative damage of synovial cells.

11. The pharmaceutical composition according to claim 7, wherein the extract of Korean chrysanthemum is a hot water extract or an organic solvent extract.

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