Composition for preventing or treating gout or carpal tunnel syndrome

Abstract

The present invention relates to a composition for the prevention, improvement, or treatment of pain including gout or carpal tunnel syndrome, containing as active ingredients a mixed medicinal herb extract of 12 types: Sanpyeoncho, Baekchul, Baekbokryeong, Cinnamon, Glycyrrhiza, Cnidium, Angelica, Dioscorea, Saussurea costus, Ginger, Pueraria root, and Hepatica nobilis. The composition has excellent antioxidant activity due to its high DPPH radical scavenging ability and high inhibitory activity of xanthan oxidase, and can be usefully used as a pharmaceutical composition or a health functional food composition for the prevention, improvement, or treatment of pain including gout or carpal tunnel syndrome through its pain relief effect for gout patients and its symptom relief effect, such as numbness in the fingers for carpal tunnel syndrome patients.

Description

Technology Field

[0001] The present invention relates to a composition for the prevention or treatment of pain, and more specifically, to a composition for the prevention or treatment of pain including gout or carpal tunnel syndrome, containing as active ingredients an extract of 12 mixed medicinal herbs: Sanpyeoncho, Mokhyang, Danggi, Cheongung, Ginger, Cinnamon, Dioscorea, Atractylodes, Poria, Pueraria root, Glycyrrhiza, and Scutellaria root. Background Technology

[0002] Pain is known to protect the body from danger and play an important role in the recovery of damaged tissues. However, pathological pain caused by viral or bacterial infections, severe inflammatory reactions around peripheral nerves, or direct damage to peripheral nerves is harmful to the human body and has a significant impact on the patient's quality of life.

[0003] Among pains, gout is a disease caused by hyperuricemia, in which uric acid, the end product of purine metabolism, remains in the blood at a high concentration. At this time, various causes can contribute to the elevated concentration of uric acid; uric acid levels may increase if the kidneys fail to sufficiently remove uric acid even though the body's uric acid production is normal, if too much uric acid is produced, or if medications cause an increase in uric acid.

[0004] Gout is a genetic disease characterized by recurring attacks; if left untreated for a long time, it leads to the destruction of bone and cartilage, and progresses to joint deformation, fibrosis, and osteotomy. If gout symptoms persist for an extended period, complications such as urinary stones and myocardial infarction may occur, and it can be accompanied by diabetes or hypertension.

[0005] Treatment for gout varies in stages depending on the symptoms, and methods ranging from dietary therapy and lifestyle modifications to the administration of drugs such as colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids, or anti-hyperuricemia drugs such as allopurinol and probenecid, are being implemented. However, there is a concern that the use of these drugs may cause many side effects, so there is a need to develop a natural gout treatment that is safe and highly effective.

[0006] Meanwhile, carpal tunnel syndrome is synonymous with carpal tunnel syndrome and is the most common compressive neuropathy in the upper extremities. It is a peripheral nerve compression syndrome in which the median nerve is compressed in the wrist area, causing numbness, pain, decreased sensation, swelling, and weakness in the hand and fingers.

[0007] The wrist is one of the parts of the body with the widest range of motion, and the tendons of the muscles involved in hand movement, sensory nerves responsible for sensation and motor nerves involved in movement, and blood vessels necessary for blood supply to the hand all extend from the arm through the wrist to the hand.

[0008] The space surrounded by the transverse carpal ligament (horizontal carpal ligament, carpal tunnel ligament, transverse carpal ligament) and surrounding tissues as the above structures pass through the wrist on the palm side is called the carpal tunnel or carpal tunnel. Carpal tunnel syndrome occurs because the median nerve, one of the structures passing through the carpal tunnel, is compressed due to increased pressure within the carpal tunnel.

[0009] Unlike tendons, nerves are soft rather than hard, making them susceptible to damage from compression. When the wrist is extended significantly, the carpal tunnel becomes smaller, and some of the structures in the palm are pushed toward the wrist, increasing the volume of the contents within the carpal tunnel and causing the compression of the median nerve to become more pronounced.

[0010] A thin membrane surrounding the muscle tendons helps each tendon slide smoothly through the carpal tunnel when gripping or extending the fingers, but if the tendons are overused, irritated, or inflamed, the surrounding membrane thickens and swells, increasing the volume of structures within the carpal tunnel and causing the carpal tunnel space to become relatively narrower, which may result in the median nerve being compressed.

[0011] A commonly used non-surgical (conservative) treatment for carpal tunnel syndrome involves temporarily immobilizing the wrist with a splint to prevent overuse and alleviate symptoms. However, a drawback of most simple immobilization devices designed to restrict wrist movement is that they are not highly effective in relieving pain.

[0012] Against this background, the inventors conducted research to develop a natural therapeutic agent for the prevention, improvement, or treatment of pain including gout and carpal tunnel syndrome. As a result, they confirmed that a mixed extract of 12 medicinal herbs—Sanpyeopcho, Baekchul, Baekbokryeong, Cinnamon, Glycyrrhiza, Cnidium, Angelica, Dioscorea, Saussurea costus, Ginger, Pueraria root, and Hepatica nobilis—has high DPPH radical scavenging ability, excellent antioxidant activity, high inhibitory activity of xanthan oxidase, pain relief effect for gout patients, and clinical symptom relief effect such as finger numbness in carpal tunnel syndrome patients, thereby completing the present invention. Prior art literature

[0013] Korean Registered Patent Publication KR 10-0201935 The problem to be solved

[0014] The object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of pain comprising a mixed extract of *Scutellaria baicalensis*, *Atractylodes macrocephala*, *Poria cocos*, *Cinnamomum cassia*, *Glycyrrhiza glabra*, *Cnidium officinale*, *Angelica gigas*, *Dioscorea opposita*, *Salvia miltiorrhiza*, *Ginger ginger*, *Pulmonaria root*, and *Scutellaria baicalensis* as an active ingredient, wherein the pain includes gout or carpal tunnel syndrome.

[0015] Another object of the present invention is to provide a method for preventing or treating pain, comprising the step of administering the pharmaceutical composition to an individual, wherein the pain includes gout or carpal tunnel syndrome.

[0016] Another objective of the present invention is to provide a health functional food composition for preventing or improving pain, comprising as an active ingredient a mixed extract of *Scutellaria baicalensis*, *Atractylodes macrocephala*, *Poria cocos*, *Cinnamomum cassia*, *Glycyrrhiza glabra*, *Cnidium officinale*, *Angelica gigas*, *Dioscorea opposita*, *Salvia miltiorrhiza*, *Ginger ginger*, *Pulmonaria root*, and *Scutellaria baicalensis*, wherein the pain includes gout or carpal tunnel syndrome. means of solving the problem

[0017] The advantages and features of the present invention and the methods for achieving them will become clear by referring to the embodiments described below in detail together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below but may be implemented in various different forms. These embodiments are provided merely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the present invention, and the present invention is defined only by the scope of the claims.

[0018] The terms used in this specification are for describing the embodiments and are not intended to limit the invention. In this specification, the singular form includes the plural form unless specifically stated otherwise in the text. The terms "comprises" and / or "comprising" used in this specification do not exclude the presence or addition of one or more other components in addition to the components mentioned. Throughout the specification, the same reference numerals refer to the same components, and "and / or" includes each of the mentioned components and all combinations of one or more. Although terms such as "first," "second," etc., are used to describe various components, these components are not limited by these terms. These terms are used merely to distinguish one component from another. Therefore, the first component mentioned below may be the second component within the technical scope of the invention.

[0019] Unless otherwise defined, all terms used herein (including technical and scientific terms) may be used in a meaning commonly understood by those skilled in the art to which the present invention pertains. Additionally, terms defined in commonly used dictionaries are not to be interpreted ideally or excessively unless explicitly and specifically defined otherwise.

[0020] The present invention provides a pharmaceutical composition for the prevention or treatment of pain comprising a mixed extract of *Scutellaria baicalensis*, *Atractylodes macrocephala*, *Poria cocos*, *Cinnamomum cassia*, *Glycyrrhiza glabra*, *Cnidium officinale*, *Angelica gigas*, *Dioscorea opposita*, *Salvia miltiorrhiza*, *Ginger ginger*, *Pulmonaria root*, and *Scutellaria baicalensis* as an active ingredient, wherein the pain includes gout or carpal tunnel syndrome.

[0021] The above extract can be extracted with a solvent selected from the group consisting of water, C1 to C4 lower alcohols, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof.

[0022] The above lower alcohol may be one or more lower alcohols selected from the group consisting of ethanol, methanol, propanol, normal-propanol, iso-propanol, butanol, normal-butanol, and iso-butanol.

[0023] The above extract can inhibit DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals.

[0024] In a specific embodiment of the present invention, the solids of the water extract and ethanol extract of the 12 mixed medicinal herbs—Sanpyeopcho, Baekchul, Baekbokryeong, Cinnamon, Glycyrrhiza, Cnidium, Angelica, Dioscorea, Saussurea costus, Ginger, Pueraria root, and Hepatica nobilis—that were freeze-dried showed antioxidant activity through DPPH radical scavenging activity of 47.2% and 30.2%, respectively, and it was confirmed that the water extract and ethanol extract containing 200 μg / mL of phenolic compounds showed antioxidant activity through DPPH radical scavenging activity of 92.3% and 81.3%, respectively.

[0025] The above extract can inhibit xanthine oxidase.

[0026] In a specific embodiment of the present invention, it was confirmed that while allopurinol, a gout inhibitor used as a positive control, showed an inhibitory activity of 58.40 to 78.58% at a treatment concentration of 50 to 200 μg / mL, the 12 mixed medicinal herb extracts of the present invention showed high xanthan oxidase inhibitory activities of 52.42 to 100% and 39.78 to 100% in water extracts and ethanol extracts containing phenolic compounds at concentrations of 50 to 200 μg / mL, respectively.

[0027] The above extract can lower blood uric acid.

[0028] In a specific embodiment of the present invention, the effect of improving gout was measured in an animal model of hyperuricemia, and it was confirmed that the 12 mixed medicinal extracts of the present invention were effective in reducing uric acid levels in both water extracts and ethanol extracts.

[0029] The above extract can be obtained by extracting at 100 to 150 ℃ for 3 to 5 hours.

[0030] The pain of the present invention may be acute pain or chronic pain. The pain refers to an unpleasant sensory and emotional experience caused by actual or potential tissue damage or intense external stimulation.

[0031] The composition of the present invention can be applied to the treatment of pain occurring in the skin or musculoskeletal system, specifically for diabetic neuropathy, diabetic peripheral neuropathy, pain caused by viral infection, nociceptive pain, facial neuralgia, postherpetic neuralgia, lower back pain, herniated disc, radiculopathy, neuropathy, hyperalgesia, pain related to central sensitization, allodynia, cancer pain, myofascial pain syndrome, carpal tunnel syndrome, elbow tunnel syndrome (ulnar neuropathy), De Quervain's syndrome, rotator cuff syndrome, osteoarthritis, tendinitis, tenosynovitis, lateral epicondylitis, medial epicondylitis, tendon injury, bursitis, ligament inflammation, tennis elbow, golf elbow, knee joint pain, and periglenoid tendinitis. It can be applied to the treatment of pain associated with one or more selected from meniscal injury, finger joint pain, carpal tendinitis, wrist sprain, ankle sprain, sprain, fibromyalgia, plantar fasciitis, inflammatory arthritis, infectious arthritis, rheumatoid arthritis, degenerative joint pain, frozen shoulder, gout, postpartum joint pain, osteomyelitis, ankylosing spondylitis, degenerative spinal disorders, lumbar spinal stenosis, cruralgia, sprain, contusion, joint pain, and sciatica, and more specifically, it can be applied to the treatment of gout or carpal tunnel syndrome.

[0032] Based on 100 parts by weight of *Sanpyeoncho*, the above extract may comprise 100 parts by weight of *Sanpyeoncho*, 20 to 70 parts by weight of *Mokhyang*, 20 to 100 parts by weight of *Danggi*, 20 to 100 parts by weight of *Cheongung*, 50 to 85 parts by weight of *Geonjang*, 20 to 85 parts by weight of *Gampi*, 20 to 100 parts by weight of *Sanyak*, 20 to 85 parts by weight of *Baekchul*, 50 to 100 parts by weight of *Baekbokryeong*, 70 to 140 parts by weight of *Galgeun*, 60 to 140 parts by weight of *Gamcho*, and 20 to 100 parts by weight of *Heecheom*, and exhibits excellent preventive or therapeutic effects for pain including gout or carpal tunnel syndrome within this weight range.

[0033] In a specific embodiment of the present invention, the extract of the present invention is prepared using a mixture of 300 to 400 g of *Sanpyeopcho*, 100 to 200 g of *Mokhyang*, 100 to 300 g of *Danggi*, 100 to 300 g of *Cheongung*, 220 to 250 g of *Geonjang*, 100 to 250 g of *Gampi*, 100 to 300 g of *Sanyak*, 100 to 250 g of *Baekchul*, 220 to 300 g of *Baekbokryeong*, 300 to 400 g of *Galgeun*, 250 to 400 g of *Gamcho*, and 100 to 300 g of *Heecheom*, and exhibits excellent preventive or therapeutic effects for pain including gout or carpal tunnel syndrome within this weight range.

[0034] The pharmaceutical composition of the present invention comprises a mixed extract of *Sanpyeopcho*, *Baekchul*, *Baekbokryeong*, *Cinnamomum cassia*, *Gamcho*, *Cheongung*, *Danggi*, *Yamyak*, *Samgyeong*, *Geonjang*, *Galgeun*, and *Hyeopcheom* as an active ingredient, and refers to a mixture in which other chemical components, such as a diluent or a carrier, are mixed with said mixed extract.

[0035] The mountain herb of the present invention is also called cold herb and has the effect of removing wind, dehumidifying, detoxifying, treating pain, cystitis, eliminating wind in the body, cooling heat, and removing toxins, and expelling waste products accumulated in the body and promoting blood circulation.

[0036] The Atractylodes macrocephala of the present invention removes dampness from the body, activates the secretion of bile, and promotes the secretion of gastric juice, thereby improving gastrointestinal function, enhancing digestion, protecting the gastric mucosa, and providing anti-inflammatory effects. It improves edema, removes body heat, soothes inflammation, and eliminates toxins to improve blood flow and facilitate blood circulation, thereby improving symptoms of swelling in the body and kidney function.

[0037] The Poria cocos of the present invention acts on the heart, nerve, spleen, and lung meridians to protect the spleen and stabilize the nerves, and has diuretic, hypoglycemic, sedative, and mild edema effects, improves kidney disease, and reduces blood cholesterol.

[0038] The cinnamon of the present invention reduces swelling and inflammation and relieves pain.

[0039] The licorice of the present invention neutralizes and alleviates the toxicity of medicinal materials, appropriately combines medicinal properties, and is effective for detoxification and blood circulation.

[0040] The Cnidium of the present invention improves blood coagulation, dissolves blood stasis and promotes the generation of new blood, stabilizes the mind and body, and enables deep sleep.

[0041] The Angelica of the present invention helps improve blood flow, improves cholesterol, supports cardiovascular health, and has a pain-relieving effect.

[0042] The yam of the present invention protects the stomach and produces enzymes having an antioxidant effect that inhibits the generation of inflammation-inducing agents, and inhibits inflammation.

[0043] The wood incense of the present invention has the effect of improving blood circulation in cases of chronic inflammation, expanding blood vessels to lower blood pressure, eliminating toxins and waste products from the body, and removing swelling and edema.

[0044] The health benefits of the present invention include warming the spleen and stomach to eliminate cold, reviving yang to open the pulse, and containing shogaol, which has excellent antibacterial effects and inhibits the growth of bacteria. In addition, it contains gingerol, an ingredient effective against raffinose inflammation, which stops inflammation, relieves pain, and expands blood vessels to promote blood circulation.

[0045] The kudzu root of the present invention removes waste products from the body, is effective for liver and stomach health, and improves digestive power.

[0046] The *Heecheom* of this invention acts on the liver and nerves, eliminates wind-dampness pathogens, and clears the meridians. It relieves numbness in the hands and feet, treats eye strain and stroke, removes harmful free radicals, and prevents oxidation in the body. The herpedin component in *Heecheom* inhibits the proliferation of inflammatory cells and contains ingredients that help alleviate pain.

[0047] The carrier of the present invention is defined as a compound that facilitates the addition of a compound into a cell or tissue. For example, dimethyl sulfoxide (DMSO) is a commonly used carrier that facilitates the introduction of many organic compounds into the cells or tissues of an organism.

[0048] The diluent of the present invention is defined as a compound that not only stabilizes the biologically active form of a target compound but is also diluted in water in which the compound is dissolved. Salts dissolved in a buffer solution are used as diluents in the field. A commonly used buffer solution is a phosphate-buffered saline solution, as this mimics the salt state of human solution. Since buffer salts can control the pH of the solution at low concentrations, it is rare for the buffer diluent to alter the biological activity of the compound.

[0049] Carriers, excipients, and diluents that may be contained in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0050] The pharmaceutical composition according to the present invention can be used by being formulated into oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, and sterile injectable solutions, each according to conventional methods.

[0051] When formulating, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

[0052] Solid dosage forms for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid dosage forms are prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc., with the above compounds. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid dosage forms for oral administration include suspensions, liquid formulations, emulsions, syrups, etc., and may include various excipients, such as humectants, sweeteners, flavorings, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.

[0053] Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used. As bases for suppositories, Witepsol, Macrogol, Tween 61, cacao oil, laurin oil, glycerogelatin, etc. may be used.

[0054] The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.

[0055] The above pharmaceutically effective amount refers to an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level may be determined based on factors including individual type and severity, age, sex, disease progression, drug activity, sensitivity to the drug, time of administration, route of administration and elimination rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. It may also be administered as a single or multiple doses.

[0056] The above composition may be administered to mammals, such as rats, mice, livestock, and humans, via various routes. Any mode of administration is expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura mater, or intracerebrovascular injection.

[0057] The treatment of the present invention refers to an approach to obtain beneficial or desirable clinical results. For the purposes of the present invention, beneficial or desirable clinical results include, without limitation, relief of symptoms, reduction of disease range, stabilization of the disease state (i.e., not worsening), delay or reduction of the rate of disease progression, improvement or temporary relief and alleviation of the disease state (partially or wholly), and whether or not detectable.

[0058] The above treatment may mean increasing the survival rate compared to the survival rate expected without treatment. Treatment refers to both therapeutic treatment and preventive or preventive measures. The above treatments include the treatment required for disabilities that have already occurred as well as disabilities that are prevented. Alleviating disease means reducing the extent of the disease state and / or undesirable clinical signs and / or slowing or prolonging the time course of progression compared to the case of no treatment.

[0059] In addition, the present invention provides a method for preventing or treating pain comprising the step of administering the above pharmaceutical composition to an individual, wherein the pain includes gout or carpal tunnel syndrome.

[0060] The subject of the present invention refers to all animals, including rats, mice, livestock, etc., including humans, to which pain is induced or may be induced.

[0061] The administration of the present invention means introducing the above pharmaceutical composition to an individual.

[0062] The pain of the present invention refers to an unpleasant sensory and emotional experience caused by tissue damage or intense external stimulation.

[0063] The gout of the present invention is a disease caused by hyperuricemia, in which uric acid, the end product of purine metabolism, remains in the blood and its concentration increases.

[0064] The carpal tunnel syndrome of the present invention is the most common compressive neuropathy occurring in the upper extremities, and is a peripheral nerve compression syndrome in which the median nerve is compressed in the wrist area, causing numbness, pain, decreased sensation, swelling, and weakness in the hand and fingers.

[0065] The prevention of the present invention refers to any act of suppressing or delaying the onset of pain, including gout or carpal tunnel syndrome, through the administration of the above pharmaceutical composition.

[0066] The treatment of the present invention refers to any act in which symptoms of pain, including gout or carpal tunnel syndrome, are improved or beneficially altered by the administration of the above pharmaceutical composition.

[0067] In addition, the present invention provides a health functional food composition for preventing or improving pain, comprising a mixed extract of *Scutellaria baicalensis*, *Atractylodes macrocephala*, *Poria cocos*, *Cinnamomum cassia*, *Glycyrrhiza glabra*, *Cnidium officinale*, *Angelica gigas*, *Dioscorea opposita*, *Salvia miltiorrhiza*, *Ginger ginger*, *Pulmonaria root*, and *Scutellaria baicalensis* as an active ingredient, wherein the pain includes gout or carpal tunnel syndrome.

[0068] The health functional food of the present invention refers to a food manufactured and processed using raw materials or ingredients having functional properties useful to the human body, and means consuming it for the purpose of obtaining useful effects for health purposes, such as regulating nutrients or physiological actions regarding the structure and function of the human body.

[0069] The health functional food of the present invention may include conventional food additives, and unless otherwise specified, suitability as a food additive is determined in accordance with the specifications and standards for the relevant item, in accordance with the general provisions and general test methods of the food additive code approved by the Ministry of Food and Drug Safety.

[0070] The health functional food composition of the present invention may contain various flavoring agents or natural carbohydrates, etc., as additional ingredients, just like conventional food compositions.

[0071] The above-described health functional food composition can be formulated in the same manner as the above-described pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, food products, confectionery, pizza, ramen, other noodles, chewing gum, candy, ice cream, alcoholic beverages, vitamin complexes, and health supplements.

[0072] For example, a health functional food in tablet form may be produced by granulating a mixture of the active ingredient of the present invention with an excipient, a binder, a disintegrant, and other additives using a conventional method, and then adding a lubricant or the like and compression molding, or by directly compression molding the mixture. In addition, the health functional food in tablet form may contain a binder or the like as needed.

[0073] Among the capsule-type health functional foods, hard capsules can be manufactured by filling a conventional hard capsule with a mixture in which the extract of the active ingredient of the present invention is mixed with additives such as excipients, and soft capsules can be manufactured by filling a capsule base such as gelatin with a mixture in which the active ingredient is mixed with additives such as excipients. The soft capsules may contain plasticizers such as glycerin or sorbitol, coloring agents, preservatives, etc., as needed.

[0074] A health functional food in the form of a pill can be prepared by molding a mixture of the active ingredient of the present invention, a mixed herbal extract, an excipient, a binder, a disintegrant, etc., using a previously known method, and if necessary, it can be coated with sucrose or other coating agents, or the surface can be coated with a substance such as starch or talc.

[0075] A health functional food in granular form can be manufactured into a granular form by a previously known method by mixing a mixture of the active ingredient of the present invention, a mixed medicinal extract, an excipient, a binder, a disintegrant, etc., and may contain flavoring agents, stimulating agents, etc. as needed. Effects of the invention

[0076] The present invention provides a composition for the prevention, improvement, or treatment of pain including gout or carpal tunnel syndrome, containing as active ingredients a mixed medicinal herb extract of 12 types: Sanpyeoncho, Baekchul, Baekbokryeong, Cinnamon, Glycyrrhiza, Cnidium, Angelica, Dioscorea, Saussurea costus, Ginger, Pueraria root, and Scutellaria root. The composition has excellent antioxidant activity due to its high DPPH radical scavenging ability and high inhibitory activity of xanthan oxidase, and can be usefully used as a pharmaceutical composition or a health functional food composition for the prevention, improvement, or treatment of pain including gout or carpal tunnel syndrome through its pain relief effect for gout patients and its symptom relief effect, such as numbness in the fingers for carpal tunnel syndrome patients. Brief explanation of the drawing

[0077] Figure 1 is a figure showing the content of phenolic compounds in the solid obtained by freeze-drying the water extract and ethanol extract of 12 mixed medicinal materials of the present invention, namely Sanpyeoncho, Baekchul, Baekbokryeong, cinnamon, licorice, Cheongung, Danggui, Sanyak, Moksang, Ginger, Galgeun, and Hichon. Figure 2 is a figure showing the content of phenolic compounds in extracts according to the type of solvent of 12 mixed medicinal materials of the present invention, including Sanpyeopcho, Baekchul, Baekbokryeong, cinnamon, licorice, Cheongung, Danggui, Sanyak, Moksang, Ginger, Galgeun, and Hichon. Figure 3 shows the results of measuring the antioxidant activity (DPPH radical scavenging ability) of the solid obtained by freeze-drying the water extract and ethanol extract of the 12 mixed medicinal materials of the present invention, namely Sanpyeoncho, Baekchul, Baekbokryeong, cinnamon, licorice, Cheongung, Danggui, Sanyak, Moksang, Ginger, Pueraria root, and Hichon, as well as the water and ethanol extract containing 200 μg / mL of phenolic compounds. Figure 4 shows the levels of uric acid in the body for an animal model of gout with induced hyperuricemia. Specific details for implementing the invention

[0078] The contents of the present invention will be explained in more detail below through the following examples and experimental examples. However, the scope of the present invention is not limited to the following examples and experimental examples, but includes variations of equivalent technical concepts.

[0079] Preparation Example 1. Preparation of materials

[0080] Prepare the following 12 medicinal herbs. The prepared herbs are Sanpyeoncho, Baekchul, Baekbokryeong, cinnamon, licorice, Cheongung, Danggui, Sanyak, Mokhyang, Ginger, Galgeun, and Hwicheom.

[0081] Preparation Example 2. Preparation of 12 Mixed Medicinal Herb Extracts

[0082] Water was added in an amount of 5 to 10 times to a mixture of 300 to 400 g of Sanpyeoncho, 100 to 200 g of Mokhyang, 100 to 300 g of Danggui, 100 to 300 g of Cheongung, 220 to 250 g of Ginger, 100 to 250 g of Ginpi, 100 to 300 g of Sanyak, 100 to 250 g of Baekchul, 220 to 300 g of Baekbokryeong, 300 to 400 g of Galgeun, 250 to 400 g of Gamcho, and 100 to 300 g of Hwicheom.

[0083] Subsequently, 12 mixed medicinal herb extracts were obtained by extracting at 100 to 150 ℃ for 3 to 5 hours.

[0084] Example 1. Quantification of phenolic compounds

[0085] The content of phenolic compounds was measured as follows. 1 mL of the mixed medicinal extract prepared in Preparation Example 2 was mixed with 1 mL of 95% ethanol and 5 mL of distilled water, respectively, and then 0.5 mL of 1N Folin-ciocalteu reagent was added to develop color. After standing for 5 minutes, 1 mL of Na2CO3 was added and left to stand for 1 hour, after which the absorbance was measured at 725 nm. The amount of the measured value was calculated from a standard curve using gallic acid.

[0086] Example 2. Measurement of DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity

[0087] DPPH radical scavenging activity was determined by adding 3 mL of 60 μM DPPH to 1 mL of the mixed medicinal herb extract prepared in Preparation Example 2, mixing the mixture, leaving it at room temperature for 15 minutes, and then measuring the absorbance at 517 nm. The result was calculated using the difference between the absorbance of the extract and the absorbance of the control group. The control group was used in which distilled water was added instead of the mixed extract.

[0088] Example 3. Analysis of Xanthine Oxidase Inhibitory Activity

[0089] Xanthine oxidase is reported to cause gout by generating uric acid from xanthine or hypoxanthine. Xanthine oxidase (XOase) inhibitory activity was measured as follows.

[0090] For the sample treatment group, 0.1 mL of enzyme solution and 0.3 mL of sample solution were added to 3 mL of substrate solution (2 mM xanthine solution) in 0.1 M potassium phosphate buffer (pH 7.5), and for the control group, 0.3 mL of distilled water was added instead of the sample solution, and the reaction was carried out at 37 ℃ for 30 minutes.

[0091] The reaction was terminated by adding 1 mL of 20% trichloroacetic acid solution to the reaction mixture, and after centrifugation, the OD value of uric acid was measured at 292 nm. The XOase inhibition rate was calculated by converting the measured value into the amount of uric acid using a standard curve based on uric acid. The XOase inhibition rate was expressed using the following formula.

[0092] XOase inhibition rate (%) = 1 - (Uric acid production of reaction group / Uric acid production of control group) x 100

[0093] Example 4. Analysis of the effect of gout improvement using a hyperuricemia model

[0094] The hyperuricemia animal model was induced by administering potassium oxonate (250 mg / kg) dissolved in PBS into the peritoneal cavity. Experimental animals used as a control group were administered only PBS.

[0095] One hour after intraperitoneal administration, the positive control drug Allopurinol (10 mg / kg) or the test substance, a mixed extract of 12 medicinal herbs (250 mg / kg), was orally administered, respectively. At this time, the number of animals per experimental group was 7.

[0096] Three hours after the administration of the test substance, orbital venous plexus blood collection was performed under isofluorane inhalation anesthesia, and the collected blood was placed in a small tube (eppendorf tube) and left for 15 to 20 minutes, after which the serum solution was separated by centrifugation at 13,000 rpm for 15 minutes.

[0097] The levels of uric acid in the serum were measured using a Toshiba Acute Biochemical Analyzer (Toshiba Medical System).

[0098] Example 5. Statistical Processing

[0099] All experiments were repeated three times, and mean values ​​were calculated using Duncan's multiple range test one way ANOVA in SPSS software (Statistical Package for Social Science, Chicago, IL, USA), and p<0.05 was analyzed as statistically significant.

[0100] Experimental Example 1. Phenolic compound content of mixed medicinal herb extract

[0101] To determine the phenolic compound content of 12 mixed medicinal herb extracts of Sanpyeoncho, Baekchul, Baekbokryeong, cinnamon, licorice, Cheongung, Danggui, Sanyak, Moksang, Ginger, Galgeun, and Hichon, water and ethanol extracts were freeze-dried to produce a solid powder, and the phenolic compound content was determined (Fig. 1).

[0102] As a result, it was confirmed that the solid content of the water extract was 21.5 μg per 1 mg and the solid content of the ethanol extract was 14.7 μg per 1 mg.

[0103] Experimental Example 2. Confirmation of the effect of solvent type on the elution of phenolic compounds

[0104] To extract phenolic compounds exhibiting physiological activity from the above 12 mixed medicinal herb extracts, the elution amount of phenolic compounds was determined using various solvents (Fig. 2).

[0105] As a result, it was confirmed that the phenolic compound content was 17.5 mg / g, 14.2 mg / g, 13.1 mg / g, 9.6 mg / g, and 5.3 mg / g in the order of water, ethanol, methanol, acetone, and butanol, and it was confirmed that the elution amount of phenolic compounds was higher when water and ethanol were used as solvents.

[0106] Experimental Example 3. DPPH Radical Scavenging Activity Analysis

[0107] DPPH radicals are used as a measure of antioxidant effect based on the degree to which the purple color is decolorized due to reduction caused by the electron-donating ability of antioxidant substances. To evaluate the antioxidant effect of the mixed medicinal herb extract, the antioxidant activity (DPPH radical scavenging ability) of the freeze-dried solids of the water extract and ethanol extract were compared with that of the water extract and ethanol extract containing 200 μg / mL of phenolic compounds (Fig. 3).

[0108] As a result, the freeze-dried solids of the water extract and ethanol extract showed antioxidant activities of 47.2% and 30.2%, respectively, and it was confirmed that the water extract and ethanol extract containing 200 μg / mL of phenolic compounds showed antioxidant activities of 92.3% and 81.3%, respectively.

[0109] Through this, the 12 mixed medicinal herb extracts of Sanpyeoncho, Baekchul, Baekbokryeong, cinnamon, licorice, Cheongung, Danggui, Sanyak, Moksang, Ginger, Pueraria root, and Hichon of the present invention are shown to have an antioxidant effect.

[0110] Experimental Example 4. Inhibitory effect of xanthine oxidase

[0111] Since xanthan oxidase (XOase) generates uric acid from xanthine or hypoxanthine and causes gout, the inhibitory effect of XOase in the human body, which is the cause of gout, was measured by the method of Example 3 above.

[0112] As a result, as shown in Table 1, allopurinol, a gout inhibitor used as a positive control, showed an inhibitory activity of 58.40 to 78.58% at a treatment concentration of 50 to 200 μg / mL, whereas the 12 mixed medicinal herb extracts of the present invention showed high xanthan oxidase inhibitory activities of 52.42 to 100% and 39.78 to 100% in water extracts and ethanol extracts containing phenolic compounds at concentrations of 50 to 200 μg / mL, respectively.

[0113] Phenolic compound content (μg / mL) Positive control (Allopurinol) Water extract 80% ethanol extract Uric acid (μg / mL) Inhibitory activity (%) Uric acid (μg / mL) Inhibitory activity (%) Uric acid (μg / mL) Inhibitory activity (%) Control 20.21±0.12 0 20.21±0.12 0 20.21±0.12 0 50 8.41±1.45 58.40±3.12 9.62±0.49 52.42±2.26 12.17±0.58 39.78±2.94 100 7.03±1.09 65.23±2.68 2.48±0.17 87.73±1.13 6.18±0.37 69.42±2.03 150 5.56±0.48 72.47±0.79 - 100.0±2.18 2.04±0.21 89.91±1.39 200 4.32±0.16 78.58±1.35 - 100.0±0.37 - 100.0±1.18

[0114] Excellent gout improvement effects were confirmed in both water extracts and ethanol extracts, and in particular, a significant gout improvement effect was observed in the water extract.

[0115] Through this, the 12 mixed medicinal herb extracts of Sanpyeoncho, Baekchul, Baekbokryeong, cinnamon, licorice, Cheongung, Danggui, Sanyak, Moksang, Ginger, Pueraria root, and Hichon of the present invention demonstrate excellent gout improvement effects.

[0116] Experimental Example 5. Gout improvement effect using a hyperuricemia model

[0117] As described in Example 4 above, the effect of improving gout in an animal model of hyperuricemia was measured. The negative control group treated with PBS alone was a group of animals without hyperuricemia. Allopurinol was used as the positive control compound administered to the animal model of hyperuricemia.

[0118] As a result, it was confirmed that the 12 mixed medicinal herb extracts of the present invention were effective in reducing uric acid levels in both water extracts and ethanol extracts (Fig. 4).

[0119] In particular, it was confirmed that the water extract of 12 mixed medicinal herbs—Sanpyeoncho, Baekchul, Baekbokryeong, Gyepi, Gamcho, Cheongung, Danggui, Sanyak, Moksang, Ginger, Galgeun, and Hwicheom—had a more effective and superior effect in reducing uric acid levels compared to the positive control group.

[0120] Through this, the 12 mixed medicinal herb extracts of Sanpyeoncho, Baekchul, Baekbokryeong, cinnamon, licorice, Cheongung, Danggui, Sanyak, Moksang, Ginger, Pueraria root, and Hichon of the present invention demonstrate excellent gout improvement effects.

[0121] Experimental Example 6. Clinical observation analysis of patients diagnosed with gout

[0122] Water extracts of 12 mixed medicinal herbs, including *Sanpyeopcho*, *Baekchul*, *Baekbokryeong*, *Gampi*, *Gamcho*, *Cheongung*, *Danggui*, *Sanyak*, *Moksyang*, *Geonggeon*, *Galgeun*, and *Hicheom*, packaged in 150 mL units, were provided to 20 patients diagnosed with gout by a specialist, and each adult was instructed to take them twice a day for 15 to 30 days.

[0123] The pain relief effect was measured using a 5-point scale as shown in Table 2 below.

[0124] 5 Pain has been greatly relieved 4 Pain relieved 3 No difference 2 Pain worsens 1 The pain has worsened significantly.

[0125] As a result, out of 20 patients, 15 had a pain relief score of 5, 4 had a score of 4, and 1 had a score of 3, indicating that most patients felt their pain was relieved.

[0126] Meanwhile, it was confirmed that there was no gout-improving effect in the 11 mixed medicinal herb extracts prepared by excluding one each of the main medicinal herbs, Sanpyeoncho, Mokhyang, Heecheom, Geongang, and Sanyak, from the mixed medicinal herbs of the present invention.

[0127] This indicates that gout is improved by taking the 12 mixed medicinal extracts of the present invention.

[0128] Experimental Example 7. Clinical observation analysis of patients diagnosed with carpal tunnel syndrome

[0129] Water extracts of 12 mixed medicinal herbs, including *Sanpyeoncho*, *Baekchul*, *Baekbokryeong*, *Gampi*, *Gamcho*, *Cheongung*, *Danggui*, *Sanyak*, *Moksyang*, *Geonggeon*, *Galgeun*, and *Hicheom*, packaged in 150 mL units, were provided to 30 patients who had been confirmed to have carpal tunnel syndrome by a specialist, and each adult was instructed to take them twice a day for 15 to 30 days.

[0130] The improvement effect of carpal tunnel syndrome was determined as complete cure, improvement, and ineffective, as shown in Table 3 below.

[0131] Complete recovery Clinical symptoms of finger numbness and pain disappear, and finger movement returns to normal. improvement Clinical symptoms of finger numbness and pain have noticeably improved invalidity Symptoms are not significantly different from before treatment

[0132] As a result, among the 30 patients treated, 24 were cured, 4 showed improvement, and 2 showed no effect, with a total treatment efficacy rate of 93.3%.

[0133] Meanwhile, it was confirmed that there was no improvement effect on carpal tunnel syndrome in the 11 mixed medicinal herb extracts prepared by excluding one each of the main medicinal herbs, Sanpyeoncho, Mokhyang, Heecheom, Geongang, and Sanyak, from the mixed medicinal herbs of the present invention.

[0134] This indicates that carpal tunnel syndrome is improved by taking the 12 mixed medicinal extracts of the present invention.

[0135] Although embodiments of the present invention have been described above, the present invention is not limited to the above embodiments and can be manufactured in various different forms, and those skilled in the art will understand that the present invention can be implemented in other specific forms without changing the technical concept or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

Claims

Claim 1 A pharmaceutical composition for the prevention or treatment of gout or carpal tunnel syndrome comprising, as active ingredients, a mixed extract of *Sanpyeopcho*, *Baekchul*, *Baekbokryeong*, cinnamon, licorice, *Cheongung*, *Danggi*, *Yamyak*, *Samgyeong*, *Geonjang*, *Galgeun*, and *Hicheom*. Claim 2 A pharmaceutical composition according to claim 1, characterized in that the extract is extracted with a solvent selected from the group consisting of water, C1 to C4 lower alcohols, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof. Claim 3 A pharmaceutical composition according to claim 2, wherein the lower alcohol is one or more lower alcohols selected from the group consisting of ethanol, methanol, propanol, normal-propanol, iso-propanol, butanol, normal-butanol, and iso-butanol. Claim 4 A pharmaceutical composition according to claim 1, wherein the extract inhibits DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals. Claim 5 A pharmaceutical composition according to claim 1, characterized in that the extract inhibits xanthine oxidase. Claim 6 A pharmaceutical composition according to claim 1, wherein the extract is characterized by lowering blood uric acid. Claim 7 A pharmaceutical composition according to claim 1, characterized in that the extract is obtained by extracting at 100 to 150 ℃ for 3 to 5 hours. Claim 8 delete Claim 9 A method for the prevention or treatment of gout or carpal tunnel syndrome comprising the step of administering the pharmaceutical composition of claim 1 to an individual other than a human. Claim 10 A health functional food composition for the prevention or improvement of gout or carpal tunnel syndrome comprising a mixed extract of *Sanpyeopcho*, *Baekchul*, *Baekbokryeong*, cinnamon, licorice, *Cheongung*, *Danggi*, *Yamyak*, *Samgyeong*, *Geojang*, *Galgeun*, and *Hicheom* as an active ingredient.

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