KR101784591B1 - Compositions for alleviating, preventing or treating inflammatory Pain comprising extract from Vitis amurensis, Glycyrrhizae and Aralia cordata - Google Patents
Compositions for alleviating, preventing or treating inflammatory Pain comprising extract from Vitis amurensis, Glycyrrhizae and Aralia cordata Download PDFInfo
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- KR101784591B1 KR101784591B1 KR1020160021072A KR20160021072A KR101784591B1 KR 101784591 B1 KR101784591 B1 KR 101784591B1 KR 1020160021072 A KR1020160021072 A KR 1020160021072A KR 20160021072 A KR20160021072 A KR 20160021072A KR 101784591 B1 KR101784591 B1 KR 101784591B1
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Abstract
The present invention relates to a composition for alleviating, preventing or treating pain comprising a blended extract of blonde hair, licorice and simplex as an active ingredient. The mixed extract of the present invention not only mitigates and treats the pain generated, but also exhibits an effect of preventing pain when administered to a subject before the pain occurs. In addition, the composition of the present invention exhibits remarkable pain relieving effect not only by intravenous injection or skin application but also by oral administration, and the composition of the present invention having such characteristics is highly applicable to foods.
Description
The present invention relates to a composition for alleviating, preventing or treating pain comprising a blended extract of blonde hair, licorice and simplex as an active ingredient.
Currently, analgesics for pain are mainly anti-inflammatory drugs such as aspirin and tylenol, and most of the morphine drugs are used for severe pain. Javelin Pharmaceuticals, a specialist in pain medicine, is developing a new pain-relieving drug. The root of the analgesic effect equivalent to intravenous morphine for treating pain after severe surgery is the nasal intramuscular morphine spray Rylomine was developed. In addition, the first painkiller "Prialt" developed by Elan, an Irish pharmaceutical company, was launched in the UK.
On the other hand, the inflammatory process is a series of complicated biochemical and cellular events that are activated in response to the presence of foreign substances or tissue damage, causing swelling and pain. The inflammation process is a defense mechanism against foreign pathogenic factors, but it can cause pain even when there is no stimulation of toxic substances. The local inflammatory response releases proinflammatory cytokinins and upregulates cyclooxygenase-2 to synthesize prostaglandins, sensitizing primary afferent neurons and causing peripheral nerve cells To activate neuroimmunity. Thus, ultimately, thermal or mechanical hypersensitivity occurs. When such an inflammatory reaction occurs, it is accompanied by inflammation, which is referred to as inflammatory pain among types of pain.
Inflammatory pain, as well as the aging society, the number of patients with degenerative arthritis and back pain-related diseases is increasing every year. However, existing opioid drugs such as morphine have limited use due to drug action in the general public. . In addition, there is a great demand for the development of analgesics for pain that does not respond to existing analgesic drugs, and because of the narcotic and serious side effects of conventional opioids, which are known to have a relatively high analgesic effect, It is necessary to develop natural resources that have no side effects and have analgesic effect.
The present inventors have tried to develop a safe material for human body which can relieve pain effectively, in particular, a plant-derived material. As a result, it has been found that a blended extract of bamboo hair, licorice and simplex is very effective for alleviating, The present invention has been completed.
Accordingly, an object of the present invention is to provide a composition for alleviating, preventing or treating pain.
Another object of the present invention is to provide a food composition and a pharmaceutical composition for alleviating, preventing or treating pain.
Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention and claims.
According to one aspect of the present invention, there is provided a composition for alleviating, preventing, or treating pain, pain, comprising a mixed extract of royal body, licorice, and simplex as an active ingredient.
Hereinafter, the present invention will be described in detail.
Compositions of the present invention include pharmaceutical compositions and food compositions.
The mixed extract of the present invention has an anti-inflammatory effect, mitigates and treats the generated pain, and has an effect of preventing pain when administered to a subject before the pain occurs. In addition, the composition of the present invention exhibits remarkable pain relieving effect not only by intravenous injection or skin application but also by oral administration, and the composition of the present invention having such characteristics is highly applicable to foods.
First, in the present specification the term "Vitis amurensis" is Vitis amurensis vine (Vitis amurensis ) is also called. The roots of the above-mentioned hair wool have been used in the treatment of urination disorders and ascites due to the elimination of customs in the oriental medicine. It is also known to be effective for hepatitis, cirrhosis, edema, nephritis, cystitis and appendicitis. In the description of the grapes described in Donguibogam, "There are two kinds of fruit, purple and white, which are purplish, and they are said to be white.""Bones are tingling, It is known that it treats, makes urine go well, helps the diet, strengthens the will, makes it fat and makes it healthy. The grape roots, "the month and drink the water in the area and hiccups stop, after pregnancy, when the cooked rice cooked in the myeongchi when you go down," he said. However, the role of leaves and stalks of the hairless broom is not known.
The term " licorice "in the present specification is one of the plants belonging to the rosewood and soybean family. "Licorice" has been reported to inhibit learning ability loss, but no other function has been reported.
The term "Aralia Cordatae Radix" in the present specification is used for muscle aches, lower body paralysis, headache, paralysis of paralysis. Unfamiliarity has an unusual direction, flavor is tough at first and slightly bitter.
In the present invention, the mixture of blonde hair, licorice and simplex can be mixed and then extracted, respectively, and mixed. When the blonde hair, licorice, and hinting used in the composition of the present invention are obtained by treating the extraction solvent, various extraction solvents may be used. According to the present invention, a polar solvent or a non-polar solvent can be used. Suitable polar solvents are (i) water, (ii) alcohols (preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, Or ethylene glycol), (iii) acetic acid, (iv) DMFO (dimethylformamide) and (v) dimethyl sulfoxide (DMSO). Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- But are not limited to, pentane, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2- chloropropane, toluene, 1- chloropropane, chlorobenzene, benzene, diethyl ether, diethylsulfide, Methane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride, and THF.
According to one embodiment of the invention, the extraction solvent used in the present invention comprises (a) water, (b) an anhydrous or a lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.) (D) acetone, (e) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and Ethyl ether. In another embodiment of the present invention, the extract of the present invention is obtained by treating water, ethanol, or a combination thereof, with a blonde hair, licorice, and hoger. According to a particular embodiment of the present invention, the extract of the present invention is obtained by treating 60 to 80% by volume of grain alcohol with the hair, liquorice and chewing gum.
The extract used in the present invention can be prepared in a powder state by an additional process such as vacuum distillation and freeze-drying or spray drying.
As used herein, the term " extract " means that it is used in the art as a crude extract as described above, but broadly includes fractions obtained by further fractionating the extract. That is, the extract includes not only those obtained by using the above-mentioned extraction solvent but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the above extract through an ultrafiltration membrane having a constant molecular weight cut-off value, and a separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) The fraction obtained by the purification method is also included in the extract of the present invention.
As used herein, the term " comprising as an active ingredient " is meant to include an amount sufficient to achieve efficacy or activity of the following mixed extracts. Since the composition of the present invention contains extracts obtained from natural plant materials such as royal burlou, licorice, and improvisant, there is no adverse effect on the human body even when administered in an excessive amount. Therefore, the quantitative upper limit of the composition of the present invention included in the composition of the present invention is And can be selected within the range.
The term " pain " is used in the present invention in its broadest sense and includes acute and chronic pain such as pain ache and pain, such as somatic pain and visceral pain; Pain, pain, inflammatory pain, dysfunctional pain, idiopathic pain, superficial pain, deep pain, itching, neuropathic pain such as centrally generated pain and peripherally generated pain, migraine, and cancer pain.
According to one embodiment of the present invention, the composition of the present invention exhibits relief, prevention or therapeutic effects against inflammatory pain.
The term " nociceptive pain " is used to include all pain caused by noxious stimuli that may or may damage nervous tissues and may include ben, cut, bruise, fracture, bone pain, bone fracture, crush injury, burn, and similar wounds. Pain receptors for tissue damage (nociceptors) are mostly located in the skin, musculoskeletal or internal organs. The term " somatic pain " is used to indicate pain that occurs in bones, joints, muscles, skin or connective tissue. This type of pain is typically very localized.
The term " visceral pain " is used herein to refer to any or all of the organs such as respiratory, gastrointestinal tract and pancreas, urinary tract and reproductive organs, Used to indicate pain that occurs. Embolic pain includes pain induced by tumor involvement of the organ capsule. Other types of visceral pain are typically caused by occlusion of the hollow viscus, characterized by intermittent cramping and severe local pain. Embolic pain may be associated with inflammation, as in the case of cystitis or reflux esophagitis.
The term " inflammatory pain " includes pain associated with active inflammation, which may be caused by trauma, surgery, infection, and autoimmune diseases.
The term " superficial pain " refers to the pain sensed by the skin segments of the nerves of the dorsal root, and is a direct pain to feel the pain at the point of stimulation.
The term " deep pain " refers to pain originating from deep organs, which varies in character and degree depending on the nature of the tissue. Particularly sensitive areas of pain are tendons, pericardium, ligaments, joints, periosteum, blood vessels and nerves. In general, deep pain is dull, spreads around, and feels wide. Pain in the deep or intestine is complicated in its mechanism, making it difficult to locate the pain rather than the surface pain, and problems such as nausea, sweating, and elevated blood pressure also appear.
The term " neuropathic pain " is used herein to denote pain resulting from sensory input of abnormal processing by the peripheral or central nervous system resulting from disturbance of the peripheral or central nervous system.
The term " procedural pain " refers to pain that occurs in internal medicine, dentistry, or surgery, and the procedure is usually scheduled or associated with acute trauma.
The term " itch " is used herein in its broadest sense and refers to all types of itchy, stinging sensations of acute intermittency and persistence that can be generally described by limiting to local. The itch may be due to idiopathic, allergic, metabolic, infectious, drug-induced, liver, kidney disease or by cancer. "Pruritus" is severe itching.
&Quot; Patient " means any animal. In one embodiment of the invention, the patient is a human. Other animals that may be treated using the composition of the invention include non-human primates (e.g., monkeys, gorillas, chimpanzees), livestock (e.g., horses, pigs, goats, rabbits, sheep, cows, llamas) But are not limited to, animals (such as guinea pigs, rats, mice, lizards, snakes, dogs, cats, ornamental fish, hamsters and birds).
Neuropathic, inflammatory, and nociceptive pain are different in etiology, pathophysiology, diagnosis and treatment. Acupuncture pain occurs in response to activation of nociceptors by a specific subset of peripheral sensory neurons, that is, intense or harmful stimuli. Acute water-soluble pain is a generally sensitive, self-limiting, and provides a biological function of protection by acting as a warning of potential or ongoing tissue damage. Pain Acceptable pain is typically very limited to locality. Examples of painful painful pain include, but are not limited to, traumatic or surgical pain, labor pain, sprains, bone fractures, burns, bumps, but are not limited to, bruises, injections, dental procedures, skin biopsies and obstructions.
Inflammatory pain is associated with joints such as postoperative, post-traumatic pain, arthritis (rheumatoid or osteoarthritis) pain, and axial low back pain. ), Pain associated with damage to muscles and tendons, or pain when there is a tissue injury or inflammation.
Pain In contrast to water-soluble pain, neuropathic pain is depicted as actual "burning," "electric," "tingling," or "shooting" do. Neuropathic pain is often defined as chronic allodynia (defined as pain due to stimuli that do not cause a normal pain response, such as a mild touch) and hyperalgesia (a high susceptibility to normal pain stimuli ) And may last for months or years after apparent healing of any damaged tissue. The composition of the present invention may be provided as a pharmaceutical composition.
When the composition of the present invention is prepared from a pharmaceutical composition, it includes not only the mixed extract of the present invention as an active ingredient, but also a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, the composition can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration, or the like.
The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001 to 100 mg / kg.
The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
According to another aspect of the present invention, there is provided a food composition for alleviating or ameliorating pain comprising as an active ingredient, a mixed extract of royal body, licorice, and simplex.
According to one embodiment of the invention, the pain relieved or prevented by the food composition of the present invention is selected from the group consisting of somatic pain, visceral pain, inflammatory pain, dysfunctional pain, idiopathic pain, Pain, superficial pain, deep pain, itching, migraine or cancer pain.
According to another embodiment of the present invention, the pain relieved or prevented by the food composition of the present invention is neuropathic pain.
When the composition of the present invention is prepared as a food composition, it contains not only the mixed extract of the present invention as an active ingredient, but also components which are ordinarily added at the time of food production. Examples thereof include protein, carbohydrate, fat, And flavoring agents. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be used as flavorings.
For example, when the food composition of the present invention is prepared as a drink, it may further contain citric acid, a liquid and sugar, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, jujube extract, licorice extract, .
The mixed extract of the present invention has an anti-inflammatory effect and not only mitigates and treats the pain generated, but also has an effect of preventing pain when administered to a subject before the pain occurs. In addition, the composition of the present invention exhibits remarkable pain relieving effect not only by intravenous injection or skin application but also by oral administration, and the composition of the present invention having such characteristics is highly applicable to foods.
FIG. 1 shows the results of confirming the pain relieving effect of the mixed extract of the present invention using an acetic acid-induced writhing test.
FIG. 2 shows the results of confirming the pain relieving effect of the mixed extract of the present invention by using a hot-plate test.
FIG. 3 shows the results of confirming the pain relieving effect of the mixed extract of the present invention using a formalin test.
FIG. 4 shows the results of confirming the inflammation-relieving effect of the mixed extract of the present invention using formalin-induced edema.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
[ Example 1] Bonn Inventive blonde hair, licorice and Virulent Preparation of mixed extracts.
In order to prepare the extract of the present invention, Glycyrrhizae roots were purchased from a pharmacy located in Daegu, and the leaves and stems of V. amurensis , and the leaves and stems of Aralia cordata , Were collected from Gyeryongsan (Daejeon, Korea), dried and used. After mixing 200 g of each of the above three materials, the mixture was extracted three times with 3 L of ethanol for 24 hours at room temperature, followed by filtration. The filtrate was concentrated under reduced pressure using a rotary evaporator to obtain 64 g of an ethanol extract, which was stored at room temperature.
[ Example 2] Bonn Identification of pain relief, prevention or therapeutic effect of the extract of the invention
1. Acetic acid-induced writhing test to determine pain response
Five-week-old male ICR mice were obtained from Samtako Inc (Gyeonggi-do, Korea) and were housed in a room at a relative humidity of 55 ± 5%, 22 ± 2 ° C and 12 hours day / night. Thereafter, acetic acid induction kinking experiment was carried out using the mouse as described in Koster et al (1959). After 20 minutes of administration of the extracts prepared in Example 1 (25, 50 and 100 mg / kg), ibuprofen (100 mg / kg) or morphine (5 mg / kg) to the mice, 0.8% acetic acid was administered intraperitoneally . Mice receiving each of the above substances were individually placed in a plastic observation chamber and the number of times that each mouse stretched the hind leg and stretched the abdomen at 10 to 40 minutes after acetic acid administration was calculated. The results are shown in Fig.
As shown in FIG. 1, in the group administered with 25, 50 and 100 mg / kg of the ethanol extract of the present invention, it was confirmed that the pain response phenomenon was remarkably reduced compared with the control group (100.0 ± 9.3) (53.6 ± 7.9, 45.18 占 7.1 and 27.0 占 5.3).
2. Hot - Confirmation of pain response by hot-plate test
The hot-plate experiments were carried out according to already known methods. The mice were placed in a hot-plate (IITC) maintained at 55 ± 1 ° C, covered with a Plexiglas wall cylinder, and the basal hot-plate latency time was set to 5 seconds or less. Respectively. (25, 50 and 100 mg / kg), ibuprofen (100 mg / kg) or morphine (5 mg / kg) prepared in Example 1 were administered to each mouse. After 15, 30, 45, 60 and 90 minutes of substance administration, the extent of exiting from the mouse hot-plate was measured and, if no such behavior was observed for 20 seconds observed, It was separated. The results are shown in Fig.
As shown in FIG. 2, it was confirmed that the ethanol extract of the present invention showed no significant difference at 25, 50 and 100 mg / kg compared to the control group. This indicates that the extract is not effective for pain caused by heat.
3. Formalin The formalin test Identify pain response
The formalin test was carried out according to known methods. After 30 minutes of administration of the extracts (25, 50 and 100 mg / kg), ibuprofen (100 mg / kg) or morphine (5 mg / kg) prepared in Example 1 to the mice, 20 μl of saline containing 2% After the dorsal surface was injected with a 30-gauge syringe, the mice were placed in an acrylic box. After this, formalin was administered for 30 minutes to observe the end. After injecting formalin, the pain response was measured for 20 to 30 minutes after injection of formalin, at which time the licking time was measured (neurogenic pain) for 0 to 5 minutes, and at the time when the inflammatory response was induced. The results are shown in Fig.
As shown in FIG. 3, in the group administered with 100 mg / kg of the ethanol extract of the present invention, the licking time was significantly longer in the secondary inflammatory reaction period (20 to 30 minutes after the formalin administration) than in the control group (99.0 ± 9.0 s) ) Was significantly reduced (38.9 ± 7.6 s).
However, in the case of the primary period (0 to 5 minutes; neurogenic pain), it was confirmed that there was no significant difference from the control group.
4. Formalin Induced Edema size Confirmed inflammatory response
After injecting formalin in the same manner as in Example 2.3, mice were excised and the volume of the edema was measured. The vertical thickness of edema from the metatarsal of the group injected with formalin before or 18 hours after injection of formalin was measured using a fine caliper (Vernier caliper 530 series, Mitutoyo, Japan). The thickness was calculated by subtracting the thickness before administration from the thickness after administration of formalin and expressed in mm. The results are shown in Fig.
As shown in FIG. 4, when the ethanol extract of the present invention was administered to mice at 25, 50 and 100 mg / kg, it was confirmed that the thickness of the tail of the mouse was significantly decreased (0.71 ± 0.03 mm) (0.33 ± 0.06, 0.43 ± 0.06, 0.37 ± 0.06mm). Thus, it was confirmed that the extract of the present invention can reduce inflammation.
Claims (5)
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| KR20190126565A (en) | 2018-05-02 | 2019-11-12 | 김진희 | A composition for improving, preventing and treating of pain containing oriental medicine herbs oil extract as an active ingredient |
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Non-Patent Citations (3)
| Title |
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| Amol Bhandage 외 2명. Evaluation of Antinociceptive Activity of Roots of Glycyrrhiza Glabra Linn. Journal of Pharmacy Research. Vol. 2, No. 5, 2009년, pp. 803-807* |
| Do Thi Ha 외 6명. Antioxidant and lipoxygenase inhibitory activity of oligostilbenes from the leaf and stem of Vitis amurensis. Journal of Ethnopharmacology. Vol. 125, 2009년, pp. 304-309* |
| Ji Yeon Jang 외 1명. Anti-nociceptive and Anti-inflammatory Effect of an Ethanol Extract of The Leaf and Stem of Aralia cordata. Natural Product Sciences. Vol. 20, No. 4, 2014년, pp. 301-305* |
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|---|---|---|---|---|
| KR20190126565A (en) | 2018-05-02 | 2019-11-12 | 김진희 | A composition for improving, preventing and treating of pain containing oriental medicine herbs oil extract as an active ingredient |
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