JP2009078980A - Pain alleviating agent and pain alleviating assistance food - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pain alleviating agent and a pain alleviating assistance food daily usable without a risk of adverse effects on the alimentary system or the psychoneurotic system and without anxiety. <P>SOLUTION: The pain alleviating agent characterized by comprising carnosine as an active ingredient can daily be used without the risk of the adverse effects and without the anxiety over a long period of time and is capable of promoting the alleviation of pains by a chemical change in living bodies accompanied by an abnormality in internal organs etc. Since the pain alleviating assistance food comprising the pain alleviating agent can be ingested as a usual meal or a usual supplement, the pain alleviating assistance food can particularly preferably be used when the continuous ingestion of the pain alleviating agent is required. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a safe pain relieving agent and a pain relieving supplement with few side effects.

  Pain (pain) plays an important warning system that informs the brain of mutations that occur in vivo. However, long-lasting pain needs to be actively removed to reduce the quality of life. In addition, long-term pain causes degeneration of the neural circuit, and pain remains as a memory, so that pain may be recognized in the brain despite the absence of pain stimulation. Relief is also very important in relieving chronic pain.

  Drugs currently used for the treatment of pain (hereinafter referred to as pain relieving agents) include non-narcotic analgesics such as aspirin (for example, Non-Patent Document 1) and narcotic analgesics such as morphine (for example, Non-patent document 2), steroids such as dexamethasone (eg, non-patent document 3), tricyclic antidepressants such as amitriptyline (eg, non-patent document 4), anticonvulsants such as carbamazepine (eg, non-patent document 5). )and so on.

“Bayer Yakuhin Co., Ltd. Product Introduction Bayer Aspirin (registered trademark)”, [online], Bayer Yakuhin Co., Ltd. website, [searched September 14, 2007], Internet <URL: http://www.bayer.co. jp / byl / cc / aspirin / contents_3_1.html> “Introduction of new drugs Peagaard (registered trademark) for the treatment of persistent cancer pain”, “Pharmaceutical News”, 2005, Vol. 14, No7 “Kobayashi Kako Co., Ltd. Product Details Mesadron (registered trademark) Attached Document”, [online], Kobayashi Kako Co., Ltd. website, [searched September 14, 2007], Internet <URL: http://www.kobayashikako.co .jp / product / prodc_dtl.html? prodcid = 144> “Manyu Pharmaceutical Co., Ltd. Product Details Tryptanol (registered trademark) package insert information”, [online], Manyu Pharmaceutical Co., Ltd. homepage, [searched September 14, 2007], Internet <URL: http: // www. banyu.co.jp/content/patients/medicine/product/tryptanol_tab25.html> "Noveltis Pharma Tegretor (registered trademark) product information package insert", [online], Novartis Pharma website, [searched September 14, 2007], Internet <URL: http://www.novartis.co.jp /product/teg/pi/pi_teg02.html>

  However, the pain relieving agents described in Non-Patent Documents 1 to 5 have serious side effects such as lethargy, dizziness, dry mouth, weight gain, memory impairment and orthostatic hypotension. For this reason, there is an urgent need to develop a safe pain relieving agent that has no serious side effects.

  The problem to be solved by the present invention is to provide a pain relieving agent and a pain relieving supplement that can be safely used on a daily basis without fear of side effects.

  As a result of intensive studies to solve the above problems, the present inventors have found that carnosine, which is a dipeptide, relieves inflammatory and neuropathic pain, leading to the present invention.

  That is, the pain relieving agent of the present invention is characterized by containing carnosine as an active ingredient.

  Carnosine is a substance that is abundant in animal brain, heart, stomach and especially skeletal muscle, and already has anti-fatigue effect (adjusts the pH value of muscles to improve the function of energy metabolism and body tissues), Known to have anti-oxidant effects (removes active oxygen which is a cause of various lifestyle-related diseases), tissue repair promotion effects (activates the fibroblast tissue of the skin and promotes the rate of collagen synthesis), etc. It is a biologically derived dipeptide that is used as a raw material for many supplements. Therefore, by taking a pain relieving agent containing carnosine as an active ingredient, pain can be relieved without side effects.

  As used herein, “reducing pain” refers to reducing inflammatory and neuropathic pain. Moreover, a pain relieving agent means what has the effect | action which relieves pain, The form is not specifically limited. For example, dosage forms used for normal oral administration or parenteral administration, and foods and drinks that are ingested orally are included. In addition, in the present invention, it is unclear as to what mechanism carnosine exhibits an action to relieve pain, but it is presumed that carnosine exerts the above-mentioned action by exerting some influence on pain transmission. Is done.

  Carnosine is preferably derived from a natural product. If these are derived from natural products, they can be used with particular peace of mind since they are only L-form as in carnosine contained in the human body as described later.

  Moreover, since the pain relief supplement containing the said pain relieving agent can be ingested as a normal meal or a supplement, it can be used especially preferably when continuous intake of a pain relieving agent is required.

  The pain relieving agent and pain relief supplement of the present invention have an action of alleviating pain, have no fear of side effects, and can be used routinely with peace of mind. Moreover, by using together with the existing pain relieving agent, the usage amount of the existing pain relieving agent can be reduced, and the risk of occurrence of side effects can be reduced.

  The carnosine used in the pain relieving agent according to the present invention may be carnosine derived from a natural product obtained from seafood or livestock meat, or carnosine chemically synthesized by means such as peptide synthesis. However, carnosine derived from a natural product is desirable for uses that are taken daily in the form of food, not for medical purposes. Carnosine may be in the form of a salt. There are D-form, L-form, and DL-form in carnosine, and any of them may be used. However, since carnosine present in the human body is all L-form, it is used as a functional food and drink as a pain relief supplement. L is preferably used for. Hereinafter, L-form carnosine is referred to as L-carnosine.

  The natural product containing L-carnosine is not particularly limited as long as it contains L-carnosine as a natural product. For example, boiled juice, tuna, salmon, etc. It is possible to use boiled juice that is discarded at the time of canned production, or extracted from inexpensive raw materials such as waste chicken meat. As a pain relieving agent or pain relief supplement containing L-carnosine as an active ingredient, natural products containing L-carnosine are used directly, or purified and purified from extracts (purified synthetic products Can be used).

  The high purity purified product of L-carnosine, for example, starting from the raw materials such as the above-mentioned boiled juice and waste chicken meat, cold water extraction, hot water extraction, subcritical extraction, solid-liquid separation by filtration, solid-liquid separation by centrifugation, Desalination by reverse osmosis membrane, desalting by electrodialysis, fractionation by ultrafiltration membrane, adsorption elution fractionation by porous resin, fractionation by molecular sieve chromatography, fractionation by ion exchange resin chromatography, vacuum concentration, atmospheric pressure It refers to those produced by extraction and purification methods such as concentration, concentration crystallization, vacuum drying, hot air drying or freeze drying. These extraction and purification methods can be performed alone or in combination. The content of the purified L-carnosine can be selected in consideration of restrictions on the production of food and drink to be taken and physical properties of the product.

  In the present embodiment, L-carnosine may be in the form of a salt, and can be a salt based on a carboxylic acid group and an amino group contained in the molecule alone or both. Examples of the salt based on the carboxylic acid group include metal salts such as sodium, potassium, calcium, magnesium, iron, zinc, copper, selenium and aluminum, and ammonium salts. Examples of salts based on amino groups include inorganic salts bonded with inorganic acids such as hydrochloric acid and sulfuric acid, and organic salts bonded with organic acids such as phosphoric acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, succinic acid and maleic acid. Is mentioned. These salts can be produced by a known method by reacting free L-carnosine with a selected acid or base. These can be used alone or in combination.

  As described above, in the present specification, the pain relieving agent refers to one having an action of relieving pain, and the form thereof is not particularly limited. For example, the dosage form used for normal oral administration or parenteral administration, and those in the form of food and drink and taken orally. Examples of dosage forms used for oral administration or parenteral administration include powders, granules, tablets, capsules, intestinal solvents, troches, liquids for internal use, liquids for external use, suspensions, emulsions, syrups, and injections. Infusion, tube feeding liquid, nasal drops, eye drops, ear drops, suppositories, shipping agents, inhalants or ointments can be arbitrarily selected according to the purpose of use. In the case of solid preparations, adjuvants such as excipients, binders, disintegrants, lubricants, corrigents, stabilizers, etc. may be used for the pain relieving agent containing L-carnosine, which is the main drug, depending on the purpose. -From the viewpoint of taste, sugar coating or film coating may be used.

  As a form to be taken orally as a food or a pain relief supplement, protein, saccharide, fat, trace element, vitamins, emulsifier, and perfume may be added to L-carnosine. In functional food and drink, it can also be set as processing forms, such as a natural liquid food, a semi-digested nutrient food, a component nutrient food, and a drink. In addition, solid or liquid foods or luxury products such as bread, noodles, rice, confectionery (biscuits, cookies, cakes, candy, chocolate, chewing gum, Japanese confectionery, etc.), mass-produced foods such as tofu and processed products thereof, Fermented foods such as refined liquor, medicinal liquor, mirin, vinegar, soy sauce, miso, dressing, yogurt, ham, bacon, sausage, mayonnaise, etc. It can also be used as beverages such as sports drinks, alcoholic drinks, and tea. Moreover, the user can widely recognize the function of food and drink by attaching a label indicating that the pain relief supplement relieves pain on the package or container of the pain relief supplement.

  The method for producing the pain relieving agent and pain relief supplement of the present embodiment varies depending on the purpose and dosage form, but can be produced and processed by conventional methods conventionally used in various fields.

  The dose of the pain relieving agent of the present embodiment varies depending on age, weight, symptoms, administration route, dosage form of the pain relieving agent, etc., but in the case of oral administration, the amount of L-carnosine is usually 1 for adults. 500 mg to 6 g per day, preferably 1 g to 5 g per day is preferred.

  Hereinafter, preferred embodiments of the present invention will be described in more detail using examples. The objects, features, and advantages of the present invention will be apparent to those skilled in the art from the description of the present specification, and those skilled in the art can easily reproduce the present invention based on the description of the present specification. The specific examples described below are provided as illustrations or illustrations of preferred embodiments of the invention and the invention is not limited thereto. It will be apparent to those skilled in the art that various modifications and variations can be made based on the description of the present specification within the spirit and scope of the present invention disclosed herein.

Example 1
“Evaluation of analgesic activity by oral administration of L-carnosine by the rising test (see Vinegar et al., Eur. J. Pharmacol., 37: 23-30 (1976))”
Male ICR mice (20-25 g, Japan SLC) were divided into 5 groups of 10 mice each, 0.5 g / kg of aspirin dissolved in 0.1% methylcellulose, or L-carnosine (Wako Pure Chemical Industries) 0.1, 0.3, 1 g / kg was orally administered through a gastric tube. One hour after the administration of each solution of aspirin and L-carnosine, a glacial acetic acid solution (0.1 ml / kg, 0.7%) was administered to the mice by intraperitoneal injection. The number of abdominal spasms (rising reactions) in all animals was counted for 10-20 minutes after administration of acetic acid. Analysis was performed blind.

  FIG. 1 shows the evaluation results of the pain relieving activity by oral administration of L-carnosine by the rising test as an average value when measurement was performed for 10 animals in each group. In addition, p in the figure means probability (probability), for example, p <0.05 represents “significant difference at 5% risk”. As shown in FIG. 1, treatment with aspirin 0.5 g / kg and L-carnosine 1 g / kg resulted in a significant reduction in the number of rising reactions compared to the solvent-treated group (0.1% CMC). Admitted. Therefore, it is clear that the administration of L-carnosine has an effect of alleviating pain as in the case of administering aspirin.

(Example 2)
“Evaluation of neuropathic pain suppression effect by oral administration of L-carnosine by footpad heat stimulation test (see Hargreaves et al., Pain., 32: 77-88 (1988))”
Twenty-four male ICR mice (20-25 g, Japan SLC) were used. The mouse was anesthetized with pentobarbital, and the skin of the left hind limb was incised so that the sciatic nerve could be seen. Twenty-one to one-third of the sciatic nerve fibers of all mice were tied with 8-0 silk and sutured at the incision site, and then left for 7 days. Neuropathic pain was evaluated by placing the mouse on a glass plate, stimulating the hind limbs with radiant heat, and measuring the latency to escape from the stimulus. The mice were divided into 2 groups of 12 mice, and the response latency to the heat stimulation was measured twice on the nerve damage side and the opposite side, and the average was used as a control. Thereafter, 0.1% methylcellulose or L-carnosine 1 g / kg was orally administered to each group of mice through a gastric tube, and against the radiation heat of both hind limbs at 30, 60, 90, 120 and 180 minutes after administration. Latency measurements were taken. Analysis was performed blind.

  The results are shown in FIG. 2 as the average value of the response latency on the neuropathy side at each measurement time when measurement was performed on 12 mice in each group. In FIG. 2, the white circle indicates the solvent treatment group (0.1% CMC), and the black circle indicates the carnosine treatment group. As shown in FIG. 2, the treatment latency of L-carnosine 1 g / kg significantly increased the response latency at 30, 60 and 90 minutes after administration, compared to the solvent-treated group (0.1% CMC). . Therefore, it is clear that administration of L-carnosine has the effect of improving hyperalgesia due to neuropathy.

  On the other hand, the results are shown in FIG. 3 as average values of reaction latencies on the opposite side of the neuropathy at each measurement time when measurement was performed on 12 animals in each group. In FIG. 3, the white circle indicates the solvent treatment group (0.1% CMC), and the black circle indicates the carnosine treatment group. As shown in FIG. 3, no significant change was observed in the response latency at each measurement time as compared with the solvent-treated group (0.1% CMC) by treatment with 1 g / kg of L-carnosine. Thus, it is clear that L-carnosine administration does not affect normal pain transmission.

  INDUSTRIAL APPLICABILITY The present invention is useful as a pain relieving agent and a pain relieving supplement that can be used on a daily basis for a long period of time without fear of side effects and is useful for patients suffering from pain or the prevention thereof. It can be suitably used as a method.

It is a figure which shows the evaluation result of the pain relieving activity by oral administration of L-carnosine by a rising test. It is a figure which shows the average value of the response latency with respect to the heat stimulus in the hind limb of the neuropathy side in each treatment group in a footpad heat stimulus test. It is a figure which shows the average value of the response latency with respect to the heat stimulus in the hind limb on the opposite side of the neuropathy in each treatment group in the footpad heat stimulus test.

Claims (3)

  A pain relieving agent comprising carnosine as an active ingredient.   The pain relieving agent according to claim 1, wherein the carnosine is derived from a natural product.   A pain relief supplement containing the pain relieving agent according to claim 1 or 2.

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