KR20090047637A - Composition for prevention and treatment of pain containing curcumin or pharmaceutically acceptable salt thereof as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing and treating pain containing curcumin or a pharmaceutically acceptable salt thereof as an active ingredient, and the composition for preventing and treating pain according to the present invention includes various stimulants including temperature, capsaicin and acid. Can significantly inhibit the activity of TRPV1, which causes all pains, including toothache and inflammation caused by them, and can effectively inhibit the pain caused by it. It can be usefully used for pain treatment and alleviation products such as functional toothpaste, functional food and food additive.

Curcumin, Capsaicin Receptor, TRPV1 / VR1, Pain Treatment Drug, Pain Control Food

Description

Composition for prevention and treatment of pain containing curcumin or pharmaceutically acceptable salt thereof as an active ingredient

The present invention relates to a composition for preventing and treating pain containing curcumin or a pharmaceutically acceptable salt thereof as an active ingredient.

Pain is a problem beyond the treatment of essential diseases in patients with cancer, ADIS, diabetes, shingles, and the like. It has been reported that chronic pain not only reduces the immune ability of the human being, but also reduces the desire to live mentally, thereby reducing the actual survival time of these patients. To date, these pain treatments are prescribed for non-narcotic analgesics (eg, aspirin, acetaminophen, NSAID-based drugs, etc.) or mild narcotic analgesics (eg, codeine) for mild pain. The final choice for is using potent narcotic analgesics (eg, morphin, fentanyl patches). Most non-narcotic analgesics have no resistance or physical dependence as a mechanism of inhibiting the synthesis of pain mediators through inhibition of cyclooxygenase enzymes, but their analgesic efficacy is limited by the ceiling effect. However, many side effects such as tolorance, physical dependence, respiratory depression and kidney failure are problematic. In order to solve such a pain problem, the development of powerful and no side effect analgesic is urgently required, and for this, the development of a new substance with a new pain suppression mechanism is required.

Vanilloid receptors (Transient Receptor Potential Vanilloid (TRPV) or Vanilloid Receptor (VR)) are promising targets for analgesic development. It is also known as a capsaicin receptor as a receptor. The receptor is known to be present in a portion of the sensory neurones whose expression is regulated by nerve growth factors. The receptor is known to selectively induce calcium (Ca ^{2 +} ) as a cation channel, and recently, the receptor TRPV1 (or VR1) has been cloned by Julius et al. To confirm its presence. Vanilloids), as well as a variety of harmful stimuli, such as hydrogen ions, thermal stimulation (> 43 ℃) was found to conduct (Tominaga et al., 1998, Neuron 21, pp531-543). From this, vanilloid receptor is expected to play a key role in the delivery of pain and noxious stimulus by acting as an integrated regulator of various noxious stimuli. Recently knockout mice have been prepared in which the gene of the vanilloid receptor has been removed [Caterina et al., 2000, Science 288, pp306-313; Davis et al., 2000, Nature 405, pp183-187], in normal behavior there was no difference from normal mice and the response was markedly attenuated in thermal stimulation and recessive hyperalgesia, indicating the importance of this receptor in adverse sensory transmission. Reaffirmed. Therefore, the inhibition of the activity of the vanilloid (capsaicin) receptor can treat or alleviate pain, and many studies are being conducted on antagonists of the vanilloid receptor.

Conventionally known antagonists of vanilloid receptors include benzamide derivatives (capsazepine), 4- (methylsulfonylamino) phenyl homologues (Korea Patent Publication No. 2005-0004006) Hydroxytetrahydro-taphthalenylurea derivative (Korean Patent Laid-Open Publication No. 2004-0108784), amide compound (Korean Patent Laid-Open Publication No. 2004-0048393), urea compound (Korean Patent Laid-Open Publication No. 2004-0041610), N-hydroxy, urea and amide compounds (Korean Patent Publication No. 2004-0034804), thiocarbamic acid derivatives (Korean Patent Publication No. 2002-0030020), thiourea derivatives (Korean Patent Publication No. 2002-0030009), and the like. .

However, most of these vanilloid (capsaicin) receptor antagonists are produced by organic synthesis, and few of the biologically stable materials have been reported in nature.

In addition, capsazepine, a compound known as an antagonist of vanilloid receptors, has been reported to have substantially no analgesic effect in vivo despite antagonistic effects in vitro. Recent experimental results show that capsazepine is a poorly soluble substance, which is very difficult to prepare in aqueous solution, and also has an analgesic effect on the mechanism of inhibiting receptor activity due to its metabolic and very anxiety after administration, which disappears immediately in vivo. It is known that it is not shown.

Curcumin, the main component of curry (turmeric), is a natural product having a vanilloid ring and has anticancer effects [Mosley CA, Liotta DC, Snyder JP, Adv. Exp. Med. Biol. 2007; 595; 77-103], anti-inflammatory and dementia effect [Yang F at al., J. Biol. Chem. 2005 Feb 18, 280 (7), 5892-5901; Republic of Korea Patent Publication No. 2002-0073847], gastric acid secretion control [Kim DC at al., Biol. Pharm. Bull. 2005 Dec; 28 (12); 2220-2224, alleviating the symptoms of diabetes [Sharma S at al., Clin. Exp. Pharmacol. Physiol. 2006 Oct; 33 (10); 940-945], wrinkle improvement effect (Korean Patent Publication No. 2005-0010093) and the like has been reported, but has not been reported for its efficacy as an analgesic.

Accordingly, the present inventors have studied intensively to find a new substance that can selectively antagonize the vanilloid (capsaicin) receptor in natural products, and curcumin inhibits the activity of the vanilloid (capsaicin) receptor to inhibit the action of capsaicin. It was found that curcumin can be used in analgesics and thereby completed the present invention.

An object of the present invention is to provide a composition for preventing and treating pain containing curcumin and its pharmaceutically acceptable salts as an active ingredient.

Another object of the present invention to provide a food composition for preventing or improving pain containing the curcumin and its pharmaceutically acceptable salts as an active ingredient.

Another object of the present invention to provide a functional toothpaste for preventing or improving pain containing the curcumin and its pharmaceutically acceptable salts as an active ingredient.

In order to achieve the above object, the present invention provides a composition for preventing and treating pain containing curcumin and its pharmaceutically acceptable salts as an active ingredient.

The present invention also provides a food composition for preventing or improving pain containing the curcumin and a pharmaceutically acceptable salt thereof as an active ingredient.

Furthermore, the present invention provides a functional toothpaste for preventing or improving pain containing the curcumin and its pharmaceutically acceptable salts as an active ingredient.

The composition for preventing and treating pain containing curcumin of Formula 1 or a pharmaceutically acceptable salt thereof according to the present invention as an active ingredient includes all of toothache and inflammation caused by various stimulants including temperature, capsaicin and acid. Significantly inhibits the activity of TRPV1 that causes pain and effectively inhibits the pain caused by it. Since it is produced from natural products, it has high biological stability, so it can be used as an analgesic, functional toothpaste for preventing and improving pain, functional foods and food additives. It can be usefully used for back pain treatment and alleviation products.

The present invention provides a composition for preventing and treating pain containing curcumin represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

Curcumin of Formula 1 according to the present invention is a yellow compound having a chemical formula of C ₂₁ H ₂₀ O ₆ and a molecular weight of 368.38, and is a natural substance having a vanilloid ring. Curcumin of Formula 1 may be used as a main component of turmeric (curry) that is extracted from turmeric by a method well known in the art, or commercially available.

The present invention includes not only curcumin represented by Formula 1 or a pharmaceutically acceptable salt thereof, but also all possible solvates and hydrates that can be prepared therefrom.

Curcumin of the formula (1) of the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid and aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. Obtained from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids. Such pharmaceutically nontoxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and iodide. Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suverate , Sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate, meth Oxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesul Nate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1- Sulfonates, naphthalene-2-sulfonates or mandelate.

The acid addition salts according to the invention are dissolved in conventional methods, for example, in the presence of an excess aqueous solution of curcumin of formula (1), and the salts are used with a water miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. It can be prepared by precipitation.

Equivalent amounts of curcumin of formula 1 and acids or alcohols in water may be heated and then the mixture is evaporated to dryness or the precipitated salts may be prepared by suction filtration.

Bases can also be used to make pharmaceutically acceptable metal salts. Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt as the metal salt. Corresponding silver salts are also obtained by reacting alkali or alkaline earth metal salts with a suitable negative salt (eg, silver nitrate).

The composition containing curcumin of Formula 1 or a pharmaceutically acceptable salt thereof according to the present invention as an active ingredient may be used for the prevention and treatment of pain such as acute pain, neuropathic pain, postoperative pain, migraine, joint pain, toothache, heat pain, and the like. It can be usefully used as a composition for. Preferably, it may be usefully used as a composition for preventing and treating pain caused by heat.

Curcumin of Formula 1 inhibits the electrical signal generated by vanilloid subtype 1 (TRPV1) of the transient receptor translocation channel included in the capsaicin receptor involved in pain.

As a result of administering curcumin of the formula 1 according to the present invention to HEK 293 cells or trigeminal ganglion neurons expressing capsaicin ion channels, the current generated by capsaicin was significantly blocked by curcumin ( FIGS. 1 to 1). 4 ), the inhibition rate increased proportionally with the curcumin dose (see FIG. 5 ). In addition, as a result of facial avoidance experiments due to heat pain in white rats, the heat pain response caused by capsaicin showed a result that the pain was relieved when curcumin was administered and the face avoidance time by heat was longer (see FIG. 7 ). From this, the composition according to the present invention can be particularly useful for the prevention and treatment of pain caused by heat.

The composition containing curcumin of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient according to the present invention may be used in the form of a general pharmaceutical preparation.

That is, the curcumin of the present invention can be administered in various formulations, oral and parenteral, in actual clinical administration. In addition, when formulated, in addition to curcumin as an active ingredient, it may be prepared by including one or more pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, as antioxidants, buffers And other conventional additives such as bacteriostatic agents can be added.

Solid preparations for oral administration may include tablets, pills, powders, granules, capsules and the like, which solid preparations contain at least one excipient in curcumin, for example starch, calcium carbonate, sucrose (Sucrose) or lactose (Lactose), gelatin, etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used.

In addition, liquid preparations for oral administration include suspending agents, liquid solutions, emulsions, and syrups, and various excipients, for example, wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents, water and liquid paraffin. This may include. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilizers, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Furthermore, the pharmaceutical compositions of the present invention can be administered parenterally, and parenteral administration is by subcutaneous injection, intravenous injection or intramuscular injection. To formulate into a parenteral formulation, the curcumin is mixed in water with a stabilizer or buffer to prepare a solution or suspension, which is formulated in unit dosage forms of ampoules or vials.

Curcumin according to the present invention is preferably included in 0.1 to 50% by weight relative to the total weight of the composition. However, the composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient, the type of disease, and the degree of progression.

The preferred dosage of curcumin according to the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, it is preferable to administer from 0.01 mg / kg to 10 g / kg, preferably from 1 mg / kg to 1 g / kg per day. Administration may be administered once a day or may be divided several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

Furthermore, the present invention provides a food composition for the prevention and improvement of pain, including curcumin and food acceptable food additives exhibiting the effect of preventing and improving pain.

The food composition of the present invention may be added to health food for the purpose of preventing and treating pain. When the curcumin of the present invention is used as an additive, the curcumin may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). Generally, in the preparation of food or beverages, the curcumin of the present invention is added in an amount of 1 to 20% by weight, preferably 5 to 10% by weight based on the raw materials. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range. have.

There is no particular limitation on the kind of food. Examples of foods to which the substance may be added include beverages, gums, vitamin complexes, or health supplements, and include all health foods in the conventional sense.

The beverage composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components, as in general beverages. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.

In addition, the compositions of the present invention include various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, And a carbonation agent used for the carbonated beverage. In addition, the composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

The present invention also provides a functional toothpaste comprising curcumin or a pharmaceutically acceptable salt thereof, which exhibits an effect of preventing and improving pain.

Since curcumin can effectively reduce toothache in which pain is increased by heat, the composition containing curcumin according to the present invention as an active ingredient can be widely applied as a component such as functional toothpaste. The composition can then be substantially solid or paste in nature, such as a dentifrice, dental dentifrice, toothpaste, gel or cream. Carriers of such solid or paste oral formulations generally contain an abrasive material. Examples of abrasive materials include insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, calcium dihydrate phosphate, dicalcium phosphate anhydrous, calcium pyrophosphate, magnesium offtophosphate, trimagnesium phosphate, calcium carbonate, aluminum silicate, zirconium silicate, Silica, bentonite and mixtures thereof can be used.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

< Example  1> Curcumin TRPV1  Measure the effect on activation

(One) TRPV1 This manifested HEK293 Curcumin from TRPV1  Effect on activation

Human embryonic kidney cells HEK293 (American Type Culture Collection, Manassas, VA) were seeded in 12-well plates, and the next day 0.5-2 μg / well TRPV 1 pcDNA construct and TRPV 1 mutant were transfected with lipofectamine 2000. Transformation was performed using an import reagent (Invitrogen). After 18-24 hours, the transformed cells were trypsinized and used for whole cell recording experiments.

After that, the membrane voltage was fixed to -60 mV, which is a general stable membrane voltage, and the current generated by capsaicin and curcumin was observed.

The membrane voltage fixing method is a method of artificially fixing membrane voltage after inserting a recording electrode into a cell to electrically manipulate the cell. Normally, cells have a potential difference around the cell membrane. At this time, the cell membrane has a stable membrane voltage, which is called a stable membrane voltage. Generally, the stable membrane voltage of the cell is -60 to -70 mV, and there is almost no current based on the cell membrane. In the membrane voltage fixation method used in this study, drugs capable of stimulating cells generate electrical signals of cells, which are recorded as currents.

Total cell current was amplified using an EPC 10 amplifier (HEKA). The recording electrode was made of borosilicate glass and was prepared to have a resistance of 3 to 5 mA when filled with standard intracellular solution. In whole cell experiments 140 mM NaCl, 5 mM KCl, 2 mM CaCl 2, 1 mM MgCl 2, 10 mM glucose and 10 mM N- [2- hydroxyethyl] piperazine -N '- [2- ethane sulfonic acid ] (N- [2-hydroxyethyl] piperazine-N '-[2-ethanesulfonic acid]; HEPES) with an external medium was used, the pH was adjusted to 7.4 using NaOH. In addition, the recording electrode solution had a composition of 140 mM CsCl ₂ , 10 mM HEPES, 5 mM EGTA, and 3 mM MgATP, and the pH was adjusted to 7.3 using CsOH. All drug solutions were applied to the cells via capillary tubes (1.1 mm inner diameter) placed around the cells to be observed by local perfusion. The flow of solution was induced at a rate of 1-5 ml / min by gravity. In addition to the other drug administration method using a pressure transmitter (Picopump, WPI) to a small amount of drug directly to the cell was used. After dosing, it was filtered at a current of 5 kHz (-3 dB, 4-pole Bessel) and analyzed using a personal computer equipped with PULSE software (HEKA). The junction potential calculated between the recording electrode and the extracellular solution used for all the cells during the sealing process was 4 mV (pipette negative, using PULSE software). No correction was made to the binding potential, and the experiment was performed at room temperature (18-22 ° C.).

The experimental results are shown in FIG. 1 .

As shown in FIG . 1 , the current response generated by capsaicin in TRPV1-expressing HEK293 cells shows that current is generated when 200 nM CAP is administered for 3 seconds after fixing the membrane voltage at -60 mV. After pretreatment with 5 μM curcumin for 2 minutes, capsaicin concurrently with curcumin decreased the current induced by capsaicin. This capsaicin induced current can be seen to recover again 10 minutes after the curcumin removal.

2 is a graph showing the magnitude of the current when capsaicin is administered for a very short time (0.5 seconds). In FIG. 2 , as shown in FIG . 1 , the capsaicin-induced current generated by a very short time of capsaicin is blocked by curcumin when curcumin and capsaicin are simultaneously administered, and the curcumin is washed again with extracellular solution. It can be seen that the recovery of the capsaicin induced currents of. Thus curcumin was found to act as a pain inhibitor caused by capsaicin.

(2) TRPV1 This exists Trigeminal ganglia  Curcumin in neurons TRPV1  Effect on activation

Trigerminal ganglion (hereinafter abbreviated as "TG") neurons from neonatal mice were rapidly removed in sterile state and stored in HBSS solution (Gibco Corporation). The resulting TG was digested with 0.1% collagenase and 1% collagenase / dispase from Boehringer Mannheim for 10 minutes each at 37 ° C. HBSS solution, 0.25% trypsin from Sigma Reacted for 10 minutes. TGs thus treated were washed three times in DMEM medium (Gibco Inc.) and resuspended in F12 medium using 10% FBS (Gibco Inc.) and 1% penicillin / streptomycin (Sigma Corp.). The TG was then centrifuged in a glass pipette sterilized with fire, resuspended in F12 medium and plated on a glass cover slip coated with polyorithine (Sigma) and laminin (Sigma). It was. The cells obtained therefrom were cultured in a 37 ° C., 5% CO ₂ incubator [Oh, SB et al. , Chemokines and glycoprotein 120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J. Neurosci., 21: 5027-35, 2001].

Since the current generated by administering capsaicin alone, capsaicin and curcumin at the same time to the trigeminal ganglion neurons, and after removing the curcumin is shown in Figure 3 by measuring the current. Subsequently, the cumulative current was measured while curcumin was administered in the middle while capsaicin was continuously administered, and is shown in FIG. 4.

As shown in FIG . 3 and FIG. 4 , it can be seen that curcumin blocks the current caused by capsaicin even in trigeminal ganglion cells in which TRPV1 is present.

In addition, in order to investigate the inhibitory effect of TRPV1 according to the concentration of curcumin, the induced current size of capsaicin was shown in FIG. 5 while varying the concentration of curcumin from 1 nM to 10 μM.

As shown in FIG . 5 , when the concentration of curcumin administered was as low as 1 nM, the capsaicin-induced current was hardly blocked as much as 10% of the inhibition rate of the current induced by capsaicin, but the concentration of curcumin administered gradually. Increasing the inhibition rate of the capsaicin-induced current was confirmed to continue to a certain level. The highest blocking effect was 11 nM and the maximum blocking effect was observed at 1 μM and 5 μM. The maximum inhibition of capsaicin was 67%.

As such, curcumin blocks the reaction of capsaicin to the capsaicin receptor (TRPV1), which causes analgesic, thereby lowering the activity of TRPV1, thereby alleviating the pain caused by curcumin according to the present invention. A composition containing a salt as an active ingredient can be usefully used for analgesics.

< Example  2> In capsaicin  by TRPV1  Caused by activation Fever  Determination of Curcumin's Effect on the Response

Behavioral experiments were performed using 250-300 g male Sprague-Dawley rats.

Specifically, six rats were placed in a cylindrical rat strap device (height 40-60 mm, length 70-120 mm) and examined for heat and sensitization pain. A hole was made in the upper part of the cylinder to apply thermal stimulation, and the light was continuously controlled for 12 hours while maintaining a constant temperature of 23 ° C. Subsequently, 30 μl of 0.1, 1, or 5 μg of capsaicin was subcutaneously injected into the left face of the rat, and then heat was irradiated with infrared heat stimulator for 9 seconds at a distance of 10 cm from the middle of the left face. and at intervals of several minutes in the same manner performed twice it is shown in FIG. 6 by measuring the avoidance delay time according to the thermal effect. Evasion delay time was determined according to the Hargreaves method.

As shown in FIG . 6 , subcutaneous injection of 0.1, 1, or 5 mg of capsaicin reduced the delay time for thermal stimulation in a concentration-dependent manner (F (3,20) = 13.485, p <0.001), It can be seen that the highest thermal stimulation occurs when the dose of capsaicin is 5 mg.

Curcumin was then administered intraperitoneally 5, 25 and 50 mg / kg, respectively, and capsaicin 5 mg was injected subcutaneously into the left face of the rat. In addition, 50, 100 ㎍ / kg of 5'-Iodoresiniferatoxin (IRTX), a TRPV1 receptor blocker, was administered as a comparison group. At this time, CAP was dissolved in 10% ethanol, 10% TWEEN 80 and 80% saline, Cur was 70% DMSO and 30% saline, and IRTX was dissolved in 1% ethanol, 3% TWEEN 80 and 96% saline.

The results are shown in FIGS . 7 and 8 .

Figure 7 is a graph showing the avoidance delay time for heat stimulation according to subcutaneous injection of 5 mg CAP after pretreatment of Cur by 5, 25, 50 mg / kg concentration in rat intraperitoneal.

As shown in FIG . 7 , it can be seen that the avoidance reflection delay time increases as the amount of curcumin is increased (F (3,20) = 13.485, p <0.001). It can be seen that show the aspect such as when administering a TRPV1 receptor blocker is conventionally used in Fig.

Therefore, curcumin can be used to alleviate heat stimulation pain caused by capsaicin and to relieve tooth pain, which is aggravated by analgesics, especially heat.

< Formulation example  1> Powder  Produce

Curcumin 20 mg

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

Curcumin 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

< Formulation example  3> Preparation of capsule

Curcumin 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

< Formulation example  4> Preparation of Injection

Curcumin 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _{4 ,} 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

< Formulation example  5> Liquid  Produce

Curcumin 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added to the mixture, and then the above ingredients are mixed, purified water is added to adjust the total amount to 100 ml, and then filled in a brown bottle. The solution is prepared by sterilization.

< Formulation example  6> Manufacture of healthy food

Curcumin 1000 mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.

< Formulation example  7> Manufacture of health drinks

Curcumin 1000 mg

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

900 ml of purified water

After mixing the above components according to a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated and then stored in the present invention For the preparation of healthy beverage compositions.

Although the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

< Formulation example  8> Preparation of Functional Toothpaste

Deionized Water

Glycerin 25 parts

Silicon dioxide 21.5 parts

Hexaforce (HMP) 6.0 parts

3.0 parts of synthetic silica

1.2 parts sodium lauryl sulfate

1.0 parts of spices

Curcumin Part 1.0

1.0 part sodium hydroxide (50% solution)

Xanthan rubber 1.0 part

0.5 parts of sodium benzoate

Titanium dioxide0.5part

0.3 part sodium saccharin

Nafluoride Part 0.242

The composition is mixed by a conventional method to prepare a toothpaste paste and put in a container to produce a functional toothpaste.

1 is a current graph showing that capsaicin-induced current is blocked by curcumin according to an embodiment of the present invention.

Figure 2 is a current graph showing that the capsaicin induced current administered for a very short time by curcumin according to an embodiment of the present invention is blocked.

3 is a current graph showing that capsaicin-induced current is blocked by curcumin according to another embodiment of the present invention.

4 is a current graph showing that capsaicin-induced current is blocked by curcumin according to another embodiment of the present invention.

5 is a graph showing the capsaicin inhibition rate for the concentration of curcumin according to an embodiment of the present invention.

6 is a graph showing the delay time of avoiding heat sensitization of rats versus the concentration of capsaicin according to an embodiment of the present invention.

7 is a graph showing the delay time of avoiding heat sensitization of rats to the concentration of curcumin according to an embodiment of the present invention.

Figure 8 is a graph showing the heat sensation avoidance delay time of the rat relative to the concentration of the conventional TRPV1 inhibitor according to a comparative example of the present invention.

CAP: capsaicin

Cur: Curcumin

Claims (9)

A composition for preventing and treating pain containing curcumin represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. <Formula 1>

[Claim 2] The composition for preventing and treating pain as claimed in claim 1, wherein curcumin is separated and purified from turmeric. The method of claim 1, wherein the curcumin inhibits the activity of the vanilloid (capsaicin) receptors involved in pain, curcumin or a pharmaceutically acceptable salt thereof as an active ingredient composition for preventing and treating pain. The curcumin or pharmaceutically acceptable according to claim 1, wherein the curcumin inhibits an electrical signal generated by vanilloid subtype 1 (TRPV1) of a transient receptor translocation channel included in a capsaicin receptor involved in pain. A composition for preventing and treating pain containing a possible salt as an active ingredient. The method of claim 1, wherein the pain is acute pain, neuropathic pain, postoperative pain, migraine, arthralgia or toothache, for the prevention and treatment of pain containing curcumin or a pharmaceutically acceptable salt thereof as an active ingredient. Composition. According to claim 1, wherein the curcumin is curcumin or a pharmaceutically acceptable salt thereof as an active ingredient, characterized in that it comprises 0.1 to 50% by weight based on the total weight of the composition. Functional toothpaste for preventing and improving pain containing curcumin represented by the formula (1) of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. Functional food for pain prevention and improvement containing curcumin represented by the formula (1) of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. The functional food for preventing and improving pain containing curcumin or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 8, wherein the functional food is a beverage, a gum, a vitamin complex, or a health supplement.

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