MX2008005256A - Extract of the family dioscoreaceae and composition for preventing or treating peripheral neuropathy comprising the same - Google Patents

Abstract

An extract of the familyDioscoreaceaeuseful for preventing or treating the peripheral neuropathy;and a pharmaceutical composition or food composition comprising the extract are provided. In addition, a pharmaceutical composition or food composition useful for preventing or treating the peripheral neuropathy comprising a compound isolated from the extract of the familyDioscoreaceaeis provided.

Description

EXTRACT OF THE GODS AND FAMILY DIOSCOREACEAE COMPOSITION COMPRISING THE SAME, TO AVOID OR TREAT PERIPHERAL NEUROPATHY Technical Field The present invention refers to an extract of the family Dioscoreaceae to avoid or treat peripheral neuropathy; and to a pharmaceutical composition or food composition, comprising the extract or a compound isolated from the extract. Previous Technique Neuropathy is a disease caused by structural or functional abnormalities of the nervous system. The nervous system is divided into the central nervous system that is distributed in the brain and spinal cord and that is involved in controlling its functions, and the peripheral nervous system that is distributed in almost all organs excluding the brain and spinal cord, involved in controlling their functions. The peripheral nervous system is subdivided into the motor nervous system, the sensory nervous system, the autonomic nervous system. A peripheral nerve, in which the neurites branch out beyond the brain and spinal cord to the body, arms and legs, transmits the sensation perceived in the arms and legs to the central nerve (brain and spinal cord), and transmits orders from the central nerve to the muscles.

The central nerve can be injured by various causes, which are collectively referred to as a peripheral neuropathy. Mono-neuropathy refers to a case where a single peripheral nerve is injured, and multiple neuropathy refers to a case where many peripheral nerves are injured at a similar level. Mono neuropathy usually occurs when a single peripheral nerve is abnormally depressed or traumatically injured during extension to the ends of arms and legs. Mono neuropathy can be treated with operations. Multiple neuropathy can be induced by various causes, such as metabolic diseases (eg diabetes, renal failure, hypothyroidism), drugs (eg antitumor agents, anti-tuberculosis drugs) or poisoning with toxic substances (eg Pb, organic solvents), poorly nutrition (eg, vitamin deficiency, alcoholism), connective tissue disorders (eg, rheumatoid arthritis, systemic lupus heritematosus), inflammatory diseases (Guillian-Barre syndrome) or genetically determined neuropathy. In addition, multiple neuropathy can be caused by cancer. So far, neuropathy has been treated with drugs used as a symptomatic therapy, which improves symptoms alone and there are almost no fundamental remedies for neuropathy.

Only epalrestat, an aldose reductase inhibitor approved by the Food and Drug Administration of the U.S.A. (FDA = Food and Drugs Administration) regarding diabetic peripheral neuropathy, one of the multiple neuropathies, but epalrestat is not used due to its low therapeutic effects (Foster DW., Harrison 's Principles of Internal Medicine 13, pl979, 1999 Stephen LD, Applied Therapeutics: the clinical use of drugs 6, p48.1-48.62, 1996). Meanwhile, a protein that affects the growth, differentiation and survival of neurons in the central nervous system (CNS = Central Nervous System) and the peripheral nervous system (PNS = Peripheral Nervous System) is collectively referred to as a neurotrophic factor (NF = Neurotrophic Factor), which is one of control factors of neurons that regulate the growth differentiation and death of neurons. Examples of NF include a neurotrophic factor induced by the brain (BDNF = Brain-Induced Neurotrophic Factor), neorotrophin, neurotrophin-3 (NT-3), NT-4, and NT-5. These NFs are synthesized in different areas and have different differentiation, different expression, and different target or target regions. A nerve growth factor (NGF = Nerve Growth Factor), one of the NFs, inhibits the degeneration and death of neurons, to avoid a decrease in the number of neurons, to protect neurons against damage, and not to retain sources of mature neurons (Hefti F., J. Neurosci., 6 (8), pp 2155-2162, 1986; and Levi-Montalcini R., et al. , Proc. Na ti. Acad. Sci. USA, 46, pp. 84-391, 1960). It is known that when the nervous system develops normally, approximately 50% of neurons as they grow are removed by cell death (Raff MC., Et al., Science, 262 (5134), pp695-70, 1993), and that NGFs secreted by a target cell, determines the survival of neurons. In order for neurons to survive, grow and differentiate in a normal state, a growth factor such as NGF is necessarily required. This feasibility of GNF has led to the development of a growth factor of recombinant human nerves in order to treat a diabetic neuropathy, one of the multiple neuropathies. However, the recombinant human nerve growth factor is still unsatisfactory in safety and efficacy (Apfel SC et al., Journal of American Medi cal Association 284 (17), pp. 2215-2221, 2000). Description Technical Problem The present invention provides herbal extracts and compounds isolated thereof, useful for preventing and treating peripheral neuropathy induced by various causes.

That is, the present invention provides an extract from the Dioscoreaceae family to avoid or treat peripheral neuropathy. The present invention also provides a pharmaceutical composition or food composition, comprising the extract or a compound isolated from the extract, as an active ingredient. Technical Solution According to one aspect of the present invention, an extract of the Dioscoreaceae family is provided to prevent or treat peripheral neuropathy, the Dioscoreaceae family is at least one selected from the group consisting of Dioscorea nipponi ca, Dioscorea septembloba, Dioscorea quinqueoloba, Dioscorea batatas, Dioscorea japonica, Dioscorea bulbifera, Dioscorea tokoro, and Dioscorea tenuipes. In accordance with another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating peripheral neuropathy, comprising a therapeutically effective amount of the extract, and a pharmaceutically acceptable carrier. According to yet another aspect of the present invention, there is provided a food composition for preventing or treating peripheral neuropathy, which comprises the extract as an active ingredient.

According to yet another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating peripheral neuropathy, comprising a therapeutically effective amount of a compound represented by formula 1 or its salt; and a pharmaceutically acceptable carrier: [Formula 1] wherein R is a hydrogen atom a C? ~ C4 alkyl group, or a saccharide. According to yet another aspect of the present invention, there is provided a food composition for preventing or treating peripheral neuropathy, comprising the compound represented by formula 1 or its salt as an active ingredient. Advantageous Effects An extract of the Dioscoreaceae family and / or a compound isolated from the extract, induces an endogenous nerve growth factor in an organism, in such a way that can be used in a wide range of applications, to prevent or treat peripheral neuropathy. Description of the Drawings Figure 1 and Figure 2 show the effect of the compound isolated from an extract, according to one embodiment of the present invention in neurite excrescence. Figure 3 is a graph illustrating a change in the level of nerve growth factor (NGF) in normal mouse serum, resulting from the administration of a compound isolated from an extract according to an embodiment of the present invention. Figure 4 is a graph illustrating a change in the level of NGF in the serum of a mouse with induced diabetes resulting from administration of an extract according to an embodiment of the present invention and a compound isolated from the extract. Figures 5 and 6 illustrate the effect of an isolated compound of an extract according to an embodiment of the present invention on the rate of transmission of the motor nerve and sensory nerve in a sciatic nerve of mice with induced diabetes (Figure 5: treatment of DG for one month, Figure 6: treatment of DG for two months). Figure 7 is a graph illustrating a change in the level of an NGF in the sciatic nerve of a mouse with induced diabetes, which results from administration of a compound isolated from an extract according to an embodiment of the present invention. Figure 8 is a graph illustrating a change in the level of sorbitol in the sciatic nerve of a mouse with induced diabetes resulting from the administration of a compound isolated from an extract according to an embodiment of the present invention. Figure 9 are images illustrating histological changes in the sciatic nerve of a mouse with induced diabetes, resulting from administration of an extract according to an embodiment of the present invention and a compound isolated from the extract. BEST MODE In the present specification, the term "peripheral neuropathy" refers to a condition of peripheral nerves (motor nerves, sensory nerves, and autonomic nerves) injured by various causes. Peripheral neuropathy can be subdivided into mono neuropathy and poly neuropathy (also called multiple neuropathy). Multiple neuropathy includes any neuropathy caused by metabolic diseases (eg diabetes, renal failure, hypothyroidism), drugs (eg antitumor agents, anti-tuberculosis drugs) or poisoning with toxic substances (eg Pb, organic solvents), poor nutrition (eg , vitamin deficiency, alcoholism), connective tissue disorders (eg, rheumatoid arthritis, systemic lupus, erythematosus), inflammatory diseases (Guillain-Barre syndrome), or genetically determined neuropathy. In addition, multiple neuropathy can influence a neuropathy caused by genetic factors and cancer. An extract of the Dioscoreaceae family according to an embodiment of the present invention or a compound isolated from the extract, derives excrescence in neurites and increases the amount of a secreted endogenous nerve growth factor, such that the nerves of the peripheral nervous system they can be effectively differentiated, protected and reinserted. In particular, the extract and / or compound allow oral administration, which improves compliance with the medication by patients. The present invention provides an extract from the Dioscorea ceae family to prevent or treat peripheral neuropathy. The Dioscoreaceae family is at least one of Dioscorea nipponica, Dioscorea septembloba, Dioscorea quinqueoloba, Dioscorea batatas, Dioscorea japonica, Dioscorea bulbifera, Dioscorea tokoro, and Dioscorea tenuipes. Preferably, the Dioscoreaceae family is Dioscorea nipponica, Dioscorea quinqueoloba, and / or Dioscorea tokoro. More preferably the Dioscoreaceae family is Dioscorea n ippon i ca. The extract according to the present invention can be obtained through an extraction process that includes extracting an integral part, root, or aerial part (for example leaf or trunk) of the Dioscoreaceae family with an extraction solvent (solvent first extraction), selected from the group consisting of water, C? ~ C4 alcohol, and a mixture of water and a C? ~ C alcohol. For example, the extract of the Dioscoreaceae family can be obtained by extracting the root of the Dioscoreaceae family with the first extraction solvent. The first extraction solvent can be a solvent mixture of water and methanol or a solvent mixture of water and ethanol. In the extraction process, the whole part, root or aerial part, preferably the root of the Dioscoreaceae family is cut into small sections, and then extracted with the first extraction solvent. At this time, the amount of the first extraction solvent may be 1 to 20 times, preferably about 3 to 10 times, greater than that of the Dioscoreaceae family. The first extraction solvent may be a solvent mixture of water and methanol (for example about 85% methanol solution) or a solvent mixture of water and ethanol (for example, about 85% ethanol solution). The extraction is not affected by the temperature and can be done in various temperature ranges, such as a temperature of 15 ° C to 100 ° C. The extraction can be done by cold extraction, hot extraction, superfluid extraction, centrifugal extraction, ultrasonic extraction or extraction of reflux cooling. The extraction time may vary according to the extraction method. For example, the extraction can be performed one or multiple times for approximately one hour to 10 days. Preferably, the extraction can be carried out two or three times at room temperature for approximately 2 days, using the first extraction. The extract obtained by extraction with the first extraction solvent may be a liquid form in which impurities in the extract are removed using a conventional method, for example filtration, or a powder form which is obtained by concentrating under reduced pressure or drying the extract liquid using a conventional method. In addition, when required, the extraction process may include obtaining a fraction that has higher contents of active ingredients. That is, the extraction process also includes: supplying the extract obtained by extraction with the first extraction solvent in water; and extracting the resulting solution with C? ~ C4 alcohol saturated with water (second extraction solvent), thereby increasing the contents of active ingredients in the extract obtained.

When the extract obtained by this extraction with the first extraction solvent is dispersed in water, a liquid form per se, obtained by extraction with the first extraction solvent, may be dispersed in water, or a powder form obtained by concentrating the liquid extract. under reduced pressure and / or drying the liquid extract using a conventional method, they can be dispersed in water. The alcohol C? ~ C saturated with water (second extraction solvent) can be butanol saturated with water. The present invention includes within its scope, a composition comprising a compound isolated from the extract, ie a steroidal saponin or a steroidal sapogenin. That is, the present invention includes a pharmaceutical composition for preventing or treating peripheral neuropathy, comprising a therapeutically effective amount of a compound represented by formula 1 or its salt; and a pharmaceutically acceptable carrier: [Formula 1] wherein R is a hydrogen atom, a group C? -C alkyl, or a saccharide. In the compound of Formula 1, R can be hydrogen or methyl, preferably hydrogen. That is, the compound of Formula 1 can be 3- ", 25R-spirost-5-en-3-ol The saccharide can be monosaccharide, disaccharide or polysaccharide, such as glucose, fructose, mannose, galactose, ribose, cellulose , glycogen, sucrose, maltose and lactose The salt of the compound of the formula 1 can be an addition salt of inorganic acid or conventional organic acid prepared from steroidal saponin or sapogenin compounds Examples of the salt of the compound of the Formula 1 include salts described in International Patent Publication No. WO2003 / 082893. These salts can be prepared in-house during separation and final purification processes of a compound, In particular, an acid addition salt can be prepared at reacting a refined compound in a free base form with a suitable organic or inorganic acid and then separating the salt produced (see SM Berge, et al., Pharmaceutical Salts, J. Pharm. ci., 66: p.1-19 (1977)). The Open Patent Publication to International Inspection Number WO2003 / 082893 and the journal of M. Berge, et al., Are used as a reference in the present invention. A base addition salt can be prepared by reacting a refined compound in a form acid with a suitable organic or inorganic base and separate the salt produced. The base addition salt may be a pharmaceutically acceptable metal or amine salt. The acid addition salt can be a salt prepared from an acid selected from hydrochloric acid, sulfuric acid, phosphoric acid and nitric acid. The base addition salt may be a salt prepared from a base selected from sodium hydroxide, potassium hydroxide and ammonium hydroxide. The compound of Formula 1 can be isolated from the extract according to one embodiment of the present invention, synthesized using a known method (see Herbert O. House, Modern Synthetic Reactions, The Benjamin Cummings Pubiishing Company, 1972), or commercially obtained (Sigma Co., USA.). The method for isolating the compound of Formula 1 from the extract can include an acid hydrolysis process and a recrystallization process, using the extract that is obtained according to an embodiment of the present invention (for example an extract obtained using the first extraction solvent and the second extraction solvent). For example, the method for isolating the compound of Formula 1 from the extract may include: Hydrolyzing with an acid such as 2.5N hydrochloric acid, at a temperature of 50 to 150 degrees C, preferably at about 94 degrees C, for 30 minutes to 3 days, preferably for about 4 hours; solvent extraction of the obtained hydrolyzate (ie aglycone sapogenin) with an organic solvent, such as chloroform, acetone, benzene, or xylene, for 1 to 60 minutes, preferably for about 15 minutes and then separating the organic layer; when it is required to concentrate the separated organic layer at a temperature of 10 to 100 degrees C, preferably 30 to 35 degrees C; recrystallizing the organic layer or the concentrated solution of the organic layer with the Cj-C alcohol or alcohol solution C? ~ C (for example 95% ethanol solution); and washing the obtained precipitate with water when required and recrystallizing with acetone. The present invention provides a pharmaceutical composition for preventing or treating peripheral neuropathy, comprising a therapeutically effective amount of an extract of the Dioscorea ceae family or a compound of Formula 1 or its salt, or a pharmaceutically acceptable carrier. The pharmaceutical composition according to the present invention includes a pharmaceutically acceptable carrier and can be formulated in an oral dosage form, external dosage form, suppository and sterile injection solution, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups or aerosols. The Porter pharmaceutically acceptable can be lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia oil, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water , methylhydroxybenzoate, propylhydroxybenzoate, talcum, magnesium stearate or mineral oil. The pharmaceutical composition can further include a diluent or excipient such as expander, binder, humectant, disintegrant or surfactant. A solid oral formulation can be a tablet, a pill, a powder, a granule or a capsule. These solid formulations may include at least one excipient selected for example from starch, calcium carbonate, sucrose, lactose and gelatin. In addition, these solid formulations may further include a lubricant such as magnesium stearate or talc. A liquid oral formulation may be a suspension, a solution, an emulsion or a syrup. In addition, the liquid oral formulation may include a diluent such as water; liquid paraffin; humectant; sweetening agent; odorizing or conservative. A parenteral formulation can be a sterile aqueous solution, a non-aqueous solution, a suspension, an emulsion, a lyophilized formulation or a suppository. Nonaqueous solvents or suspending agents may be propylene glycol, polyethylene glycol, oil natural such as olive oil or injectable esters, such as ethyl acetate. Suppository vehicles can be witepsol, macrogol, Tween 61, cocoa butter, Laurin or glycerogelatine. In the pharmaceutical composition according to the present invention, a dose of the Dioscorea ceae family extract or the compound of Formula 1 can vary depending on the condition or body weight of the patient, the seriousness of the disease, dosage forms, routes of administration and the period of administration, and may be determined in an appropriate manner by a person having ordinary skill in the specialty. For example, the extract of the Dioscorea ceae family or the compound of Formula 1 can be administered in an amount of 0.0001 to 1000 mg / kg, preferably 0.001 to 1000 mg / kg, per day. The administration can be completed once or several times a day. In the pharmaceutical composition according to the present invention, the amount of the Dioscorea ceae family extract or the compound of Formula 1 can be in the range of 0.001 to 50 weight percent based on 100 weight percent of the pharmaceutical composition. The pharmaceutical composition can be administered to mammals, such as rats, mice, cattle or humans, through various routes, for example oral, rectal, intravenous, intramuscular, subcutaneous, through Intrauterine dura injection or through intracerebroventricular injection. The present invention includes within its scope, a food composition for preventing or treating peripheral neuropathy, comprising an extract of the Dioscorea ceae family or the compound of Formula 1 as an active ingredient. The food composition according to the present invention can be used as a functional health food. According to Article 6727 of the Korean Law for Functional Health Foods, "functional health food" refers to a food that is produced and processed using a source or component that transports good functions in the human body. The "function" refers to an intake that aims to achieve good effects of health, that is, a nutrient control with respect to the structure and function of the human body or a physiological operation. The food composition according to the present invention can include a conventional food additive. The conformity of the "food additive" is determined whenever there are no other regulations, in consideration with the norm and criteria of the corresponding item according to the General Rule of the Food Additives Code and general tests approved by the Korean Food and Drug Administration. The items cited in the "food additive code" include a chemically synthesized substance such as ketone, glycine, potassium citrate, nicotinic acid or cinnamic acid; natural additives such as khaki color, licorice extract, crystalline cellulose, caoliang color or guar gum; or formulation and mixture such as L-sodium glutamate formulation, alkaline additives for needles, preservatives or tar-colored formulation. The food composition according to the present invention may include the Dioscorea ceae family extract or the compound of Formula 1 in an amount of 0.01 to 95 weight percent, preferably 1 to 80 weight percent, based on 100 percent of the food composition in order to avoid and / or treat peripheral neuropathy. In addition, in order to avoid and / or treat peripheral neuropathy, the food composition can be produced without being processed into tablets, capsules, powder, granules, liquid phase or pills. For example, in order to produce a functional health food in a tablet form, a mixture of Dioscorea ceae family extract or the compound of Formula 1, an excipient, a binder, a disintegrant and other additives, can be granulated using a conventional method and then a molding process is carried out compression with a lubricant. Alternatively, the mixture can be directly subjected to the compression molding process. In addition, when required, the food formulated for health in a tablet form may include sweetening agents, and when required, the health food formulated in a tablet form may be coated with coating materials. Among the functional foods for health in a capsule form, a hard capsule formulation can be produced by filling a conventional hard capsule with a mixture of the Dioscoreaceae family extract or a compound of Formula 1 and an additive, such as an excipient. , or granules of the mixture, or granules coated with the mixture, and a soft capsule formulation can be produced by filling a gelatin capsule holder with the mixture of the Dioscoreaceae family extract or the compound of Formula 1 and an additive, such as an excipient. When required, the soft capsule formulation can include plasticizer, such as glycerin or sorbitol, a coloring agent and a preservative. A functional food for health in a pill form can be produced by molding a mixture of the Dioscorea ceae family extract or the Formula 1 compound, with an excipient, a binder and a disintegrant using a convenient method. When required, the Functional food for health in a pill form can be coated with white sugar or other coating materials, or it can be covered with starch, talc or other materials. A functional health food in a granule form can be produced by granulating a mixture of the Dioscoreaceae family extract or the compound of Formula 1, an excipient, a binder and a disintegrant, using a convenient method. When required, the health functional food in a granule form may include a flavoring agent and a sweetening agent. The excipient, binder, disintegrant, lubricant, sweetening agent and flavoring agent employed in the present invention can be defined as corresponding materials having the same or similar functions described with reference known in the art (The Korean pharmacopoeia review, Moonsungsa Publication Co., Korea Pharmaceutical University Association, fifth edition, pp. 33-48, 1989). Mode for the Invention The present invention will be described in greater detail with reference to the following examples. These examples are for illustrative purposes only and are not intended to limit the scope of the present invention Example 1: Preparation of the Extract Dioscorea Nipponi ca dries and its root is cut into small sections. 500 g of the sample are added to 10% 85% methanol solution and then extracted three times (each for 2 hours) at room temperature. This extraction process is repeated twice. The resulting supernatants are collected and concentrated under reduced pressure, thereby obtaining 74 g of a crude extract. The 74 g of the crude extract are suspended in 1 1 of distilled water, 1 1 of water saturated with butanol are added and then the generated organic layer is separated, which is repeated five times. The organic layers obtained are collected together and dried under reduced pressure. As a result, 17 g of Dioscorea Nipponica extract is obtained. Example 2: Preparation of Dioscorea extract quinqueoloba is dried and its root is cut into small sections. The 500 g of the sample is added to a solution of 85% ethanol and then extracted three times (each for 2 hours) at room temperature. This extraction process is repeated twice. The resulting supernatants are collected and concentrated under reduced pressure, thereby obtaining 90 g of a crude extract. The 90 g of the crude extract is suspended in 1 1 of distilled water. 1 1 of water saturated with butanol are added and then the generated organic layer is separated, which is repeated five times. The organic layers obtained are completely collected and dried under reduced pressure. As a result, 26 g of Dioscorea quinqueoloba extract is obtained. Example 3: Preparation of Extract Dioscorea tokoro dries and its root is cut into small sections. The 300 g of the sample are added to 3 1 of 85 percent ethanol solution and then extracted three times (each for 2 hours) at room temperature. This extraction process was repeated twice. The resulting supernatants are collected and concentrated under reduced pressure, thereby obtaining 35 g of a crude extract. The 35 g of the crude extract is suspended in 0.5 1 of distilled water, 0.51 of water saturated with butanol are added and then the generated organic layer is separated, which is repeated five times. The organic layers obtained are collected together and dried under reduced pressure. As a result, 11 g of Dioscorea tokoro extract is obtained. Example 4: Separation of Active Compound 1 g of the Diosphore nipponica extract obtained in Example 1 is hydrolysed at 94 degrees C for 4 hours by adding 10 ml of 2.5 N HCl. Then, the resulting hydrolyzate is extract with 10 ml of chloroform for 15 minutes. The chloroform layer is separated, filtered and then concentrated under reduced pressure at a temperature of 30-35 degrees C. The residue obtained is recrystallized at 4 degrees C using 5 ml of 95 percent ethanol solution. The recrystallized precipitate is filtered, washed with water, recrystallized at 4 degrees C using 3 ml of acetone and then filtered to obtain approximately 100 mg of precipitate. The precipitate is identified as 3beta, 25R-spirost-5-en-3-ol represented by Formula 2. [Formula 2] (1) Formula: C? 7H4203 (2) Molecular Weight: 414.62 (3) Melting Point: 204-207 degrees C (4) [«] 25D -129 ° (5) NMR Data: Reference to Table 1 Table 1 Experimental Example 1: Measurement of Neurite Excrescence In an incubator with conditions including C02 at 5 percent and a temperature of 37 degrees C, PC 12 cells (pheochromocytoma, ATCC Number: CRL-1721) were cultured in a RPMI 1640 medium supplemented with horse serum (10%, v / v), fetal bovine serum (5%, v / v), and penicillin-streptomycin 1 ^. In order to find the effect of the compound of Formula 2 on the excitation of neurites, the media supplemented with 2% horse serum, 1% fetal bovine serum and penicillin-streptomycin 1 percent are added to each 6-well plate coated with poly-d-lysine and then the PC12 cells are inoculated in 5 * 104 cells per well. After 24 hours, these wells are treated with 10 '' l / ml ethanol, 10 μg / Ml of compound of Formula 2, and 50 ng / Ml of a nerve growth factor (R & amp; amp;; D system, USA), respectively. After 48 hours, the length of the neurite is measured using an inverted image contrast microscope (CK-2, Olympus, USA) (see Figure 1 and Figure 2). With reference to Figures 1 and 2, the neurite excrescence is not observed in the group injected with ethanol (control), but the neurite excrescence is induced both in the group treated with compounds of Formula 2 (DG) and in the group treated with nerve growth factor. Accordingly, it was found that the compound of the Formula 2 induces differentiation of PC 12 cell by inducing neurite excrescence. Experimental Example 2: Factor Level Measurement of Growth of Nerves in Serum of Mice The compound of Formula 2 is dissolved in 0.2 ml of a solution of dimethylsulfoxide: ethanol (3: 1), and then orally administered once to mice with 7 weeks of age ICR (n = 7) in an amount of 10 mg / kg. After 24 hours, the amount of an endogenous nerve growth factor is measured by ELISA. As a control group, an ICR mouse was orally administered once with 0.2 ml of dimethyl sulfoxide: ethanol (3: 1). Then, the amount of nerve growth factor in the control group was measured in the same manner as described above. With reference to FIG. 3 the group administered with compound of Formula 2 (DG 10 mg / kg P.O) showed a nerve growth factor in the serum approximately 2.5 times higher than the control group. These results show that the compound of Formula 2 can treat lung disease by suppressing the degeneration and death of neurons in a mouse and in this way avoiding a decrease in the number of neurons. Experimental Example 3: Measurement of Nerves Growth Factor Level in Serum of Mice with Diabetes Induced. A mouse with diabetes induced by alloxan, is prepared as an animal model that has diabetic neuropathy, one of the multiple neuropathies.

Male ICR mice of 7 weeks of age were subjected to food abstinence for 18 hours, and then they were once injected with alloxan dissolved in physiological saline by intraperitoneal injection in an amount of 160 mg / kg to induce diabetes. Mice that maintain their fasting blood sugar at 200 mg / dl or more for one week, this is mice with induced diabetes were selected and then divided into a control group (n = 10), a group with extract administered (n = 10), and a group with compounds administered (n = 10). The control group is administered with 0.2 ml of a solution of dimethylsulfoxide: ethanol (3: 1), the group administered with extract is administered with extract obtained according to Example 1, dissolved in a solution of dimethyl sulfoxide: ethanol (3). : 1) in an amount of 100 mg / kg, and the group administered with compounds is administered with compound of Formula 2 dissolved in a solution of dimethylsulfoxide: ethanol (3: 1) in an amount of 10 mg / kg. All groups were administered orally three times a week and the entire administration period was one month. The amount of endogenous nerve growth factor in serum was measured by ELISA. With reference to FIG. 4, the amounts of endogenous nerve growth factor in the serum both the group administered with extract (DN 100 mg / kg p.o) and the group administered with compound (DG 10 mg / kg p.o) were three or four times higher than the control group to which only vehicle is injected respectively. These results show that the extract and the compound of the present invention can treat diabetic neuropathy by suppressing the degeneration and death of neurons in diseases with nerve injury caused by diabetes and in this way avoiding a decrease in the number of neurons. Experimental Example 4: Measurement of Transmission Velocity of Motor Nerve and Sciatic Nerve Sensorial Nerve in Mice with Induced Diabetes. The therapeutic effect of the compound according to the present invention in diabetic neuropathy, one of the multiple neuropathies, is identified by measuring the effect of the compound according to the present invention on the speed of transmission of the motor nerve and the sensory nerve in the sciatic nerve . Male ICR mice of 7 weeks of age were subjected to food abstinence for 18 hours, and then alloxan dissolved in physiological saline was injected once by intraperitoneal injection in an amount of 160 mg / kg, to induce diabetes. Mice that maintain their fasting blood sugar at 200 mg / dL or more for one week, this is mice with induced diabetes, were selected and then divided into a control group (n = 7) and a group administered with compound ( n = 7). The control group is administered with 0. 2 ml of the solution of dimethylsulfoxide: ethanol (3: 1) and the group administered with compound is administered with compound of Formula 2 dissolved in a solution of dimethylsulfoxide: ethanol (3: 1) in an amount of 10 mg / kg. Male ICR mice of 7 weeks of age in which diabetes is not induced, were grouped as a normal group (n = 7) and the normal group was administered with 0.2 ml of a solution of dimethylsulfoxide: ethanol (3: 1). All groups were administered orally three times a week and the entire administration period was 2 months. Mice with complete administration were sacrificed by cervical dislocation and then the skin and muscle in the femoral region were quickly removed. Then, left and right sciatic nerves were separated respectively in a stretch of 20 mm or more and stored in physiological saline while air flows through the physiological saline. The separated sciatic nerves are placed on a 20 mm round measuring plate. Then, a sensor and a stimulus probe are connected to respective neurotherms and the electrical conductivity is measured using a digital storage oscilloscope to estimate the speed of nerve transmission (see FIGS 5 and 6). In general, myelin is a phospholipid membrane that surrounds axons with several layers, and is also called myelin lining. As a plastic lining of a cable electrical, myelin through a white lipid material, prevents electrical signals transmitted by neurons from leaking or dispersing. Myelin is regularly spaced between ranvier nodes (a portion of myelin reforming nodes) where myelin does not form and surrounds axons. The electrical signal is transmitted over space, impulses are rapidly transmitted over neurons, and myelin increases the speed of electrical impulse. Accordingly, when myelin is destroyed by nerve injury due to diabetes-induced neuropathy, axons stop their function and decrease the nerve transmission rate. During one month of a period of induced diabetes, the group administered with compound (DM-DG) showed a sensory nerve transmission rate 25% higher than the control group of induced diabetes (DM), to which only the vehicle is administered (See Fig. 5). During 2 months of a period of induced diabetes, the group administered with compound (DM-DG) showed a sensory nerve transmission rate 45% higher than the control group and showed a motor nerve transmission rate 40% higher than the control group. control (see FIG 6). Accordingly, it was found that the compound according to the present invention has a therapeutic effect on nerve injury due to diabetic neuropathy by increasing the speed of transmission of the sensory nerve and the motor nerve of a mouse with induced diabetes. Experimental Example 5: Measurement of Nerve Growth Factor Level in Sciatic Nerve in Mice with Diabetes Induced. ICR male mice with 7 weeks of age were subjected to food abstinence for 18 hours, and then they were once injected with aloxane dissolved in physiological saline by intraperitoneal injection in an amount of 160 mg / kg to induce diabetes. Mice that maintain their fasting blood sugar at 200 mg / dl or more for one week, this is mice with induced diabetes were selected and then divided into a control group (n = 5) and a group with compound administered (n = 5). The control group is administered with 0.2 ml of a solution of dimethylsulfoxide: ethanol (3: 1) and the group administered with compounds is administered with the compound of Formula 2 dissolved in a solution of dimethylsulfoxide: ethanol (3: 1) in an amount of 10 mg / kg. All groups were administered orally three times a week and the entire administration period was one month. The amount of an endogenous nerve growth factor in the sciatic nerve was measured by ELISA (see FIG.7) With reference to FIG.7, it was found that the nerve growth factor in the sciatic nerve of the group administered with compound (DG 10 mg / kg P.O) was approximately 30% higher than for the control group to which only the vehicle was injected. Accordingly, it is considered that the results shown in FIGS. 5 and 6 are obtained from the nerve protection function of the nerve growth factor. Experimental Example 6: Measurement of Amount Change of Sorbitol in Sciatic Nerve in Mouse with Diabetes Induced. The therapeutic effect of the compound according to the present invention in neuropathy is identified by measuring a change in the amount of sorbitol in the sciatic nerve. Male ICR mice of 7 weeks of age were subjected to food abstinence for 18 hours, and then they were injected with aloxane dissolved in physiological saline by intraperitoneal injection in an amount of 160 mg / kg to induce diabetes. Mice that maintain their fasting blood sugar at 200 mg / dl or more for one week, this is mice with induced diabetes were selected and then divided into a control group (n = 3) and a group administered with compound (n = 3). The control group is administered with 0.2 ml of a solution of dimethylsulfoxide: ethanol (3: 1) and the group administered with compounds, is administered with the compound of Formula 2 dissolved in a solution of dimethylsulfoxide: ethanol (3: 1) in an amount of 10 mg / kg.

Male ICR mice of 7 weeks of age in which diabetes is not induced, were grouped as a normal group (n = 3) and the normal group was administered with 0.2 ml of a solution of dimethylsulfoxide: ethanol (3: 1). The normal group, the control group and the administered compound were administered orally three times a week and the entire administration period was 2 weeks. Mice with complete administration were sacrificed by cervical dislocation and then the amount of sorbitol in the sciatic nerve is measured by HPLC (see FIG 8). A polyol route refers to a process in which glucose is converted sorbitol by aldose reductase and sorbitol is changed into fructose by sorbitol dehydrogenase. In a hyperglycemic state, such as diabetes, excess glucose enters the cells and sorbitol is generated and accumulated by the polyol path. At this time, the nerves can be injured by osmotic operation that directs water to the cells. Accordingly, as a result of measuring the effect of the compound according to the present invention on the accumulation of sorbitol in the sciatic nerve of the induced diabetes mouse as illustrated in FIG. 8, it was found that sorbitol in the sciatic nerve of the control group with induced diabetes (DM-CON) was approximately 40% higher than the normal group, but sorbitol in the sciatic nerve of the group administered with compound (DM.DG) it was 10% lower than the control group with induced diabetes (DM-CON). These results show that the compound according to the present invention can partially decrease aggressive factors that cause nerve injury. Experimental Example 7: Histological Comparison of Sciatic Nerves of Mice with Induced Diabetes. The therapeutic effect of the compound according to the present invention in neuropathy was identified by measuring a histological change of the sciatic nerve. Male ICR mice of 7 weeks of age were subjected to food abstinence for 18 hours, and then they were injected with aloxane dissolved in physiological saline by intraperitoneal injection in an amount of 160 mg / kg to induce diabetes. Mice that maintain their fasting blood sugar at 200 mg / dL or more for one week, this is mice with diabetes induced by the selected ones and then divided into a control group (n = 5), a group with administered extract (n = 5), and a group with compound administered (n = 3). The control group is injected with 0.2 ml of a solution of dimethylsulfoxide: ethanol (3: 1), the group administered with extract is administered with extract obtained according to Example 1 dissolved in a solution of dimethyl sulfoxide: ethanol (3: 1) in an amount of 100 mg / kg, and the group administered with compound is administered with compound of Formula 2 dissolved in a solution of dimethylsulfoxide: ethanol (3: 1) in an amount of 10 mg / kg. All groups were treated three times by oral administration for a week and the entire administration period was 2 months. Mice with complete administration were sacrificed by cervical dislocation and then the sciatic nerve was separated, stained according to the following conditions and then observed using a microscope with 600x, 1200x focal. (1) prefixed: 2.5% glutaraldehyde, 12 or more hours. (2) washing: pH 7.4, buffer solution with 0.1M phosphate, 15 minutes / twice (3) postfixed: osmium tetroxide Os04 1%, 60 minutes (4) wash: pH 7.4, buffer solution with 0.1M phosphate, 5 minutes / twice (5) dehydration: 50, 70, 80, 90% alcohol: 10 minutes / each 100% alcohol: 15 minutes / twice (6) substituting: Propylene oxide, 15 minutes / twice (7) permeating: Propylene oxide (1), EPOK 812 (2), 12 or more hours (8) Embedded: EPOK 812 refined (80 ° C polymerization): 12 or more hours. (9) sectioned: semi-thin section, 35-95 // m (10) stained: 1% toluidine blue FIG. 9A and 9B show the results obtained with amplification 600 (9A) and amplification 1200 (9B), respectively. In the group with induced diabetes (DM), the axon and myelin in the central part of the sciatic nerve are significantly destroyed. However, in the group administered with compound (DM-DG) and the group administered with extract (DM-DN), the axon and myelin in the central part of the sciatic nerve were clearly observed. These results show that the extract of the compound according to the present invention can protect and treat nerves injured by neuropathy. The compound according to the present invention is Formula in the following forms. However, these formulation examples are for illustrative purposes only and are not intended to limit the scope of the present invention Formulation Example: Tablet Formulation Compound of Formula 2 200 mg Lactose 100 mg Starch 100 mg Own magnesium stearate These components mixed and compressed into tablets according to a conventional tablet formulation method. Formulation Example 2: Liquid Formulation Compound of Formula 2 1000 mg CMC-Na 20 g Isomerized sugar 20 g Own lemon flavor Purified water is added in such a way that the volume of the entire solution was 1000 M £. These components were mixed according to a conventional liquid formulation method, filled in a brown bottle and sterilized, thereby producing the liquid formulation. Formulation Example 3: Formulation Capsule Compound of Formula 2 300 mg Crystalline cellulose 3 mg Lactose 14.8 mg Magnesium stearate 0.2 mg These components were mixed according to a conventional capsule formulation method, and then filled to a gelatin capsule, thereby producing the capsule formulation. Formulation Example 4: Injection Formulation Compound of Formula 2 300 mg Mannitol 180 mg Sterile injectable distilled water 2974 mg Na2HP0412H20 26 mg An injection containing the components having amounts described above by an ampule (2 M £) they are manufactured according to a conventional injection manufacturing process.

Claims (16)

1. CLAIMS 1. An extract from a Dioscorea ceae family to avoid treating peripheral neuropathy, the Dioscoreaceae family is at least one selected from the group consisting of Dioscorea nipponica, Dioscorea septembloba, Dioscorea quinqueoloba, Dioscorea batatas, Dioscorea japonica, Dioscorea bulbifera, Dioscorea tokoro, and Dioscorea tenuipes.
2. 2 . The extract according to claim 1, characterized in that the family Dioscoreaceae is Dioscorea nipponica, Dioscorea quinqueoloba, or Dioscorea tokoro.
3. 3 . The extract according to claim 1, characterized in that the peripheral neuropathy is multiple neuropathy.
4. 4. The extract according to claim 1, characterized in that the extract is obtained by performing an extraction process which comprises extracting a whole part, root or aerial part of the Dioscoreaceae family with a first extracting solvent selected from the group consisting of water, C? -C4 alcohol, and a mixture of water and a C? ~ C4 alcohol.
5. 5. The extract according to claim 1, characterized in that the extract is obtained by performing an extraction process that comprises extracting the root of the Dioscoreaceae family with a first extraction solvent.
6. 6. The extract according to claim 1, characterized in that the first extraction solvent is a mixture of water and methanol or a mixture of water and ethanol.
7. The extract according to claim 4, characterized in that the extraction process further comprises dispersing the extract obtained by extraction with the first extraction solvent in water and extracting with a C? -C alcohol saturated with water (second solvent). extraction).
8. 8. The extract according to claim 7, characterized in that the second extraction solvent is butanol saturated with water.
9. 9. A pharmaceutical composition for preventing or treating peripheral neuropathy, comprising a therapeutically effective amount of an extract of any of claims 1 to 8, and a pharmaceutically acceptable carrier.
10. 10. A food composition for preventing or treating peripheral neuropathy, comprising the extract of any one of claims 1 to 8 as an active ingredient.
11. 11. A pharmaceutical composition for avoiding or treating peripheral neuropathy, comprising a therapeutically effective amount of a compound represented by Formula 1 or its salt; and a pharmaceutically acceptable carrier. [Formula 1] wherein R is a hydrogen atom, a C? -C4 alkyl group or a saccharide.
12. 12. The pharmaceutical composition according to claim 11, characterized in that R is a hydrogen atom.
13. 13. The pharmaceutical composition according to claim 11, characterized in that the saccharide is selected from the group consisting of glucose, fructose, mannose, galactose, ribose, cellulose, glycogen, sucrose, maltose and lactose.
14. 14. A food composition for preventing or treating peripheral neuropathy, characterized in that it comprises a compound represented by Formula 1 or its salt as an active ingredient: [Formula 1] wherein R is a hydrogen atom, a C? -C alkyl group or a saccharide.
15. 15. The food composition according to claim 14, characterized in that R is a hydrogen atom.
16. 16. The food composition according to claim 14, characterized in that the saccharide is selected from the group consisting of glucose, fructose, mannose, galactose, ribose, cellulose, glycogen, sucrose, maltose and lactose.