JP2005289979A - Nerve growth factor synthesis promoter - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a nerve growth factor synthesis promoter which has no risk of side effects such as hormone imbalance after its administration or ingestion and is capable of efficiently producing NGF (nerve growth factor) in vivo for improving QOL (quality of life) in the forthcoming aging society. <P>SOLUTION: This nerve growth factor synthesis promoter disclosed herein can be used for indirectly increasing the amount of NGF in vivo in stead of directly administering NGF when preventing and/or treating senile dementia of Alzheimer type, diabetic neuropathy, or the like. The nerve growth factor synthesis promoter contains a plant belonging to the genus Carum of the family Umbelliferae and/or an extract thereof as an active ingredient. An extract derived from the seeds of the plant is especially useful. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a nerve growth factor synthesis promoter, and more particularly to a composition containing a component capable of promoting the production of nerve growth factor (NGF) contributing to the differentiation and growth of nerve cells in the cell.

  In recent years, with the shift to an aging society, senile dementia tends to increase, which has become a very large social problem. In order to improve QOL (Quality of Life; so-called quality of life) in old age, suppression of such dementia is a very important concern. In addition, the suppression of dementia is also related to a reduction in insurance medical expenses and is one of the social demands.

  Alzheimer type dementia is known as a typical example of senile dementia. A characteristic pathological finding in Alzheimer-type dementia is the selective loss of forebrain basal cholinergic neurons. As a result of the loss of neurons, a marked decrease in the amount of acetylcholine in the cerebral cortex is recognized, and it is considered that a large disturbance in neuronal activity occurs.

  Conventionally, as a therapeutic agent for Alzheimer-type dementia that can contribute to the normal activity of such neurons, a pharmaceutical that inhibits cholinesterase, which is a degrading enzyme of acetylcholine, has been developed. However, the treatment using the drug is merely positioned as a symptomatic therapy, and is not a causal therapy aiming at least to remove the cause of the dementia.

  On the other hand, nerve growth factor (NGF) exerts both the differentiation promoting action on undifferentiated neurons and the survival maintenance action on mature neurons, and enhances survival maintenance on forebrain basal area cholinergic neurons in cultured cells. It is known that it acts on the cell and contributes to the regeneration of nerve fiber cells (Non-patent Document 1). In addition, the NGF content in the hippocampus of aging rats (28 months old) is reduced by about 40% compared to mature young rats (6 months old), and the amount of NGF messenger RNA is also reduced by about 50% in the entire forebrain. Has been reported (Non-patent Document 2). Furthermore, according to a maze learning experiment using non-aged rats (Non-patent Document 3), in the group in which NGF was continuously administered to aging rats, the ability to retain what was once memorized in maze learning was significantly improved. At this time, it has been reported that cholinergic neurons in the forebrain basal cortex such as the Meinert basal ganglia are enlarged by NGF administration.

  Therefore, increasing the amount of NGF in vivo is useful for the prevention and / or treatment of central nervous system dysfunction such as Alzheimer's dementia and peripheral nerve dysfunction such as diabetic neuropathy. Conceivable.

  However, there are several problems in increasing the amount of NGF in the living body immediately. That is, NGF is a protein having a high molecular weight, and as such, it is difficult to pass through the blood brain barrier. Therefore, in the case of preventing and / or treating central nervous system dysfunction such as dementia, Although it is conceivable to administer NGF directly indoors, in practice, it is extremely difficult to use NGF directly in the clinical field, including many problems in preparation of preparations, administration methods and the like.

  Therefore, in the prevention and / or treatment of the above-mentioned disorders, instead of directly administering NGF, for example, a substance that can secondarily increase the amount of NGF in the brain (a substance that can promote the synthesis of nerve growth factor) The use of is being considered.

  Examples of substances that can promote nerve growth factor synthesis include catecholamines such as epinephrine or norepinephrine. According to reports, when such catecholamines are allowed to act on fibroblasts, the amount of NGF produced by the cells increases (Non-patent Document 4).

  However, all of these catecholamines are hormones. Therefore, it is feared that administration of these substances will disrupt hormone balance in the living body and cause other problems.

Similarly, the use of nerve growth factor production promoter having for an active ingredient a substance such as prostaglandin D ₂ or J ₂ has been proposed (Patent Document 1). However, these are also in-vivo substances, and there are concerns about unexpected side effects due to an increase in the in-vivo content after administration, so it is not always safe considering the point of continuous administration.

  Thus, a substance that can promote the synthesis of nerve growth factor is also desired to have the ability to maintain high safety for the human body. Therefore, as an example of a substance having the ability, searching for a plant having an effect of promoting NGF production in a living body or a component thereof has been performed. Examples of plants having such ability or components thereof include rosemary / sage and extracts thereof (Patent Documents 2 and 3); Yamabushitake and extracts thereof (Patent Documents 4 and 5); kerosene and extracts thereof (Patent Literature 6); Kinusaganatake and its extract (Patent Literature 7); Beech Haritake and its extract (Patent Literature 8); Tea component theanine (Patent Literature 9); and Euphorbia plant component (Patent Literature 10); Can be mentioned. However, while the above plants or their components all have the effect of promoting NGF production, the effects are still not sufficient, and the search for further plants and their components is desired.

H. Hatanaka et al., “Neurosci. Lett.”, 1988, 90, p. 63-68 L. Larkfors et al., “Mol. Brain Res.”, 1987, Volume 3, p. 55-60 W. Fischer et al., “Nature”, 1987, 329, p. 65-68 Y. Fukukawa et al., “J. Biol. Chem.”, 1986, 261, p. 6039-6047 JP-A-7-291867 JP 2001-158745 A JP 2001-233835 A JP-A-9-59171 JP-A-9-59172 JP 11-269125 A Japanese Patent Laid-Open No. 9-20714 JP-A-9-124541 JP 7-173059 A JP-A-7-149633

  The present invention is intended to solve the above problems, and its purpose is to improve the quality of life of an aging society, so there is no concern about side effects such as disrupting hormone balance after administration or ingestion, Another object of the present invention is to provide a nerve growth factor synthesis promoter capable of efficiently producing NGF in vivo.

  The present invention is a nerve growth factor synthesis promoter containing as an active ingredient a plant belonging to the genus Cariaceae and / or an extract of the plant.

  In one embodiment, the active ingredient is the seed of the plant and / or an extract derived from the seed of the plant.

  In one embodiment, the Celiaceae caraway plants are Carum copticum, Carum bulbocasatatanum, Carum carvi, Carum gaidnerum bulgari and Carum gairdner bulmu It is at least one plant selected from the group consisting of Carum roxburghianum).

  In a further embodiment, the Aceraceae caraway plant is Ajowan.

  The present invention is also a food and drink obtained by adding a plant extract belonging to the genus Cariaceae.

  In one embodiment, the plant extract of the genus Ceramaceae is added at a ratio of 0.1% by weight or more based on the total amount of the content composition.

  In one embodiment, the plant extract of the genus Cariaceae is an extract derived from the seed of the plant.

  In one embodiment, the Celiaceae caraway plants are Carum copticum, Carum bulbocasatatanum, Carum carvi, Carum gaidnerum bulgari and Carum gairdner bulmu It is at least one plant selected from the group consisting of Carum roxburghianum).

  In a further embodiment, the Aceraceae caraway plant is Ajowan.

  The present invention also eliminates a decrease in memory ability or learning ability due to nerve growth factor content in vivo, containing a plant belonging to the genus Cariaceae and / or an extract of the plant as an active ingredient. It is a food and drink with the indication.

  According to the present invention, NGF can be produced indirectly without administering NGF directly into the living body, and the NGF content in the living body can be efficiently increased. Furthermore, according to the present invention, there is no worry about side effects such as disrupting hormone balance after administration or ingestion. Therefore, the nerve growth factor synthesis promoter of the present invention is used for the prevention and / or treatment of peripheral neuropathy such as diabetic neuropathy, and memory, learning, or neuropathy caused by Alzheimer-type dementia and cerebrovascular disorder. Useful.

  Hereinafter, the nerve growth factor synthesis promoter of the present invention, which is the first invention, will be described.

  The nerve growth factor synthesis promoter of the present invention contains a plant belonging to the genus Carraceae itself, an extract of the plant or a combination thereof as an active ingredient.

  The plant belonging to the genus Cariaceae used in the present invention is a dicotyledonous plant, and specific examples thereof include Ajowan (Carum copticum), also known as Trachyspermum ammi, Ligusticum ajowan (Rigisticam). Ajowan)), Calum bulbocasatatanum, Carle carbus (Carum carvi), Carum gairdneri and Carum roxburghiam (Carum roxburgh), Carum roxburgh. Ajowan is an annual plant native to West Asia, and the leaves are split into filaments and have white petals, usually growing to a height of 50 to 100 cm. , As a folk remedy, for example, that in India its seeds can be used as an antiparasitic or analgesic; in Indonesia, it can be used as an anthelmintic or appetite enhancer; and in China, treatment of digestive diseases or bladder stones It is known that it can be used as a medicine. Ajowan seeds are also known to be used in cooking as a spice since ancient times. As a plant belonging to the genus Carraceae used in the present invention, Ajowan (Carum copticum) is more preferable.

  In the present invention, the plant belonging to the genus Cariaceae includes the plant itself as it is (for example, whole plants and parts such as seeds, leaves, stems, roots or petals, and combinations thereof, preferably May be used in the form of a dry body), or may be used in the form of an extract obtained by subjecting the plant body to an extraction operation as described later (that is, once isolated through the extraction operation). May be used. When the plant body itself is used as it is, it is preferably pulverized into a powder having a predetermined size using a crushing means known to those skilled in the art (for example, a mill or a mortar). The size of the powder obtained by crushing is not particularly limited.

  In the present invention, it is preferable to use the seed of the plant or an extract thereof because it is relatively easy to obtain and has a superior ability to produce NGF in vivo.

  The plant of the genus Cariaceae, the plant extract or a combination thereof is contained in the nerve growth factor synthesis promoter of the present invention in an amount as an active ingredient. The content of the plant belonging to the genus Ceramaceae itself, the extract of the plant or a combination thereof is not necessarily limited, but preferably 0.0001 wt. Based on the total amount of the nerve growth factor synthesis promoter of the present invention. % To 100% by weight, more preferably 0.001% to 100% by weight, and still more preferably 0.1% to 100% by weight. When the content of the plant belonging to the genus Cariaceae, the extract of the plant, or a combination thereof satisfies 0.0001% by weight or more, the nerve growth factor synthesis promoter of the present invention can be used in vivo. NGF can be produced more efficiently, and as a result, the in vivo NGF content can be increased.

  When the plant belonging to the genus Cariaceae used in the present invention is contained in the form of an extract, the extract can be obtained, for example, by performing the following extraction operation.

  First, the whole plant of the above-mentioned Aceraceae caraway genus plant, or a part such as seed, leaf, stem, root or petal, or a combination thereof is preferably crushed to a predetermined size.

  In addition, this crushed material may be immersed in hexane for a predetermined time (for example, 8 hours to 72 hours) as necessary. By soaking in hexane, the parent hexane component that does not contribute to the object of the present invention (that is, promotes NGF production) or has an adverse effect is eluted from the crushed material. More specifically, essential oil components of the plant that can be used for aromatherapy and the like are eluted from the plant by this operation. The temperature set in such elution is room temperature, for example. After soaking for a predetermined time, the mixture is filtered and the residue is removed.

  Next, the crushed material or residue is immersed in the extraction solvent.

  Examples of extraction solvents that may be used include water, methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol, hydrophilic alcohols such as ethylene glycol, propylene glycol or glycerin; acetone, methyl ethyl ketone, ethyl acetate, ethers , Non-hydrophilic solvents such as chloroform or dichloromethane; or combinations thereof. In consideration of safety in the living body having low toxicity, water, ethyl alcohol, or a mixed solvent of water and ethyl alcohol is preferable. When a mixed solvent is used, the mixing ratio of each extraction solvent constituting the mixed solvent is not particularly limited, and can be appropriately selected by those skilled in the art.

  In the extraction operation, the ratio of use of the extraction solvent to the plant belonging to the genus Cariaceae or the crushed product thereof is preferably 2 to 20 times by weight, more preferably based on the weight of the plant or the crushed product thereof. 4 to 12 times the weight. The extraction temperature is preferably set to 0 ° C to 50 ° C. Moreover, the time for which the plant is immersed in this extraction operation is preferably 12 hours to 120 hours. In addition, while the said plant is immersed, the mixture of this celery family Caraway genus plant or its crushed material, and an extraction solvent may be stirred using a suitable means. By performing such an extraction operation, it is relatively or almost avoided that components that are likely to be toxic to the human body contained in the plant move to the extraction solvent side, but can contribute to the promotion of NGF production. The active ingredient elutes preferentially.

  Next, the mixture is subjected to operations such as filtration and centrifugation, and the plant belonging to the genus Cariaceae or the crushed material thereof is removed. The remaining extract is concentrated to a syrup form using means known to those skilled in the art, or subjected to a technique such as concentration to dryness or spray drying, preferably in the form of a dry solid. Is processed. Thus, an extract can be obtained from a plant belonging to the genus Cariaceae used in the present invention. In addition, the obtained extract may be refine | purified using a method well-known to those skilled in the art as needed.

  The nerve growth factor synthesis promoter of the present invention may contain other components according to the purpose in addition to the above-mentioned plant belonging to the genus Cariaceae and / or an extract of the plant as an active ingredient. Examples of other ingredients that may be included in the present invention include water; alcohol; processed meat products; rice, wheat, corn, potatoes, sweet potatoes, soy, kombu, wakame, tengusa and other common food materials and their powders; Sugars such as starch, starch syrup, lactose, glucose, fructose, sucrose, mannitol; general food additives such as spices, sweeteners, edible oils, vitamins; surfactants; excipients; coloring agents; preservatives; Coating aids; lactose; dextrin; corn starch; sorbitol; crystalline cellulose; polyvinyl pyrrolidone; The nerve growth factor synthesis promoter of the present invention may further contain other drugs (including traditional Chinese medicine) as necessary. The content of such other components and / or other drugs is not particularly limited, and an appropriate amount can be selected by those skilled in the art.

  The nerve growth factor synthesis promoter of the present invention is not necessarily limited to in vivo or in vitro, and can be used in all applications where it is desired to promote NGF production in cells. That is, the nerve growth factor synthesis promoter of the present invention may be used, for example, as a pharmaceutical composition such as a pharmaceutical product or quasi-drug as it is or in combination with another pharmaceutical composition. It may be used as a kind of additive added to health foods, etc., and may be used as it is or in combination with other feed materials as a feed composition used in production fields such as livestock or farmed fish Alternatively, it may be used as it is or in combination with other cosmetic materials as a cosmetic composition such as cosmetics, but is not particularly limited thereto.

  Here, when the nerve growth factor synthesis promoter of the present invention is used as a pharmaceutical composition, the dosage form is not particularly limited, and is processed into an appropriate dosage form according to the method described in the Japanese Pharmacopoeia. More specific examples of dosage forms include, for pharmaceutical compositions intended for oral administration, dosage forms such as capsules, tablets, powders, granules, fine granules, sustained-release agents, In the case of a pharmaceutical composition intended for parenteral administration, dosage forms such as injections and infusions can be mentioned. Since the dose can be easily varied depending on conditions such as the body weight of the subject person, it can be appropriately selected by those skilled in the art.

  The nerve growth factor synthesis promoter of the present invention can enhance NGF production in the living body, and as a result, can efficiently increase the NGF content in the living body. Furthermore, the nerve growth factor synthesis promoter of the present invention does not have the worry of side effects such as disrupting hormone balance after administration or ingestion. Therefore, the nerve growth factor synthesis promoter of the present invention is used for the prevention and / or treatment of peripheral neuropathy such as diabetic neuropathy, and memory, learning or neuropathy caused by Alzheimer's dementia and cerebrovascular disorder. Useful.

  Next, the food / beverage of this invention which is 2nd invention is demonstrated.

  The food and drink of the present invention is made by adding a plant extract belonging to the genus Cariaceae. That is, the food and drink of the present invention is obtained by adding an extract of the plant once isolated from a plant belonging to the genus Cariaceae for the production of food and drink.

  The plant belonging to the genus Ceramaceae used in the food and drink of the present invention is the same as that used for the nerve growth factor synthesis promoter of the present invention. The plant extract is also produced in the same manner as described above. In addition, in the food and drink of the present invention, pre-extraction with hexane as described above for the plant, from components that have been safely removed in advance from components such as essential oil components that are likely to be toxic to the human body, It is preferable to use an extract obtained by further extraction.

  In the food and drink of the present invention, the plant extract belonging to the genus Cariaceae is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, with respect to the total content composition (food or drink). Even more preferably, it is contained in a proportion of 0.5 wt% to 40 wt%. Furthermore, in the present invention, such a plant extract belonging to the genus Cariaceae is preferably 0.01% in terms of the dry solid weight after removal of the parent hexane component with respect to the total amount of the content composition. % To 100% by weight, more preferably 0.1% to 40% by weight, even more preferably 0.5% to 40% by weight. As used herein, the term “after removal of the parent hexane component” means that the whole plant and / or a part of the plant belonging to the genus Carraceae used in the present invention is a solvent comprising n-hexane. It refers to the state after the parent hexane component (component that can be dissolved in the hexane solvent) contained in the plant is removed by extraction. Further, the term “dried product after removal of the parent hexane component” used in the present specification means an extraction operation using the above extraction solvent on the residue of the plant belonging to the genus Carraceae after removal of the parent hexane component. It can be a residue in which the weight does not change and the weight is almost constant when concentrated and dried, and it is a paste-like product containing a dry solid and a trace amount of oily components. Both are included.

  Ajowan seeds used for cooking as a spice since ancient times, even if the above parent hexane component is removed and the above extraction operation is performed, it is converted to the dry solid weight after removal of the parent hexane component, and usually 3 at most Only extracts below% can be obtained. In addition, Ajowan itself has components that may be toxic to the human body, so it was said that large intake should be avoided. For this reason, even if it is used for food, it has been limited to use in a minute amount such as spices. On the other hand, in the food and drink of the present invention, an extract of a plant belonging to the genus Cariaceae that has been extracted as described above is used. That is, the above-described extraction operation removes or reduces the components that are likely to be toxic in advance, so that the food and drink of the present invention can freely extract the extract from a low concentration to a high concentration. It is possible to make it contain in a ratio. Furthermore, the food and drink of the present invention can be used in combination with other food and drink materials as will be described later, for example, functions required for food and drink itself such as nutrition and life support, and in vivo as described above. It has both functions that can contribute to the promotion of NGF production.

  The food and drink of the present invention may contain other food and drink materials in addition to the above plant extract of the genus Cariaceae. Examples of such other food and drink materials include water, alcohol, processed meat products, rice, wheat, corn, potato, sweet potato, soybeans, kombu, wakame, tengusa, starch, starch syrup, lactose, glucose, fructose, Sucrose, mannitol, other common spices, sweeteners, edible oils, vitamins, surfactants, excipients, colorants, preservatives, coating aids, lactose, dextrin, corn starch, sorbitol, crystalline cellulose, Polyvinyl pyrrolidone and combinations thereof can be mentioned, but not particularly limited thereto. The content of such other food and drink materials can be appropriately selected by those skilled in the art.

  The food and drink of the present invention includes any form of food or beverage (for example, liquid beverage), and more specific examples include tea beverages and coffee beverages in the form of liquid, paste, solid, etc. , Soft drinks, milk drinks, confectionery, syrup, processed fruit products, processed vegetables, pickles, livestock meat products, fish products, delicacies, cans / bottles, instant food / drinks, oral liquid, liver oil drop, in mouth Although a refreshing agent, jelly, etc. are mentioned, it is not specifically limited to these. The food and drink of the present invention can be produced using techniques known to those skilled in the art.

  The food and drink of the present invention also has various functions utilizing the NGF synthesis promoting action of the active ingredient by including the plant of the genus Cariaceae and / or an extract of the plant as an active ingredient. The food and drink which attached | subjected display may be sufficient. Specific examples of foods and drinks that are labeled as having such a function include foods for specified health use and foods for special uses. As an example of the function to be given to the display, the expression method itself is not particularly limited, but promotes the synthesis or production of nerve growth factor; reduces the memory ability or learning ability due to the nerve growth factor content in the living body. Eliminate; prevent, treat or suppress progression of dementia caused by nerve growth factor content in vivo; prevent, treat or inhibit progression of Alzheimer's disease caused by nerve growth factor content in vivo; Prevention, treatment or suppression of progression of onset of peripheral nerve dysfunction caused by nerve growth factor content in vivo; The display may be expressed in a format that allows the user to substantially understand the above-described functions. For example, the display is performed on the exterior or interior package of the food or drink, a product catalog, a brochure, a poster, or the like. obtain.

  Hereinafter, the present invention will be described specifically by way of examples. However, the present invention is not limited by these.

<Example 1: Production 1 of Ajowan extract>
2 g of dried seed of Ajowan was ground in a mortar, immersed in 10 mL of 99.5% ethyl alcohol, and shaken at 70 rpm to 80 rpm for 24 hours. The mixture was filtered using a filter paper (No. 2 manufactured by ADVANTEC) to collect the filtrate, and the extractant was removed using a rotary evaporator to obtain an extract A. This extract A was dissolved in 2 mL of dimethyl sulfoxide (DMSO). The obtained solution itself was used as a nerve growth factor synthesis promoter and used in Examples described later.

<Example 2: NGF production promoting effect of Ajowan extract>
A mouse fibroblast cell line (LM cell) was suspended in Medium 199 medium (Gibco) containing 5% peptone (Becton Dickinson), and the number of cells was 5 to 10 × 10 ³ / well (flat bottom 96 wells). Plate; made by Corning) and cultured in a CO ₂ incubator (37 ° C., 5% CO ₂ ) for 3 days. Next, this medium was a Medium 199 medium containing 5% bovine serum albumin (manufactured by SIGMA), and the nerve growth factor synthesis promoter obtained in Example 1 was used in a ratio of 3200 times based on the volume of the medium. The solution was replaced with a solution diluted to 1 and cultured for 20 hours. After completion of the culture, the supernatant was collected as a test solution.

  On the other hand, 50 μL of 1 μg / mL anti-NGF antibody (Promega) solution was dispensed into each well of a 96-well microplate (Corning) and allowed to stand overnight at 4 ° C. The plate was washed with PBS (−) containing 0.05% Tween 20, and then 100 μL of 1% bovine serum albumin solution was dispensed and allowed to stand overnight at 4 ° C. for blocking. Next, the plate was washed with PBS (−) containing 0.05% Tween 20, and then 80 μL of the sample solution was dispensed into each well. Then, after reacting at room temperature for 1 hour, the plate was washed with PBS (−) containing 0.05% Tween20.

  Next, 0.4 μl / ml of β-galactosidase-labeled anti-NGF antibody (Roche) solution 0.4 unit / mL was dispensed into each hole of the plate, and further reacted at room temperature for 1 hour. After the plate was washed with PBS (-) containing 0.05% Tween 20, 200 mg of 0.5 mg / mL 4-methylumbelliferyl-β-D-galactoside (manufactured by SIGMA) solution was added to each well of the plate. The solution was dispensed and reacted at 37 ° C. for 2 hours. The fluorescence intensity of the produced 4-methylumbelliferone was measured with a fluorescence plate reader, and the content of NGF contained in the sample solution was calculated using a standard curve obtained from the standard solution. The results are shown in Table 1.

<Example 3>
In place of 5% bovine serum albumin-containing Medium 199 medium containing the nerve growth factor synthesis promoter obtained in Example 1 at a rate of 3200-fold dilution, Example 1 was diluted to a rate of 1600-fold based on the volume of the medium. The content of NGF contained in the sample solution was calculated in the same manner as in Example 2 except that 5% bovine serum albumin-containing Medium 199 medium containing a nerve growth factor synthesis promoter was used. The results are shown in Table 1.

<Comparative Example 1>
Instead of 5% bovine serum albumin-containing Medium 199 medium containing the nerve growth factor synthesis promoter obtained in Example 1 at a ratio of 3200-fold dilution, 5% bovine serum albumin containing no such nerve growth factor synthesis promoter The content of NGF contained in the sample solution was calculated in the same manner as in Example 2 except that the containing Medium 199 medium was used. The results are shown in Table 1.

  As shown in Table 1, when the results obtained in Examples 2 and 3 were compared with the results obtained in Comparative Example 1, the nerve growth factor synthesis of the present invention comprising an Ajowan seed ethyl alcohol extract was used. It can be seen that the promoter significantly promotes the production of NGF. It should be noted that no cytotoxicity was observed at the concentration at which this effect was found in Examples 2 and 3.

<Example 4: Production 2 of Ajowan extract>
2 g of dried seed of Ajowan was crushed with a mortar, immersed in 10 mL of n-hexane, and allowed to stand for 16 hours. Thereafter, the mixture was centrifuged to remove the hexane extract, and the residue was dried under reduced pressure overnight. Thereafter, the residue was immersed in 10 mL of 99.5% ethyl alcohol and shaken at 70 rpm to 80 rpm for 24 hours. The mixture was filtered using a filter paper (No. 2 manufactured by ADVANTEC) to collect the filtrate, and the extraction solvent was removed using a rotary evaporator and concentrated to obtain 54 mg of Extract B. The content of the extract contained in the dried seeds of Ajowan used in this example is 2.7% by weight in terms of the weight of the dried solids after removal of the parent hexane component with respect to the weight of the dried seeds. I understood.

  This extract B was dissolved in 2 mL of dimethyl sulfoxide (DMSO) to obtain a 67.5 mg / mL solution. This solution itself was used as a nerve growth factor synthesis promoter and used in Examples described later.

<Example 5>
In Example 2, nerve growth factor synthesis promotion obtained in Example 4 instead of the Medium 199 medium containing 5% bovine serum albumin containing the nerve growth factor synthesis promoter obtained in Example 1 at a ratio of 3200-fold dilution The content of NGF contained in the sample solution was calculated in the same manner as in Example 2 except that the agent was adjusted to 84.4 μg / mL in 5% bovine serum albumin-containing Medium 199 medium. The results are shown in Table 2.

<Example 6>
In Example 2, nerve growth factor synthesis promotion obtained in Example 4 instead of the Medium 199 medium containing 5% bovine serum albumin containing the nerve growth factor synthesis promoter obtained in Example 1 at a ratio of 3200-fold dilution The content of NGF contained in the sample solution was calculated in the same manner as in Example 2 except that the agent was adjusted to 42.2 μg / mL with Medium 199 medium containing 5% bovine serum albumin. The results are shown in Table 2.

<Comparative example 2>
In Example 2, such nerve growth factor synthesis promoter is not contained in place of 5% bovine serum albumin-containing Medium 199 medium containing the nerve growth factor synthesis promoter obtained in Example 1 at a ratio of 3200-fold dilution. The content of NGF contained in the sample solution was calculated in the same manner as in Example 2 except that the Medium 199 medium containing 5% bovine serum albumin was used. The results are shown in Table 2.

  As shown in Table 2, when the results obtained in Examples 5 and 6 were compared with the results obtained in Comparative Example 2, the nerve growth factor synthesis promoter of the present invention significantly promoted NGF production. You can see that It should be noted that no cytotoxicity was observed at the concentration at which this effect was found in Examples 5 and 6.

<Example 7: Production 3 of Ajowan extract>
10 g of dried seed of Ajowan was ground in a mortar, immersed in 50 mL of 99.5% ethyl alcohol, and shaken at 70 rpm to 80 rpm for 24 hours. The mixture was filtered using filter paper (No. 2 manufactured by ADVANTEC) to collect the filtrate, and the extraction solvent was removed using a rotary evaporator to obtain an extract. This extract was separated using 90 mL of chloroform and 90 mL of distilled water, the aqueous layer was separated, the extraction solvent was concentrated using a rotary evaporator, and lyophilized. The obtained lyophilized product was separated using 90 mL of n-butanol and 90 mL of distilled water, the n-butanol layer was separated, and the extraction solvent was removed using a rotary evaporator to obtain an extract. The obtained extract was dissolved in distilled water and used as a nerve growth factor synthesis promoter, and used in Examples described later.

<Example 8>
In Example 2, nerve growth factor synthesis promotion obtained in Example 7 instead of the Medium 199 medium containing 5% bovine serum albumin containing the nerve growth factor synthesis promoter obtained in Example 1 at a ratio of 3200-fold dilution The content of NGF contained in the sample solution was calculated in the same manner as in Example 2 except that the agent was adjusted to 25 μg / mL in 5% bovine serum albumin-containing Medium 199 medium. The results are shown in Table 3.

<Example 9>
In Example 2, nerve growth factor synthesis promotion obtained in Example 7 instead of the Medium 199 medium containing 5% bovine serum albumin containing the nerve growth factor synthesis promoter obtained in Example 1 at a ratio of 3200-fold dilution The content of NGF contained in the sample solution was calculated in the same manner as in Example 2 except that the agent was adjusted to 12.5 μg / mL with Medium 199 medium containing 5% bovine serum albumin. The results are shown in Table 3.

<Comparative Example 3>
In Example 2, such nerve growth factor synthesis promoter is not contained in place of 5% bovine serum albumin-containing Medium 199 medium containing the nerve growth factor synthesis promoter obtained in Example 1 at a ratio of 3200-fold dilution. The content of NGF contained in the sample solution was calculated in the same manner as in Example 2 except that the Medium 199 medium containing 5% bovine serum albumin was used. The results are shown in Table 3.

  As shown in Table 3, when the results obtained in Examples 8 and 9 were compared with the results obtained in Comparative Example 3, the nerve growth factor synthesis promoter of the present invention significantly promoted NGF production. You can see that It should be noted that no cytotoxicity was observed at the concentration at which this effect was found in Examples 8 and 9.

<Example 10: Production of juice>
The following ingredients are formulated so that the total is 100% by weight.

  All the above ingredients are mixed and stirred at room temperature to make a juice as a uniform solution.

<Example 11: Production of candy>
The following ingredients are formulated so that the total is 100% by weight.

  Sugar, starch syrup and purified water are mixed in a pan and heated with stirring to a uniform liquid. Then, it puts into a suitable type | mold, the extract B and the fragrance | flavor which were obtained in Example 4 are added, it cools to room temperature, and a candy is produced.

  The nerve growth factor synthesis promoter of the present invention prevents, treats and / or prevents the onset of peripheral neuropathy such as diabetic neuropathy, and memory, learning or neuropathy caused by Alzheimer's dementia and cerebrovascular disorder. Useful for inhibiting progression.

Claims (10)

  A nerve growth factor synthesis promoter comprising a plant belonging to the genus Cariaceae and / or an extract of the plant as an active ingredient.   The nerve growth factor synthesis promoter according to claim 1, wherein the active ingredient is seed of the plant and / or an extract derived from the seed of the plant.   The plant belonging to the genus Carraceae is comprised of Carum copterum, Carum bulbocasatatanum, Carum carvi, Carum gaidneri and Carm roxburg. The nerve growth factor synthesis promoter according to claim 1 or 2, which is at least one kind of plant selected from the above.   The nerve growth factor synthesis promoter according to claim 3, wherein the plant belonging to the genus Cariaceae is Ajowan.   Foods and drinks made by adding plant extracts belonging to the genus Cariaceae.   The food and drink according to claim 5, wherein the plant extract of the genus Cariaceae is added at a ratio of 0.1 wt% or more with respect to the total amount of the content composition.   The food or drink according to claim 5 or 6, wherein the plant extract belonging to the genus Cariaceae is an extract derived from the seeds of the plant.   The plant belonging to the genus Carraceae is comprised of Carum copterum, Carum bulbocasatatanum, Carum carvi, Carum gaidneri and Carm roxburg. The food or drink according to any one of claims 5 to 7, which is at least one kind of plant selected from the above.   The food and drink according to claim 8, wherein the plant belonging to the genus Cariaceae is Ajowan. A plant belonging to the genus Cariaceae and / or an extract of the plant as an active ingredient
A food or drink with an indication that it is intended to eliminate a decrease in memory or learning ability due to the nerve growth factor content in the living body.