WO2010084661A1 - Composition, food, food material, pharmaceutical preparation, cosmetic and commodity each containing isothiocyanate compound - Google Patents

Abstract

Provided is a composition having an activity to promote the production and release of a calcitonin gene-related peptide (CGRP) and an activity to promote the secretion of insulin-like growth factor-1 (IGF-1).  The composition can contribute to the prevention of various diseases, the improvement in QRL, the increase in beauty and the like. The composition comprises a combination of an isothiocyanate compound and at least one substance selected from a group consisting of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol and Haccho miso (a kind of fermented soybean paste).

Description

Compositions containing isothiocyanates, foods, food materials, pharmaceuticals, cosmetics and household goods

The present invention has an action to promote the production and release of calcitonin gene-related peptide (CGRP) and an action to promote the secretion of insulin-like growth factor-1 (IGF-1), and various diseases such as hypertension, obesity and other lifestyle-related diseases, and cognition The present invention relates to isothiocyanates-containing compositions, foods, food materials, medicines, and cosmetics for the purpose of prevention of diseases and depression, improvement of QOL, and beauty.

In modern society, various diseases have become a problem due to changes in lifestyle and eating habits and increased social stress. For example, lifestyles such as high blood pressure and obesity, dementia, depression and the like can be mentioned. These are problems of increased medical expenses and declining birthrate and aging, and it is desirable not to rely on treatment with drugs that have side effects, but to prevent lifestyle habits and eating habits and prevent recurrence.
Calcitonin gene related peptide (CGRP) is a peptide consisting of 37 amino acids whose structure is very similar to that of calcitonin which is a hormone, and this gene is on the same gene as calcitonin gene and is produced by its alternative splicing.
CGRP suppresses vasodilation, osteoblast proliferation, osteoclast activation, appetite suppression, and HF _k B activation, thereby suppressing TNF-α production and cancer cell apoptosis. Facilitate. In addition, by acting on CGRP vascular endothelial cells, production of prostaglandins such as NO and PGI ₂ is enhanced, but these substances exert a TNF-α production inhibitory action in addition to the blood flow increasing action .
Furthermore, CGRP is known to exert an important effect on the circulatory system, including systemic vasodilation, positive chronotropism and inotropic activity, extracorporeal excretion of NaCl, coronary vasodilation, and renal blood. It has a flow increase effect etc.
Furthermore, CGRP has been shown to promote the production of insulin-like growth factor in liver as well as in all tissues (see Non-patent Documents 1 to 4 above).
Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a molecular weight of about 7500, which has a structure and action very similar to insulin (see, for example, Non-Patent Document 5). IGF-1 is known to actively maintain cells in a healthy state, such as promoting cell differentiation and promoting cell growth (see, for example, Non-Patent Documents 6, 7 and 8).
In recent years, as an edible composition having a calcitonin gene related peptide (CGRP) production and release promoting action, the gastric mucosa combining capsaicin release promoting action of calcitonin gene related peptide and isoflavone promoting production of calcitonin gene related peptide For the prevention and treatment of disorders, lifestyle-related diseases, obesity, malignancy and osteoporosis, for the reduction of organ transplant rejection, for the prevention and alleviation of organ damage associated with the body invasive reaction to invasive factors such as infection, and for hair growth, Edible compositions have been proposed (see Patent Document 1).
Isothiocyanates, which are known to be abundant in cruciferous plants, have been reported in several cases for their physiological activity. However, there is no mention that isothiocyanates promote the secretion of CGRP and IGF-1, etc. There is also no description suggesting a relationship between crucifers and isothiocyanates and CGRP or IGF-1.
The IGF-1 secretion promoting action of a food ingredient having an IGF-1 secretion promoting action, or several kinds of food ingredients has been reported as described above. However, these ingredients may be irritating ingredients, and it is difficult to take large amounts of single ingredients on a daily basis. From a nutritional point of view, it is desirable to consume as much food or food ingredients as possible.
Okaji Kenji, "Bio-invasion and diseases-from severe sepsis to lifestyle-related diseases," Hyundai Medical, 2003 Harada N. et al. Am. J. Physiol. Gastrointest. Liver. Physiol. 2003 Jul 31 Vignery A. et al. Bone 1996 Vol. 18 No. 4 331-335 Philpott MP. et al. J. Invest. Dermatol. 1994 Vol. 102 No. 6 857-861 Goodman-Gillman Pharmacology Book [Bottom] Basics and Clinical Practice of Drug Treatment-10th Edition-Chapter 61. Insulin, Oral Hypoglycemic Drugs and Pharmacology of Splenic Endocrine 2003, p 2144 監: Shuji Takanori, Hidetoshi Fukuda, Akinori Akaike Tokyo Published by Kamogawa Bookstore Corn K J. et al. J. Biol. Chem. 1996 Vol. 271 No. 46 28853-28860 Braham C. et al. Dermatology 2002 Vol. 20 No. 4 325-329 Roubenoff R. et al. Am. J. Med. 2003 Vol. 115 No. 6 501-502 JP 2005-68129 A

Therefore, the object of the present invention is to provide a composition, food, food material, medicine and cosmetics exhibiting CGRP and IGF-1 secretion promoting action for the purpose of preventing various diseases mentioned above or improving QOL and beauty. is there.

In order to solve the above-mentioned problems, according to the composition of the present invention, isothiocyanates and at least one selected from the group consisting of isoflavones, raspberry ketones, capsiates, gluconic acid, chlorogenic acid, cocoa polyphenols, and hachicho-miso Contained in combination, it is characterized in that it exhibits a production and release promoting action of calcitonin gene-related peptide (CGRP) or an insulin-like growth factor-1 (IGF-1) secretion promoting action.
In order to solve the above-mentioned problems, according to the food, food material, medicine and cosmetics of the present invention, isothiocyanates and isoflavones, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, and Haccho miso from the group It is characterized in that it contains at least one selected in combination and exhibits a production and release promoting action of calcitonin gene-related peptide (CGRP) or an insulin-like growth factor-1 (IGF-1) secretion promoting action.

The present invention contains isothiocyanates and at least one selected from the group consisting of isoflavones, raspberry ketones, capsiates, gluconic acid, chlorogenic acid, cocoa polyphenols, and haccho miso to produce calcitonin gene related peptide (CGRP) And, since it has been made to exhibit a release promoting action and a secretion promoting action of insulin-like growth factor-1 (IGF-1), effects such as prevention of various diseases, improvement of QOL, and beauty can be exhibited.

Hereinafter, the present invention will be specifically described.
As described above, the composition of the present invention is a combination of isothiocyanates with at least one selected from the group consisting of isoflavones, raspberry ketones, capsiates, gluconic acid, chlorogenic acids, cocoa polyphenols, and haccho miso. And each of these components as an essential component. Such a configuration significantly promotes the production and release of calcitonin gene-related peptide and promotes the secretion of IGF-1. Here, the essential component refers to an optional component, and refers to a component which is necessarily contained in the constitution, and is not subject to quantitative restriction.
The isothiocyanates used in the present invention are 4-methylsulfinylbutyl isothiocyanate, 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinylhexyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, Allyl isothiocyanate, secondary butyl isothiocyanate, 3-butenyl isothiocyanate, 4-pentenyl isothiocyanate, 5-hexenyl isothiocyanate, 5-methyl thiopentyl isothiocyanate, 6-methyl thiohexyl isothiocyanate, 7-methyl thioheptyl isothiocyanate , 8-Methylthiooctyl isothiocyanate, β-phenethyl isothiocyanate, benzyl isothio Aneto, phenyl isothiocyanate, and phenethyl isothiocyanate and the like are used in combination these alone, or plural kinds. However, the isothiocyanates that can be used in the present invention are not limited to the above compounds, and all isothiocyanates can be used as a raw material.
The above-mentioned isothiocyanates are also effective in chemically synthesized ones, and the effect is not different depending on the synthesis method and the source material, and they do not affect the present invention at all.
The chemical synthesis of isothiocyanates is specifically described as follows.
In principle, it follows the method of Kiaer et al. (Kiaer et al. Acta Chem. Scand, 11, 1298, 1957). Using ω-chloroalkenol as the starting material and refluxing with CH ₃ -SNa, ω-methylthioalkenol is obtained to act on SOCl ₂ to obtain ω-chloroalkenol methyl sulfide.
Next, an amino group is introduced using the Gabriel method to form N- (ω-methylthioalkyl) -phthalimide, to which hydrazine hydrate is added and refluxed to obtain ω-methylthioalkylamine. Furthermore, according to the method of Li et al. (Lietal. J. Org. Chem., 62, 4539, 1997), the methylthio group is oxidized with mCPBA of ω-methylthioalkylisothiocyanate obtained via lautim disulfide, ω Methylsulfinylalkyl isothiocyanate is obtained.
In the present invention, isothiocyanates can be obtained from cruciferous plants mainly from natural resources. Moreover, although the method includes grinding or grating treatment, extraction treatment with a solvent, and drying treatment singly or in combination, the method is not limited at all in the present invention.
Examples of the raw materials containing the above-mentioned isothiocyanates include the following. For example, Batissidae (Bataceae), Brassicaceae (Brassicaceae), Breschnadidae (Bretschneideraceae), Citrusaceae (Capparaceae), Papaya (Caricaceae), Euphorbiaceae (Euphorbiaceae), Gyrostemonidae (Gyrostemonaceae), Limnantes ( Limnanthaceae), Wasabinaceae (Moringaceae), Pentadipiprandaceae (Pentadiplandraceae), Phytolaccidae (Phytolaccaceae), Tobellanaceae (Pittosporaceae), Prunellanaceae (Resedaceae), Salvadoriaceae (Salvadoraceae), Touariaceae (Tovar) plants of the family Luceidae (Tropaeolaceae), for example, Batis maritima (Japanese name unknown), wasabi (Wasabia japonica), horseradish (Armoracia rusticana), mustard (Brassica juncea), broccoli (Brassica oleracea var. italica) ), Arabidopsis thaliana, Capsella bursa-pastoris, Watercress (Nasturtium officinale), Bretschneidera sinensis (Japanese name unknown), Caper (Capparis spinosa), Papaya (Carica papaya), Drypetes rox urghii (alias); Putranjiva roxburghii (Japanese name unknown), Tersonia brevipes (Japanese name unknown), Limnanthes douglasii (Japanese name unknown), Japanese horseradish (Moringa oleifera), Pentadiplandra brazzeana (Japanese name unknown), pokemon pokebo (Phytolacca) Bursaris spinosa var. Incana (Japanese name unknown), Shinobumokusou (Reseda alba), Salvadora persica (Japanese name unknown), Tovaria pendula (Japanese name unknown), Kumquat deer (Tropaeolum majus) etc. can be used. However, the isothiocyanates which can be used in the present invention are not limited to those obtained from the above-mentioned plant species, and all natural resources containing isothiocyanates can be used as a raw material.
On the other hand, the origin of isoflavones used in the present invention is not particularly limited, and examples thereof include soybean seeds, soya root and foods using them. Among them, soybean hypocotyl is advantageous because it contains a large amount of isoflavone. It is also possible to use foods such as natto.
Among the above isoflavones, daidzein, genistein, glycitein, soy in, genistin, glycitin, 6 ′ ′-O-malonyl soyin, 6 ′ ′-O-malonylgenistin, 6 ′ ′-O-malonylglycitin, 6 ′ ′-O-acetyl soy In, 6 ′ ′-O-acetylgenistin, 6 ′ ′-O-acetylglycitin and 6 ′ ′-O-succinylsaidsine found in natto, 6 ′ ′-O-succinilgenistin, 6 ′ ′-O-succinylglycitin and puerarin In the present invention, the above-mentioned various isoflavones are used alone or in combination of two or more.
It is also possible to use soy and soy foods, soy hypocotyls, extracts of soda rootstock and purified products thereof because high concentrations of isoflavones are used. The solvent for extracting isoflavones is not particularly limited, but it is preferable to use water or an alcohol such as ethanol. In addition, as a method of purification, although it is possible to use a synthetic adsorbent, ion exchange resin, ultrafiltration or the like, it is not particularly limited. The extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
The raspberry ketone used in the present invention is not particularly limited, but it is desirable to use raspberry-derived raspberry ketone from the viewpoint of easy collection and safety. Also, the capsiate used in the present invention is not particularly limited, but it is desirable to use the variety "CH-19 sweet" selected and bred from pepper, from the viewpoint of easy collection and safety.
The above raspberry ketone and capsiate may be used as they are by grinding raspberry or the above-mentioned specific pepper variety as it is, but since raspberry ketone or capsiate having a high concentration is used, the extract or its purified product may be used. It is also possible to use. The solvent for extracting raspberry ketone and capsiate is not particularly limited, but it is preferable to use water or an alcohol such as ethanol. In addition, as a method of purification, although it is possible to use a synthetic adsorbent, ion exchange resin, ultrafiltration or the like, it is not particularly limited. The extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
In addition, as the capsiate used in the present invention, capsaicin may be used, or peppers of generally grown varieties or extracts thereof may be used. Stimulative, long-term, it is difficult for all people to use on a daily basis. Therefore, it is desirable to use capsiate which is considered to be less irritating.
Although gluconic acid used in the present invention is not particularly limited, it is desirable to use gluconic acid derived from honey or royal jelly from the viewpoint of easy intake and safety. In addition, miso and vinegar may be used. Furthermore, the chlorogenic acid used in the present invention is not particularly limited, but it is desirable to use coffee bean-derived chlorogenic acid from the viewpoint of easy collection and safety.
The above gluconic acid and chlorogenic acid can be used by grinding honey and royal jelly or coffee beans as it is, but using gluconic acid and chlorogenic acid with high concentration, their extracts and their purification It is also possible to use a thing. The solvent for extracting gluconic acid and chlorogenic acid is not particularly limited, but it is preferable to use water or an alcohol such as ethanol. Moreover, although the method of refinement | purification can use synthetic adsorbent, ion exchange resin, ultrafiltration etc., it is not specifically limited. The extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
As gluconic acid used in the present invention, it is also possible to use calcium gluconate, potassium gluconate, copper gluconate, sodium gluconate, magnesium gluconate, manganese gluconate and the like as gluconate.
The cocoa polyphenols used in the present invention can also be taken from foods that use cocoa, such as chocolate and cocoa. Moreover, in order to use a high concentration cocoa polyphenol, it is also possible to use its extract and its refinement | purification thing. The solvent for extracting cocoa polyphenol is not particularly limited, but it is preferable to use water or an alcohol such as ethanol. Moreover, although the method of refinement | purification can use synthetic adsorbent, ion exchange resin, ultrafiltration etc., it is not specifically limited. The extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
Hatcho miso used in the present invention is mainly made in Okazaki City, Aichi Prefecture. The soybean miso is characterized by being aged for 2 years or more. You may ingest Hachicho miso itself, or you may ingest various processed foods such as miso soup prepared using Haccho miso. Alternatively, an extract of Haccho Miso may be used. The solvent to be extracted is not particularly limited, but it is preferable to use water or an alcohol such as ethanol. Moreover, although the method of refinement | purification can use synthetic adsorbent, ion exchange resin, ultrafiltration etc., it is not specifically limited. The extract or purified liquid may be used as it is, or a concentrate obtained by concentrating them or a powder obtained by drying the extract or purified liquid may be used.
The composition of the present invention comprises, as essential components, isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol, and at least one of hachicho-miso and the isothiocyanates obtained as described above. A mixture of these may be used directly as it is, but generally, a solution or dispersion of these in a suitable liquid carrier or a mixture in a suitable powder carrier is used.
And, the content for the above-mentioned isothiocyanates to become an active ingredient is usually preferably in the range of 0.0001 to 0.5% by weight (hereinafter abbreviated as "%") in the liquid form, and it is preferable In the case of 0.001 to 20% in the case of granules, it is preferable that the range of 0.001 to 10% is in the case of granules. The content of isoflavone as an active ingredient is generally preferably 0.001 to 0.5% by weight (hereinafter abbreviated as "%") in the liquid preparation, and 0. The range of 01 to 80% is preferable, and in the case of granules, the range of 0.01 to 40% is preferable. On the other hand, the content for the raspberry ketone to be an active ingredient is usually preferably in the range of 0.05 to 20% in the solution, and preferably in the range of 0.05 to 100% in the case of powders. In the case of granules, it is preferably in the range of 0.05 to 100%.
In addition, the content for the above-mentioned capsiate to become an active ingredient is usually suitably in the range of 0.0001 to 0.05% in the liquid preparation and in the range of 0.0001 to 5% in the dust preparation. In the case of granules, it is preferable to be in the range of 0.0001 to 5%.
Furthermore, the content for the above-mentioned gluconic acid to become an active ingredient is usually suitably in the range of 0.05 to 10% in the liquid preparation, and in the range of 0.05 to 20% in the powder preparation In the case of granules, the preferred range is 0.05 to 10%.
In addition, the content for the chlorogenic acid to be an active ingredient is generally preferably in the range of 0.05 to 20% in the liquid preparation and in the range of 0.05 to 10% in the dust In the case of granules, the preferred range is 0.05 to 10%. In addition, the content for the above-mentioned cocoa polyphenol to become an active ingredient is usually suitably in the range of 0.5 to 20% in the liquid preparation and in the range of 0.5 to 10% in the case of powders. In the case of granules, it is preferable that it is in the range of 0.5 to 10%.
In addition, the content for the above-mentioned Haccho miso to become an active ingredient is usually suitable in the range of 10 to 100% in the liquid preparation, and preferably in the range of 20 to 50% in the powder preparation, In the case of granules, it is preferable that it is in the range of 20 to 50%.
In the present invention, the ratio of the above-mentioned isothiocyanates to the above-mentioned isoflavones etc (isoflavones, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, haccho miso) is important, and isothiocyanates: isoflavone = 1. It is preferable to contain in a weight ratio of 1: 1 to 1: 1000, and more preferable is a range of a weight ratio of isothiocyanates: isoflavone = 1: 10 to 1: 500. Further, it is preferable to contain isothiocyanates: raspberry ketone in a weight ratio of 1: 1 to 1: 10000, and more preferably in a weight ratio range of isothiocyanates: raspberry ketone 1: 100 to 1: 6000. Further, it is preferable to contain isothiocyanates: capsiate in a weight ratio of 100: 1 to 1: 100, and more preferably in a weight ratio range of isothiocyanates: capsiate = 20: 1 to 1:20. .
Furthermore, it is preferable to contain isothiocyanates: gluconic acid in a weight ratio of 10: 1 to 1: 1000, and more preferably, a range of a weight ratio of isothiocyanates: gluconic acid = 1: 1 to 1: 200. It is.
Further, it is preferable to contain isothiocyanates: chlorogenic acid = 10: 1 to 1: 1000 in weight ratio, and more preferably, isothiocyanates: chlorogenic acid = 1: 1 to 1: 200 in weight ratio range It is. Further, it is preferable to contain isothiocyanates: cocoa polyphenol = 10: 1 to 1: 2000 in weight ratio, and more preferably, a range of isothiocyanates: cocoa polyphenol = 1: 40 to 1: 400 in weight ratio It is. Moreover, it is preferable to contain it by the weight ratio of isothiocyanates: haccho miso = 1: 10-1: 50000, More preferably, the range of the weight ratio of isothiocyanates: haccho miso = 1: 600-1: 6000 It is. That is, when both are contained in such a proportion, the synergistic effect of both can effectively obtain the calcitonin gene-related peptide production and release promoting action required in the present invention. In addition, isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol, and Haccho miso can be used in combination within the above range.
The edible composition of the present invention is expected to have the same action and effect as the above-mentioned action and effect seen when administered to humans not only in humans but also in animals such as pets and livestock. And, depending on conditions such as the sex, weight, age, etc. of the person to be administered, the dose differs depending on the difference between the organisms to be administered and which one of the various effects described above is to be obtained. It is set appropriately. For example, for an adult, the mixture of the above isoflavones etc. and isothiocyanates can be divided into several doses so as to be 10 to 5000 mg per day. In addition, in animals such as pets and livestock, it is preferable that the above-mentioned mixture is contained in the animal feed in the range of 0.001 to 5%, and is administered in the range of 1 to 5000 mg / kg body weight per day.
The composition of the present invention can be taken alone, but can also be used by being added to various food products or medicines. Specifically, liquid foods such as soft drinks, tea beverages, drinks, alcoholic beverages, solid foods such as fruits, breads, noodles, seasonings, etc., pharmaceuticals such as powders, granules, capsules and tablets Add to quasi-drugs etc.
The composition of the present invention can also obtain the same effect as taking it orally or applying it by sniffing the isothiocyanate contained or exposing it to volatilized isothiocyanates. . Specifically, it can be used by blending it into an aroma oil, a fragrance, daily necessities for perfume, cosmetics, perfumes, fibers or resins, etc. and volatilizing the components.
In the present invention, when exposed to volatilized isothiocyanate, the concentration is not limited, but it is desirable that the concentration is within the range that can be recognized by human being without causing irritation or discomfort. There is no particular relationship between the concentration and the effect.
In the present invention, when it is added to aromatic oils, fragrances, daily necessities such as perfumes, cosmetics, perfumes, fibers or resins, etc. and volatilized isothiocyanates, aroma components, perfumes, etc. It can be chosen freely and does not adversely affect its effect. It can be used by blending it into a flavor that is easy to use.
Hereinafter, the present invention will be specifically described by way of examples.

Test Example 1 Changes in IGF-1 and CGRP Concentrations in Mice by Administration of Isothiocyanates A standard diet was prepared for C57BL / 6 mice (male, 5 mice in each group) of 6-8 weeks divided into 16 groups. A test product was administered. After administration for 4 weeks, various organs collected under anesthesia were immersed in 1 N acetic acid solution, homogenized, and centrifuged to measure IGF-1 concentration in the supernatant. Blood was also collected to measure plasma IGF-1 and CGRP concentrations. The concentrations of IGF-1 and CGRP in mouse brain and plasma are shown in Table 1. The isothiocyanates utilized 6-methylsulfinyl hexyl isothiocyanate (hereinafter abbreviated as 6-MSITC) in the examples.
Here, the above 16 groups are administered 6-MSITC (MS), isoflavone (IS), 6-MSITC + isoflavone (MS + IS) administered, raspberry ketone (RA) administered, 6-MSITC Raspberry ketone (MS + RA) administration group, capsiate (CE) administration group, 6-MSITC + capsiate (MS + CE) administration group, gluconic acid (GA) administration group, 6-MSITC + gluconic acid (MS + GA) administration group, chlorogenic acid (CA) administration group 6-MSITC + chlorogenic acid (MS + CA) administration group, cocoa polyphenol (CP) administration group, 6-MSITC + cocoa polyphenol (MS + CP) administration group, Haccho miso (HM) administration group, 6-MSITC + Haccho miso (MS + HM) administration group Any of non-administration group (standard diet only, control group) Or to belong.
That is, each group is added to the standard diet, and in the MS administration group, 6-MSITC is administered at 0.1 mg / kg / day. In the IS administration group, 50 mg / kg / day of isoflavone was administered. In the RA administration group, 400 mg / kg / day of raspberry ketone was administered. In the CE administration group, administration of 0.1 mg / kg of capsiate. In the GA administration group, gluconic acid was administered at 1 mg / kg / day. In the CA administration group, chlorogenic acid was administered at 1 mg / kg / day. In the CP administration group, 50 mg / kg / day of cocoa polyphenol was administered. In the HM administration group, Haccho Miso was administered at 600 mg / kg / day. Furthermore, the combination of MS + IS, MS + RA, MS + CE, MS + GA, MS + CA, MS + CP, and MS + HM was performed using these combinations.

The results show that intake of 6-MSITC promotes secretion of IGF-1 and CGRP, and further, at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols and haccho miso It was confirmed that the combined use of 6-MSITC intensified its action.

[Test Example 2] The effect of improving learning function by isothiocyanates For the mice divided into 16 groups (5 mice in each group), in addition to the standard diet for 4 weeks a test product is administered, and then the Morris water maze test is carried out for 5 days And assessed the impact on the learning function.
Here, the above 16 groups are administered 6-MSITC (MS), isoflavone (IS), 6-MSITC + isoflavone (MS + IS) administered, raspberry ketone (RA) administered, 6-MSITC Raspberry ketone (MS + RA) administration group, capsiate (CE) administration group, 6-MSITC + capsiate (MS + CE) administration group, gluconic acid (GA) administration group, 6-MSITC + gluconic acid (MS + GA) administration group, chlorogenic acid (CA) administration group 6-MSITC + chlorogenic acid (MS + CA) administration group, cocoa polyphenol (CP) administration group, 6-MSITC + cocoa polyphenol (MS + CP) administration group, Haccho miso (HM) administration group, 6-MSITC + Haccho miso (MS + HM) administration group Any of the non-administration group (standard diet only, control group) Or to belong.
That is, each group is added to the standard diet, and in the MS administration group, 6-MSITC is administered at 0.1 mg / kg / day. In the IS administration group, 50 mg / kg / day of isoflavone was administered. In the RA administration group, 400 mg / kg / day of raspberry ketone was administered. In the CE administration group, 0.1 mg / kg of capsiate was administered. In the GA administration group, gluconic acid was administered at 1 mg / kg / day. In the CA administration group, chlorogenic acid was administered at 1 mg / kg / day. In the CP administration group, cocoa polyphenol 50 mg / kg / day was administered. In the HM administration group, Haccho Miso was administered at 600 mg / kg / day. Furthermore, the combination of MS + IS, MS + RA, MS + CE, MS + GA, MS + CA, MS + CP, and MS + HM was performed using these combinations. The time to reach the platform is shown in Table 2.

From this result, it is confirmed that intake of 6-MSITC improves learning function, and further, at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol, and hachicho-miso and 6-MSITC It was confirmed that the combined use intensified the action.

Test Example 3 Test of nerve regeneration effect in mouse brain by 6-MSITC administration After Example 2, the brains of mice used in the experiment were collected, and the influence on nerve regeneration was evaluated. At that time, newborn neurons were detected by using 5-bromo-2-deoxyuridine (Brdu) and Brdu antibodies.
Histological evaluation was performed by measuring left and right hippocampal neuronal layer length and neuronal cell number and calculating the number per unit length (mm). As a result, the number of neoplastic cells was significantly increased in the MS administration group as compared to the control group. In addition, in the group administered in combination with MS and other test substances, the tendency to increase was more remarkable. For example, in the control group, it was 2.4 ± 0.8, whereas in the MS administration group it was 5.8 ± 1.1, in the MS + IS administration group it was 6.7 ± 1.3. It was piece / mm.
From this result, it is confirmed that the nerve cells are regenerated by taking 6-MSITC, and further, a combination of 6-MSITC with at least one of isoflavone, raspberry ketone, capsiate, gluconic acid chlorogenic acid, cocoa polyphenol and hacho-miso Was confirmed to intensify its action.

[Test Example 4] Evaluation of antidepressant action by 6-MSITC administration As in Example 2, divided into 16 groups, the effect on the antidepressant action in mice receiving the standard diet and each test sample was examined by tail suspension test . Male mice weighing 20-25 g and 8 weeks old were used. The tail of the mouse was pinched and hung upside down with a wooden clip fixed at a height of 35 cm from the floor on a stand 60 cm high. The mouse is active at first, but gives up gradually to move. The antidepressant effect of the administered ingredients was evaluated as shortening of the non-moving time (inactive time) within 6 minutes after the start of suspension.
As a result, in the MS administration group, the inactive time was significantly reduced by 30% as compared with the control group. Furthermore, in each group which received combining MS and other materials, it was shortened from 35% to 40% compared with the control group. The results show that the antidepressant effect is obtained by taking 6-MSITC, and the action is also obtained by combining 6-MSITC with at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols and haccho miso. Was confirmed to strengthen.

Test Example 5 Test of action to promote calcitonin gene related peptide production by 6-MSITC in ovariectomized rats and effect on osteoporosis 80 SD female rats (5 rats per group, divided into 17 groups) Twenty groups of 21 groups were given an ovariectomized rat on day 10 after excision and a standard diet [Ca-deficient diet (Ca: 0.004%, P: 0.3%)] etc. I kept it for 28 days. Thereafter, they were fasted overnight (18 hours), and rats in all groups were sacrificed and femurs were removed therefrom.
As shown in Table 3 below, the 16 groups from which the ovaries were removed were, for example, the 6-MSITC (MS) administration group, the isoflavone (IS) administration group, 6-MSITC + isoflavone (MS + IS IS Administration group, raspberry ketone (RA) administration group, 6-MSITC + raspberry ketone (MS + RA) administration group, capsiate (CE) administration group, 6-MSITC + capsiate (MS + CE) administration group, gluconic acid (GA) administration group, 6-MSITC + glucone Acid (MS + GA) administration group, chlorogenic acid (CA) administration group, 6-MSITC + chlorogenic acid (MS + CA) administration group, cocoa polyphenol (CP) administration group, 6-MSITC + cocoa polyphenol (MS + CP) administration group, Haccho miso (HM) Administration group, 6-MSITC + Haccho miso (MS + HM) administration , It belongs to one of the non-administered group (standard diet only. Control group).
That is, each group is added to the standard diet, and in the MS administration group, 6-MSITC is administered at 0.1 mg / kg / day. In the IS administration group, 50 mg / kg / day of isoflavone was administered. In the RA administration group, raspberry ketone 400 mg / kg / day was administered. In the CE administration group, 0.1 mg / kg of capsiate was administered. In the GA administration group, gluconic acid was administered at 1 mg / kg / day. In the CA administration group, chlorogenic acid 1 mg / kg / day was administered. In the CP administration group, 50 mg / kg / day of cocoa polyphenol was administered. In the HM administration group, Haccho Miso was administered at 600 mg / kg / day. Furthermore, the combination of MS + IS, MS + RA, MS + CE, MS + GA, MS + CA, MS + CP, and MS + HM was performed using these combinations.
Then, based on the femur removed from the 17 groups described above, that is, the normal group (without ovariectomy) and the control group (ovariectomy) and 15 test groups (administration of ovariectomy + 6-MSITC etc.) The weight was measured and the volume was measured by a pycnometer to calculate bone density. In addition, measurement of calcitonin gene related peptide concentration (CGRP) in bone tissue was also performed. These results are shown together in Table 3 below. Each data shows the average value in each group.

From the results of Table 3, it can be seen that intake of 6-MSITC promotes production and release of calcitonin gene-related peptide, and can prevent and treat osteoporosis, and isoflavones, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, It has been confirmed that the action is enhanced by the combination of 6-MSITC with at least one of cocoa polyphenol and hacho-miso.

[Test Example 6] Test for promoting production of calcitonin gene-related peptide by administration of 6-MSITC and effect on hypertension in stroke-prone spontaneously hypertensive rats (SHR-SP) Test of 18-week-old male SHRSP / 1zm rat As in 2, the group was divided into 16 groups of 5 animals, and each of the test samples served as a control group in addition to the standard diet in groups 1 to 15.
Then, tail blood pressure was measured on the 50th day of administration. As a result, in the MS administration group (248 ± 6.3 mmHg), the blood pressure was significantly lowered compared to the control group (281 ± 5.2 mmHg). Furthermore, in the group which combined MS + each test diet, the blood pressure lowering tendency was more pronounced.
From the above results, it can be seen that intake of 6-MSITC has an effect on hypertension since it promotes production and release of calcitonin gene-related peptide. Furthermore, it has been confirmed that the action is enhanced by the combination of 6-MSITC with at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol and Haccho miso.

[Test Example 7] Test of production promoting action and hair growth effect of calcitonin gene-related peptide and hair growth effect in hair follicles by isoflavone and capsaicin C3H / He mice purchased at 3 weeks of age, 10 groups randomly After dividing into 16 groups and 1 week of acclimatization rearing, Group 1 was reared with a feed adjusted to have an intake of 6-MSITC of 0.1 mg / kg body weight / day. Group 2 was reared with a feed adjusted to have an intake of isoflavone (IS) of 40 mg / kg body weight / day. In group 4, the animals were reared with a feed adjusted to have an intake of raspberry ketone (RA) of 600 mg / kg body weight / day. In group 6, the animals were fed with a feed adjusted to have an intake of capsiate (CE) of 1 mg / kg body weight / day. In group 8, the animals were fed with a feed adjusted to have an intake of gluconic acid (GA) of 4 mg / kg body weight / day. In group 10, the animals were fed with a feed adjusted to have an intake of chlorogenic acid (CA) of 3 mg / kg body weight / day. In group 12, the animals were fed with a feed adjusted to have an intake of cocoa polyphenol (CP) of 200 mg / kg body weight / day. In group 14, the animals were reared with a feed adjusted to have an intake of 600 mg / kg body weight / day of Haccho Miso (HM). Moreover, in groups 3, 5, 7, 9, 11, 13, and 15, breeding was performed by a combination of these breeding methods (combination shown in Table 4 below). Group 16 was a control group. Then, she was shaved at 6 weeks of age and observed the condition of hair growth thereafter.
That is, the number of mice in which hair regeneration was completed within 40 days after the start of the intake of the test feed was measured. The results are shown in Table 4 below.

From the results of Table 4 above, it was recognized that 6-MSITC had a hair growth effect. Furthermore, it has been confirmed that the action is enhanced by the combination of 6-MSITC with at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenol and Haccho miso. In addition, at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, and haccho miso and 6-MSITC are simultaneously measured as a result of measuring the amount of calcitonin gene-related peptide and insulin-like growth factor in hair follicles. It was found that the given group was significantly more than the other groups.

[Test Example 8] Hair growth effect on humans A group of five volunteers, divided into a total of 16 groups, targeted to male volunteers (30 to 50 years old) who had hair loss and thin hair problems. And in the group 1 of them, 1 mg of 6-MSITC is ingested daily by administration of a tablet containing 6-MSITC (MS), and in group 2 is 50 mg of isoflavone daily by administration of a tablet containing isoflavone (IS) I was given In group 4, 600 mg of raspberry ketone was ingested daily by administration of a tablet containing raspberry ketone (RA). In group 6, 2 mg of capsiate was taken daily by administration of a tablet containing capsiate (CE). In group 8, 100 mg of gluconic acid was ingested daily by administration of a tablet containing gluconic acid (GA). In group 10, 100 mg of chlorogenic acid was ingested daily by administration of a tablet containing chlorogenic acid (CA). In group 12, 600 mg of cocoa polyphenol was ingested daily by administration of a tablet containing cocoa polyphenol (CP). In group 14, Hachidamei (HM) was ingested 5000 mg a day. Groups 3, 5, 7, 9, 11, 13, 15 were also ingested with these combinations as shown in Table 5. Group 16 was ingested a simulated tablet. This was done for six months.
Next, the number of hair loss collected during the above test (before taking the sample, after taking three months, and after taking six months) was measured to evaluate the hair loss improving effect. In addition, the measurement method of the above-mentioned hair loss performed four days continuous hair washing, collected the hair loss of the last three days with the fine nonwoven fabric of mesh, counted the number, and was performed. And the judgment of the said evaluation was shown as follows from the change of the number of hair loss in each time with respect to sampling before.
+++: The number of hair loss has been reduced by 30 or more, and a remarkable effect was observed.
++: The number of hair loss has been reduced by more than 20, and a considerable effect was observed.
+: The number of hair loss was reduced by 10 or more, and a slight effect was observed.
±: Decrease or decrease in the number of hair loss was less than 10, and almost no effect was observed.

From the results in Table 5 above, when 6-MSITC is ingested alone or in combination with at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, and Haccho miso together with 6-MSITC, a simulated tablet is obtained. Hair loss was improved compared to the group who received Also, in the group in which 6-MSITC and isoflavone or royal jelly were simultaneously ingested, a remarkable improvement effect on hair loss was observed.

[Test Example 9] Assay of skin IGF-1 production promoting effect by lotion containing isothiocyanates 6% relative to 3 groups of 3 groups of hairless mice (5 animals in each group) divided into 4 groups A lotion containing .01% and 0.1% of each concentration was applied, and IGF-1 concentration in epidermal tissue and dermal tissue was measured after 30 minutes. Also, using the remaining one group as a control group, a lotion without 6-MSITC was applied and the same measurement was performed. The results are shown in Table 6.

From the results in Table 6, it can be seen that application of a lotion containing 0.001% or 0.01% of 6-MSITC significantly increases the IGF-1 concentration in the epidermis and dermis relative to the control group.

[Test Example 10] Test of hair growth effect on humans by applying lotion containing isothiocyanates The subject was a volunteer male (30 to 50 years old) having hair loss and thin hair trouble, and was divided into a total of 9 groups of 5 persons. .
In groups 1 to 8, 1 ml of a lotion containing 0.01% of 6-MSITC is applied to the scalp once a day, and in group 2, isoflavone is taken as a 50 mg tablet daily, and in group 3 raspberry ketone is daily It was ingested in a 600 mg tablet. In group 4, capsiate was ingested in 2 mg tablets per day, and in group 5 gluconic acid was ingested in 100 mg tablets per day. Furthermore, in group 6, chlorogenic acid was ingested in 100 mg tablets per day, and in group 7, cocoa polyphenol was ingested in 600 mg tablets per day. In group 8, Hachcho miso was ingested in a daily dose of 5000 mg tablets, and group 9 was similarly applied with a lotion containing no 6-MSITC as a control group, and ingested simulated tablets. This was done for six months.
Next, the number of hair loss collected during the above test (before the start of application of the lotion, after 3 months of application and after 6 months of application) was measured to evaluate the hair loss improving effect. In addition, the measurement method of the above-mentioned hair loss performed four days continuous hair washing, collected the hair loss of the last three days with the fine nonwoven fabric of mesh, counted the number, and was performed. And judgment of the above-mentioned evaluation was displayed as follows from change of the number of hair loss in each time to before the start of application of a lotion.
+++: The number of hair loss decreased by 30 or more, and a remarkable effect was recognized.
++: The number of hair loss decreased by 20 or more, and a considerable effect was recognized.
+: The number of hair loss decreased by 10 or more, and a slight effect was recognized.
±: The decrease in the number of hair loss is less than or increased by 10, and it can not be said to be effective.
The results are shown in Table 7 below.

From the results of Table 7 above, in the group to which the lotion containing 6-MSITC was applied, the improvement effect on hair loss was observed, and further, the remarkable improvement effect was recognized by simultaneously consuming isoflavones and the like. In addition, as a condition of this test, it was clearly stated that the test should be stopped promptly if an undesirable phenomenon such as inflammation or skin trouble appears during the use test, but such a test is not preferable in this test. There was no response and no test dropouts. That is, it has been shown that applying a lotion containing 6-MSITC can provide a significant hair loss improving effect safely without side effects or adverse effects, and by simultaneously consuming isoflavone etc. It was shown to be strengthened.

[Test Example 11] Improvement of learning function by exposure to isothiocyanates The test product was exposed for 4 weeks to 2 groups (5 animals in each group), then Morris water maze test was performed for 5 days, and learning function The impact on the The test product used 6-methylthiohexyl isothiocyanate (6-MTITC), was not exposed to the control group, and was under normal breeding conditions. 6-MTITC was volatilized with a commercially available aroma oil aromatic container in a cage for rearing mice.
As a result, the group exposed to 6-MTITC significantly shortened the time to reach the platform from the third day after the start in the water maze test. This was exactly the same as when 6-MSITC was ingested. From this, it was confirmed that exposure to isothiocyanates provides the same effect as ingestion.

The composition of the present invention comprises, as essential components, at least one of isoflavone, raspberry ketone, capsiate, gluconic acid, chlorogenic acid, cocoa polyphenols, and hacho-miso and 6-MSITC, and is derived from insulin-like growth factor-I. By promoting the production of calcitonin gene-related peptide having a function to have an effect of preventing and treating hypertension, dementia, and osteoporosis, it has an antidepressant action, an improvement effect of learning function, and further a hair growth effect such as hair. In addition, it has a mild action, no side effects, and high safety. Such a composition of the present invention is expected to be greatly useful in preventing or treating diseases that cause problems in modern life, or overcoming physical complexes.

Claims (20)

1. A combination of isothiocyanates and at least one member selected from the group consisting of isoflavones, raspberry ketones, capsiates, gluconic acid, chlorogenic acid, cocoa polyphenols, and haccho miso to promote production and release of calcitonin gene related peptide (CGRP) An isothiocyanate-containing composition characterized by exhibiting an action or insulin-like growth factor-1 (IGF-1) secretion promoting action.
2. In Claim 1, isothiocyanates are 4-methylsulfinylbutyl isothiocyanate, 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinylhexyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, allyl. Isothiocyanate, secondary butyl isothiocyanate, 3-butenyl isothiocyanate, 4-pentenyl isothiocyanate, 5-hexenyl isothiocyanate, 5-methyl thiopentyl isothiocyanate, 6-methyl thiohexyl isothiocyanate, 7-methyl thioheptyl isothiocyanate, 8-Methylthiooctyl isothiocyanate, β-phenethyl isothiocyanate, benzyl isothiocyanate Sulfonate composition of claim 1 which is one type or more selected from the group of phenyl isothiocyanate and phenethyl isothiocyanate.
3. The composition according to claim 1, wherein the isothiocyanates are chemically synthesized.
4. The composition according to claim 1, wherein the isothiocyanates are obtained by treating or crushing a cruciferous plant, extracting with a solvent, or drying, alone or in combination.
5. The composition according to claim 1, wherein the composition has an insulin-like growth factor-1 (IGF-1) secretion promoting effect by sniffing the smell of isothiocyanates.
6. The composition according to claim 1, which exhibits an insulin-like growth factor-1 (IGF-1) secretagogue action by being exposed to the volatilized isothiocyanates.
7. A combination of isothiocyanates and at least one member selected from the group consisting of isoflavones, raspberry ketones, capsiates, gluconic acid, chlorogenic acid, cocoa polyphenols, and haccho miso to promote production and release of calcitonin gene related peptide (CGRP) Food, food material or medicine characterized by exhibiting action or insulin-like growth factor-1 (IGF-1) secretion promoting action.
8. The food, food material or medicament according to claim 7, which exhibits insulin-like growth factor-1 secretion promoting action and improves learning function.
9. The food, food material or medicament according to claim 7, which exhibits insulin-like growth factor-1 secretion promoting effect according to claim 7, and prevents and treats dementia and Parkinson's disease.
10. The food, food material or medicament according to claim 7, which exhibits insulin-like growth factor-1 secretion promoting effect according to claim 7, and prevents and treats depression.
11. The food, food material or medicine according to claim 7, which exhibits insulin-like growth factor-1 secretion promoting effect and treats osteoporosis.
12. The food, food material or pharmaceutical cosmetic product according to claim 7, which exhibits an insulin-like growth factor-1 secretion promoting effect to prevent and treat hypertension.
13. The food, food material or medicament according to claim 7, which has insulin-like growth factor-1 secretion promoting action and hair growth.
14. The isothiocyanates according to claim 7 are 4-methylsulfinylbutyl isothiocyanate, 5-methylsulfinylpentyl isothiocyanate, 6-methylsulfinylhexyl isothiocyanate, 7-methylsulfinylheptyl isothiocyanate, 8-methylsulfinyloctyl isothiocyanate, allyl. Isothiocyanate, secondary butyl isothiocyanate, 3-butenyl isothiocyanate, 4-pentenyl isothiocyanate, 5-hexenyl isothiocyanate, 5-methyl thiopentyl isothiocyanate, 6-methyl thiohexyl isothiocyanate, 7-methyl thioheptyl isothiocyanate, 8-Methylthiooctyl isothiocyanate, β-phenethyl isothiocyanate, benzyl isothiocyanate Sulfonate, phenyl isothiocyanate and food according to claim 7, which is one or more selected from the group of PEITC, food materials or medicines.
15. The food, food material or medicine according to claim 7, wherein the isothiocyanate is chemically synthesized.
16. The food, food material or food material according to claim 7, wherein the isothiocyanate is obtained by treating or grinding the cruciferous plant, extracting with a solvent, or drying treatment alone or in combination. Medicine.
17. The food, food material or medicine according to claim 7, which exhibits an insulin-like growth factor-1 (IGF-1) secretion promoting action by smelling the isothiocyanate.
18. The food, food material or medicine according to claim 7, which exhibits insulin-like growth factor-1 (IGF-1) secretion promoting action by exposure to volatilized isothiocyanates.
19. A cosmetic which exhibits the insulin-like growth factor-1 (IGF-1) secretion promoting action using the composition of claim 1 or the food, food material or medicament of claim 7 for hair growth.
20. An insulin-like growth factor-1 by using the composition according to claim 1 or the food, food material or medicine according to claim 7 for daily use and sniffing the smell of isothiocyanates or exposing to volatilized isothiocyanates (IGF-1) Daily necessities and general merchandise exhibiting a secretion promoting action