WO2005099686A1 - Edible composition having effects of promoting the production and release of calcitonin gene-related peptide - Google Patents

Edible composition having effects of promoting the production and release of calcitonin gene-related peptide Download PDF

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Publication number
WO2005099686A1
WO2005099686A1 PCT/JP2005/003839 JP2005003839W WO2005099686A1 WO 2005099686 A1 WO2005099686 A1 WO 2005099686A1 JP 2005003839 W JP2005003839 W JP 2005003839W WO 2005099686 A1 WO2005099686 A1 WO 2005099686A1
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Prior art keywords
capsaicin
edible composition
isoflavone
related peptide
calcitonin gene
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PCT/JP2005/003839
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French (fr)
Japanese (ja)
Inventor
Kenji Okajima
Toshiya Toda
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Fujicco Co., Ltd.
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Priority claimed from JP2004113228A external-priority patent/JP4213617B2/en
Application filed by Fujicco Co., Ltd. filed Critical Fujicco Co., Ltd.
Publication of WO2005099686A1 publication Critical patent/WO2005099686A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
    • C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones

Definitions

  • Edible composition having calcitonin gene-related peptide production and release promoting action
  • the present invention relates to an edible composition having a calcitonin gene-related peptide production and release promoting action. More specifically, the present invention relates to the prevention and treatment of gastric mucosal injury, lifestyle-related diseases, obesity, malignant tumors, etc., the prevention and treatment of osteoporosis, the reduction of organ transplant rejection, and the biological invasion of invasive factors such as infection. The present invention relates to an edible composition for preventing and reducing organ damage due to a reaction, and for hair growth. Background art
  • TNF- ⁇ is basically the substance that plays the most important role in host defense in the stress reaction, activates monocytes, neutrophils, vascular endothelial cells, etc., and plays a major role in the expansion of the inflammatory response.
  • ⁇ NF- ⁇ production becomes excessive due to strong and continuous stress', circulatory disorders such as thrombus formation and apoptosis of parenchymal cells may occur.
  • thrombus formation and apoptosis of parenchymal cells may occur.
  • cachexia organ dysfunction and morphological changes are caused, the living body falls into so-called cachexia, and various disease symptoms appear. From this point of view, if many etiologies are regarded as stressors, the reaction to them can be considered to be the pathological condition of the disease and the clinical symptoms.
  • TNF- ⁇ gastric mucosa caused by TNF-. It is also known that increased production of TNF- ⁇ increases the risk of developing lifestyle-related diseases such as diabetes, hypertension, hyperlipidemia and arterial sclerosis, as well as cancer and osteoporosis.
  • a calcitonin gene-related peptide plays an important role in suppressing the production of TNF- ⁇ .
  • the calcitonin gene-related peptide is a peptide consisting of 37 amino acids whose structure is very similar to that of the hormone calcitonin. This gene is on the same gene as the calcitonin gene, and its alternative splicing (alternative splicing) Generated.
  • the calcitonin gene-related peptide inhibits vasodilation, osteoblast proliferation, suppression of osteoclast activation, suppression of appetite, and suppression of NF ⁇ B activity, such as TNF-a. promote apoptosis of inhibiting the production and cancer cells.
  • calcitonin gene-related peptide acts on vascular endothelial cells, NO and, although the production of prostaglandin prostaglandin such as PGI 2 is enhanced, these substances, In addition to the action of blood perfusion, it exerts an inhibitory effect on TNF production and calcitonin gene-related peptide is known to have an important effect on the circulatory system. It has chronotropic and inotropic effects, excretion of NaC1 in the body, coronary vasodilation, and renal blood flow.
  • TNF- ⁇ production also inhibits TNF- ⁇ production and have an anti-inflammatory effect, but at the same time, disrupt organ protection mechanisms. Further, etc. which is one I Ndometashin of non-steroidal anti-inflammatory drugs, TNF-by win suppress a large amount of production of PGE 2 induced by alpha, but to relieve the symptoms of fever and pain and swelling, at the same time Inhibits COX-1, which is required for the production of prostaglandins that are important for organ protection.
  • the calcitonin gene-related peptide suppresses the excessive production of TNF- ⁇ causing the above harm and induces insulin-like growth factor, as described above.
  • Insulin-like growth factor promotes hair follicle growth and is thought to play an important role in the transition from quiescence to anagen in the hair cycle and prolongation of anagen.
  • Non-Patent Document 1 Kenni Okajima, “Biological Invasion and Disease From Single Sepsis to Lifestyle-related Diseases” Hyundai Medical Co., Ltd., 2003
  • Non-Patent Document 2 Harada N, Okajima K, Uchiba ⁇ , Katsuragi ⁇ , Cont ribution of capsaicin—sensitive sensory neurons to stress-induced increa se in gastric tissue levels of prostaglandins in rats, Am J Physiol Ga strointest Liver Physiol, 2003 Jul 31 [Epub ahead of print]
  • Non-Patent Document 3 Vignery A, McCarthy TL, The neuropeptide calcitonin gene— related peptide stimulates insulin-like growth factor 1 product ion by primary fetal rat osteoblasts ⁇ Bone s 1996, Vol 18, No 4, 331-335
  • Non-Patent Document 4 Philpott MP, Sanders DA, Kealey T, Effects of insul in and insulin-like growth factors on cultured human hair follicles: IGF-1 1 at physiologic concentrations is an important regulator of hair follicle growth in vitro, J Invest Dermatol, 1994, Vol 102, No 6, 857-861
  • conventional drugs that have been used to suppress the excessive production of TNF- ⁇ as described above have problems with side effects. Therefore, it cannot be said that it is favorable for human health.
  • an edible composition that does not cause such a problem and has the effect of significantly promoting the production and release of a calcitonin gene-related peptide that plays an important role in suppressing TNF- ⁇ overproduction, etc.
  • the present invention has been made in view of such circumstances, and has an effect of preventing and treating gastric mucosal injury, lifestyle-related diseases, obesity, malignant tumors and osteoporosis, an effect of reducing organ transplant rejection, and an invasive factor such as infection. It is an object of the present invention to provide an edible composition using natural ingredients that have a preventive and alleviating effect on organ damage caused by a biological invasive reaction to the skin, a hair-growth effect, and are gentle to the human body and have no side effects. Disclosure of the invention
  • the present inventors have conducted intensive studies to achieve the above object, and as a result, found that the combination of isoflavones and capsaicin significantly promoted the production and release of calcitonin gene-related peptides. That is, the present invention provides an edible composition having a calcitonin gene-related peptide production and release promoting action of the following (1) to (11).
  • An edible composition comprising isoflavones and force psycin as essential components and having a calcitonin gene-related peptide production and release promoting action.
  • An edible composition for preventing and treating gastric mucosal injury comprising isoflavones and capsaicin as essential components, and having an activity of promoting the production and release of a force / lecitonin gene-related peptide.
  • An edible composition for preventing and treating lifestyle-related diseases which has isoflavone and capsaicin as essential components, and has an activity of promoting the production and release of a power / lecitonin gene-related peptide.
  • An edible composition for obesity prevention and medical treatment which comprises isoflavone and capsaicin as essential components and has an activity of promoting the production and release of force / lecitonin-gene-related peptide.
  • An edible composition for preventing malignant tumor occurrence, preventing recurrence and treating which has isoflavone and capsaicin as essential components and has an action of promoting calcitonin gene-related peptide production and release.
  • An edible composition for the prevention and treatment of osteoporosis comprising isoflavone and force psicin as essential components and having a calcitonin gene-related peptide production and release promoting action
  • An edible composition for reducing organ transplant rejection which has isoflavone and capsaicin as essential components and has a calcitonin gene-related peptide production and release promoting action
  • An edible composition for hair growth comprising isoflavones and capsaicin as essential components, and having an action of promoting calcitonin gene-related peptide production and release.
  • the present inventors have found that, in a water immersion restraint stress gastric mucosal lesion model, sensory nerves stimulated by capsaicin, one of the vanilloid compounds of the pungent component of pepper, that is, the sensory nerves that are sensitive to capsaicin are activated. power calcitonin gene-related base peptide is released, at the same time with the production of TN F- alpha is inhibited, vascular endothelial NO synthase (eNOS) activation, via enhanced production of NO, PG I 2 and PGE
  • eNOS vascular endothelial NO synthase
  • This mechanism of action is used to prevent and treat gastric mucosal injury, lifestyle diseases such as diabetes, hypertension, hyperlipidemia and arteriosclerosis, obesity, malignant tumors, and osteoporosis, and to reduce rejection after organ transplantation.
  • lifestyle diseases such as diabetes, hypertension, hyperlipidemia and arteriosclerosis, obesity, malignant tumors, and osteoporosis
  • ⁇ Effective for preventing and reducing organ damage due to biological invasive reactions to various invasive factors, and for hair growth in male pattern hair loss.
  • the edible composition of the present invention has a special defect in the combination of isoflavone and capsaicin, and contains these components as essential components. With such a configuration, production and release of the calcitonin gene-related peptide can be delicately promoted.
  • the essential components refer to the optional components, which are components that are always contained in the composition, and are not subject to quantitative restrictions.
  • the origin of izoflavone used in the present invention is not particularly limited, and includes, for example, soybean seeds, kakkon-o and foods using them. Above all, soybean hypocotyls are convenient because they contain a large amount of isoflavones. It is also possible to use food such as natto.
  • the above-mentioned isoflavones may be used alone or in combination of two or more in the invention. Because of the high concentration of isoflavones, it is also possible to use extracts of soybeans, soybean foods, soybean hypocotyls, kuzu, etc., and their purified products.
  • the solvent for extracting the isoflavone is not particularly limited, but it is preferable to use water or an alcohol such as ethanol.
  • the method of purification can use a synthetic adsorbent, an ion exchange resin, ultrafiltration, or the like, but is not particularly limited.
  • the extract or the purified liquid may be used as it is, or a concentrated liquid obtained by concentrating them or a powder obtained by drying and extracting the extracted liquid or the purified liquid may be used.
  • the origin of capsaicin used in the present invention is not particularly limited, but it is preferable to use pepper.
  • Nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin are known.
  • the above-mentioned various capsaicins are used alone or in combination of two or more.
  • Pepper can be used as it is after being ground or powdered. However, it is also possible to use an industrially produced pepper extract because of using high concentration of cabsaicin. Pepper extract extracted from pepper with aqueous ethanol, pepper oleoresin extracted mainly from nonpolar to intermediate polar organic solvents such as hexane and ether, and pepper oleoresin are re-extracted with ethanol, and insoluble matter is filtered off. Can be used according to its characteristics.
  • the edible composition of the present invention contains isoflavone and psisaicin obtained as described above as essential components, and a mixture of these may be used directly as it is, but generally, These are used by dissolving or dispersing them in an appropriate liquid carrier or mixing them in an appropriate powder carrier.
  • the content of the isoflavone to be an active ingredient is preferably in the range of 0.001 to 0.5% by weight (hereinafter abbreviated as “%”) in the case of a liquid.
  • the content is preferably in the range of 0.01 to 80%, and in the case of granules, the content is preferably in the range of 0.01 to 40%.
  • the content of the above-mentioned capsaicin as an active ingredient is preferably in the range of 0.001 to 0.05% for liquids, and in the case of powders. Is preferably in the range of 0.001 to 5%, and in the case of granules, it is preferably in the range of 0.001 to 5%.
  • the ratio between the above isoflavone and capsaicin is important, and the isoflavone / capsaicin is preferably contained in a weight ratio of 50,000 O: 1 to 1:10, more preferably isoflavone: capsaicin.
  • Bon: capsaicin 500: 1 to 1: 1 weight ratio range. That is, when both are contained at such a ratio, the synergistic effect of both allows the calcitonin gene-related peptide production and release promoting actions required in the present invention to be effectively obtained. .
  • the edible composition of the present invention is expected not only to humans but also to animals such as pets and livestock, to have the same effect as the above-mentioned effect observed when administered to humans.
  • the above-mentioned mixture of isoflavone and capsaicin can be administered in several divided doses to give a daily dose of 10 to 400 mg.
  • the above mixture is contained in animal feed at a rate of 0.001 to 5%, and a range of 1 to 40 mg / kg body weight per day. It is preferred that it be administered.
  • the edible composition of the present invention having a calcitonin gene-related peptide production and release promoting action is not particularly limited in its shape and eating and drinking method as long as it contains isoflavone and capsaicin as active ingredients as described above. More specifically, it can be used for general foods such as beverages, cooked foods, desserts, confectioneries, dairy products, foods, breads, etc. ⁇ Solid or semi-solid preparations such as tablets, powders, and granules I can give it.
  • Optional ingredients other than isoflavones and capsaicin include, for example, sweeteners, seasonings, acidulants, flavorings such as umami, emulsifiers, dispersants, antioxidants, preservatives, ⁇ thickeners, binders, fragrances, etc.
  • sweeteners seasonings, acidulants, flavorings such as umami, emulsifiers, dispersants, antioxidants, preservatives, ⁇ thickeners, binders, fragrances, etc.
  • excipients, binders, disintegrants, film agents, lubricants, fillers, diluents, pH adjusters, emulsifiers, dispersants examples include stabilizers, flavoring agents, coloring agents, and the like.
  • the above-mentioned five groups consisted of the isoflavone-administered group, the cypressic acid-administered group, the isoflavone + cabsaicin-administered group, and the non-administered group (of the normal diet), as shown in Table 1 below.
  • capsaicin was dissolved in a 10% aqueous ethanol solution containing 10% Tween 20, and orally administered one hour before restraint by water immersion (administration of lmg / kg body weight as capsaicin). Further, in the isoflavone + cabsaicin administration group, both were administered in the same manner as described above.
  • the above five groups namely, a normal group (norma 1; no water immersion restraint), a control group (Control; water immersion restraint) and three test groups (water immersion restraint + isoflavone, water immersion restraint + cabsaicin, water Based on the stomach excised from immersion restraint + isoflavone + capsaicin), the gastric injury index and gastric calcitonin gene-related peptide concentration (CGRP) were measured. The results are shown in Table 1 below. Each data shows the average value of each group.
  • Example 2 administering test for gastric ulcer patients
  • the subjects were those who had endoscopic gastric ulcers and were divided into 4 groups, each group consisting of 4 persons.
  • group 1 of which, isoflavone-containing tablets (isoflavone extract; Fujiflaco P40) were used to administer 4 Omg of isoflavones per day, and in group 2, tablets containing capsaicin were used.
  • the administration resulted in ingestion of lmg of power petitisin per day.
  • Group 3 received tablets containing both, and gnolepe 4 received pseudo tablets. This was done for 20 days.
  • the patient was granted permission for subjective symptoms during the administration period, and after the administration, an endoscopy of the stomach was performed.
  • the results are shown in Table 2 below. Each data shows the average value in each group.
  • the 80-day-old SD female pets divided into 5 groups (6 per group. Of the 5 groups, 4 groups were ovariectomized and 10 days post-excision rats)
  • the animals were fed a standard diet [power deficiency diet (Ca: 0.004%, P: 0.3%)] and the like, and bred for 28 days. After that, they were fasted for 1 ⁇ (18 hours), all rats were sacrificed, and their femurs were removed.
  • the above five groups consisted of the isoflavone-administered group, the capsa ⁇ T-sin-administered group, the isoflavone-capsaicin-administered group, and the non-administered group (standard diet), as shown in Table 3 below. Only) belongs to the misalignment.
  • the isoflavone-administered group in addition to the standard diet, 1% arbor, soybean suspended in an aqueous solution of oral xypropylcellulose was orally administered during the breeding period (the soybean intake was 9 Omg / kg body weight / day. Administration).
  • the 18-week-old male SHRS PZ 1 zm rats were divided into 4 groups of 6 animals per group.
  • Group 1 was fed on a diet supplemented with soybean germ extract (Fujiflavone P40) so that the isoflavone intake was 9 Omg / kg body weight Zday.
  • Group 2 was fed on a diet prepared such that the intake of force psycin was 1 mg Zkg body weight / day.
  • Group 3 received both isoflavone and force psycin.
  • Group 4 was the control group.
  • Tail blood pressure measurement on day 50 of administration 260 ⁇ 5.2 mmHg for group 1, 268 ⁇ 10.4 mmHg for group 2, 246 ⁇ 4.4 mmHg for group 3, and 279 soil for group 4 3.1 mmH (Group 3 was significantly different from Group 4).
  • the measured value of calcitonin gene-related peptide in the blood was highest in group 4 as well. This allows simultaneous administration of isoflavone and capsaicin It can be seen that doing so promotes the production of the calcitoun gene-related peptide and is therefore effective for hypertension.
  • the feed given to each of the above groups consisted of a standard diet (calcium-deficient diet (Ca: 0.004%, P: 0.3%)), isoflavone (0% isoflavone in the standard diet). Feed containing 25%), capsaicin (feed containing 0.005% capsaicin added to the standard diet), isoflavone + capsaicin (feed containing 0.25% isoflavone and 0.005% capsaicin added to the standard diet). Either.
  • a liver metastasis model was created by transplanting a highly metastatic human colon cancer cell line. Ten days after cancer cell transplantation, hepatic ischemia-reperfusion was performed, and the number of metastatic cancer cells was counted thereafter.
  • group 1 of the above 4 groups was bred on a diet supplemented with soybean germ extract (Fujiflavone P40) so that isoflavone intake was 9 OmgZkg g body weight Zday.
  • Gnorape 2 was fed on a diet prepared so that the capsaicin intake was 1 mg / kg body weight / day.
  • Group 3 received both isoflavones and capsaicin, and group 4 was the control group.
  • Liver extirpated from all the prescribed rats divided into 4 gnolops (5 per group) were stored in organ preservation solution for 24 hours, and then transplanted into syngeneic rats. At this time, the lymphocyte of the peripheral blood was separated, and the molecules on the cell surface were analyzed by FACS.
  • group 1 of the above 4 groups should be adjusted so that the amount of isoflavone is 9 Omg / kg body weight / day: a diet supplemented with bean germ extract (Fujiflavon ⁇ 40)
  • Group 2 was fed a diet prepared so that capsaicin intake was lmg / kg body weight / day.
  • Group 3 received both isoflavone and capsaicin
  • group 4 served as a control group, and as a result of the experiment as described above, groups 1 and 2 showed a lower rate of settlement than group 4. It was slightly expensive.
  • Manako and calcitonin gene-related peptides also showed significantly higher levels than the other groups. This shows that simultaneous administration of isoflavone and capsaicin promoted the production of canolecitonin gene-related peptides and reduced the rejection of organ transplantation.
  • Endotoxin 5 mg / kg body weight was intravenously injected to all the predetermined rats divided into 4 groups (5 rats per group), a shock model was prepared, and the blood pressure was measured.
  • soybean germ extract (Fujiflavone P40) was added to Group 1 of the above 4 groups so that the amount of isoflavone was 9 Omg / kg body weight / day.
  • Group 2 was fed a diet prepared so that the capsaicin intake was 1 mg Z kg body weight / day.
  • Group 3 received both isoflavones and capsaicin, and group 4 was the control group.
  • mice purchased at the age of 3 weeks were randomly divided into 4 groups of 1 gnolap and 10 mice. After 1 week of acclimatized breeding, group 1 had a higher isoflavone intake. The animals were reared on a diet supplemented with soybean germ extract (Fujif 4bon P40) so that 9 O mg / kg body weight Z day was obtained. Group 2 was prepared so that capsaicin intake capacity S 2 mg / kg body weight Z day The feed was raised. Group 3 received both isoflavone and capsaicin, and Group 4 served as a control. The hair was cut at the age of 6 weeks, and the state of hair growth was observed. That is, the number of mice whose hair regeneration was completed within 40 days after the start of ingestion of the test feed was measured. The results are shown in Table 5 below.
  • the edible fibrous composition comprising isoflavone and capsaicin as essential components according to the present invention has a function of suppressing the production of inflammatory cytokines such as TNF- ⁇ and the like, which are promoted by social and psychological or physical stress. Promotes the production and release of calcitonin gene-related peptides that have the function of inducing growth-like growth factors, thereby preventing gastric mucosal injury, lifestyle-related diseases, obesity, preventing the occurrence and recurrence of malignant tumors, and preventing osteoporosis. It has preventive and therapeutic effects, has the effect of reducing rejection after organ transplantation, has the effect of preventing and treating organ damage due to invasive reactions after infection, surgery, and trauma, and has the effect of hair growth on the hair.
  • Such an edible composition of the present invention plays a significant role in preventing or treating diseases that are a major problem in modern life, or in overcoming physical complexes. Expected to stand
  • CGRP Calcitonin gene-related peptide (per stomach tissue weight)
  • CGRP Calcitonin gene-related peptide (per bone, tissue weight)
  • CGRP Calcitonin gene-related peptide (per stomach tissue weight)

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Abstract

An edible composition having effects of promoting the production and release of a calcitonin gene-related peptide. Namely, an edible composition comprising isoflavone and capsaicin as the essential components and having effects of promoting the production and release of a calcitonin gene-related peptide; and an edible composition comprising the above-described edible composition for preventing and treating gastric mucosal injury, life style-related diseases, obesity, malignant tumor and osteoporosis, relieving rejection accompanying organ transplantation, preventing and relieving organ injury caused by vital invasion reactions against invasive factors such as infection, and stimulating hair (for example, head hair) growth. This edible composition exerts effects of preventing and treating gastric mucosal injury and so on and these effects are mild without any risk of side effect.

Description

カルシトニン遺伝子関連べプチド産生及び放出促進作用を有する可食性組成物 技術分野 Edible composition having calcitonin gene-related peptide production and release promoting action
本発明は、 カルシトニン遺伝子関連べプチド産生および放出促進作用を有する 可食性組成物に関する。 詳しくは、 本発明は、 胃粘膜傷害， 生活習慣病， 肥満， 悪性腫瘍等の発生予防と治療用、 骨粗鬆症の予防と治療用、 臓器移植拒絶反応軽 減用、 感染等の侵襲要因に対する生体侵襲反応に伴う臓器障害の予防と軽減用、 ならびに、 育毛用等の、 可食性組成物に関するものである。 背景技術  The present invention relates to an edible composition having a calcitonin gene-related peptide production and release promoting action. More specifically, the present invention relates to the prevention and treatment of gastric mucosal injury, lifestyle-related diseases, obesity, malignant tumors, etc., the prevention and treatment of osteoporosis, the reduction of organ transplant rejection, and the biological invasion of invasive factors such as infection. The present invention relates to an edible composition for preventing and reducing organ damage due to a reaction, and for hair growth. Background art
現代社会においては、 多かれ少なかれ生体の内部環境を撹乱させるような社会 的、 心理的および身体的なストレスを避けて生活することはできない。 ストレス と疾病の関連の重要性は、 社会的心理的ストレッサーが、 その発症に深くかかわ つている病態、 すなわち消化性潰瘍、 過敏性大腸症候群、 気管支喘息、 高血圧、 虚血性心疾患および糖尿病などにおいて指摘されてきたが、 これらのほかにも、 社会的心理的ストレスにより免疫能が低下し、 感染症や発癌などのリスクが増加 することも知られている。 また、 薄毛、 抜け毛に悩む男女が增加しているが、 こ れも、 遺伝的素因、 老化などの要因以外に、 ストレスの影響が大きいことが指摘 されている。  In modern society, it is not possible to live without social, psychological and physical stress that more or less disrupts the internal environment of the living body. The importance of the link between stress and illness is pointed out in conditions that social and psychological stressors are deeply involved in its onset, such as peptic ulcer, irritable bowel syndrome, bronchial asthma, hypertension, ischemic heart disease and diabetes In addition to these, it is also known that social and psychological stress reduces immunity and increases the risk of infections and carcinogenesis. In addition, men and women suffering from thinning and hair loss are increasing, but it is also pointed out that stress is significant in addition to factors such as genetic predisposition and aging.
一方、 感染や外傷などといった、 身体への物理ィ匕学的ストレッサーに対する生 体反応は、 社会的心理的ストレッサーに対する生体反応と極めて類似しており、 これらの生体反応の発現に T N F— αなどの炎症性サイトカインが重要であるこ とが明らかになつてきた。  On the other hand, the biological response to physical and physical stressors, such as infection and trauma, is very similar to the biological response to social and psychological stressors. The importance of inflammatory cytokines has emerged.
T N F— αは、 基本的にはス トレス反応における生体防御に最も重要な役割を 果たす物質であり、 単球、 好中球および血管内皮細胞などを活性化し、 炎症反応 の拡大に大きく関与する。 しかしながら、 強力で継続的なストレスにより上記 Τ N F - αの産生が過剰になる 'と、 血栓形成などの循環障害や実質細胞のアポト一 シスを引き起こすことで臓器機能障害や形態変化などを惹起し、 生体をいわゆる 悪液質に陥れ、 さまざまな疾病症状が現れるようになる。 このような観点から、 多くの病因をストレッサーと考えれば、 それらに対する反応が、 その疾病の病態 であり、 また、 臨床症状であると考えることができる。 TNF-α is basically the substance that plays the most important role in host defense in the stress reaction, activates monocytes, neutrophils, vascular endothelial cells, etc., and plays a major role in the expansion of the inflammatory response. However, if the ΤNF-α production becomes excessive due to strong and continuous stress', circulatory disorders such as thrombus formation and apoptosis of parenchymal cells may occur. By causing cis, organ dysfunction and morphological changes are caused, the living body falls into so-called cachexia, and various disease symptoms appear. From this point of view, if many etiologies are regarded as stressors, the reaction to them can be considered to be the pathological condition of the disease and the clinical symptoms.
たとえば、 消化性潰瘍の発症は、 T N F— によって惹起される胃粘膜の炎症 が重要な原因となっている。 また、 TN F— αの産生亢進によって、 糖尿病、 高 血圧、 高脂血症および動脈硬ィ匕などの生活習慣病や、 癌、 骨粗鬆症の発症リスク が大きくなることが知られている。  For example, the development of peptic ulcers is largely due to inflammation of the gastric mucosa caused by TNF-. It is also known that increased production of TNF-α increases the risk of developing lifestyle-related diseases such as diabetes, hypertension, hyperlipidemia and arterial sclerosis, as well as cancer and osteoporosis.
TN F— αの産生の抑制には、 神経べプチドの一種であるカルシトニン遺伝子 関連べプチドが重要な役割を果たしている。 カルシトニン遺伝子関連べプチドは 、 ホルモンであるカルシトニンと構造が非常に類似した 37個のアミノ酸からなる ぺプチドで、 この遺伝子はカルシトニン遺伝子と同じ遺伝子上にあり、 そのオル タナティブ ·スプライシング (alternative splicing) により生成される。 カル シトニン遺伝子関連ペプチドは、 血管拡張作用、 骨芽細胞の增殖、 また破骨細胞 の活性化抑制、 食欲の抑制、 さらに N F κ Bの活' I"生ィ匕を抑制して、 T N F— aの 産生抑制や癌細胞のアポトーシスを促進する。 また、 カルシトニン遺伝子関連ぺ プチドが血管内皮細胞に作用することにより、 N Oや、 P G I 2 などのプロスタ グランジンの産生が亢進するが、 これらの物質は、 血流增カ 13作用に加えて T N F 一 ο;産生抑制作用を発揮する。 さらに、 カルシトニン遺伝子関連ペプチドは、 循 環器系にも重要な作用を及ぼすことが知られており、 全身の血管拡張作用、 陽性 変時及び変力作用、 N a C 1の体外***作用、 冠血管拡張作用、 及び腎血流増加 作用などを有している。 A calcitonin gene-related peptide, a type of neuropeptide, plays an important role in suppressing the production of TNF-α. The calcitonin gene-related peptide is a peptide consisting of 37 amino acids whose structure is very similar to that of the hormone calcitonin. This gene is on the same gene as the calcitonin gene, and its alternative splicing (alternative splicing) Generated. The calcitonin gene-related peptide inhibits vasodilation, osteoblast proliferation, suppression of osteoclast activation, suppression of appetite, and suppression of NFκB activity, such as TNF-a. promote apoptosis of inhibiting the production and cancer cells. in addition, by calcitonin gene-related peptide acts on vascular endothelial cells, NO and, although the production of prostaglandin prostaglandin such as PGI 2 is enhanced, these substances, In addition to the action of blood perfusion, it exerts an inhibitory effect on TNF production and calcitonin gene-related peptide is known to have an important effect on the circulatory system. It has chronotropic and inotropic effects, excretion of NaC1 in the body, coronary vasodilation, and renal blood flow.
現在、 T N F - αの過剰な産生に起因すると考えられる上記疾病の治療に種々 の薬剤が用いられている。 し力 し、 多くのものは対症療法的な薬剤であり、 病態 の主原因にかかわるものではなく、 むしろ副作用が問題となる場合が多い。 たと えば、 消化性潰瘍治療では、 H2 ブロッカーのように胃酸分泌を強力に抑制する 薬剤が用いられることが多いが、 長期に胃酸分泌を抑制すると、 胃酸による胃粘 膜防御機構が作動しなくなり、 胃痛などの自覚症状の改善や胃酸による胃粘膜の 表面的な自己消化は軽減ざれるものの、 胃粘膜の炎症は軽減されず、 むしろ增悪 し、 胃粘膜の萎縮やひいては胃癌の発生母地を形成することになる。 また、 ステロイ ドは、 T N F— αの産生を阻害し抗炎症作用を持つが、 同時に 臓器保護機構を破綻させる。 さらに、 非ステロイド系抗炎症剤のひとつであるィ ンドメタシンなどは、 T N F— αによって誘導される大量の P G E2 の産生を抑 制することにより、 発熱や痛みや腫れの症状を緩和するが、 同時に臓器保護に重 要なプロスタグランジンの産生に必要な C O X—1を阻害する。 At present, various drugs are used for the treatment of the above-mentioned diseases possibly caused by excessive production of TNF-α. However, many are symptomatic drugs, not related to the main cause of the condition, and often have side effects. For example, in peptic ulcer treatment, but strongly agents that inhibit gastric acid secretion as H 2 blockers are often used, long term when suppressing gastric acid secretion, gastric by gastric acid mucosal defense mechanisms can not work However, the improvement of subjective symptoms such as stomach pain and the superficial autolysis of the gastric mucosa caused by stomach acid cannot be reduced, but the inflammation of the gastric mucosa is not reduced. However, atrophy of the gastric mucosa and, consequently, the formation of gastric cancer origin. Steroids also inhibit TNF-α production and have an anti-inflammatory effect, but at the same time, disrupt organ protection mechanisms. Further, etc. which is one I Ndometashin of non-steroidal anti-inflammatory drugs, TNF-by win suppress a large amount of production of PGE 2 induced by alpha, but to relieve the symptoms of fever and pain and swelling, at the same time Inhibits COX-1, which is required for the production of prostaglandins that are important for organ protection.
ところで、 カルシトニン遺伝子関連ペプチドは、 先に述べたように、 上記悪害 をもたらす T N F— αの過剰な産生を抑制するとともに、 インスリン様成長因子 を誘導する。 インスリン様成長因子は、 毛包の成長を促進し、 毛周期における休 止期から成長期への移行と成長期の延長に関して重要な働きをしていると考えら れている。  By the way, the calcitonin gene-related peptide suppresses the excessive production of TNF-α causing the above harm and induces insulin-like growth factor, as described above. Insulin-like growth factor promotes hair follicle growth and is thought to play an important role in the transition from quiescence to anagen in the hair cycle and prolongation of anagen.
【非特許文献 1】 岡嶋研ニ著 「生体侵襲と疾患一重症敗血症から生活習慣病 まで」 現代医療社、 2 0 0 3年  [Non-Patent Document 1] Kenni Okajima, "Biological Invasion and Disease From Single Sepsis to Lifestyle-related Diseases" Hyundai Medical Co., Ltd., 2003
【非特許文献 2】 Harada N、 Okajima K、 Uchiba Μ、 Katsuragi Τ、 Cont ribution of capsaicin— sensitive sensory neurons to stress-induced increa se in gastric tissue levels of prostaglandins in rats 、 Am J Physiol Ga strointest Liver Physiol、 2003 Jul 31 [Epub ahead of print]  [Non-Patent Document 2] Harada N, Okajima K, Uchiba Μ, Katsuragi Τ, Cont ribution of capsaicin—sensitive sensory neurons to stress-induced increa se in gastric tissue levels of prostaglandins in rats, Am J Physiol Ga strointest Liver Physiol, 2003 Jul 31 [Epub ahead of print]
【非特許文献 3】 Vignery A、 McCarthy TL、 The neuropeptide calcitoni n gene— related peptide stimulates insulin - like growth factor 1 product io n by primary fetal rat osteoblasts^ Bones 1996、 Vol 18、 No 4、 331-335[Non-Patent Document 3] Vignery A, McCarthy TL, The neuropeptide calcitonin gene— related peptide stimulates insulin-like growth factor 1 product ion by primary fetal rat osteoblasts ^ Bone s 1996, Vol 18, No 4, 331-335
【非特許文献 4】 Philpott MP、 Sanders DA、 Kealey T、 Effects of insul in and insulin-like growth factors on cultured human hair follicles : IGF 一 1 at physiologic concentrations is an important regulator of hair folli cle growth in vitro 、 J Invest Dermatol 、 1994, Vol 102 、 No 6、 857-861 し力 しながら、 上記のように T N F— αの過剰な産生を抑制するために用いら れてきた従来の薬剤では、 副作用を伴うといった問題があることから、 人体の健 康上好ましいとはいえない。 そのため、 このような問題を生じず、 T N F— α過 剰産生の抑制等に重要な役割を果たすカルシトニン遺伝子関連べプチドの、 産生 およぴ放出を著明に促進し得る作用を有する可食性組成物が求められている。 本発明は、 このような事情に鑑みなされたもので、 胃粘膜傷害， 生活習慣病， 肥満， 悪性腫瘍および骨粗鬆症の予防及び治療効果、 臓器移植拒絶反応を軽減す る効果、 感染等の侵襲要因に対する生体侵襲反応に伴う臓器障害の予防及び軽減 効果、 さらには育毛効果を有し、 しかも人体にやさしく副作用のない自然の成分 を用いた可食性組成物の提供をその目的とする。 発明の開示 [Non-Patent Document 4] Philpott MP, Sanders DA, Kealey T, Effects of insul in and insulin-like growth factors on cultured human hair follicles: IGF-1 1 at physiologic concentrations is an important regulator of hair follicle growth in vitro, J Invest Dermatol, 1994, Vol 102, No 6, 857-861 However, conventional drugs that have been used to suppress the excessive production of TNF-α as described above have problems with side effects. Therefore, it cannot be said that it is favorable for human health. As a result, an edible composition that does not cause such a problem and has the effect of significantly promoting the production and release of a calcitonin gene-related peptide that plays an important role in suppressing TNF-α overproduction, etc. Things are required. The present invention has been made in view of such circumstances, and has an effect of preventing and treating gastric mucosal injury, lifestyle-related diseases, obesity, malignant tumors and osteoporosis, an effect of reducing organ transplant rejection, and an invasive factor such as infection. It is an object of the present invention to provide an edible composition using natural ingredients that have a preventive and alleviating effect on organ damage caused by a biological invasive reaction to the skin, a hair-growth effect, and are gentle to the human body and have no side effects. Disclosure of the invention
本発明者らは、 上記の目的を達成するため鋭意検討した結果、 イソフラボンと カプサイシンを組み合わせることによってカルシトニン遺伝子関連べプチドの産 生おょぴ放出が著明に促進されることを見いだし、 本発明を完成するにいたった すなわち、 本発明は、 以下の （1 ) から （1 1 ) の、 カルシトニン遺伝子関連 ぺプチド産生および放出促進作用を有する可食性組成物を要旨とするものである  The present inventors have conducted intensive studies to achieve the above object, and as a result, found that the combination of isoflavones and capsaicin significantly promoted the production and release of calcitonin gene-related peptides. That is, the present invention provides an edible composition having a calcitonin gene-related peptide production and release promoting action of the following (1) to (11).
( 1 ) イソフラボンと力プサイシンを必須成分とし、 カルシトニン遺伝子関連べ プチド産生および放出促進作用を有する可食性組成物。 (1) An edible composition comprising isoflavones and force psycin as essential components and having a calcitonin gene-related peptide production and release promoting action.
( 2 ) イソフラボンとカブサイシンを必須成分とし、 力/レシトニン遺伝子関連べ プチド産生および放出促進作用を有する、 胃粘膜傷害予防及び治療用可食性組成 物。  (2) An edible composition for preventing and treating gastric mucosal injury, comprising isoflavones and capsaicin as essential components, and having an activity of promoting the production and release of a force / lecitonin gene-related peptide.
( 3 ) イソフラボンとカブサイシンを必須成分とし、 力/レシトニン遣伝子関連べ プチド産生および放出促進作用を有する、 生活習慣病予防及び治療用可食性組成 物。  (3) An edible composition for preventing and treating lifestyle-related diseases, which has isoflavone and capsaicin as essential components, and has an activity of promoting the production and release of a power / lecitonin gene-related peptide.
( 4 ) イソブラボンとカブサイシンを必須成分とし、 力/レシトニン遗伝子関連べ プチド産生および放出促進作用を有する、 肥満予防及び、冶療用可食性組成物。  (4) An edible composition for obesity prevention and medical treatment, which comprises isoflavone and capsaicin as essential components and has an activity of promoting the production and release of force / lecitonin-gene-related peptide.
( 5 ) イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連べ プチド産生おょぴ放出促進作用を有する、 悪性腫瘍発生予防， 再発予防及ぴ治療 用可食性組成物。  (5) An edible composition for preventing malignant tumor occurrence, preventing recurrence and treating, which has isoflavone and capsaicin as essential components and has an action of promoting calcitonin gene-related peptide production and release.
( 6 ) イソフラボンと力プサイシンを必須成分とし、 カルシトニン遺伝子関連ぺ プチド産生および放出促進作用を有する、 骨粗鬆症予防及び治療用可食性組成物 (7) イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連ぺ プチド産生および放出促進作用を有する、 臓器移植拒絶反応軽減用可食性組成物 (6) An edible composition for the prevention and treatment of osteoporosis, comprising isoflavone and force psicin as essential components and having a calcitonin gene-related peptide production and release promoting action (7) An edible composition for reducing organ transplant rejection, which has isoflavone and capsaicin as essential components and has a calcitonin gene-related peptide production and release promoting action
(8) イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連ぺ プチド産生および放出促進作用を有する、 感染， 外傷， 手術等の侵襲要因に対す る生体侵襲反応に伴う臓器障害の予防及び軽減用可食性組成物。 (8) Essence of isoflavones and cabsaicin as essential components, which have calcitonin gene-related peptide production and release-promoting effects. Prevention and reduction of organ damage caused by biological invasive reactions to invasive factors such as infection, trauma, and surgery. Composition.
(9) イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連べ プチド産生おょぴ放出促進作用を有する、 育毛用可食性組成物。  (9) An edible composition for hair growth, comprising isoflavones and capsaicin as essential components, and having an action of promoting calcitonin gene-related peptide production and release.
(10) イソフラボンが、 大豆由来のイソフラボンである (1 ) から (9) のい ずれかに記載の可食性組成物。  (10) The edible composition according to any one of (1) to (9), wherein the isoflavone is a soybean-derived isoflavone.
(1 1) カプサイシンが、 唐辛子由来のカブサイシンである (1) から (10) のいずれかに記載の可食性組成物。  (1 1) The edible composition according to any one of (1) to (10), wherein the capsaicin is capsaicin derived from pepper.
本発明者らは、 水浸拘束ストレス胃粘膜病変モデルにおいて唐辛子の辛味成分 のバニロイド化合物のひとつであるカブサイシンによって刺激される知覚神経、 すなわちカブサイシン感受性知覚神経が活性化される結果、 その神経末端より力 ルシトニン遺伝子関連べプチドが放出され、 TN F— αの産生が抑制されると同 時に、 血管内皮型 NO合成酵素 （eNOS) を活性化し、 NOの産生亢進を介し て、 PG I 2や PGE2 などのプロスタグランジン及ぴインスリン様成長因子の 生成が亢進することを、 先に見いだしている。 そして、 この作用機構は、 胃粘膜 の傷害、 糖尿病、 高血圧、 高脂血症および動脈硬化などの生活習慣病や肥満、 悪 性腫瘍、 骨粗鬆症の予防及び治療、 臓器移植後の拒絶反応の柽減ゃ様々な侵襲要 因に対する生体侵襲反応に伴う臓器障害の予防及び軽減、 さらには、 男性型脱毛 における育毛に対し、 有効である。 The present inventors have found that, in a water immersion restraint stress gastric mucosal lesion model, sensory nerves stimulated by capsaicin, one of the vanilloid compounds of the pungent component of pepper, that is, the sensory nerves that are sensitive to capsaicin are activated. power calcitonin gene-related base peptide is released, at the same time with the production of TN F- alpha is inhibited, vascular endothelial NO synthase (eNOS) activation, via enhanced production of NO, PG I 2 and PGE We have previously found that production of prostaglandins such as 2 and insulin-like growth factor is enhanced. This mechanism of action is used to prevent and treat gastric mucosal injury, lifestyle diseases such as diabetes, hypertension, hyperlipidemia and arteriosclerosis, obesity, malignant tumors, and osteoporosis, and to reduce rejection after organ transplantation.予 防 Effective for preventing and reducing organ damage due to biological invasive reactions to various invasive factors, and for hair growth in male pattern hair loss.
本発明者らは、 このような知見に基づいて、 さらに検討を重ねた結果、 主に大 豆種子に含まれるダイゼイン、 ゲニスティン、 グリシティン、 ダイズイン、 ゲニ スチン、 グリシチン、 6 " 一 O—マロ二ノレダイズイン、 6 " 一 O—マロ二ルゲニ スチン、 6 " 一 O—マロニノレグリシチン、 6 " —O—ァセチノレダイズィン、 6 " 一 O—ァセチルゲニスチン、 6 " 一 O—ァセチルダリシチンや納豆にみられる 6 " 一 O—サクシニルダ、ィズィン、 6 " 一 O—サクシニルゲニスチン及び 6 " — O —サクシニルダリシ ンなどのイソフラボン類が神経成長因子 （nerve growth f actor ； NGF ) の産 を增加させることによって、 カブサイシン感受性知覚神経 のカルシトニン遣伝チ関連ペプチドの産生促進作用を著明に增強し、 さらに、 力 プサイシンにより産; が増加したカルシトニン遺伝子関連べプチドの放出を促進 し、 それらの結果、 T N F— αの産生抑制、 N Oの産生亢進、 プロスタク、ランジ ン生成、 インスリン镔成長因子の産生も促進されることを見いだし、 本 明を完 成したものである。 発明を実施するため (^最良の形態 As a result of further studies based on such findings, the present inventors have found that daidzein, genistein, glycitin, soybean, genistein, glycitin, glycitin, and 6 "-O-maloninorezyin, which are mainly contained in soybean seeds. , 6 "-O-malonilgenistin, 6" -O-maloninoleglycin, 6 "-O-acetinoledaisin, 6" -O-acetylgenistin, 6 "-O-acetildali Seen in cytin and natto 6 Isoflavones such as 1-O-succinilda, isidin and 6 "-O-succinylgenistin and 6" -O-succinyldaricin increase cabsaicin by increasing the production of nerve growth factor (NGF). It markedly enhanced the production of calcitonin transducing peptide-related peptides in susceptible sensory nerves. In addition, it promoted the release of calcitonin gene-related peptides, which were increased by force psycin; and as a result, TNF-α It has been found that the suppression of production, the promotion of NO production, the production of prostaglandin, the production of langin, and the production of insulin 镔 growth factor are also promoted, thus completing the present invention.
つぎに、 本発明の案施の形態について詳しく説明する。  Next, embodiments of the present invention will be described in detail.
本発明の可食性組 物は、 先にも述べたように、 イソフラボンとカプサイシン との組み合わせに特跌を有するものであり、 これら各成分を、 必須成分として含 有するものである。 このような構成によって、 カルシトニン遺伝子関連ペプチド の産生および放出が奢明に促進されるようになる。 ここで、 必須成分とは、 任意 成分に対するもので って、 構成上必ず含有される成分のことをいい、 量的な制 約は受けない。  As described above, the edible composition of the present invention has a special defect in the combination of isoflavone and capsaicin, and contains these components as essential components. With such a configuration, production and release of the calcitonin gene-related peptide can be delicately promoted. Here, the essential components refer to the optional components, which are components that are always contained in the composition, and are not subject to quantitative restrictions.
本発明に用いるィゾフラボンの由来は、 特に限定されるものではなく、 たとえ ば大豆種子、 葛根お tぴそれらを用いた食品などがあげられる。 なかでも大豆の 胚軸にはイソフラボンが多量に含まれるため都合が良い。 また、 納豆などの食品 を用いることも可能である。  The origin of izoflavone used in the present invention is not particularly limited, and includes, for example, soybean seeds, kakkon-o and foods using them. Above all, soybean hypocotyls are convenient because they contain a large amount of isoflavones. It is also possible to use food such as natto.
上記イソブラボン【こは、 ダイゼイン、 ゲニスティン、 グリシティン、 タ、ィズィ ン、 ゲニスチン、 グ! シチン、 6 " — O—マロニルダィズィン、 6 " 一 O—マロ ニノレゲニスチン、 6 " 一 O—マロニノレグリシチン、 6 " —0—ァセチノレダイズィ ン、 6 " 一 O—ァセ ルゲニスチン、 6 " 一 O—ァセチルダリシチンゃ 内豆にみ られる 6 " 一 O—サグシニルダィズイン、 6 " 一 O—サクシニルゲニスチン、 6 " 一 O—サクシニルダリシチン及びプェラリンなどが含まれる。 なお、 上記の各 種イソフラボンは、 発明において、 単独であるいは二種以上併せて用！/、られる 濃度の高いイソフラボンを使用するため大豆や大豆食品、 大豆胚軸、 葛 など の抽出物やその精製物を用いることも可能である。 イソフラボンを抽出する溶媒 は、 特に限定されるものではないが、 水又はエタノールなどのアルコールを用い るのが好ましい。 また、 精製の方法は、 合成吸着剤やイオン交換樹脂、 限外ろ過 などを使用することが可能であるが、 特に限定されるものではない。 抽出液又は 精製液は、 そのまま使用しても良いが、 それらを濃縮した濃縮液、 もしくは、 抽 出液又は精製液を乾燥したあと粉末化したものを使用しても良い。 The above isoblavone [This is Daidzein, Genistin, Glicitin, Ta, Isin, Genistin, Gu! Citin, 6 "-O-malonildizin, 6" 1-O-Malo Ninolegenistin, 6 "1-O-Maroninole Glycitin, 6 "-0-acetinoledizin, 6" -O-acelugenistin, 6 "-O-acetyldaricin. 6" -1O-sagsinildizin found in inner beans , 6 "-O-succinylgenistin, 6" -O-succinyldaricitin, pellarin, etc. The above-mentioned isoflavones may be used alone or in combination of two or more in the invention. Because of the high concentration of isoflavones, it is also possible to use extracts of soybeans, soybean foods, soybean hypocotyls, kuzu, etc., and their purified products. The solvent for extracting the isoflavone is not particularly limited, but it is preferable to use water or an alcohol such as ethanol. In addition, the method of purification can use a synthetic adsorbent, an ion exchange resin, ultrafiltration, or the like, but is not particularly limited. The extract or the purified liquid may be used as it is, or a concentrated liquid obtained by concentrating them or a powder obtained by drying and extracting the extracted liquid or the purified liquid may be used.
本発明に用いるカプサイシンの由来は、 特に限定されるものではないが、 唐辛 子を用いることが望ましい。  The origin of capsaicin used in the present invention is not particularly limited, but it is preferable to use pepper.
唐辛子に含まれるカプサイシン類としてカブサイシン、 ジヒドロカブサイシン Capsaicin and dihydrocapsaicin in capsicum
、 ノルジヒドロカプサイシン、 ホモカプサイシン、 ホモジヒドロカプサイシンが 知られている。 なお、 上記の各種カプサイシン類は、 本発明において、 単独であ るいは二種以上併せて用いられる。 , Nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin are known. In the present invention, the above-mentioned various capsaicins are used alone or in combination of two or more.
唐辛子は粉碎、 粉末ィ匕したものをそのまま使用することができるが、 濃度の高 いカブサイシンを使用するため工業的に製造された唐辛子抽出物を使用すること も可能である。 唐辛子を含水エタノールで抽出したトウガラシエキストラク ト、 へキサンやエーテルなどの主として非極性から中間極性有機溶剤で抽出したトウ ガラシオレオレジン、 さらにトウガラシオレオレジンをエタノールで再抽出し、 不溶物をろ別したトウガラシアブソリュートなどをその特性に応じて使用するこ とができる。  Pepper can be used as it is after being ground or powdered. However, it is also possible to use an industrially produced pepper extract because of using high concentration of cabsaicin. Pepper extract extracted from pepper with aqueous ethanol, pepper oleoresin extracted mainly from nonpolar to intermediate polar organic solvents such as hexane and ether, and pepper oleoresin are re-extracted with ethanol, and insoluble matter is filtered off. Can be used according to its characteristics.
本発明の可食'性組成物は、 上述のようにして得られたィソフラボンと力プサイ シンとを必須成分とするものであり、 これらを混合したものをそのまま直接使用 してもよいが、 一般には、 これらを、 適当な液状担体に溶解あるいは分散させた り、 適当な粉末担体に混合させたものを使用する。 そして、 上記イソフラボンが 有効成分となり得るための含有量は、 通常、 液剤では 0 . 0 0 1〜0 . 5重量％ (以下、 「％」 と略す） の範囲であると好適であり、 粉剤の場合は 0 . 0 1〜 8 0 %の範囲であると好適であり、 粒剤の場合は 0 . 0 1〜 4 0 %の範囲であると 好適である。 ま ^、 上記カブサイシンが有効成分となり得るための含有量は、 通 常、 液剤では 0 . 0 0 0 1〜 0 . 0 5 %の範囲であると好適であり、 粉剤の場合 は 0 . 0 0 0 1〜 5 %の範囲であると好適であり、 粒剤の場合は 0 · 0 0 0 1〜 5 %の範囲であると好適である。 そして、 本発明においては、 上記イソブラボン とカプサイシンとの割合が重要であり、 イソフラボン：カプサイシン = 5 0 0 O ： 1 ~ 1 ： 1 0の重量比で含有していると好ましく、 より好ましくは、 イソフラ ボン：カプサイシン = 5 0 0 ： 1〜1 ： 1の重量比の範囲である。 すなわち、 こ のような割合で双方が含有していると、 双方の相乗効果により、 本発明において 要求されるカルシトニン遺伝子関連べプチド産生および放出促進作用が効果的に 得られるようになるからである。 The edible composition of the present invention contains isoflavone and psisaicin obtained as described above as essential components, and a mixture of these may be used directly as it is, but generally, These are used by dissolving or dispersing them in an appropriate liquid carrier or mixing them in an appropriate powder carrier. In general, the content of the isoflavone to be an active ingredient is preferably in the range of 0.001 to 0.5% by weight (hereinafter abbreviated as “%”) in the case of a liquid. In the case, the content is preferably in the range of 0.01 to 80%, and in the case of granules, the content is preferably in the range of 0.01 to 40%. In general, the content of the above-mentioned capsaicin as an active ingredient is preferably in the range of 0.001 to 0.05% for liquids, and in the case of powders. Is preferably in the range of 0.001 to 5%, and in the case of granules, it is preferably in the range of 0.001 to 5%. In the present invention, the ratio between the above isoflavone and capsaicin is important, and the isoflavone / capsaicin is preferably contained in a weight ratio of 50,000 O: 1 to 1:10, more preferably isoflavone: capsaicin. Bon: capsaicin = 500: 1 to 1: 1 weight ratio range. That is, when both are contained at such a ratio, the synergistic effect of both allows the calcitonin gene-related peptide production and release promoting actions required in the present invention to be effectively obtained. .
本発明の可食性組成物は、 人間のみでなく、 ペットや家畜等の動物においても 、 人間に投与した際にみられる前述の作用効果と同様の作用効果が期待されるも のである。 そして、 その投与童は、 投与対象とする生物の違い、 前述の各種作用 効果のうちのいずれを得ることを目的とするのかといった違い、 投与される者の 性別、 体重、 年齢等の条件に応じて適宜設定される。 例えば、 成人に対しては、 上記イソブラボンとカプサイシンとの混合物を 1日あたり 1 0〜4 0 0 m gとな るよう、 数回に分けて投与することができる。 また、 ペットや家畜等の動物にお いては、 動物用飼料に上記混合物を 0 . 0 0 1〜5 %の範囲で含有させ、 1 日当 たり 1〜4 0 O m g / k g体重の範囲となるよう投与するのが好ましい。  The edible composition of the present invention is expected not only to humans but also to animals such as pets and livestock, to have the same effect as the above-mentioned effect observed when administered to humans. Depending on the differences in the organisms to be administered, whether the purpose is to achieve any of the various effects described above, and the gender, weight, age and other conditions of the recipient. Is set as appropriate. For example, for an adult, the above-mentioned mixture of isoflavone and capsaicin can be administered in several divided doses to give a daily dose of 10 to 400 mg. In addition, for animals such as pets and livestock, the above mixture is contained in animal feed at a rate of 0.001 to 5%, and a range of 1 to 40 mg / kg body weight per day. It is preferred that it be administered.
本発明のカルシトニン遺伝子関連べプチド産生および放出促進作用を有する可 食性組成物は、 上述したようにイソフラボンとカプサイシンを有効成分として含 むものであれば、 その形状や飲食方法を特に問うものではない。 具体的には、 飲 料や調理食品、 デザート、 菓子、 乳製品、 麵類、 パン類などの一般的な食品のほ 力 \ 好ましくは錠剤、 粉剤、 顆粒剤などの固形物や半固形剤をあげることができ る。  The edible composition of the present invention having a calcitonin gene-related peptide production and release promoting action is not particularly limited in its shape and eating and drinking method as long as it contains isoflavone and capsaicin as active ingredients as described above. More specifically, it can be used for general foods such as beverages, cooked foods, desserts, confectioneries, dairy products, foods, breads, etc. \ Solid or semi-solid preparations such as tablets, powders, and granules I can give it.
イソフラボンとカブサイシン以外の任意成分としては、 たとえば、 甘味料、 塩 味料、 酸味料、 うまみ料などの調味料、 乳化剤、 分散剤、 抗酸化剤、 防腐剤、 增 粘剤、 結合剤、 香料などがあ^ られる。 また、 錠剤や粉剤、 顆粒剤などの場合は 、 賦形剤、 結合剤、 崩壌剤、 皮膜剤、 滑沢剤、 增量剤、 希釈剤、 p H調整剤、 乳 化剤、 分散剤、 安定化剤、 嬌味嬌臭剤、 着色剤などが例示できる。  Optional ingredients other than isoflavones and capsaicin include, for example, sweeteners, seasonings, acidulants, flavorings such as umami, emulsifiers, dispersants, antioxidants, preservatives, 增 thickeners, binders, fragrances, etc. There is. In the case of tablets, powders, granules, etc., excipients, binders, disintegrants, film agents, lubricants, fillers, diluents, pH adjusters, emulsifiers, dispersants, Examples include stabilizers, flavoring agents, coloring agents, and the like.
以下に、 実施例をあげて本発明を具体的に説明する。 (実施例 1 ) Hereinafter, the present invention will be described specifically with reference to Examples. (Example 1)
〔水浸拘束ストレス胃粘膜病 モデルにおけるィソフラボンと力プサイシンによ るカルシトニン遺伝子関連ぺプチドの産生および放出促進作用と胃粘膜傷害抑制 作用の検定〕  [Test of the effects of isoflavone and psisaicin on the production and release of calcitonin gene-related peptide and on the inhibition of gastric mucosal injury in water immersion-restrained gastric mucosal disease model]
5群に分けたウィスター系雄ラット （280〜320 g、 1群あたり 8匹） を 24時間絶食させた後、 4群については水温 22°Cの水槽内に設置したストレス ゲージに 8時間拘束した （水 拘束群） 。 拘束後、 全群のラットを屠殺し、 胃の 摘出をおこなった。  Five Wistar male rats (280-320 g, 8 rats per group) divided into 5 groups were fasted for 24 hours, and 4 groups were restrained for 8 hours by a stress gauge installed in a water tank at a water temperature of 22 ° C. (Water restraint group). After detention, all groups of rats were sacrificed and their stomachs removed.
ここで、 上記 5群は、 後記の表 1に示すように、 上記絶食前に投与した飼料等 から、 イソフラボン投与群、 力プサイシン投与群、 イソフラボン +カブサイシン 投与群、 非投与群 （普通食の ） のいずれかに属する。 すなわち、 イソフラボン 投与群では、 水浸拘束処理前 2 8日よりイソフラボンの摂取量が 90 m g / k g 体重 Zd a yとなるよう大豆 B芽抽出物 （フジフラボン P I 0、 フジッコ社製） を添加した飼料で飼育を行つこ。 また、 カプサイシン投与群では、 カブサイシン を、 10 %の T w e e n 20を含む 10 %ェタノール水溶液に溶かし、 水浸拘束 の 1時間前に経口投与した （方プサイシンとして lmg/k g体重の投与） 。 さ らに、 イソフラボン +カブサイシン投与群では、 その両方を、 上記と同様にして 投与した。  Here, as shown in Table 1 below, the above-mentioned five groups consisted of the isoflavone-administered group, the cypressic acid-administered group, the isoflavone + cabsaicin-administered group, and the non-administered group (of the normal diet), as shown in Table 1 below. Belongs to any of In other words, in the isoflavone-administered group, a soybean B bud extract (Fujiflavone PI 0, manufactured by Fujico) was added so that the isoflavone intake was 90 mg / kg body weight Zd ay from 28 days before the water immersion restraint treatment. Keep breeding. In the capsaicin-administered group, capsaicin was dissolved in a 10% aqueous ethanol solution containing 10% Tween 20, and orally administered one hour before restraint by water immersion (administration of lmg / kg body weight as capsaicin). Further, in the isoflavone + cabsaicin administration group, both were administered in the same manner as described above.
そして、 上記 5群、 すなわち、 正常群 （n o rma 1 ；水浸拘束なし） と対照 群 （Co n t r o l ；水浸拘 ) と 3つのテスト群 （水浸拘束 +イソフラボン、 水浸拘束 +カブサイシン、 水浸拘束 +イソフラボン +カブサイシン） から摘出さ れた胃をもとに、 その胃部傷 指数、 胃部カルシトニン遺伝子関連ペプチド濃度 (CGRP) の測定を行った。 これらの結果を、 下記の表 1に併せて示す。 なお 、 各データは、 それぞれの群での平均値を示すものである。  The above five groups, namely, a normal group (norma 1; no water immersion restraint), a control group (Control; water immersion restraint) and three test groups (water immersion restraint + isoflavone, water immersion restraint + cabsaicin, water Based on the stomach excised from immersion restraint + isoflavone + capsaicin), the gastric injury index and gastric calcitonin gene-related peptide concentration (CGRP) were measured. The results are shown in Table 1 below. Each data shows the average value of each group.
【表 1】  【table 1】
上記表 1の結果より、 ィソアラボンとカブサイシンを同時に摂取することは、 胃部のカルシトユン遺伝子闋塞ぺプチドの産生を促進し、 胃粘膜の傷害を予防及 ぴ治療しうることがわかる。  From the results in Table 1 above, it can be seen that simultaneous ingestion of isoaravone and capsaicin can promote production of the calcitoun gene 闋 -peptide in the stomach and prevent and treat gastric mucosal injury.
(実施例 2) 〔胃潰瘍患者への投与試験〕 (Example 2) (Administration test for gastric ulcer patients)
内視鏡で胃潰瘍が認められている磨、者を対象とし、 1グループ 4人の計 4ダル ープにわけた。 そして、 そのうちのグループ 1では、 イソフラボンを含む錠剤 ( イソフラボン抽出物；フジッコ社製 フジフラボン P 4 0を使用） の投与により 1日 4 O m gのイソフラボンを摂取させ、 グループ 2では、 カプサイシンを含む 錠剤の投与により 1日 l m gの力プチイシンを摂取させた。 また、 グループ 3に はその両方を含む錠剤を投与し、 グノレープ 4には擬似錠剤を投与した。 これを 2 0日間にわたって行った。  The subjects were those who had endoscopic gastric ulcers and were divided into 4 groups, each group consisting of 4 persons. In group 1, of which, isoflavone-containing tablets (isoflavone extract; Fujiflaco P40) were used to administer 4 Omg of isoflavones per day, and in group 2, tablets containing capsaicin were used. The administration resulted in ingestion of lmg of power petitisin per day. Group 3 received tablets containing both, and gnolepe 4 received pseudo tablets. This was done for 20 days.
そして、 投与期間中の自覚症状の権認を行うとともに、 投与終了後、 胃の内視 鏡検査を行った。 この結果を、 下記 O表 2に併せて示す。 なお、 各データは、 そ れぞれのグループでの平均値を示す のである。  The patient was granted permission for subjective symptoms during the administration period, and after the administration, an endoscopy of the stomach was performed. The results are shown in Table 2 below. Each data shows the average value in each group.
【表 2】  [Table 2]
上記表 2の結果より、 イソフラボンとカプサイシンを同時に摂取することで胃 潰瘍に対して著明な改善効果が認められた。  From the results shown in Table 2 above, a marked improvement effect on gastric ulcer was recognized by taking isoflavone and capsaicin at the same time.
(実施例 3 )  (Example 3)
〔卵巣摘出ラットにおけるイソブラ;^ンとカプサイシンによるカルシトニン遺伝 子関連べプチドの産生促進作用と骨粗鬆症に対する効果の検定〕  [Test of calcitonin gene-related peptide-stimulating effect of isoprene and capsaicin in ovariectomized rats on osteoporosis]
5群に分けた 8 0日齢の S D系雌ヲット （1群あたり 6匹。 なお、 上記 5群の うちの 4群は、 卵巣摘出がなされた、 摘出後 1 0日目のラット） に、 標準食 〔力 ルシゥム欠乏飼料 （C a ： 0 . 0 0 4 %、 P ： 0 . 3 %) ] 等を投与して、 2 8 日間飼育した。 その後、 1晚 （1 8時間） 絶食させ、 全群のラットを屠殺し、 そ こから大腿骨を摘出した。  The 80-day-old SD female pets divided into 5 groups (6 per group. Of the 5 groups, 4 groups were ovariectomized and 10 days post-excision rats) The animals were fed a standard diet [power deficiency diet (Ca: 0.004%, P: 0.3%)] and the like, and bred for 28 days. After that, they were fasted for 1 晚 (18 hours), all rats were sacrificed, and their femurs were removed.
ここで、 上記 5群は、 後記の表 3に示すように、 上記絶食前に投与した飼料等 から、 イソフラボン投与群、 カプサ^ Tシン投与群、 イソフラボン +カブサイシン 投与群、 非投与群 （標準食のみ） のレ、ずれかに属する。 すなわち、 イソフラボン 投与群では、 標準食以外に、 1 %ヒ 、口キシプロピルセルロース水溶液に懸濁し たダイズインを、 飼育期間中、 経口投与 （ダイズインの摂取量が 9 O m g / k g 体重/ d a yとなるよう投与） した。 カブサイシン投与群では、 標準食以外に、 力プサイシンを 1 0 %の T w e e n 2 0を含む 1 0 %ェタノール水溶液に溶かし たものを、 飼育期間中、 経口投与 （カブサイシンの摂取量が lmgZk g体重 Z d a yとなるよう投与） した。 さらに、 イソフラボン +カプサイシン投与群では 、 その両方を投与した。 Here, as shown in Table 3 below, the above five groups consisted of the isoflavone-administered group, the capsa ^ T-sin-administered group, the isoflavone-capsaicin-administered group, and the non-administered group (standard diet), as shown in Table 3 below. Only) belongs to the misalignment. In other words, in the isoflavone-administered group, in addition to the standard diet, 1% arbor, soybean suspended in an aqueous solution of oral xypropylcellulose was orally administered during the breeding period (the soybean intake was 9 Omg / kg body weight / day. Administration). In the capsaicin-administered group, in addition to the standard diet, force psycin was dissolved in a 10% aqueous ethanol solution containing 10% Tween 20. Were orally administered during the breeding period (administration so that the intake of cabsaicin would be lmgZkg body weight Zday). Furthermore, in the isoflavone + capsaicin administration group, both were administered.
そして、 上記 5群、 すなわち、 正常群 （n o rma 1 ；卵巣摘出なし） と対照 群 （C o n t r o 1 ；卵巣摘出） と 3つのテスト群 （卵巣摘出 +イソフラボン、 卵巣摘出 +カブサイシン、 卵巣摘出 +イソフラボン カプサイシン） から摘出さ れた大腿骨をもとに、 その湿重量を測定するととも【こ、 ピクノメーターによりそ の体積を測定し、 骨密度を算出した。 また、 骨組織のカルシトニン遺伝子関連べ プチド濃度 （CGRP) の測定も行った。 これらの結果を、 下記の表 3に併せて 示す。 なお、 各データは、 それぞれの群での平均値を示すものである。  And the above 5 groups, ie, normal group (no rma 1; no ovariectomy), control group (Contro 1; ovariectomy) and three test groups (ovariectomy + isoflavone, ovariectomy + cabsaicin, ovariectomy + isoflavone) Based on the femur extracted from (capsaicin), the wet weight was measured, and the volume was measured using a pycnometer to calculate the bone density. We also measured the calcitonin gene-related peptide concentration (CGRP) in bone tissue. The results are shown in Table 3 below. Each data shows the average value of each group.
【表 3】  [Table 3]
上記表 3の結果より、 イソフラボンとカブサイシンを同時に摂取することは、 カルシトニン遺伝子関連べプチドの産生および放出を促進し、 骨粗鬆症を予防及 ぴ治療しうることがわかる。  From the results in Table 3 above, it can be seen that simultaneous ingestion of isoflavone and capsaicin can promote the production and release of calcitonin gene-related peptides and prevent and treat osteoporosis.
(実施例 4)  (Example 4)
〔脳卒中易発症高血圧自然発症ラット （SHR— SP) におけるイソフラボンと 力プサイシンによるカノレシト二ン遺伝子関連ぺプチドの産生促進作用と高血圧に 対する効果の検定〕  [Test of the effect of isoflavone and psisaicin on the production of canolecitin gene-related peptide and its effect on hypertension in stroke-prone spontaneously hypertensive rats (SHR-SP)]
18週齢の雄性 SHRS PZ 1 zmラットを、 1グループ 6匹の計 4グループ にわけた。 そして、 そのうちのグループ 1は、 イソフラボンの摂取量が 9 Omg /k g体重 Zd a yとなるように大豆胚芽抽出物 （フジフラボン P 40) を添カロ した飼料で飼育した。 グループ 2は、 力プサイシンの摂取量が 1 m g Z k g体重 /d a yとなるよう調製した飼料で飼育した。 グループ 3は、 イソフラボンと力 プサイシンの両方の投与を行った。 グループ 4は、 対照群とした。  The 18-week-old male SHRS PZ 1 zm rats were divided into 4 groups of 6 animals per group. Group 1 was fed on a diet supplemented with soybean germ extract (Fujiflavone P40) so that the isoflavone intake was 9 Omg / kg body weight Zday. Group 2 was fed on a diet prepared such that the intake of force psycin was 1 mg Zkg body weight / day. Group 3 received both isoflavone and force psycin. Group 4 was the control group.
投与 50日目の尾部血圧測定で、 グループ 1は 260±5· 2 mmH g、 ダル ープ 2は 268±10. 4mmHg、 グループ 3は 246±4. 4mmHg、 グ ループ 4は 279土 3. 1 mmH であった （グループ 3は、 グループ 4に対し て有意差あり） 。 また、 血中のカルシトニン遺伝子関連ペプチドの測定値もダル ープ 4が最も高かった。 これにより、 イソフラボンとカプサイシンを同時に投与 することは、 カルシトユン遺伝子関連ペプチドの産生を促進するため、 高血圧に 対して効果があることがわかる。 Tail blood pressure measurement on day 50 of administration: 260 ± 5.2 mmHg for group 1, 268 ± 10.4 mmHg for group 2, 246 ± 4.4 mmHg for group 3, and 279 soil for group 4 3.1 mmH (Group 3 was significantly different from Group 4). In addition, the measured value of calcitonin gene-related peptide in the blood was highest in group 4 as well. This allows simultaneous administration of isoflavone and capsaicin It can be seen that doing so promotes the production of the calcitoun gene-related peptide and is therefore effective for hypertension.
(実施例 5) 子関連べプチドの産生およぴ放出促進作用と食欲抑制による肥満防止効果の検定 ]  (Example 5) Assay for promoting obesity by promoting production and release of offspring-related peptides and suppressing appetite]
5群に分けた 80日齢の SD系雌ラット （1群あたり 7匹。 なお、 上記 5群の うちの 4群は、 卵巣摘出がなされた、 摘出後 10日目のラット） を、 28日間飼 育した。 そして、 飼育期間中、 飼料は自由に摂取させた。 ただし、 上記各群に与 えた飼料は、 後記の表 4に示すように、 標準食 〔カルシウム欠乏飼料 （Ca ： 0 . 004%、 P ： 0. 3%) 〕 、 イソフラボン （標準食にイソフラボン 0. 25 %を添加した飼料） 、 カブサイシン （標準食にカプサイシン 0. 005%を添加 した飼料） 、 イソフラボン +カブサイシン （標準食にイソフラボン 0. 25%と カプサイシン 0. 005%とを添加した飼料） のいずれかである。  80-day-old SD female rats divided into 5 groups (7 rats per group; 4 of the 5 groups mentioned above were ovariectomized and 10 days after excision) for 28 days They were bred. During the breeding period, they were allowed to feed freely. However, as shown in Table 4 below, the feed given to each of the above groups consisted of a standard diet (calcium-deficient diet (Ca: 0.004%, P: 0.3%)), isoflavone (0% isoflavone in the standard diet). Feed containing 25%), capsaicin (feed containing 0.005% capsaicin added to the standard diet), isoflavone + capsaicin (feed containing 0.25% isoflavone and 0.005% capsaicin added to the standard diet). Either.
そして、 上記 5群、 すなわち、 正常群 （n o r ma 1 ；卵巣摘出なし） と対照 群 （c o n t r o 1 ；卵巣摘出） と 3つのテスト群 （卵巣摘出 +イソフラボン 0 . 25%添加飼料、 卵巣摘出 +カブサイシン 0. 005%添加飼料、 卵巣摘出 + イソフラボン 0. 25%+カプサイシン 0. 005 %添加飼料） について、 平均 摂餌量と最終体重の測定を行った。 これらの結果を、 下記の表 4に併せて示す。 なお、 各データは、 それぞれの群での平均値を示すものである。  The above five groups, namely, a normal group (nor ma 1; no ovariectomy), a control group (contro 1; ovariectomy), and three test groups (ovariectomy + 0.25% isoflavone-added feed, ovariectomy + capsaicin) The average food intake and final body weight were measured for the diet supplemented with 0.005%, ovariectomized + isoflavone 0.25% + capsaicin supplemented with 0.005%). The results are shown in Table 4 below. Each data shows the average value of each group.
【表 4】  [Table 4]
上記表 4の結果より、 イソフラボンとカプサイシンを同時に摂取することは、 カルシトニン遺伝子関連べプチドの産生おょぴ放出を促進し、 食欲を抑制し肥満 を予防及び治療しうることがわかる。  From the results in Table 4 above, it can be seen that simultaneous ingestion of isoflavones and capsaicin can promote the production and release of calcitonin gene-related peptides, suppress appetite, and prevent and treat obesity.
(実施例 6)  (Example 6)
〔大腸癌細胞高転移株を移植して作成した 汙転移モデルにおけるイソフラボンと カブサイシンによるカルシトニン遺伝子関連ぺプチドの産生促進作用と悪性腫瘍 に対する効果の検定〕  [Test for the effect of isoflavone and capsaicin on the promotion of calcitonin gene-related peptide production and malignant tumors in metastasis models prepared by transplanting high metastatic colorectal cancer cells]
4グループに分けた （ 1グループあたり 5匹） 所定のラットの脾臓すべてに、 ヒト大腸癌細胞高転移株を移植し、 肝転移モデルを作成した。 癌細胞移植後 10 日目に肝の虚血再灌流を行い、 その後に転移した癌細胞数を計測した。 Divided into 4 groups (5 per group) A liver metastasis model was created by transplanting a highly metastatic human colon cancer cell line. Ten days after cancer cell transplantation, hepatic ischemia-reperfusion was performed, and the number of metastatic cancer cells was counted thereafter.
ところで、 癌細胞移植前 28日より、 上記 4グループのうちのグループ 1は、 イソフラボンの摂取量が 9 OmgZk g体重 Zd a yとなるように大豆胚芽抽出 物 （フジフラボン P40) を添加した飼料で飼育し、 グノレープ 2は、 カプサイシ ンの摂取量が 1 m g / k g体重/ d a yとなるよう調製した飼料で飼育した。 グ ループ 3は、 イソフラボンとカプサイシンの両方の投与を行い、 グループ 4は、 対照群とした。  By the way, from day 28 before cancer cell transplantation, group 1 of the above 4 groups was bred on a diet supplemented with soybean germ extract (Fujiflavone P40) so that isoflavone intake was 9 OmgZkg g body weight Zday. Gnorape 2 was fed on a diet prepared so that the capsaicin intake was 1 mg / kg body weight / day. Group 3 received both isoflavones and capsaicin, and group 4 was the control group.
そして、 上記のようにして計測した結果、 グループ 1、 2はグループ 4と比較 して転移癌細胞数が少なかったものの、 有意な差ではな；^つた。 これに対して、 グループ 3は、 有意に転移が抑制された。 また、 カルシ トニン遺伝子関連べプチ ドの量も他グループよりも高い値を示した。 これにより、 イソフラボンとカプサ ィシンを同時に投与することは、 カルシトニン遺伝子関連べプチドの産生を促進 し、 悪性腫瘍の転移に対して効果があることがわかる。  And as a result of the measurement as described above, the number of metastatic cancer cells in groups 1 and 2 was smaller than that in group 4, but was not a significant difference; In contrast, group 3 had significantly reduced metastasis. In addition, the amount of calcitonin gene-related peptide was higher than in other groups. This indicates that simultaneous administration of isoflavone and capsaicin promotes the production of calcitonin gene-related peptides and is effective for metastasis of malignant tumors.
(実施例 7) 遺伝子関連べプチドの産生促進作用と高血圧に対する効凍の検定〕  (Example 7) Test for effect of promoting production of gene-related peptide and effect of freezing on hypertension)
4グノレープに分けた ( 1グループあたり 5匹) 所定のラットすべてから摘出し た肝を、 臓器保存液に 24時間保存した後、 同系ラットに移植手術を行った。 こ のようにして着生率をみると同時に、 抹消血のリンパ球を分離し、 F ACSにて 細胞表面の分子について解析を行った。  Liver extirpated from all the prescribed rats divided into 4 gnolops (5 per group) were stored in organ preservation solution for 24 hours, and then transplanted into syngeneic rats. At this time, the lymphocyte of the peripheral blood was separated, and the molecules on the cell surface were analyzed by FACS.
ところで、 肝移植前 28日より、 上記 4グループのうちのグループ 1は、 イソ フラボン量が 9 Omg/k g体重/ d a yとなるように: 豆胚芽抽出物 （フジフ ラボン Ρ 40) を添加した飼料で飼育し、 グループ 2は、 カプサイシン摂取量が lmg/k g体重/ d a yとなるよう調製した飼料で飼 した。 グループ 3は、 イソフラボンとカブサイシンの両方の投与を行い、 グループ 4は、 対照群とした そして、 上記のようにして実験を行った結果、 グループ 1、 2はグループ 4と 比較して着生率が若干高かった。 これに対して、 グループ 3は、'明らかに着生率 が向上し、 移植免疫寛容状態になっていることがわかった。 まナこ、 カルシトニン 遺伝子関連ぺプチドの量も他グループよりも明らかに高い値を示した。 これによ り、 イソフラボンとカプサイシンを同時に投与することは、 カノレシトニン遺伝子 関連べプチドの産生を促進し、 臓器移植の拒絶反応が軽減されたことがわかる。 By the way, from day 28 before liver transplantation, group 1 of the above 4 groups should be adjusted so that the amount of isoflavone is 9 Omg / kg body weight / day: a diet supplemented with bean germ extract (Fujiflavon Ρ40) Group 2 was fed a diet prepared so that capsaicin intake was lmg / kg body weight / day. Group 3 received both isoflavone and capsaicin, group 4 served as a control group, and as a result of the experiment as described above, groups 1 and 2 showed a lower rate of settlement than group 4. It was slightly expensive. Group 3, on the other hand, was Was improved, and it became clear that transplantation tolerance was established. Manako and calcitonin gene-related peptides also showed significantly higher levels than the other groups. This shows that simultaneous administration of isoflavone and capsaicin promoted the production of canolecitonin gene-related peptides and reduced the rejection of organ transplantation.
(実施例 8 ) (Example 8)
〔ェンドトキシンによるショックモデルに対するイソフラボンとカプサイシンに よるカルシトニン遺伝子関連べプチドの産生促進作用と血圧低下に対する効果の 検定〕  [Test for the effect of isoflavone and capsaicin on calcitonin gene-related peptide production promotion and blood pressure reduction in endotoxin-induced shock model]
4グループに分けた ( 1グループあたり 5匹) 所定のラットすべてに、 エンド トキシン 5 m g / k g体重を静脈注射し、 ショックモデルを作成し、 血圧の測定 を行った。  Endotoxin 5 mg / kg body weight was intravenously injected to all the predetermined rats divided into 4 groups (5 rats per group), a shock model was prepared, and the blood pressure was measured.
ところで、 エンドトキシン投与前 2 8日より、 上記 4グループのうちのグルー プ 1は、 イソフラボン量が 9 O m g / k g体重 / d a yとなる ように大豆胚芽抽 出物 （フジフラボン P 4 0 ) を添加した飼料で飼育し、 グループ 2は、 カプサイ シン摂取量が 1 m g Z k g体重/ d a yとなるよう調製した飼料で飼育した。 グ ループ 3は、 イソフラボンとカプサイシンの両方の投与を行い、 グループ 4は、 対照群とした。  By the way, from day 28 before administration of endotoxin, soybean germ extract (Fujiflavone P40) was added to Group 1 of the above 4 groups so that the amount of isoflavone was 9 Omg / kg body weight / day. Group 2 was fed a diet prepared so that the capsaicin intake was 1 mg Z kg body weight / day. Group 3 received both isoflavones and capsaicin, and group 4 was the control group.
そして、 上記のようにして測定を行った結果、 グループ 1、 2はグループ 4と 比較して血圧の低下がやや抑えられた。 これに対して、 グループ 3は、 著明な血 圧低下抑制効果が認められた。 また、 カルシトニン遺伝子関連ペプチドの量も他 グループよりも明らかに高い値を示した。 これにより、 イソフラボンとカプサイ シンを同時に投与することは、 カルシトニン遺伝子関連べプチ ドの産生を促進し 、 感染に対する過剰な生体侵襲反応が抑えられたことがわかる。  Then, as a result of the measurement as described above, the decrease in blood pressure was slightly suppressed in groups 1 and 2 compared to group 4. On the other hand, in Group 3, a remarkable effect of suppressing hypotension was observed. In addition, the amount of the calcitonin gene-related peptide was clearly higher than the other groups. This indicates that simultaneous administration of isoflavone and capsaicin promoted the production of calcitonin gene-related peptides and suppressed excessive bioinvasive response to infection.
(実施例 9 )  (Example 9)
〔イソフラボンとカプサイシンによる毛包中のカルシトニン遣ィ云子関連べプチド およびィンスリン様成長因子の産生促進作用と育毛効果の検定〕  [Assay for the effect of isoflavone and capsaicin on the promotion of the production of calcitonin-secreting peptide and insulin-like growth factor in hair follicles and hair growth effect]
3週齢で購入した C 3 H/H e系マウスを、 ランダムに 1グノレープ 1 0匹とし 4グループに分け、 1週間の馴化飼育後、 グループ 1はイソブラボンの摂取量が 9 O m g / k g体重 Z d a yとなるように大豆胚芽抽出物 （フジフヲボン P 4 0 ) を添加した飼料で飼育し、 グループ 2は、 カプサイシンの摂取量力 S 2 m g / k g体重 Z d a yとなるよう調製した飼料で飼育した。 グループ 3は、 イソフラポ ンとカプサイシンの両方の投与を行い、 グループ 4は、 対照群とし fこ。 そして、 6週齢で毛刈りを行い、 その後の発毛の状況を観察した。 すなわち、 試験飼料の 摂取開始後 4 0日以内に毛の再生が完了したマウスの数の測定を行った。 この結 果を、 下記の表 5に示す。 C 3 H / He mice purchased at the age of 3 weeks were randomly divided into 4 groups of 1 gnolap and 10 mice. After 1 week of acclimatized breeding, group 1 had a higher isoflavone intake. The animals were reared on a diet supplemented with soybean germ extract (Fujif 4bon P40) so that 9 O mg / kg body weight Z day was obtained. Group 2 was prepared so that capsaicin intake capacity S 2 mg / kg body weight Z day The feed was raised. Group 3 received both isoflavone and capsaicin, and Group 4 served as a control. The hair was cut at the age of 6 weeks, and the state of hair growth was observed. That is, the number of mice whose hair regeneration was completed within 40 days after the start of ingestion of the test feed was measured. The results are shown in Table 5 below.
【表 5】  [Table 5]
上記表 5の結果より、 イソフラボンとカブサイシンを同時に摂取 "ることによ り、 著明な育毛効果のあることが認められた。 また、 毛包中のカルシトニン遺伝 子関連べプチドおよびィンスリン様成長因子の量を測定した結果、 ソフラボン とカプサイシンを同時に与えたグループ 3がグループ 1、 2、 4と J:ヒ較して有意 に多いことがわかった。 産業上の利用可能性  From the results in Table 5 above, it was confirmed that simultaneous intake of isoflavone and capsaicin had a significant hair-growth effect. In addition, calcitonin gene-related peptides and insulin-like growth factors in hair follicles As a result, it was found that group 3 which received soflavone and capsaicin at the same time was significantly higher than groups 1, 2, and 4 compared to groups J and H.
本発明の、 イソフラボンとカブサイシンを必須成分とする可食性糸且成物は、 社 会的心理的、 あるいは身体的ストレスによって宂進する、 T N F— οίなどの炎症 性サイトカインの産生を抑える働きとインスリン様成長因子を誘導する働きを持 つカルシトニン遺伝子関連べプチドの産生おょぴ放出を促進することにより、 胃 粘膜傷害、 生活習慣病、 肥満、 悪性腫瘍の発生予防及び再発予防効杲、 骨粗鬆症 を予防及び治療する効果を持ち、 臓器移植後の拒絶反応の軽減、 感染， 手術， 外 傷後の侵襲反応による臓器障害の予防および治療効果、 さらには頭髮等の育毛効 果を有する。  The edible fibrous composition comprising isoflavone and capsaicin as essential components according to the present invention has a function of suppressing the production of inflammatory cytokines such as TNF-οί and the like, which are promoted by social and psychological or physical stress. Promotes the production and release of calcitonin gene-related peptides that have the function of inducing growth-like growth factors, thereby preventing gastric mucosal injury, lifestyle-related diseases, obesity, preventing the occurrence and recurrence of malignant tumors, and preventing osteoporosis. It has preventive and therapeutic effects, has the effect of reducing rejection after organ transplantation, has the effect of preventing and treating organ damage due to invasive reactions after infection, surgery, and trauma, and has the effect of hair growth on the hair.
また、 本発明のカルシトェン遺伝子関連べプチド産生および放出促進作用を有 する可食性組成物は、 食品として長年使用されてきた唐辛子に含まれるカブサイ シンと大豆に含まれるイソフラボンを有効成分とするものであり、 全性につい ては問題がなく、 その作用も穏やかで副作用の心配がないという利^がある。 そして、 このような本発明の可食性組成物は、 現代の生活にぉ 、て問題となる 疾病の予防や治療、 あるいは身体的コンプレックスの克服を図る上で、 大きく役 に立つことが期待される In addition, the edible composition of the present invention which has a calcitoen gene-related peptide production and release promoting action comprises cabsaicin contained in pepper, which has been used as a food for many years, and isoflavone contained in soybean, as active ingredients. Yes, there is no problem with the wholeness, and there is an advantage that the action is mild and there is no concern about side effects. Such an edible composition of the present invention plays a significant role in preventing or treating diseases that are a major problem in modern life, or in overcoming physical complexes. Expected to stand
6 【表 1】 6 【table 1】
Figure imgf000018_0001
Figure imgf000018_0001
CGRP ：カルシトニン遺伝子関連べプチド （胃組織重量あたり）  CGRP: Calcitonin gene-related peptide (per stomach tissue weight)
* ：対照群に対して pく 0.05で有意差あり、 * * ：対照群に対して pく 0.01で有意差あり  *: Significantly different from control group at p <0.05, * *: significantly different from control group at p <0.01
【表 2】 [Table 2]
Figure imgf000018_0002
Figure imgf000018_0002
+++：著明な改善がみられる、 ++ :改善がみられる、 +若干の改善がみられる 土：変化なし、 一：若干の悪化がみられる +++: marked improvement, ++: improvement, + slight improvement Soil: no change, 1: slight deterioration
【表 3】 [Table 3]
Figure imgf000019_0001
Figure imgf000019_0001
CGRP ：カルシトニン遺伝子関連ペプチド （骨,袓織重量あたり）  CGRP: Calcitonin gene-related peptide (per bone, tissue weight)
* ：対照群に対して ρく 0.05で有意差あり、 * * ：対照群に対して ρく 0.01で有意差あり *: Significantly different from control group at ρ 0.05, **: Significant difference from control group at ρ 0.01
* * * ：対照群に対して ρく 0.005で有意差あり * * *: Significantly different from control group at ρ 0.00 0.005
【表 4】 [Table 4]
Figure imgf000020_0001
Figure imgf000020_0001
CGRP ：カルシトニン遺伝子関連ペプチド （胃組織重量あたり）  CGRP: Calcitonin gene-related peptide (per stomach tissue weight)
* ：対照群に対して ρく 0.05で有意差あり、 * * ：対照群に対して ρく 0.01で有意差あり  *: Significantly different from control group at ρ 0.05, **: Significant difference from control group at ρ 0.01
【表 5】 [Table 5]
Figure imgf000020_0002
Figure imgf000020_0002
9  9

Claims

請求の範囲 The scope of the claims
1 . イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連 プ チド産生および放出促進作用を有することを特徴とする可食性組成物。 1. An edible composition comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
2 . イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連ぺプ チド産生および放出促進作用を有することを特徴とする、 胃粘膜傷害予防及 治 療用可食性組成物。  2. An edible composition for preventing and treating gastric mucosal injury, comprising isoflavone and capsaicin as essential components, and having a calcitonin gene-related peptide production and release promoting action.
3 . イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連ぺプ チド産生および放出促進作用を有することを特徴とする、 生活習慣病予防及 治 療用可食性組成物。  3. An edible composition for preventing and treating lifestyle-related diseases, comprising isoflavone and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
4 . イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連ぺプ チド産生および放出促進作用を有することを特徴とする、 肥満予防及び治療月可 食性組成物。  4. An edible composition for preventing and treating obesity, comprising isoflavones and capsaicin as essential components, and having a calcitonin gene-related peptide production and release promoting action.
5 . イソフラボンとカプサイシンを必須成分とし、 カルシトニン遺伝子関連ぺプ チド産生および放出促進作用を有することを特徴とする、 悪性腫瘍発生予防， 再 発予防及び治療用可食性組成物。  5. An edible composition for preventing malignant tumor occurrence, preventing recurrence and treating, comprising isoflavone and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
6 . イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連ペプ チド産生および放出促進作用を有することを特徴とする、 骨粗鬆症予防及ぴ抬療 用可食性組成物。  6. An edible composition for preventing and treating osteoporosis, comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
7 . イソフラボンとカブサイシンを必須成分とし、 カルシトニン遺伝子関連ぺプ チド産生および放出促進作用を有することを特徴とする、 臓器移植拒絶反応輕減 用可食性組成物。  7. An edible composition for reducing organ transplant rejection, which comprises isoflavone and capsaicin as essential components, and has an activity of promoting calcitonin gene-related peptide production and release.
8 . イソフラボンとカプサイシンを必須成分とし、 カルシトニン遺伝子関連ぺプ チド産生および放出促進作用を有することを特徴とする、 感染， 外傷， 手術等の 侵襲要因に対する生体侵襲反応に伴う臓器障害の予防及び軽減用可食性組成 ¾。  8. Prevention and reduction of organ damage caused by biologically invasive response to invasive factors such as infection, trauma, surgery, etc., characterized by having isoflavone and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action. For edible composition ¾.
9 . イソフラボンと力プサイシンを必須成分とし、 力ルシト二ン遺伝子関連ぺプ チド産生および放出促進作用を有することを特徴とする、 育毛用可食性組成^；。 9. An edible composition for hair restoration ^; comprising isoflavones and force psycin as essential components, and having an effect of promoting the production and release of a force-lucitonin gene-related peptide.
10. イソフラボンが、 大豆由来のイソブラボンである請求項 1〜 9のいずれ力 一項に記載の可食性組成物。 10. The edible composition according to any one of claims 1 to 9, wherein the isoflavone is soybean-derived isoflavone.
11. カプサイシンが、 唐辛子由来のカプサイシンである請求項 1〜10のい" f れか一項に記載の可食性組成物。  11. The edible composition according to any one of claims 1 to 10, wherein the capsaicin is capsaicin derived from pepper.
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000059523A1 (en) * 1999-04-08 2000-10-12 Metagenics, Inc. Composition and method for treatment of inflammation and pain in mammals
JP2002275062A (en) * 2001-02-12 2002-09-25 Warner Lambert Co Treating agent for disease and disorder mediated by nuclear factor kappa b
EP1329222A1 (en) * 2001-12-18 2003-07-23 Daicho Kikaku Incorporated Company Isoflavone compositions for use in medicine
JP2003286180A (en) * 2002-03-28 2003-10-07 Fuji Oil Co Ltd Obesity inhibitor and food containing the same
JP2004059454A (en) * 2002-07-25 2004-02-26 Japan Energy Corp QUINAZOLONE DERIVATIVE AND NF-kappaB ACTIVATION INHIBITOR
JP2005068129A (en) * 2003-10-31 2005-03-17 Kenji Okajima Edible composition having promoting activity against production and release of calcitonin gene-associated peptide

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000059523A1 (en) * 1999-04-08 2000-10-12 Metagenics, Inc. Composition and method for treatment of inflammation and pain in mammals
JP2002275062A (en) * 2001-02-12 2002-09-25 Warner Lambert Co Treating agent for disease and disorder mediated by nuclear factor kappa b
EP1329222A1 (en) * 2001-12-18 2003-07-23 Daicho Kikaku Incorporated Company Isoflavone compositions for use in medicine
JP2003286180A (en) * 2002-03-28 2003-10-07 Fuji Oil Co Ltd Obesity inhibitor and food containing the same
JP2004059454A (en) * 2002-07-25 2004-02-26 Japan Energy Corp QUINAZOLONE DERIVATIVE AND NF-kappaB ACTIVATION INHIBITOR
JP2005068129A (en) * 2003-10-31 2005-03-17 Kenji Okajima Edible composition having promoting activity against production and release of calcitonin gene-associated peptide

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
BAXA D.M. ET AL: "Genistein reduces NF-kappa B in T lymphoma cells via a caspase-mediated cleavage of I kappa B alpha.", BIOCHEMICAL PHARMACOLOGY., vol. 66, 2003, pages 1009 - 1018, XP002989167 *
HARADA N. ET AL: "Contribution of capsaicin-sensitive sensory neurons to stress-induced increases in gastric tissue levels of prostaglandins in rats.", AM J PHYSIOL., vol. 285, December 2003 (2003-12-01), pages G1214 - G1224, XP002989169 *
INOUE D. AND MATSUMOTO T. ET AL: "Hone Taisha Kiso Kenkyu no Shinpo.", JAPANESE JOURNAL OF CLINICAL MEDICINE., vol. 60, 28 March 2002 (2002-03-28), pages 25 - 33, XP002992643 *
MILLET I. ET AL: "Inhibition of NF-kappaB Activity and Enhancement of Apoptosis by the Neuropeptide Calcitonin Gene-related Peptide.", THE JOURNAL OF BIOLOGICAL CHEMSITRY., vol. 275, no. 20, 19 May 2000 (2000-05-19), pages 15114 - 15121, XP002989170 *
PHILPOTT M.P. ET AL: "Effects of Insulin and Insulin-Like Growth Factors on Cultured Human Hair Follicles: IGF-I at Physiologic Concentrations is an Important Regulator of Hairfollicle Growth in Vitro.", THE JOURNAL OF INVESTIGATIVE DERMATOLOGY., vol. 102, 1994, pages 857 - 861, XP001095971 *
SINGH S. ET AL: "Capsaicin (8-Methyl-N-Vanillyl-6-Nonenamide) Is a Potent Inhibitor of Nuclear Transcription Factor-KappaB Activator by Diverse Agents.", THE JOURNAL OF IMMUNOLOGY., vol. 157, no. 10, 1996, pages 4412 - 4420, XP002989168 *
VIGNERY A. ET AL: "The Neuropeptide Calcitonin Gene-Related Peptide Stimulates Insulin-like Growth Factor I Production by Primary Fetal Rat Osteoblasts.", BONE., vol. 18, no. 4, April 1996 (1996-04-01), pages 331 - 335, XP002065011 *

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