JP2022056264A - Composition containing turmeric oil for vascular protection, and food and beverage and perfume containing the composition - Google Patents

Abstract

To provide a composition containing turmeric oil for vascular protection inhibiting vascular injury or vascular protection including repair of the vascular injury, and food and beverage and perfume containing such the composition.SOLUTION: The composition according to the present invention, and the food and beverage and the perfume containing such the composition contain turmerones which are one or more compounds selected from the group consisting of AR-turmerone, α-turmerone and β-turmerone to inhibit vascular injury such as fibril damage of blood vessel wall, abdominal aortic aneurysms or breast aortic aneurysms, or repair such vascular injuries, and the food and beverage and the perfume containing such the composition.SELECTED DRAWING: Figure 1

Description

The present invention relates to compositions containing turmeric oil for vascular protection, as well as foods and drinks and flavors containing such compositions. More specifically, it contains turmerons, which are one or more compounds selected from the group consisting of AR-termeron, α-termeron and β-termeron, such as vascular wall fibrosis, abdominal aortic aneurysm, or thoracic aortic aneurysm. With respect to compositions for inhibiting or repairing vascular injury, as well as foods and drinks and fragrances comprising such compositions.

Abdominal aortic aneurysm (AAA) is an aneurysm that occurs in the abdominal aorta located below the diaphragm and is the most frequent aortic aneurysm. It is said that the weakening of the aortic wall is greatly involved in the occurrence of abdominal aortic aneurysm, and it is thought that it is caused by structural abnormalities or destruction of the wall due to inflammatory diseases, congenital connective tissue abnormalities, atherosclerosis, etc. There is.

In general, many of the causes of aortic aneurysm are also called arteriosclerosis. Arteriosclerosis is a condition in which the walls of arteries become thicker or harder, and their flexibility and elasticity are reduced. Hypertension, dyslipidemia, smoking, etc. have been pointed out as risk factors for arteriosclerosis. As preventive measures for such risk factors, doctors may recommend controlling blood pressure, reducing cholesterol intake in the diet, smoking cessation, and the like. However, little is known about food ingredients that are effective for positively preventing aortic aneurysm and arteriosclerosis that causes it.

In addition, the relationship between smoking and arteriosclerosis suggests that nicotine, the main component of tobacco smoke, is closely associated with the development and rupture of abdominal aortic aneurysms in recent studies of abdominal aortic aneurysms. (See Non-Patent Document 1). Nicotine induces weakening of the vessel wall by increasing oxidative stress and matrix metalloproteinase (MMP) -2 expression and degrading elastin present in the media of the vessel wall. Nicotine is thought to promote the development of abdominal aortic aneurysm by the above mechanism.

Under such circumstances, attempts have been made to create a disease model of abdominal aortic aneurysm using nicotine (Non-Patent Document 2 and Non-Patent Document 3). It is also suggested that this disease model may be used for screening for drugs that prevent other common abdominal aortic aneurysms that are not directly caused by nicotine, although nicotine is used. This is because the process leading to abdominal aortic aneurysm is considered to be common whether or not it is nicotine-mediated.

Using a disease model of abdominal aortic aneurysm using nicotine, we have already found a health food or pharmaceutical composition containing sesamine and / or sesamolin as an active ingredient to prevent deterioration of blood vessels. (Patent Document 1). However, there is a further need to screen various compounds with other excellent effects and to synthesize new compounds to help prevent abdominal aortic aneurysm.

International Publication WO2020 / 003363

Kugo H, Zaima N, Tanaka H, Urano T, Unno N, Moriyama T (2017) The effects of nicotine administration on the pathophysiology. Biotech Histochem. 92 (2): 141-148.

Markus U Wagenhaeuser et al. (2018) Chinese Nicotine Exposure Industries Murine Aortic Remodeling and Stiffness Segmentation-Implications for Abdominal Abdominal. Front Physiol. 2018 Oct 31; 9: 1459. doi: 10.389 / fphys. 2018.01459.

As mentioned above, from the viewpoint of preventing the occurrence of abdominal aortic aneurysm, a method for preventing deterioration of blood vessels is required. However, little is known about methods of preventing the deterioration of blood vessels that lead to the development of abdominal aortic aneurysms, especially food ingredients that are useful in such methods.

As a result of diligent studies, the present inventors prevent nicotine-induced deterioration of blood vessels by turmerons, which are one or more compounds selected from the group consisting of AR-turmeron, α-termeron and β-termeron. It was found to have an effect.
As a result, the present inventors contain turmerons, which are one or more compounds selected from the group consisting of AR-turmeron, α-termeron and β-termeron, as an active ingredient in order to prevent deterioration of blood vessels. It has led to the creation of compositions, as well as foods and drinks and flavors containing such compositions.
That is, the present inventors contain, as an active ingredient, turmerons which are one or more compounds selected from the group consisting of AR-turmeron, α-termeron and β-termeron, which have solved the problems of the prior art. For the first time, we have developed a composition for preventing deterioration of blood vessels, as well as foods and drinks and flavors containing such a composition.

The invention according to claim 1 relates to a composition for protecting blood vessels, which contains turmeric oil.

In the invention according to claim 2, the active ingredient of the turmeric oil is turmeric, and the turmeric is a group consisting of AR-turmeric (chemical 1), α-turmeric (chemical 2) and β-turmeric (chemical 3). The composition according to claim 1, which is one or more compounds selected from the above.

The invention according to claim 3 relates to the composition according to claim 1 or 2, wherein the vascular protection comprises inhibiting the vascular injury or repairing the vascular injury.

The invention according to claim 4 relates to the composition according to claim 1 to 3, wherein the vascular injury is a vascular injury modeled by nicotine-induced fibrous destruction of the vascular wall.

The invention according to claim 5 relates to the composition according to claim 1 to 4, wherein the vascular injury is an abdominal aortic aneurysm or a thoracic aortic aneurysm.

The invention according to claim 6 relates to the composition according to claim 1 to 5, which is administered by oral administration or nasal administration.

The invention according to claim 7 is used to include in at least one selected from the group consisting of foods, beverages, flavors, aroma oils, odor bags, incense sticks, cigarettes, and electronic cigarettes, according to claims 1 to 6. With respect to the described composition.

The invention according to claim 8 relates to a food or drink containing the composition according to claims 1 to 6.

The invention according to claim 9 relates to a fragrance containing the composition according to claims 1 to 6.

According to the first aspect of the present invention, since it is a composition for protecting blood vessels containing turmeric oil, it is possible to easily and efficiently exert protection against blood vessel deterioration.

According to the invention of claim 2, the active ingredient of the turmeric oil is turmeric, and the turmeric is one or more compounds selected from the group consisting of AR-turmeric, α-turmeric and β-turmeric. Therefore, it is possible to easily and efficiently exert vascular protection against vascular deterioration.

According to the invention of claim 3, since the blood vessel protection includes inhibiting the blood vessel damage or repairing the blood vessel damage, it can exert an effect on various blood vessel protections.

According to the invention of claim 4, since the vascular injury is a vascular injury modeled by the fiber destruction of the vascular wall caused by nicotine, it is easy to cope with the vascular deterioration of the vascular wall caused by nicotine. It is possible to efficiently exert vascular protection.

According to the invention of claim 5, since the composition according to claim 1 to 4, wherein the vascular injury is an abdominal aortic aneurysm or a thoracic aortic aneurysm, is effective prevention against an abdominal aortic aneurysm or a thoracic aortic aneurysm. Can have an effect.

According to the invention of claim 6, since it is administered by oral administration or nasal administration, it can be easily administered to a subject.

According to the invention of claim 7, various products are used for inclusion in at least one selected from the group consisting of foods, beverages, flavors, aroma oils, odor bags, incense sticks, cigarettes, and electronic cigarettes. It can exert the effect of protecting blood vessels against deterioration of blood vessels.

According to the invention of claim 8, since it is a food or drink containing the composition according to claims 1, it is possible to obtain a food or drink having an effect of protecting blood vessels against blood vessel deterioration.

According to the invention of claim 9, since it is a fragrance containing the composition according to claims 1, it is possible to obtain a fragrance product having an effect of protecting blood vessels against blood vessel deterioration.

It is a figure which shows the experimental system for nasal or pulmonary administration of turmeric oil. Cotton wool impregnated with turmeric oil is attached to the inside of the lid of the Erlenmeyer flask, and the mice in the flask are exposed to turmeric oil and absorb the turmeric oil nasally or pulmonary. It is a figure which shows the effect of the turmeric oil exposure to the vascular injury of a mouse by EVG staining. The grouping of samples was as follows. Group C: Turmeric oil exposure 0 minutes + MF food + tap water (no turmeric oil, control without nicotine treatment), Group T: Turmeric oil exposure 60 minutes + MF food + tap water (with turmeric oil, no nicotine treatment), CN group : Turmeric oil exposure 0 minutes + MF diet + 0.5 mg / mL nicotine solution (without turmeric oil, with nicotine treatment), TN group: Turmeric oil exposure 60 minutes + MF diet + 0.5 mg / mL nicotine solution (with turmeric oil, with nicotine treatment) ). Elastic fibers in the abdomen of mice in each group were stained with Elastica van Gieson (EVG) and observed. The figure is a bar graph showing the elastic plate fracture rate in each group. It is a figure which shows the effect of the turmeric oil exposure on the vascular injury of a mouse by observation of MMP-2 which is an extracellular matrix degrading enzyme. The grouping of samples was as follows. Group C: Turmeric oil exposure 0 minutes + MF food + tap water (no turmeric oil, control without nicotine treatment), Group T: Turmeric oil exposure 60 minutes + MF food + tap water (with turmeric oil, no nicotine treatment), CN group : Turmeric oil exposure 0 minutes + MF diet + 0.5 mg / mL nicotine solution (without turmeric oil, with nicotine treatment), TN group: Turmeric oil exposure 60 minutes + MF diet + 0.5 mg / mL nicotine solution (with turmeric oil, with nicotine treatment) ). MMP-2 was immunostained and observed in the medial and adventitia of the mice of each group. The figure is a bar graph showing the MMP-positive area (%) in each group. It is a figure which shows the effect of the turmeric oil exposure on the vascular injury of a mouse by observation of MMP-9 which is an extracellular matrix degrading enzyme. The grouping of samples was as follows. Group C: Turmeric oil exposure 0 minutes + MF food + tap water (no turmeric oil, control without nicotine treatment), Group T: Turmeric oil exposure 60 minutes + MF food + tap water (with turmeric oil, no nicotine treatment), CN group : Turmeric oil exposure 0 minutes + MF diet + 0.5 mg / mL nicotine solution (without turmeric oil, with nicotine treatment), TN group: Turmeric oil exposure 60 minutes + MF diet + 0.5 mg / mL nicotine solution (with turmeric oil, with nicotine treatment) ). MMP-9 was immunostained and observed in the medial and adventitia of the mice of each group. The figure is a bar graph showing the MMP-positive area (%) in each group. It is a figure which shows the measurement result of the concentration of the turmeric (α-turmeric, β-turmeric, AR-turmeric) transferred to the serum when the turmeric oil was exposed to a mouse in a flask or orally administered. .. The grouping of samples was as follows. Group C: 2% CMC + no exposure, ET group: turmeric oil exposed for 60 minutes, LT group: turmeric oil 0.02 mg / g (emulsified with CMC) orally administered, HT group: turmeric oil 0.03 mg / g (with CMC) (Emulsification) is orally administered. The measurement results of the concentration of turmeric (α-termeron, β-termeron, AR-termeron) transferred to the abdominal blood vessel or the thoracic blood vessel when the turmeric oil was exposed in a flask to the mouse or orally administered are shown. It is a figure. The grouping of samples was as follows. Group C: 2% CMC + no exposure, ET group: turmeric oil exposed for 60 minutes, LT group: turmeric oil 0.02 mg / g (emulsified with CMC) orally administered, HT group: turmeric oil 0.03 mg / g (with CMC) (Emulsification) is orally administered.

Hereinafter, preferred embodiments of the composition for preventing vascular deterioration according to the present invention will be described.

As used herein, vascular deterioration is used interchangeably with vascular injury and generally refers to the degradation of elastin in the walls of blood vessels in blood vessels modeled by, but not limited to, ingestion of nicotine. Point to. By degrading elastin in the vessel wall, the vessel wall loses elasticity and promotes the development of abdominal aortic aneurysm and the rupture of abdominal aortic aneurysm. However, the deterioration of blood vessels in the present specification includes cases where elastin degradation of blood vessel walls is not always obvious, and is indicated by, for example, molecular markers observed with deterioration of blood vessels or the quantification or detection of specific proteins. Includes all types of vascular damage that can be detected.

As used herein, vascular protection includes inhibiting vascular damage, repairing vascular damage, or maintaining good condition of blood vessels. In addition, this vascular protection broadly includes the general concept of preventing, inhibiting, and blocking deterioration of the vascular wall, such as the degradation of elastin in the vascular wall, and the physiological or chemical mechanism of its protection is specific. Not limited to things.

The composition for preventing the deterioration of blood vessels of the present invention, and foods and drinks and flavors containing such a composition contain turmeric oil as an active ingredient. The active ingredient of this turmeric oil is turmeric, and the turmeric is one or more compounds selected from the group consisting of AR-turmeric, α-turmeric and β-turmeric.

The AR-turmeron has a CAS number 532-65-0 and has a structure represented by the following formula (formulation 4).

The α-turmeron has CAS No. 82508-15-4 and has a structure represented by the following formula (Chemical formula 5).

The β-turmeron has CAS No. 82508-14-3 and has a structure represented by the following formula (Chemical formula 6).

In the present invention, standard products can be used as turmeric oil, AR-turmeric, α-turmeric, and β-turmeric.
Further, those obtained from an extract such as curry spice can be used, and in particular, those obtained from an extract of turmeric can be used.

Turmeric (English name: Turmeric, scientific name: Curcuma longa) is a monocotyledonous plant of the genus Turmeric in the family Zingiberaceae. It is a perennial plant native to India and has a well-developed rhizome. The rhizome is used as a raw material and dye for curry powder.

As the composition for preventing the deterioration of blood vessels of the present invention of the present invention, those containing AR turmeron, α-turmeron and β-termeron as active ingredients can be used.
AR-turmeric, α-turmeric and β-turmeric are suitably extracted from the rhizome of turmeric by steam distillation, hexane extraction, or ethyl acetate extraction. The reason is that by extracting the rhizome of turmeric by steam distillation, hexane extraction, or ethyl acetate extraction, a large amount of AR-turmeron, α-termeron, and β-termeron can be eluted.

The composition for inhibiting or repairing vascular injury of the present invention includes turmeric oil, AR-turmeric, α-turmeric or β-turmeric as an active ingredient, or turmeric oil. An extract containing the contained extract can be used as an active ingredient, and the extract containing turmeric can be used.

Turmeric oil, AR-turmeric, α-turmeric or β-turmeric are suitably extracted from the rhizome of turmeric by steam distillation, hexane extraction, or ethyl acetate extraction. The reason is that by extracting the rhizome of turmeric by steam distillation, hexane extraction, or ethyl acetate extraction, a large amount of turmeric oil, AR-turmeric, α-turmeric or β-turmeric can be eluted.

Turmeric oil, AR-turmeric, α-turmeric or β-turmeric can be used alone or in admixture of two or more.
When turmeric oil, AR-turmeric, α-turmeric or β-turmeric are mixed and used, the mixing ratio is not particularly limited, and the mixture is mixed at an arbitrary ratio, for example, between 1:99 and 99: 1. Can be used.
As described in detail in the following examples, turmeric oil, AR-turmeric, α-turmeric or β-turmeric has an action of preventing deterioration of blood vessels (for example, decomposition of elastin), and thus these are active ingredients. The composition of the present invention contained in the above can be used for various purposes including pharmaceutical use.

For example, when a pharmaceutical composition for preventing deterioration of blood vessels is used as a pharmaceutical preparation, it is used as a preventive agent for deterioration of blood vessels in mammals (particularly humans).
In addition, the pharmaceutical preparation used for nicotine replacement therapy contains a pharmaceutical composition for preventing deterioration of blood vessels of the present invention, and for the purpose of preventing deterioration of blood vessels due to the influence of nicotine intake in nicotine replacement therapy. A pharmaceutical composition for preventing deterioration may be used.

Pharmaceutical compositions for preventing deterioration of blood vessels include tablets, powders, fine granules, granules, coated tablets, capsules, syrups, troches, inhalants, suppositories, and injections by conventional methods. , Ointment, eye ointment, eye drop, nasal drop, ear drop, bop, lotion and other pharmaceutical formulations.

Excipients, binders, lubricants, colorants, flavoring agents, and optionally stabilizers, emulsifiers, absorption enhancers, surfactants, pH adjusters, preservatives, anti-formulas commonly used for formulation. An oxidant or the like can be used, and an ingredient and a blending amount generally used as a raw material for a pharmaceutical preparation are appropriately selected and formulated by a conventional method.

When a pharmaceutical preparation containing a pharmaceutical composition for preventing deterioration of blood vessels is administered, the form thereof is not particularly limited, and any commonly used method may be used, and oral administration or parenteral administration may be used.
As the dose of the pharmaceutical product, a pharmaceuticalally effective amount can be appropriately selected according to the degree of symptoms, age, sex, body weight, administration form, specific type of disease, and the like.
As an example of the dose, in the case of oral administration, the amount of the active ingredient is usually about 3 to 3000 mg / kg in adults, and this may be administered once to several times a day.

Further, from the viewpoint of contributing to general health, the composition of the present invention may be used for various purposes related to oral, nasal or pulmonary ingestion of foods, beverages, flavors, etc., even if it is not necessarily for pharmaceutical use. Can be used for various products.

For example, foods for preventing deterioration of blood vessels of the present invention include, for example, various types of foods such as refreshing drinking water, dairy products (processed milk, yogurt), confectionery (jelly, chocolate, biscuits, gum, tablets) or supplements. Foods or health foods, but are not limited to these. In this specification, health food refers to all foods that are widely sold and used as foods that contribute to the maintenance and promotion of health, and is a concept that includes foods with functional claims, foods with nutritional function, and foods for specified health use. ..

The amount of turmeric oil, AR-turmeric, α-turmeric or β-turmeric added as an active ingredient in a food is not particularly limited and may be appropriately determined according to the type of food. As an example, the above-mentioned extract may be added so that the dry weight of the extract is in the range of 0.0005 to 50% by weight.

The food for preventing the deterioration of blood vessels of the present invention contains excipients, taste agents, colorants, preservatives, thickeners, stabilizers, gelling agents, antioxidants and the like as other ingredients. You may.
Of these, the excipient is not limited to these, for example, powders such as fine particle silicon dioxide, sucrose fatty acid ester, crystalline cellulose / sodium carboxymethyl cellulose, calcium hydrogen phosphate, wheat starch, rice starch, corn. Starch such as starch, potato starch, dextrin, cyclodextrin, crystalline cellulose, lactose, glucose, sugar, reduced malt sugar, water candy, fructo-oligosaccharide, galactooligosaccharide, soybean oligosaccharide, isomaltooligosaccharide, xylooligosaccharide, maltooligosaccharide, milk Examples thereof include sugars such as fruit oligosaccharides and sugar alcohols such as sorbitol, eristol, xylitol, lactitol and mannitol. These excipients can be used alone or in combination of two or more.

Examples of the flavoring agent include bontan extract, lychee extract, apple juice, orange juice, yuzu extract, peach flavor, ume flavor, sweetener Acesulfam K, sucralose, eristol, oligosaccharide, mannose, and the like. Examples thereof include, but are not limited to, xylitol, isomerized sugar, green tea which is a tea component, oolong tea, vanaba tea, tochu tea, iron Kannon tea, hatomugi tea, amachazuru tea, makomo tea, kelp tea, and yogurt flavor.

Moreover, the composition of this invention may be added to a beverage. Beverages include orange, apple, grape, peach, passion fruit, juice with fruit juice such as sea urchin, green tea, oolong tea, banaba tea, tochu tea, iron Kannon tea, hatomugi tea, amachazuru tea, makomo tea, kelp tea, etc. Examples include, but are not limited to, alcoholic beverages such as coffee, cocoa, lactic acid beverages, dairy beverages, beer, whiskey, chewy, and various cocktails.

Furthermore, the composition of the present invention can also be ingested by direct inhalation as a scent component. The composition of the present invention may be inhaled as it is as a volatile component of turmeric oil, or may be used in combination with other scent components (for example, citrus flavors). Due to its inhalable nature, it can also be added to at least one selected from the group consisting of fragrances, aroma oils, odor bags, incense sticks, cigarettes, and electronic cigarettes. The compositions of the present invention are absorbed nasally or pulmonary and are transferred into the blood.

Hereinafter, the effects of the present invention will be clarified by explaining the embodiments of the present invention.
However, the present invention is not limited to the following examples.

<Preparation of steam distillation>
1 kg of turmeric rhizome was crushed, and 20 kg of agglomerate was recovered by passing steam under normal pressure through the pulverized rhizome. The aggregate was centrifuged to obtain 25 g of a pale yellow oily liquid.

<Preparation of hexane extract>
1 kg of turmeric rhizome was pulverized, stirred and extracted with 5000 ml of hexane at 40 ° C. for 1 hour, and 4200 ml of the supernatant was filtered through a filter paper.
Then, the residue was stirred and extracted with 2500 ml of hexane at 40 ° C. for 0.5 hours, and filtered through a filter paper. The solvent contained in the obtained extract was distilled off with an evaporator (40 ° C.) to obtain a turmeric hexane extract.

<Preparation of ethyl acetate extract>
The residue after hexane extraction of turmeric was dried, stirred and extracted with 5000 ml of ethyl acetate at 40 ° C. for 1 hour, and 4800 ml of the supernatant was filtered through a filter paper. The solvent contained in the obtained extract was distilled off by an evaporator (40 ° C.) to obtain an ethyl acetate extract of turmeric.
The yields of the hexane extract and the ethyl acetate extract are shown in Table 1 below.

Hexane extracts were analyzed using GCMS under the following conditions.
Column; Intertcap Pure Wax (0.25i.d. × 0.25μm × 60m)
-Injection volume; 1.0 μl
・ Temperature rise; hold at 50 ° C for 2 minutes, temperature rise at 2.5 ° C / min → up to 240 ° C ・ Vaporization room temperature; 250 ° C
・ Carry gas flow rate; helium 1.2 ml / min ・ split ratio; 1/80
From the results of GCMS analysis, the compounds were estimated to be AR-termeron, α-termeron and β-termeron by the attached library search (wiley7n and NIST08).
The hexane extract contained 9.9% AR-turmeron, 30.4% α-termeron, and 11.5% β-termeron.

The hexane extract was fractionated under the following HPLC conditions.
Column; L-column ODS (20id × 250 mm)
-Mobile phase; water: acetonitrile (20:80, v / v)
-Flow velocity: 18.9 ml / min
-Column temperature; room temperature-detection; UV 243 nm
-Injection volume; 10 μl
As the active ingredient of the hexane extract, pale yellow oily substances were obtained from the fractions of RT7.5, 10.5 and 11.0, respectively.

The pale yellow oily substance was analyzed under the GCMS conditions described in the above paragraph [0066], and from the results, the compounds were AR-turmeron and α-, respectively, using the attached library search (wiley7n and NIST08) and NMR analysis. Confirmed to be turmeron and β-termeron (Hideji Itokawa, Fusayoshi Hirayama, Kazuko Funakoshi and Koichi Takeya Chem. Pharma.Pharm.Pharm.Bull.33 (8) 34-34 (8) 34 , Hideji Itokawa Yakugaku zashhi 112 (11), confirmed by comparison with the literature values of 817-823).

<Effect of administration of turmeric oil on vascular protection>
Next, in order to confirm the presence or absence of the effect of turmeric oil on preventing blood vessel deterioration, a test was conducted in which turmeric oil was administered to mice.

The test procedure is described in detail below.
First, 4-week-old male Slc / ddY mice (Nippon SLC Co., Ltd.) were acclimatized for 5 days, and the mice were randomly assigned to the following four groups.
Group C: Turmeric oil exposure 0 minutes + MF food + tap water (control without turmeric oil, no nicotine treatment)
Group T: Turmeric oil exposure 60 minutes + MF food + tap water (with turmeric oil, without nicotine treatment)
CN group: Turmeric oil exposure 0 minutes + MF diet + 0.5 mg / mL nicotine solution (without turmeric oil, with nicotine treatment),
TN group: Turmeric oil exposure 60 minutes + MF diet + 0.5 mg / mL nicotine solution (with turmeric oil, with nicotine treatment)

In the present invention, turmeric oil exposure was carried out using an experimental system in which mice were exposed to gaseous turmeric oil and turmeric oil was administered nasally or pulmonary. We investigated the possibility that administration using this system could be used in the same way as oral administration.
An experimental system in which mice are exposed to gaseous turmeric oil is shown in FIG. Place the mouse in the Erlenmeyer flask, attach cotton wool impregnated with turmeric oil to the inside of the lid of the Erlenmeyer flask, and leave it for 60 minutes as one cycle, and perform exposure treatment for 3 cycles per week. , Mice were exposed to turmeric oil. It was confirmed that mice absorb turmeric oil nasally or pulmonary (see below).

Mice in group C (control group) and group T (turmeric oil exposed group) were fed distilled water for 2 weeks. In addition, in this example, turmeric oil isolated from the hexane extract was used.
On the other hand, for mice in the CN group (control + nicotine group) and TN group (turmeric oil exposure + nicotine group), 0.5 mg of nicotine (manufactured by Wako Pure Chemical Industries, Ltd.) was added to tap water instead of tap water. A nicotine solution containing at a concentration of / ml was supplied for 2 weeks.
At the same time, MF diet (solid powder feed for experimental animals, manufactured by Oriental Yeast Co., Ltd.) was fed to mice in each group for 2 weeks.
Group C (control group) and CN group (control + nicotine group) did not undergo the above-mentioned turmeric oil exposure during the 2-week experimental period.
The T group (turmeric oil exposure group) and the TN group (turmeric oil exposure + nicotine group) were subjected to the above-mentioned turmeric oil exposure treatment three times a week in a cycle of 60 minutes each.

After 2 weeks of turmeric oil exposure and diet, mice in each group were sacrificed.
Blood, as well as thoracic and abdominal aorta, were isolated from the sacrificed mice.
Serum was isolated from the collected blood, and the isolated thoracic and abdominal aortas were immobilized with 4% paraformaldehyde (manufactured by Nakaraitesk Co., Ltd.) and immersed in a 10% sucrose solution, and then O.D. C. T. It was embedded in a company (manufactured by Sakura Finetech Japan Co., Ltd.) and used as a measurement sample.
The measurement sample was stored at −80 ° C. until use.

Next, a cross section of a thoracic aorta and an abdominal aorta having a thickness of 5 μm was prepared using a cryostat (CM1850, manufactured by Leica Biosystems), and these were mounted on a slide glass.

From the fracture rate of the elastic plate wavy structure, the degree of decomposition of the elastic plate wavy structure containing elastin in the blood vessel wall can be confirmed.
Therefore, by calculating the defect rate of the elastic plate wavy structure, it is possible to confirm whether or not the decomposition of elastin by nicotine and the presence or absence of the preventive effect of turmeric oil on the decomposition of elastin caused by nicotine.
For the defect rate of the elastic plate wavy structure, the elastic fibers were stained by EVG staining, and the region where the corrugated structure was deleted due to the flattening or fragmentation of the elastic plate was confirmed, and the defective region with respect to the total area of the elastic plate was confirmed. It was obtained by calculating the ratio of the area of.

The cross section of the prepared abdominal aorta was stained with EVG, and the defect rate of the elastic plate wavy structure was measured. In the C group and the T group, the elastic plate wavy structure was densely laminated (elastic plate fracture rate 14 to 19%), but in the CN group, the elastic plate wavy structure was significantly destroyed (elasticity). Board destruction rate 26%). However, in the TN group, a significant recovery of the broken elastic plate wavy structure was observed (elastic plate fracture rate 15%).
From this result, it was found that turmeric oil can prevent damage to the elastic plate wavy structure containing elastin due to the influence of nicotine ingestion on the vascular wall of the thoracic aorta (Fig. 2).

Next, the effect of exposure to turmeric oil on vascular injury in nicotine-treated mice was investigated by observing the extracellular matrix-degrading enzymes MMP-2 and MMP-9. The presence of these enzymes was detected by immunostaining, respectively.

The immunostaining of MMP-2 shown in FIG. 3 shows that exposure to turmeric oil increases the MMP-2 positive area in the CN group compared to the C group and the TN group compared to the CN group in the intima. Showed a tendency to suppress the increase in MMP-2 positive area due to nicotine.

The immunostaining of MMP-9 shown in FIG. 4 showed that exposure to turmeric oil increased the MMP-9 positive area in the CN group compared to the C group and in the TN group compared to the CN group in the outer membrane. It was shown to suppress the increase in MMP-9 positive area by nicotine.

Next, an experiment was conducted to investigate the transfer to blood vessels when exposed to gaseous turmeric oil in a flask and when turmeric oil was orally administered.
First, 4-week-old male Slc / ddY mice (Nippon SLC Co., Ltd.) were acclimatized for 5 days, and the mice were randomly assigned to the following four groups.
Group C: 2% CMC + no exposure ET group: exposed to turmeric oil for 60 minutes LT group: turmeric oil 0.02 mg / g (emulsified with CMC) orally administered HT group: turmeric oil 0.03 mg / g (emulsified with CMC) Oral administration 30 minutes after oral administration or 60 minutes after exposure to turmeric oil, each mouse is slaughtered, blood is collected and dissected, and the turmeric oils (α-termeron, β-termeron, AR-termeron) in each are The concentration was measured.

The measurement results in serum showed that all turmerons were significantly increased in the ET group compared with the C group, and that the transfer amount of AR-turmeron was the same in the ET group and the LT group (Fig.). 5). From this result, it was shown that turmerons can be transferred into the blood at the same level as oral administration by exposure in a gaseous state.

The measurement results of the concentrations of turmeric (α-termeron, β-termeron, AR-termeron) transferred to the abdominal blood vessels or thoracic blood vessels were significant in the ET group in all the turmerons in the abdominal blood vessels as compared with the C group. It was shown that there was no difference, and that all turmerics were significantly increased in the ET group compared to the C group in the thoracic blood vessels (Fig. 6), and in the experimental system of the present invention, the exposure / exposure in the thoracic blood vessels was shown. It is shown that turmerons caused by oral administration were significantly observed.

Since the composition according to the present invention, and foods and drinks and flavors containing such a composition contain turmeric oil, AR-turmeric, α-turmeric or β-turmeric as an active ingredient, deterioration of blood vessels should be prevented. Can be done. Therefore, the present invention can be suitably used as a food, beverage, or flavor for preventing deterioration of blood vessels.

Claims (9)

A composition for protecting blood vessels, containing turmeric oil. The composition according to claim 1, wherein the active ingredient of the turmeric oil is turmeric, and the turmeric is one or more compounds selected from the group consisting of AR-turmeric, α-turmeric and β-turmeric. The composition according to claim 1 or 2, wherein the vascular protection comprises inhibiting the vascular injury or repairing the vascular injury. The composition according to claim 1-3, wherein the vascular injury is a vascular injury modeled by nicotine-induced fibrosis of the vascular wall. The composition according to claim 1 to 4, wherein the vascular injury is an abdominal aortic aneurysm or a thoracic aortic aneurysm. The composition according to claim 1 to 5, which is administered by oral administration or nasal administration. The composition according to claims 1 to 6, which is used to be included in at least one selected from the group consisting of foods, beverages, flavors, aroma oils, odor bags, incense sticks, cigarettes, and electronic cigarettes. A food or drink containing the composition according to any one of claims 1 to 6. A fragrance containing the composition according to any one of claims 1 to 6.

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