JP2018043949A - COMPOSITION FOR ACTIVATING Tie2 - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide convenient means to activate Tie2, and improve blood flow and lymph flow, thus improving symptoms of a body.SOLUTION: A composition for activating Tie2 contains at least one selected from the group consisting of Backhousia citriodora extract, Houttuynia cordata extract, wormwood extract, Fragaria vesca extract, raspberry leaf extract, Echinacea extract, and Orthosiphon Stamineus Benth extract.SELECTED DRAWING: None

Description

  The present invention relates to a composition for Tie2 activity.

  Tie2 (endothelium-specific receptor tyrosine kinase 2) is a receptor tyrosine kinase expressed in vascular endothelial cells and has recently been shown to be deeply involved in aging. Furthermore, it has been found that it acts on skin epidermis cells, chondrocytes, etc. in relation to angiogenesis, and is also involved in lipid, sugar, and energy metabolism. Attention has been paid.

  Tie2 is known to strengthen the connection between endothelial cells / mural cells and endothelial cells and contribute to the stabilization of the structure of blood vessels and lymphatic vessels. Since Tie2 decreases (inactivates) due to aging and disease, nutrients leak from blood vessels, especially in middle-aged and elderly people, and waste and water are accumulated in the body without being collected from leaking from lymphatic vessels. Adverse effects such as swelling and stiffness of the body and coldness of limbs are likely to occur.

  For this reason, methods and materials for simply activating Tie2 are required, and materials that suggest various Tie2 activations have been studied (for example, Patent Documents 1 to 6).

JP 2011-102273 A JP 2011-102274 A JP 2011-102275 A JP 2013-241356 A JP 2014-097977 A Japanese Patent Laying-Open No. 2015-168656

  An object of the present invention is to provide a means for easily activating Tie2. Another object of the present invention is to improve blood flow and lymph flow, thereby improving various symptoms of the body.

  The present inventors have found that the koji leaf extract has the ability to activate Tie2, and have made further improvements to complete the present invention.

The invention encompasses, for example, the subject matter described in the following sections.
Item 1.
A composition for Tie2 activity, comprising at least one selected from the group consisting of a lemon myrtle extract, a dokudami extract, a mugwort extract, a wild strawberry extract, a raspberry leaf extract, an echinacea extract, and a cumistin extract.
Item 2.
Item 2. The composition according to Item 1, comprising at least one selected from the group consisting of a lemon myrtle extract, a wild strawberry extract, and a raspberry leaf extract.
Item 3.
Item 3. The composition according to Item 1 or 2, which is an oral composition.
Item 4.
Item 4. The composition according to any one of Items 1 to 3, which is a pharmaceutical composition or a food composition.
Item 5.
A composition for Tie2 activity comprising a step of subjecting at least one selected from the group consisting of lemon myrtle, dokudami, mugwort, wild strawberry, raspberry leaf, echinacea, and cumistin to extraction with water, ethanol, or a water-ethanol mixture. Manufacturing method.
Item 6.
A dried tea leaf or tea bag for Tie2 activity comprising at least one dried product selected from the group consisting of lemon myrtle, dokudami, mugwort, wild strawberry, raspberry leaf, echinacea, and cumistin.
Item 7.
Item 5. The composition according to any one of Items 1 to 4, which is for swelling improvement, blood flow improvement, lymph flow improvement, body stiffness improvement, cold improvement, or skin wrinkle, sagging or roughness improvement.
Item 8.
For swelling improvement, blood flow improvement, lymph flow improvement, body stiffness improvement, cold improvement, or wrinkle, sagging or roughening improvement,
Including at least one selected from the group consisting of Lemon Myrtle Extract, Dokudami Extract, Artemisia Extract, Wild Strawberry Extract, Raspberry Leaf Extract, Echinacea Extract, and Cumistin Extract,
Composition.
Item 9.
For swelling improvement, blood flow improvement, lymph flow improvement, body stiffness improvement, cold improvement, or wrinkle, sagging or roughening improvement,
Including at least one dried product selected from the group consisting of Lemon Myrtle, Dokudami, Artemisia, Wild Strawberry, Raspberry Leaf, Echinacea, and Cumistin.
Dry tea leaves or tea bags.

  According to the composition containing an extract of a specific plant according to the present invention, Tie2 can be easily activated. In addition, blood flow improvement and lymph flow can be improved easily, and thus various symptoms of the body can be improved.

The Tie2 activation examination result when using a lemon myrtle extract, a Dokudami extract, a mugwort extract, a wild strawberry extract, a raspberry leaf extract, an echinacea extract, or a cumistin extract is shown.

  Hereinafter, each embodiment of the present invention will be described in more detail.

  Compositions encompassed by the present invention include extracts of certain plants (particularly herbs). Specifically, it includes at least one selected from the group consisting of a lemon myrtle extract, a dokudami extract, a mugwort extract, a wild strawberry extract, a raspberry leaf extract, an echinacea extract, and a cumistin extract. A composition containing at least a lemon myrtle extract is more preferable.

  The extract of these specific plants is preferably an extract obtained from each plant by extraction with water, ethanol or a water-ethanol mixture.

  Lemon Myrtle (Backhouse citriodora) is used as a tea leaf for herbal tea, as well as being used for cooking and medicinal herbs by Aboriginal Australian natives. As a site | part of the lemon myrtle used for extraction, a leaf (a leaf axis and a petiole are included) and a branch are preferable, for example, and a leaf is more preferable. Moreover, it is preferable that each site | part used for extraction is dried. For example, dry leaves and dry branches are preferable, and dry leaves are more preferable.

  Dokudami may be used as tea leaves, especially after drying the leaves. As the site of the wolfberry used for extraction, whole plants (for example, flowers, leaves, stems, roots, etc.) can be used, and leaves are particularly preferable. Moreover, it is preferable that each site | part used for extraction is dried. For example, dry leaves and dry stems are preferable, and dry leaves are more preferable. Each part is preferably roasted after drying.

  As a part of mugwort used for extraction, whole plants (for example, flowers, leaves, stems, roots, etc.) can be used, leaves or stems are preferable, and young leaves are particularly preferable. Moreover, it is preferable that each site | part used for extraction is dried. For example, dry leaves and dry stems are preferable, and dry leaves are more preferable. Each part is preferably roasted after drying.

  As a part of wild strawberry used for extraction, whole plants (for example, flowers, leaves, stems, roots, etc.) may be used, and among them leaves are preferable. Moreover, it is preferable that each site | part used for extraction is dried. For example, dry leaves and dry stems are preferable, and dry leaves are more preferable.

  The raspberry leaf is a raspberry leaf, and the raspberry leaf used for extraction is not particularly limited, but a leaf is preferable. Moreover, it is preferable that the leaf used for extraction is dried (dry leaf).

  As a part of echinacea used for extraction, whole plants (for example, flowers, leaves, stems, roots, etc.) may be used, and ground parts are preferable, and leaves, stems, and flowers are more preferable. Moreover, it is preferable that each site | part used for extraction is dried. For example, dry leaves and dry stems are preferable, and dry leaves are more preferable.

  As the site of cumistin used for extraction, whole plants (for example, flowers, leaves, stems, etc.) may be used, and leaves are particularly preferable. Moreover, it is preferable that each site | part used for extraction is dried (dry leaf). Each part is preferably roasted after drying.

  Next, extraction of each plant will be described. Each plant may be subjected to an extraction operation separately, or one or a mixture of two or more plants may be subjected to an extraction operation.

  As described above, the extraction solvent used for extraction is preferably water, ethyl alcohol, or a water-ethyl alcohol mixture, more preferably water or a water-ethyl alcohol mixture, and even more preferably water. When a water-ethyl alcohol mixture is used, the mixing ratio of the two is not particularly limited. For example, the mass ratio of water: ethyl alcohol is 10:90 to 90:10, or 20:80 to 80:20.

  The extraction temperature is not particularly limited, and can be appropriately set from 0 ° C. to the boiling point of the solvent depending on the extraction solvent. More specifically, when the solvent is a water-ethyl alcohol mixture, the extraction temperature is preferably 30 ° C. to boiling point, more preferably about 60 to 80 ° C. When the solvent is water, the extraction temperature can be carried out at a temperature where the water is liquid (0 to 100 ° C.), preferably about 60 to 100 ° C., more preferably about 70 to 100 ° C. The extraction time is not particularly limited, and can be set as appropriate. For example, when the solvent is a water-ethyl alcohol mixture, it can be appropriately set according to the mixing ratio of ethyl alcohol and the extraction temperature, and is usually about several tens of seconds to 24 hours, about 1 minute to 4 hours. Preferably there is. When the solvent is water, the extraction time is about several tens of seconds to 24 hours, and preferably about 1 minute to 4 hours. The ratio between the extracted plant part and the extraction solvent is not particularly limited and can be set as appropriate. For example, the solvent is preferably 2 to 1000 parts by weight, more preferably 2 to 50 parts by weight, and still more preferably about 3 to 30 parts by weight with respect to 1 part by weight of the extracted plant part. The aqueous extract (aqueous extract) obtained by the extraction method as described above can be separated from the leaves using conventional methods such as filtration and centrifugation. The aqueous extract may be used as it is or after being concentrated. Concentration can be performed using a conventional method. For example, the concentration can be performed at about 30 to 50 ° C. under a reduced pressure of about 30 to 40 mmHg. Moreover, after concentration, solid content (for example, extract powder) can also be obtained by means such as freeze drying, spray drying, granulation drying, and the like. At that time, an excipient such as dextrin may be added. In this case, the powder may be used as an extract as it is, and after the powder is produced, it may be mixed and granulated with an optional component as necessary, and used in the form of granules or fine granules.

  The content of the plant extract in the composition according to the present invention is not particularly limited as long as it is within the range where the effects of the present invention are exhibited. For example, it is preferable that 0.1-100 mass% of plant extracts are contained in conversion of dry mass, and it is more preferable that 1-99 mass% is contained.

  In addition, the composition according to the present invention can be taken in one or a plurality of times (preferably 2 to 3 times). The subject of application is preferably a human, but may be a non-human mammal other than a human. Even when the subject of application is a non-human mammal (eg, a pet or livestock, more specifically, a dog, cat, cow, pig, chicken, sheep, etc.), the administration or intake amount of the human should be set as appropriate. Can do. Moreover, it is preferable that the application method to the living body of the composition according to the present invention is applied orally (that is, an oral composition).

  As described above, the composition according to the present invention can activate Tie2. When Tie2 is activated, the connection between endothelial cells / wall cells and endothelial cells is strengthened, and the structures of blood vessels and lymph vessels are stabilized. Thereby, various symptoms (problems) of the body can be improved. In particular, Tie2 decreases with aging and diseases, and is suitable for middle-aged and elderly people (for example, those over 30 years old, over 40 years old, over 50 years old, or over 60 years old) to improve various symptoms of the body. Such symptoms are not particularly limited, and include symptoms caused by unstable structures of blood vessels and lymph vessels, especially nutrients leaking from blood vessels, or waste products and water from lymph vessels. Symptoms caused by accumulation in the body without being collected for leakage are included. More specifically, for example, swelling of the body (especially hands, feet, face, etc.), cooling of the body (especially feet, hands, etc.), stiffness of the body (especially shoulders, waist, neck), skin (especially facial skin). ), Various symptoms such as wrinkles, sagging, and roughness are effective and effective in improving these symptoms. Therefore, the composition according to the present invention is intended for not only subjects who exhibit such symptoms, but also subjects who are expected to exhibit such symptoms in the future, and such symptoms. It is effective for a wide range of subjects such as those who want to avoid as much as possible. In particular, it is particularly suitable for middle-aged and older people (for example, 30 years old or older, 40 years old or older, 50 years old or older, or 60 years old or older), especially middle-aged women.

  The composition according to the present invention contains each of the above plant extracts, and can further contain other components.

  Examples of other components include rosehip extract, hibiscus extract, ginger extract, pearl barley extract, chamomile (chamomile) extract, onion extract and the like. As these extracts, those extracted from appropriate parts among the parts (leaves, stems, roots, fruits, etc.) of each plant can be used.

  The rosehip extract is preferably an extract from fruits, and more preferably an extract from dried fruits. The hibiscus extract is preferably an extract from straw and more preferably an extract from dry straw. The ginger extract is preferably an extract from the root (tuberous root). The pearl barley extract is preferably an extract from fruit (seed), and more preferably an extract from dried fruit. The chamomile extract is preferably an extract from a flower, and more preferably an extract from a dried flower. The onion extract is preferably an extract from the edible leaf (the thick part of the leaf), and is an extract from the epidermis of the part (called the “onion skin”). It is more preferable. In addition, extraction can be performed on the conditions similar to the extraction conditions of each said plant.

  As the other components, known components can be appropriately selected and used according to the field in which the composition is used. For example, a pharmaceutically or food hygienically acceptable carrier can be used.

  The composition according to the present invention can be preferably used as, for example, a pharmaceutical composition or a food composition (including a beverage composition and a food additive composition).

  When used as a pharmaceutical composition, other components include pharmaceutically acceptable bases, carriers, and / or additives (eg, solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders). , Disintegrants, lubricants, etc.). The form of the pharmaceutical composition is not particularly limited, and examples thereof include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, creams, and poultices. These forms of pharmaceutical preparations can be prepared by a conventional method by combining the other components and the above plant extracts as necessary.

  When used as a food composition, examples of other components include bases, carriers, additives, and other components and materials that can be used as food. Also, the form of the food composition is not particularly limited. For example, processed foods, health foods (dietary supplements, nutritional functional foods, foods for the sick, foods for specified health, functional indication products, etc.), supplements, sick people Foods for hospitals (hospital foods, sick foods, nursing foods, etc.) can be exemplified. These can be prepared by conventional methods. In particular, when preparing a food composition as a health food (dietary supplement, nutritional functional food, food for the sick, food for specified health use, functional labeling product, etc.) or supplement, continuous intake is easy to perform. Thus, for example, it is preferable to prepare in the form of granules, capsules, tablets (including chewable agents), beverages (beverage powders, drinks, etc.), among others, capsules, tablets, tablets, beverage powders, drinks, etc. Although the form is preferable from the viewpoint of easy intake, it is not particularly limited thereto. When used as a food additive composition among food compositions, examples of the form include liquid, powder, flake, granule, and paste. More specifically, seasonings (soy sauce, sauce, ketchup, dressing, etc.), flakes (sprinkles), grilled meat sauce, spices, roux paste (carrere paste, etc.) and the like can be exemplified.

  In addition, one preferable form of the composition according to the present invention may be tea.

  Moreover, this invention also includes the raw material for obtaining the said extract. For example, dry tea leaves or tea bags containing the dried products of the above plants are also included. Furthermore, the present invention also includes the dried tea leaves or tea bags for improving various symptoms, including the dried product of each plant.

  These dry tea leaves or tea bags may further contain other components. For example, one or two kinds of dried rosehip fruit, dried hibiscus meal, ginger root (preferably dried ginger root), dried barley seed (seed), dried chamomile flower, onion skin (preferably dried onion skin), etc. It may be included in combination of more than one species.

  These dry tea leaves or tea bags are preferable because water (including hot water) can be used to easily obtain tea contained in the composition according to the present invention.

  In addition, although content in particular of the dried material of each said plant in these dry tea leaves or tea bags is not restrict | limited, For example, 20-100 mass parts of dried lemon myrtle is with respect to 100 mass parts of whole plant dried material. Preferably, 25 to 90 parts by mass are more preferable.

In this specification, “including” includes “consisting essentially of” and “consisting of” (The term “comprising” includes “consisting essentially of” and “consisting of.”).

  Hereinafter, the present invention will be specifically described, but the present invention is not limited to the following examples. Hereinafter, “%” represents “% by mass” unless otherwise specified.

Examination of Tie2 Activation Using HUVEC (Human Umbilical Vascular Endothelial Cells), it was examined whether the extract from each plant activates Tie2.

HUVECs were cultured in the growth medium described in Table 1 below (37 ° C., 5% CO ₂ ), and Tie2 activation was examined in a low serum medium.

  The lemon myrtle extract was prepared as follows using a machine-dried dried plant. 4 g of lemon myrtle plant body (mainly dry leaves) dried in a container was weighed, and 100 ml of boiling distilled water was added thereto and immersed for 5 minutes. The tea leaves were filtered using a tea bag filter, cooled to room temperature, and then filtered with a 0.22 μm pore size PES filter (Mirex GP, Millipore). The amount of soluble solid content was measured using a digital refractometer (RX-5000α, Atago Co., Ltd.). The solution was diluted with sterilized distilled water so that the soluble solid content was 0.5%. A sample mother liquor was prepared so that the soluble solid content was 0.5%. And 120 microliters of the said sample mother liquid and 1080 microliters of low serum culture media were mixed, and the obtained liquid mixture was made into the sample containing culture medium, and examination was performed using this.

  For the dokudami extract, mugwort extract, wild strawberry extract, raspberry leaf extract, echinacea extract, and cumistin extract, purchase a commercially available tea bag and weigh 4 g of each tea leaf inside the tea bag. Thereafter, a sample-containing medium was prepared in the same manner as in the case of using the lemon myrtle.

  Table 2 shows a list of processing methods for each tea leaf contained in the commercially available tea bags used and the parts used in the plants.

In the examination, cells (HUVEC) were cultured for 60 minutes in a sample-containing medium (37 ° C., 5% CO ₂ ), and the measurement kit Tie2 activation assay (Phospho / Total Tie-2 ELISA assay, R & D systems) was used. Activity was measured. In addition, as a positive control, angiopoietin-1 (Angiopoietin-1) which is a ligand of Tie2 was used instead of the measurement sample (concentration in medium: 1 μg / ml). PBS (phosphate buffered saline) was used as a negative control.

  The measurement results are shown in FIG. In FIG. 1, the Tie2 activation effect of each sample is shown as a relative value when the Tie2 activity in the negative control is 1. In all the plant extracts examined, the Tie2 activation effect superior to the negative control could be confirmed. In particular, raspberry leaf was confirmed to have the same effect as the positive control, and lemon myrtle and wild strawberry were confirmed to be far superior to the positive control.

Study using tea bags <Preparation of tea bags>
Various components were mixed at the blending ratio shown in Table 3 below to prepare dry tea leaves. Each raw material is a dried product of each plant part mechanically dried. The tea leaves were put in a tea bag and used as a test sample (tea bag).

<Test methods and results>
Questions from the “Worker's Fatigue Accumulation Self-Diagnosis Checklist” prepared by the Ministry of Health, Labor and Welfare for women in their 30s to 60s who have a habit of drinking tea. The subject was checked for subjective symptoms according to the items described. The subjective symptoms were answered about the physical condition for several days before the check. Then, the total score obtained was totaled, and 100 women with a total score of 9 or more were selected. The 100 people took tea prepared from a test sample (tea bag) once a day for 6 weeks. At this time, at the time of intake 0 weeks (immediately before intake) and 2 weeks, the following items were self-evaluated. In addition, at the time of 0 weeks of intake, check the “subject symptoms of the most recent 1 week” at that time, and at the time of 2 weeks of intake, check the “subject symptoms of the most recent 2-3 days” at that time. received.
・ Shoulders are stiff ・ Hands and feet are cold ・ Neck is stiff ・ Foot is easy to swell ・ Skin is dry ・ Skin is easy to be rough ・ It feels like there is no firmness ・ The face tends to be dull ・The face tends to sag and the face tends to swell Note that the self-evaluation was specifically performed in the following seven stages.
7). Very applicable 6. Applicable 5. Somewhat applicable 4. 2. I can't say either. Not so much 2. Not applicable 1. Does not apply at all

  Table 4 shows the results of the above self-evaluation. In Table 4, “Before” indicates the 0-week time point, and “After” indicates the 2-week time point. In any self-assessment item, it was confirmed that the symptoms were significantly improved.

  From the above, the tea obtained from tea leaves, which are mainly composed of lemon myrtle and also contain strawberry leaves, dokudami, mugwort, etc., activates Tie2, improves blood flow and improves lymph flow, and thus various symptoms of the body. I found that it can be improved.

Claims (9)

A composition for Tie2 activity, comprising at least one selected from the group consisting of a lemon myrtle extract, a dokudami extract, a mugwort extract, a wild strawberry extract, a raspberry leaf extract, an echinacea extract, and a cumistin extract. The composition according to claim 1, comprising at least one selected from the group consisting of a lemon myrtle extract, a wild strawberry extract, and a raspberry leaf extract. The composition according to claim 1 or 2, which is an oral composition. The composition according to any one of claims 1 to 3, which is a pharmaceutical composition or a food composition. A composition for Tie2 activity comprising a step of subjecting at least one selected from the group consisting of lemon myrtle, dokudami, mugwort, wild strawberry, raspberry leaf, echinacea, and cumistin to extraction with water, ethanol, or a water-ethanol mixture. Manufacturing method. A dried tea leaf or tea bag for Tie2 activity comprising at least one dried product selected from the group consisting of lemon myrtle, dokudami, mugwort, wild strawberry, raspberry leaf, echinacea, and cumistin. The composition according to any one of claims 1 to 4, which is used for improving swelling, improving blood flow, improving lymph flow, improving body stiffness, improving cold, or improving wrinkles, sagging or roughness of skin. For swelling improvement, blood flow improvement, lymph flow improvement, body stiffness improvement, cold improvement, or wrinkle, sagging or roughening improvement,
Including at least one selected from the group consisting of Lemon Myrtle Extract, Dokudami Extract, Artemisia Extract, Wild Strawberry Extract, Raspberry Leaf Extract, Echinacea Extract, and Cumistin Extract,
Composition. For swelling improvement, blood flow improvement, lymph flow improvement, body stiffness improvement, cold improvement, or wrinkle, sagging or roughening improvement,
Including at least one dried product selected from the group consisting of Lemon Myrtle, Dokudami, Artemisia, Wild Strawberry, Raspberry Leaf, Echinacea, and Cumistin.
Dry tea leaves or tea bags.