JP2020048580A - Tie2 activator, vascular maturing agent, vascular stabilizing agent, and food and drink - Google Patents

Abstract

To provide a Tie2 activator, angiogenesis inhibitor, vascular maturing agent, vascular normalizing agent and vascular stabilizing agent, and food and drink, which have excellent Tie2 activating action, angiogenesis inhibiting action, vascular maturing action, vascular normalizing action and vascular stabilizing action, and have high safety.SOLUTION: The present invention provides a Tie2 activator, vascular maturing agent, vascular stabilizing agent, and food and drink, containing, as an active ingredient, an extract from a flower of a chrysanthemum with at least one of water, a hydrophilic solvent, and a solvent extract mixture of water and a hydrophilic solvent.SELECTED DRAWING: None

Description

  The present invention relates to a Tie2 activator, an angiogenesis inhibitor, a blood vessel maturation agent, a blood vessel normalizing agent, a blood vessel stabilizing agent, and a food or drink.

  A blood vessel has a structure in which vascular endothelial cells and vascular wall cells (vascular smooth muscle cells and perisite) adhere indirectly or directly via an extracellular matrix. It has a function of supplying to tissues and removing wastes from living tissues.

  In general, the formation of blood vessels is based on vasculogenesis, in which new blood vessels are formed, and angiogenesis, in which a new network of blood vessels is formed by elongation and branching of the formed existing blood vessels. And two stages. The former involves the action of vascular endothelial growth factor (VEGF) and is involved in a very wide range of angiogenesis from the initial development of blood vessels called angiogenesis to the subsequent angiogenesis, and the latter is angiopoietin. (Ang) acts to control adhesion between vascular endothelial cells and vascular wall cells and to contribute to the structural stabilization of blood vessels.

  Under normal oxygen conditions, vascular endothelial cells and the vascular wall cells lining the blood vessels are tightly adhered to each other, and the vascular structure is kept stable. Cells may detach from vascular endothelial cells, causing the growth of disordered blood vessels. Such a phenomenon (angiogenesis) is often observed in diseases mainly involving vascular lesions such as tumors, rheumatoid arthritis, diabetic retinopathy, hyperlipidemia, and hypertension.

  It is known that such angiogenesis is suppressed by activating a receptor tyrosine kinase Tie2 (Tyrosine kinase with Ig and EGF homology domain 2) expressed in vascular endothelial cells (for example, see Patent Document 1). ). In ischemic diseases caused by suppression of vascular narrowing or vasodilation, it has been reported that the activation of Tie2 causes the vascular cavity to be enlarged (for example, see Non-Patent Document 1). It has also been reported that activation of Tie2 suppresses cell death of vascular endothelial cells (for example, see Non-Patent Document 2).

Thus, activation of Tie2 is known not only to suppress angiogenesis, but also to mature, normalize, and stabilize blood vessels.
For example, in vascular regeneration medicine, it is known that activation of Tie2 induces adhesion between vascular endothelial cells and vascular wall cells in blood vessels to mature blood vessels.
For example, in diseases such as tumors and diabetic retinopathy in which vascular wall cells do not adhere to vascular endothelial cells and disordered blood vessels grow, the activation of Tie2 converts vascular wall cells to endothelial cells. It is known to adhere and normalize blood vessels.
For example, it is known that activation of Tie2 suppresses instability of blood vessels and stabilizes blood vessels with respect to environmental factors that disrupt various intracellular and extravascular structures.

  As a naturally occurring substance that suppresses angiogenesis by activating Tie2, an extract of cinnamon is known (for example, see Patent Document 1), but there is a problem that the activity is insufficient. In addition, suramin is known as a substance that suppresses angiogenesis (for example, see Patent Document 2), but there is a problem that safety is not excellent.

  Therefore, rapid development of highly safe substances having excellent Tie2 activating action, angiogenesis inhibitory action, vascular maturation action, vascular normalization action, and vascular stabilization action is strongly demanded. is the current situation.

JP 2009-263358A Japanese Patent Publication No. 9-503488

Science. 1999. Dec. 24; 286 (5449): 2511-4. P. N. A. S. 2004. Apr. 13; 101 (15): 5553-8.

  An object of the present invention is to solve the above conventional problems and achieve the following objects. That is, an object of the present invention is to provide a highly safe Tie2 activator having an excellent Tie2 activation action. Another object of the present invention is to provide a highly safe angiogenesis inhibitor having an excellent angiogenesis inhibitory action. Another object of the present invention is to provide a highly safe blood vessel maturation agent having an excellent blood vessel maturation effect. Another object of the present invention is to provide a highly safe blood vessel normalizing agent having a blood vessel normalizing action. Another object of the present invention is to provide a highly safe vascular stabilizer having a vascular stabilizing effect. Further, the present invention has at least one of excellent Tie2 activating action, angiogenesis inhibitory action, vascular maturation action, vascular normalization action, and vascular stabilization action, and is highly safe. The purpose is to provide food and drink.

  As a result of intensive studies conducted by the present inventors to solve the above-mentioned problems, the following extracts have excellent Tie2 activation, angiogenesis inhibitory, blood vessel maturation, blood vessel normalization, and blood vessel stabilization. The present invention has been found to have an effect, and the present invention has been completed.

The present invention is based on the above findings by the present inventors, and means for solving the above problems are as follows. That is,
<1> At least one of a Kiraya extract, a yellowish extract, a ginkgo extract, an oyster extract, a turmeric extract, a chrysanthemum extract, a jujube extract, a wolfberry extract, a chamomile extract, and a butcher bloom extract A Tie2 activator characterized by containing an extract as an active ingredient.
<2> At least one of a Kiraya extract, a yellowish extract, a ginkgo extract, an oyster extract, a turmeric extract, a chrysanthemum extract, a jujube extract, a wolfberry extract, a chamomile extract, and a butcher bloom extract An anti-angiogenic agent comprising an extract as an active ingredient.
<3> At least one of a Kiraya extract, a yellow extract, a ginkgo extract, an oyster extract, a turmeric extract, a chrysanthemum extract, a jujube extract, a wolfberry extract, a chamomile extract, and a butcher bloom extract A blood vessel maturation agent, a blood vessel normalizing agent, or a blood vessel stabilizing agent, characterized by containing an extract as an active ingredient.
<4> The Tie2 activator according to <1>, the angiogenesis inhibitor according to <2>, the vascular maturation agent, the vascular normalizing agent or the vascular stabilization according to <3>. A pharmaceutical composition comprising at least one of agents.

ADVANTAGE OF THE INVENTION According to the Tie2 activator of this invention, the above-mentioned various problems in the past are solved, and the Tie2 activator which has the outstanding Tie2 activation effect and is highly safe can be provided.
ADVANTAGE OF THE INVENTION According to the angiogenesis inhibitor of this invention, the above-mentioned problems in the prior art can be solved, and an angiogenesis inhibitor having an excellent angiogenesis inhibitory action and high safety can be provided.
According to the blood vessel maturation agent, blood vessel normalizing agent, and blood vessel stabilizing agent of the present invention, the above-mentioned conventional problems can be solved, and an excellent blood vessel maturation action, blood vessel normalization action, and blood vessel A stabilizing and highly safe blood vessel maturation agent, blood vessel normalizing agent, and blood vessel stabilizing agent can be provided.
ADVANTAGE OF THE INVENTION According to the food-drinks of this invention, the said problems in the past were solved, and at least any one of the outstanding Tie2 activation effect, angiogenesis inhibitory effect, vascular maturation effect, vascular normalization effect, and vascular stabilization effect. It is possible to provide a highly safe food or drink having the above-mentioned action.

(Tie2 activator, angiogenesis inhibitor, vascular maturation agent, vascular normalization agent, vascular stabilizer, and food and drink)
The Tie2 activator, angiogenesis inhibitor, blood vessel maturation agent, blood vessel normalizing agent, and blood vessel stabilizer, food and drink, and pharmaceutical composition of the present invention include a Kiraya extract, a yellowish extract, Ginkgo extract, oyster extract, turmeric extract, chrysanthemum extract, jujube extract, wolfberry extract, chamomile extract, and at least one extract of butcher bloom extract as an active ingredient, further necessary It contains other components accordingly.

  The Tie2 activator has a Tie2 activating action of phosphorylating Tie2 to convert it to its activated form (phosphorylated Tie2). When Tie2 is activated, it induces autophosphorylation of the intracellular tyrosine kinase domain, and induces adhesion between vascular endothelial cells and vascular wall cells. In an ischemic disease caused by suppression of vascular narrowing or vasodilation, the activation of Tie2 causes the vascular cavity to be enlarged. In addition, activation of Tie2 suppresses cell death of vascular endothelial cells.

  The angiogenesis inhibitor has an angiogenesis inhibitory effect of suppressing a network of new blood vessels formed from existing blood vessels. In a hypoxic state, the activation of Tie2 is temporarily suppressed, the adhesion between vascular endothelial cells and vascular wall cells is dissociated, and a new vascular network is formed from the dissociated vascular endothelial cells. An angiogenesis inhibitor can suppress the uncontrolled growth of blood vessels due to such vascular wall cells not adhering to endothelial cells.

  The vascular maturation agent induces adhesion between vascular endothelial cells and vascular wall cells, so that intravascular endothelial cells (cells and humoral factors) are not easily leaked out of blood vessels. It has a maturation effect of forming adhesion spots. In vascular regenerative medicine, activation of Tie2 can induce adhesion between vascular endothelial cells and vascular wall cells in blood vessels to mature blood vessels.

  The vascular normalizing agent enhances adhesion between vascular endothelial cells and promotes lining of vascular endothelial cells to vascular endothelial cells, thereby causing disordered vascular permeability and disordered growth of blood vessels. It has a normalizing action to make abnormal blood vessels normal. In addition, in diseases such as tumors and diabetic retinopathy, in which vascular wall cells do not adhere to vascular endothelial cells and disorderly blood vessels grow, the activation of Tie2 converts vascular wall cells to endothelial cells. It is possible to adhere and normalize blood vessels.

  The vascular stabilizing agent has a function of inhibiting damage to existing blood vessels, dissociation between vascular endothelial cells, and dissociation of vascular endothelial cells and vascular wall cells, and a stabilizing effect of suppressing cell death of vascular endothelial cells. Have. In addition, with respect to environmental factors that disrupt various intracellular and extracellular vascular structures, activation of Tie2 can suppress instability of blood vessels and stabilize blood vessels.

  The pharmaceutical composition is a composition comprising at least one of the Tie2 activator, the angiogenesis inhibitor, the blood vessel maturation agent, the blood vessel normalizing agent, and the blood vessel stabilizer, It has at least one of Tie2 activating action, angiogenesis inhibitory action, vascular maturation action, vascular normalization action, and vascular stabilization action.

<Kiraya extract>
The Kiraya is an evergreen small tree of the genus Rosaceae, and its scientific name is Quillaja saponaria . The killayas are native to the Chile, Bolivia and Peru regions of South America and are readily available from these regions. The bark contains tannins and triterpene saponins. Compared with saponins obtained from other plants, the saponin of Kiraya (Kiraya saponin) is known for having excellent surface activity and homogeneity, and solubilizing food emulsifiers, vitamin E, and flavors. It is also widely used in industrial fields such as dentifrice and beverage foaming agents, toiletries and photographic films.

The extraction site of the Kiraya is not particularly limited and may be appropriately selected depending on the purpose.Examples include leaves, branches, stems, bark, flowers, fruits, and roots. Among these, the bark is preferable.
As a method for preparing the extraction site of Kiraya, it can be obtained by drying each site and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. The drying may be performed in the sun or using a commonly used dryer.

  The Kiraya extract can be easily obtained by a method generally used for extracting plants. The extract of Kiraya is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a diluted solution of the extract, a concentrated solution, and a dried extract of the extract.

  The method for extracting the Kiraya is not particularly limited and may be appropriately selected depending on the intended purpose.For example, the extraction site of the Kiraya, which is the raw material for extraction, is charged into a treatment tank filled with an extraction solvent, and the extraction is performed as necessary. After the soluble component is eluted with appropriate stirring, a method of obtaining an extract by removing the extract residue by filtration is used.

  There are no particular restrictions on the extraction conditions (extraction time and extraction temperature) of the Kiraya and the amount of the extract solvent used in the Kiraya, and they can be appropriately selected according to the purpose.

  The extraction solvent for Kiraya is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . Further, it is preferable to use the extraction solvent for Kiraya at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the Kiraya extract is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid partition extraction, various types of chromatography, and membrane separation.

  The concentration of the Kiraya extract is not particularly limited and may be appropriately selected depending on the intended purpose; however, it is preferably from 6.25 μg / mL to 12.5 μg / mL.

<Yellow extract>
The Huanggai is an evergreen tree of the genus Huanggai, and the scientific name is Engelhardtia chrysolepis . The Huang Gui is native to southern China and is readily available from these areas. The yellow cabbage leaves have a weak sweet taste and have been used for a long time for purposes such as antipyretic, reduced obesity and detoxification.

There is no particular limitation on the extraction portion of the yellowish lime, and it can be appropriately selected according to the purpose. Examples thereof include leaves, branches, stems, bark, flowers, fruits, roots, and the like. Of these, leaves are preferred.
As a method for preparing the above-mentioned extraction site in yellow, it can be obtained by drying each site and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. The drying may be performed in the sun or using a commonly used dryer.

  The yellowish extract can be easily obtained by a method generally used for extracting plants. There are no particular restrictions on the extract of Huang Gui, and it can be appropriately selected according to the purpose. Examples thereof include a diluent of the extract, a concentrated solution, and a dried extract of the extract.

  There is no particular limitation on the extraction method of the yellow rafter, which can be appropriately selected according to the purpose.For example, the extraction site of the yellow rafter, which is an extraction raw material, is charged into a treatment tank filled with an extraction solvent, A method in which a soluble component is eluted with appropriate stirring as needed, and then filtered to remove an extraction residue to obtain an extract.

  There are no particular restrictions on the extraction conditions (extraction time and extraction temperature) and the amount of the extraction solvent used, and they can be appropriately selected according to the purpose.

  There is no particular limitation on the extraction solvent in yellow, and it can be appropriately selected according to the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . Further, it is preferable that the yellow solvent is used at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the extract of Huang Gui is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid distribution extraction, various types of chromatography, and membrane separation.

  The concentration of the extract is not particularly limited and may be appropriately selected depending on the purpose. The concentration is preferably 200 μg / mL to 400 μg / mL.

<Ginkgo extract>
The ginkgo is a deciduous tree of the genus Ginkgo , Ginkgo biloba , and the scientific name is Ginkgo biloba . The ginkgo is distributed worldwide by artificial transplantation and is readily available from these areas. The height of the ginkgo stalk is 20 m to 30 m, which is a kind of gymnosperm. The ginkgo component contains ginkgolide, flavonoids and the like, and is incorporated as a health food.

The extraction site of the ginkgo is not particularly limited and can be appropriately selected depending on the purpose.Examples include a leaf, a branch, a trunk, a bark, a flower, a fruit, and a root. Among these, leaves are preferred.
The method for preparing the extraction sites of the ginkgo can be obtained by drying each site and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. The drying may be performed in the sun or using a commonly used dryer.

  The ginkgo extract can be easily obtained by a method generally used for extracting plants. The extract of Ginkgo is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a dilute solution of the extract, a concentrated solution, and a dried extract.

  The method of extracting the ginkgo is not particularly limited and can be appropriately selected depending on the purpose.For example, the extraction site of the ginkgo as an extraction raw material is put into a treatment tank filled with an extraction solvent, and the extraction is performed as necessary. After the soluble component is eluted with appropriate stirring, a method of obtaining an extract by removing the extract residue by filtration is used.

  The conditions for extracting the ginkgo (extraction time and temperature) and the amount of the extraction solvent for the ginkgo are not particularly limited and can be appropriately selected depending on the purpose.

  The extraction solvent for ginkgo is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . Further, it is preferable that the extraction solvent for ginkgo is used at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the ginkgo extract is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid distribution extraction, various types of chromatography, and membrane separation.

  The concentration of the ginkgo extract is not particularly limited and may be appropriately selected depending on the intended purpose; however, it is preferably from 100 μg / mL to 200 μg / mL.

<Oyster extract>
The oysters are a general term for bivalves belonging to the order Myrtaceae. The oysters used are those collected in Hiroshima Prefecture, but can be easily obtained from coastal regions around the world. The oysters are rich in high-quality proteins, taurine, glycogen, zinc, minerals, and the like, and have been widely used as raw materials for Chinese medicine since ancient times.

  The oyster extract can be easily obtained by a method generally used for oyster extraction. The oyster extract is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a diluted solution of the extract, a concentrated solution, and a dried extract.

  The method of extracting the oysters is not particularly limited and may be appropriately selected depending on the purpose. For example, (1) chilled oysters and frozen oysters are charged into an extraction can and hot water at 80 ° C to 100 ° C is added. (2) The oyster hot water extraction residue is charged into a reaction vessel equipped with stirring blades, and subjected to a protease enzymatic degradation treatment at 30 ° C to 50 ° C. And then heating at 90 ° C. to inactivate, clarifying and filtering, and then concentrating under reduced pressure.

  The oyster extraction solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . The oyster extraction solvent is preferably used at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The amount of the oyster extraction solvent used is not particularly limited and can be appropriately selected depending on the purpose.

  The method for purifying the oyster extract is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid distribution extraction, various types of chromatography, and membrane separation.

  The concentration of the oyster extract is not particularly limited and may be appropriately selected depending on the intended purpose; however, the concentration is preferably 200 μg / mL to 400 μg / mL.

<Turmeric extract>
The turmeric is a rootstock of the genus Curcuma (turmeric), and the scientific name is Curcuma longa . The turmeric is distributed in tropical Asia, is grown in India, Okinawa, southeast China and Southeast Asia, and is readily available from these regions. It is known that the yellow curcumin contained in the root mass of turmeric has an antioxidant effect, a liver function improving effect, a prostatic hypertrophy suppressing effect, and the like. On the other hand, turmeric also contains an essential oil component called sesquiterpene. The fleshy rhizome of turmeric is used as a medicinal and currant flour as an important flavor and yellow pigment.

The extraction site of the turmeric is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include leaves, stems, flowers, fruits, rhizomes, roots, and the like. Especially, a rhizome part is preferable.
The method for preparing the turmeric extraction site can be obtained by drying each site and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. The drying may be performed in the sun or using a commonly used dryer.

  The turmeric extract can be easily obtained by a method generally used for extracting a plant. The turmeric extract is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include a diluent of the extract, a concentrated solution, and a dried extract of the extract.

  The method for extracting the turmeric is not particularly limited and can be appropriately selected depending on the purpose.For example, the extraction part of the turmeric, which is an extraction raw material, is charged into a treatment tank filled with an extraction solvent, and the turmeric is extracted as needed. After the soluble component is eluted with appropriate stirring, a method of obtaining an extract by removing the extract residue by filtration is used.

  The turmeric extraction conditions (extraction time and extraction temperature) and the amount of the turmeric extraction solvent used are not particularly limited, and can be appropriately selected depending on the purpose.

  The turmeric extraction solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . The turmeric extraction solvent is preferably used at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the turmeric extract is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include purification methods such as liquid-liquid distribution extraction, various types of chromatography, and membrane separation.

  The concentration of the turmeric extract is not particularly limited and may be appropriately selected depending on the intended purpose; however, it is preferably 25 μg / mL to 40 μg / mL.

<Chrysanthemum extract>
The chrysanthemum is a short-day plant of the genus Asteraceae, and the scientific name is Chrysanthemum morifolimium syn. It is. The chrysanthemum is native to Japan and is readily available. The chrysanthemum flower part has been used as a medicinal substance in China for a long time, and is also used as a tea and alcohol in Japan, and is also used for cooking as an edible, effective for dizziness, headache, eye strain, etc. It is said that.

The chrysanthemum extraction site is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include leaves, stems, flowers, fruits, and roots. Parts are preferred.
The chrysanthemum chrysanthemum extraction site can be prepared by drying each part and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. The drying may be performed in the sun or using a commonly used dryer.

  The chrysanthemum extract can be easily obtained by a method generally used for extracting plants. The extract of chrysanthemum is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a diluent of the extract, a concentrated solution, and a dried extract of the extract.

  The method for extracting the chrysanthemum is not particularly limited and may be appropriately selected depending on the purpose.For example, the extraction site of the chrysanthemum, which is an extraction raw material, is charged into a treatment tank filled with an extraction solvent, and the extraction is performed as needed. After the soluble component is eluted with appropriate stirring, a method of obtaining an extract by removing the extract residue by filtration is used.

  The conditions for extracting the chrysanthemum (extraction time and extraction temperature) and the amount of the chrysanthemum extraction solvent used are not particularly limited, and can be appropriately selected depending on the purpose.

  The chrysanthemum extraction solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . The chrysanthemum extraction solvent is preferably used at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the chrysanthemum extract is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid distribution extraction, various types of chromatography, and membrane separation.

  The concentration of the chrysanthemum extract is not particularly limited and may be appropriately selected depending on the intended purpose. The concentration is preferably 200 µg / mL to 400 µg / mL.

<Jujube extract>
The jujube is a tall deciduous of rhamnaceae jujube genus, the scientific name is a Ziziphus jujuba. The jujube is native to northern Africa and western Europe and is readily available from these regions. The fruit of the jujube has been used for medicinal purposes since ancient times, and contains vitamin C and the like as its components.

The extraction site of the jujube is not particularly limited and can be appropriately selected depending on the purpose.Examples include a leaf, a branch, a trunk, a bark, a flower, a fruit, and a root. Among these, the fruit part is preferable.
As a method for preparing the extraction site of the jujube, it can be obtained by drying each site and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. The drying may be performed in the sun or using a commonly used dryer.

  The jujube extract can be easily obtained by a method generally used for extracting a plant. The extract of the jujube is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a dilute solution of the extract, a concentrated solution, and a dried extract.

  The method for extracting the jujube is not particularly limited and can be appropriately selected depending on the purpose.For example, the extraction site of the jujube, which is a raw material for extraction, is charged into a treatment tank filled with an extraction solvent, and the extraction method is required. After the soluble component is eluted with appropriate stirring, a method of obtaining an extract by removing the extract residue by filtration is used.

  There are no particular limitations on the jujube extraction conditions (extraction time and extraction temperature) and the amount of the jujube extraction solvent used, and they can be appropriately selected depending on the purpose.

  The jujube extraction solvent is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . The jujube extraction solvent is preferably used at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the jujube extract is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid partition extraction, various types of chromatography, and membrane separation.

  The concentration of the jujube extract is not particularly limited and may be appropriately selected depending on the purpose. The concentration is preferably 200 μg / mL to 400 μg / mL.

<Wolfberry extract>
The wolfberry is a deciduous shrub of the genus Solanaceae, and the scientific name is Lycium chinense . The wolfberry is distributed in Japan and Korea, China, Taiwan, and the like, and is easily available from these regions. The wolfberry fruit is pickled into sake to make wolfberry wine, and is also widely used as raw food, dried fruit, and as a medicine table for porridge. The soft young leaves of the wolfberry are widely used for food.

The extraction portion of the wolfberry is not particularly limited and can be appropriately selected depending on the purpose.Examples include leaves, branches, stems, bark, flowers, fruits, and roots. Among these, the fruit part is preferable.
The method for preparing the above-mentioned wolfberry extraction sites can be obtained by drying each site and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. The drying may be performed in the sun or using a commonly used dryer.

  The wolfberry extract can be easily obtained by a method generally used for extracting a plant. The extract of wolfberry is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a dilute solution of the extract, a concentrated solution, and a dried extract of the extract.

  The method for extracting the wolfberry is not particularly limited and can be appropriately selected depending on the purpose.For example, the extraction site of the wolfberry, which is an extraction raw material, is charged into a treatment tank filled with an extraction solvent, and the extraction is performed as necessary. After the soluble component is eluted with appropriate stirring, a method of obtaining an extract by removing the extract residue by filtration is used.

  The conditions for extracting the wolfberry (extraction time and extraction temperature) and the amount of the wolfberry extraction solvent used are not particularly limited and can be appropriately selected depending on the purpose.

  The wolfberry extraction solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . The wolfberry extraction solvent is preferably used at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the wolfberry extract is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid distribution extraction, various types of chromatography, and membrane separation.

  The concentration of the wolfberry extract is not particularly limited and may be appropriately selected depending on the intended purpose. The concentration is preferably 100 μg / mL to 400 μg / mL.

<Chamomile extract>
The chamomile is a cold-resistant annual of the genus Asteraceae, and its scientific name is Matricaria chamomilla (alias: chamomile). The origin of the chamomile is a region from Europe to West Asia, and is easily available from these regions. The leaves of the chamomile are pinnate compound leaves, the flower is about 3 cm in diameter, the central tubular flower is yellow, the tongue flower is white, and has a peculiar strong aroma similar to apple. The chamomile is used as a medicinal herb such as a stomachic, an antiperspirant, an anti-inflammatory, and a medicine for gynecological diseases.

  The extraction site of the chamomile is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a leaf, a stem, a flower, a fruit, and a root, and a flower is preferred.

  The method for preparing the extraction portion of the chamomile can be obtained by drying each portion and then pulverizing it as it is or using a crusher and subjecting it to solvent extraction. The drying may be performed in the sun or using a commonly used dryer.

  The chamomile extract can be easily obtained by a method generally used for extracting a plant. The extract of the chamomile is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include a dilute solution of the extract, a concentrated solution, and a dried extract of the extract.

  The method for extracting the chamomile is not particularly limited and can be appropriately selected depending on the purpose.For example, the extraction site of the chamomile, which is an extraction raw material, is charged into a treatment tank filled with an extraction solvent, and the extraction is performed as necessary. After the soluble component is eluted with appropriate stirring, a method of obtaining an extract by removing the extract residue by filtration is used.

  The extraction conditions (extraction time and extraction temperature) of the chamomile and the amount of the chamomile extraction solvent used are not particularly limited, and can be appropriately selected depending on the purpose.

  The extraction solvent for the chamomile is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . In addition, it is preferable to use the chamomile extraction solvent at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the chamomile extract is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid partition extraction, various types of chromatography, and membrane separation.

  The concentration of the chamomile extract is not particularly limited and may be appropriately selected depending on the intended purpose. The concentration is preferably 200 μg / mL to 400 μg / mL.

<Butcher bloom extract>
The Butcher Bloom is a perennial evergreen shrub of the genus Nymphalidae , and its scientific name is Ruscus aculeatus (Japanese name: Nagi- kida , also known as Butcher's Bloom). The origin of the Butcher Bloom is Europe and is readily available from these regions. The butcher bloom is dioecious, with flowers blooming from spring to summer and red fruits in winter. The butcher bloom leaves are degenerate, the terminal stems are flattened like leaves and have sharp thorns at the tips.

  The extraction site of the butcher bloom is not particularly limited and may be appropriately selected depending on the purpose.Examples include leaves, stems, flowers, fruits, roots, rhizomes, and the like. Among them, the rhizome is preferable.

  The method for preparing the extraction sites of the butcher bloom can be obtained by drying each site and then pulverizing it as it is or using a crusher to extract the solvent. The drying may be performed in the sun or using a commonly used dryer.

  The butcher bloom extract can be easily obtained by a method generally used for extracting a plant. The extract of the butcher bloom is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a diluent of the extract, a concentrated solution, and a dried extract.

  The method of extracting the butcher bloom is not particularly limited and can be appropriately selected depending on the intended purpose.For example, the extraction site of the butcher bloom, which is an extraction raw material, is charged into a treatment tank filled with an extraction solvent, A method in which a soluble component is eluted with appropriate stirring as needed, and then filtered to remove an extraction residue to obtain an extract.

  The conditions for extracting the butcher bloom (extraction time and temperature) and the amount of the extraction solvent used for the butcher bloom are not particularly limited and can be appropriately selected depending on the purpose.

  The extraction solvent for the butcher bloom is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include water, a hydrophilic solvent, and a mixed solvent thereof. The water is not particularly limited and can be appropriately selected depending on the intended purpose.For example, pure water, tap water, well water, spa water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like. The hydrophilic solvent is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, and the like. Lower aliphatic ketones; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin; The mixed solvent is not particularly limited and may be appropriately selected depending on the intended purpose. When a lower alcohol is used, 1 to 90 parts by mass relative to 10 parts by mass of water is used. Is used, 1 to 40 parts by mass with respect to 10 parts by mass of water, and 1 to 90 parts by mass with respect to 10 parts by mass of water is preferably added when polyhydric alcohol is used. . The butcher bloom extraction solvent is preferably used at a temperature from room temperature to the boiling point of the solvent or lower. Among these, extraction using hot water is preferred.

  The method for purifying the butcher bloom extract is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include purification methods such as liquid-liquid partition extraction, various types of chromatography, and membrane separation.

  The concentration of the butcher bloom extract is not particularly limited and may be appropriately selected depending on the purpose. However, the concentration is preferably 50 μg / mL to 200 μg / mL, more preferably 100 μg / mL to 200 μg / mL.

<Other ingredients>
The other components are not particularly limited and may be appropriately selected depending on the intended purpose. For example, excipients, desiccants, preservatives, strengthening agents, thickeners, emulsifiers, antioxidants, sweeteners , Acidulants, seasonings, coloring agents, fragrances, etc., whitening agents, humectants, oily components, ultraviolet absorbers, surfactants, thickeners, alcohols, powder components, coloring agents, aqueous components, water, skin nutrition Agents and the like.
The other components are not particularly limited and may be appropriately selected depending on the intended purpose.Specifically, hyaluronic acid, hyaluronic acid hydrolyzate, collagen, collagen hydrolyzate, ascorbic acid, ascorbic acid Acid derivative, ascorbic acid glycoside, coenzyme Q10, propolis, royal jelly, royal jelly protein hydrolyzate, fucoidan, aloe powder, aloe extract, blueberry powder, blueberry extract, isoflavone, noni powder, noni extract, garlic powder, garlic Extracts, turmeric powder, chitosan, glucosamine, chlorella powder, chlorella extract, carnitine, maca powder, maca extract, cassis powder, cassis extract, Hanabitaketake powder, Hanabitaketake extract, and other plants that are considered to be effective for beauty Powder and / or extract And the like.

<Application>
The Tie2 activator, angiogenesis inhibitor, blood vessel maturation agent, blood vessel normalizing agent, and blood vessel stabilizer of the present invention, and the pharmaceutical composition have excellent Tie2 activation action, angiogenesis inhibitory action, It has a vascular maturation effect, a vascular normalization effect, and a vascular stabilization effect, so it is a disease mainly involving vascular lesions such as tumors, rheumatoid arthritis, diabetic retinopathy, hyperlipidemia, and hypertension, and atopic disease. It can be suitably used as a drug for allergic diseases such as dermatitis, and hay fever, and a safe preventive drug for these diseases, and its compounding amount, usage, and dosage form are appropriately determined according to the purpose of use. You can choose.

  It has been confirmed that the Tie2 activator, angiogenesis inhibitor, blood vessel maturation agent, blood vessel normalizing agent, and blood vessel stabilizer of the present invention are not digestible in the digestive tract. Therefore, it can be suitably used as foods and drinks such as beauty foods and drinks and health foods and drinks, and its compounding amount, usage, and dosage form can be appropriately selected according to the purpose of use.

  The blending amount can be appropriately adjusted depending on the physiological activity of the extract, etc., but the Kiraya extract, the Huangqi extract, the Ginkgo extract, the oyster extract, the turmeric extract, the chrysanthemum extract 0.0001% by mass to 20% by mass, and preferably 0.0001% by mass, in terms of the purified product of at least one of the product, the jujube extract, the wolfberry extract, the chamomile extract, and the butcher bloom extract. It is more preferably from 10% by mass to 10% by mass.

  The usage is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include oral, parenteral, and external administration forms.

  The dosage form is not particularly limited and can be appropriately selected depending on the purpose. For example, oral administration preparations such as tablets, powders, capsules, granules, extracts, and syrups, injections, and infusions And parenteral preparations such as suppositories, ointments, creams, emulsions, lotions, packs, and external preparations such as bath preparations and hair cosmetics.

  Hereinafter, examples of the present invention will be described, but the present invention is not limited to these examples.

[Test Example 1: Tie2 activating action (immunoassay) test]
(Example 1: Kiraya extract)
Normal human umbilical vein endothelial cells (HUVEC) cultured to confluence were seeded in a 96-well plate at 2.0 × 10 ⁴ cells / 0.1 mL / well, and a medium for low serum vascular endothelial cell growth (Kurashiki The cells were cultured overnight using Humedia-EG2) (manufactured by Co., Ltd.). Next, the HUVEC after overnight culture was replaced with 0.1 mL of vascular endothelial cell basal medium (Kurashiki Spinning Co., Ltd., Humedia-EB2) 3 hours before cell stimulation (addition of a test sample), and cultured again. Was done. Thereafter, 0.1 mL of a Kiraya extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) adjusted to the concentration shown in Table 1 with Humedia-EB2 as a test sample was added to the well, and incubation was performed for 10 minutes. After the incubation, the amount of phosphorylated Tie2 and the amount of total Tie2 relative to the total Tie2 were measured using an immunoassay kit (manufactured by R & D Systems, Human Phospho-Tie2 (Y992) Immunoassay) according to the protocol. The ratio was calculated.
Similarly, the ratio of phosphorylated Tie2 to total Tie2 was calculated for dimethyl sulfoxide (DMSO) used as a negative control.
Then, the Tie2 activation rate was calculated according to the following formula (1), and the phosphorylation action was evaluated. Table 1 shows the results.
Tie2 activation rate (%) =
[{(Measured value of phosphorylated Tie2 when test sample is added) / (measured value of total Tie2 when test sample is added)} / ｛(measured value of phosphorylated Tie2 in negative control) / (in negative control Measured value of total Tie2) ｅ] × 100 (1)

(Example 2: Yellow myth extract)
In Example 1, the same procedure as in Example 1 was carried out except that the Kiraya extract was changed to a yellowish extract (Huangyi Extract Powder MF, manufactured by Maruzen Pharmaceutical Co., Ltd.) and the concentrations shown in Table 1 were used. Tested. Table 1 shows the results.

(Example 3: Ginkgo extract)
In Example 1, in the same manner as in Example 1 except that the Kiraya extract was changed to a ginkgo extract (Ginkgo leaf dry extract F, manufactured by Maruzen Pharmaceutical Co., Ltd.), and the concentrations shown in Table 1 were used. Tested. Table 1 shows the results.

(Example 4: Oyster extract)
In Example 1, the test was performed in the same manner as in Example 1 except that the Kiraya extract was changed to an oyster extract (Oyster extract powder, manufactured by Maruzen Pharmaceutical Co., Ltd.) and the concentrations shown in Table 1 were used. . Table 1 shows the results.

(Example 5: Turmeric extract)
In Example 1, in the same manner as in Example 1 except that the Kiraya extract was changed to a turmeric extract (Maruzen Pharmaceutical Co., Ltd., turmeric concentrated extract powder M) and the concentrations shown in Table 1 were used. Tested. Table 1 shows the results.

(Example 6: Chrysanthemum extract)
In Example 1, in the same manner as in Example 1 except that the Kiraya extract was changed to a chrysanthemum extract (Kikuhana Extract Powder MF, manufactured by Maruzen Pharmaceutical Co., Ltd.) and the concentrations shown in Table 1 were used, Tested. Table 1 shows the results.

(Example 7: Jujube extract)
In Example 1, the same procedure as in Example 1 was carried out, except that the Kiraya extract was changed to a jujube extract (Taiso extract powder MF, manufactured by Maruzen Pharmaceutical Co., Ltd.), and the concentrations shown in Table 1 were used. Tested. Table 1 shows the results.

(Example 8: wolfberry extract)
In Example 1, in the same manner as in Example 1 except that the Kiraya extract was changed to a wolfberry extract (Mokuzen Pharmaceutical Co., Ltd., wolfberry extract powder MF), and the concentrations shown in Table 1 were used. Tested. Table 1 shows the results.

(Example 9: chamomile extract)
In Example 1, in the same manner as in Example 1 except that the Kiraya extract was changed to a chamomile extract (manufactured by Maruzen Pharmaceutical Co., Ltd., chamomile extract powder MF), and the concentrations shown in Table 1 were used. Tested. Table 1 shows the results.

(Example 10: Butcher bloom extract)
In Example 1, in the same manner as in Example 1 except that the Kiraya extract was changed to Butcher Bloom extract (Butcher's Bloom extract, manufactured by Maruzen Pharmaceutical Co., Ltd.) and the concentrations described in Table 1 were used. Thus, Example 5 was obtained. Table 1 shows the results.

(Reference Example 1: Positive control)
Reference Example 1 was prepared in the same manner as in Example 1, except that the Kiraya extract was changed to Angiopoietin-1 (manufactured by R & D system) as a positive control, and the concentrations shown in Table 1 were used. And Table 1 shows the results.

[Test Example 1: Test result]
The test results of the Tie2 activating action (immunoassay) will be described.
When the Tie2 activating effect was evaluated using the immunoassay kit, it was confirmed that Tie2 was phosphorylated and activated by the extract used in the examples. In the system to which DMSO as a negative control was added, remarkable phosphorylation of Tie2 was not observed. In the system to which Angiopoietin-1, which is a positive control of Reference Example 1, was added, Tie2 was phosphorylated and activated. Here, it is known that phosphorylation of Tie2 causes vascular maturation, vascular normalization, and vascular stabilization, and suppresses angiogenesis.
From the above, it was suggested that the extract used in the examples has a Tie2 phosphorylation effect, suppresses angiogenesis, and induces maturation of blood vessels, normalization of blood vessels, and stabilization of blood vessels. .

The Tie2 activator, angiogenesis inhibitor, blood vessel maturation agent, blood vessel normalizing agent, and blood vessel stabilizer of the present invention, and the pharmaceutical composition have excellent Tie2 activation action, angiogenesis inhibitory action, It has a vascular maturation effect, a blood vessel normalization effect, and a blood vessel stabilization effect, so it has pharmaceuticals for diseases mainly involving vascular lesions such as tumors, rheumatoid arthritis, diabetic retinopathy, hyperlipidemia, and hypertension. It can be widely used as a safe preventive drug for these diseases.
In addition, it has been confirmed that the Tie2 activator, angiogenesis inhibitor, blood vessel maturation agent, blood vessel normalizing agent, and blood vessel stabilizer of the present invention are not digestible in the digestive tract. Therefore, it can be widely used as food and drink such as beauty food and drink and health food and drink.

Claims (3)

  A Tie2 activator comprising, as an active ingredient, at least one of a water extract of a chrysanthemum flower part, a hydrophilic solvent extract, and a mixed solvent extract of water and a hydrophilic solvent.   A water extract of a flower part of chrysanthemum, a hydrophilic solvent extract, and / or a mixed solvent extract of water and a hydrophilic solvent are contained as active ingredients, and a vascular maturation effect based on a Tie2 activation effect or A blood vessel maturation agent or a blood vessel stabilizing agent, which has a blood vessel stabilizing action. A food or drink used for activation of Tie2, maturation of blood vessels, and / or stabilization of blood vessels,
A food or drink comprising at least one of the Tie2 activator according to claim 1, the blood vessel maturation agent according to claim 2, and the blood vessel stabilizing agent according to claim 2.