KR20230033210A - Compositions having the effects of improving blood circulation including blendings of Curcuma longa, Mulberry or Eucommia ulmoides Oliver extracts - Google Patents

Abstract

The present invention relates to a composition which contains, as a main component, a mixture of extracts of Curcuma longa, Morus alba, or Eucommia ulmoides effective in improving blood circulation, which if effective in improving blood circulation and/or improving blood flow. The composition of the present invention exhibits effects of increasing the amount of nitric oxide (NO) released from cells and improving vasoconstrictor relaxation. Therefore, according to the present invention, it is possible to provide a functional composition expected to be effective in preventing or treating diseases or disorders related to blood circulation.

Description

Functional composition having the effect of improving blood circulation containing a mixture of turmeric, mulberry or eucommia extracts

The present invention relates to a functional composition comprising, as a main component, a mixture of turmeric, mulberry or Eucommia extracts having a blood circulation improving effect.

For those with cerebrovascular disease or those at high risk of these diseases, that is, those with high blood pressure and obesity, diabetes, or those with high blood pressure who are over 40 years old and smoke, blood circulation improvement is a priority for the treatment of related diseases. people who need it

The purpose of developing medicines or foods for improving blood circulation is to improve blood flow through suppression of platelet aggregation or relaxation of blood vessels. Among them, the platelet aggregation inhibition mechanism may cause various interactions and side effects in the process of improving platelet function related to or unrelated to vitamin K, and is not a desirable direction for the development of health functional foods. Therefore, as a mechanism for improving blood flow through vascular relaxation, it is known as a desirable research and development direction for medicines or foods for improving blood circulation to improve blood flow and expand blood vessels through the release of nitric oxide (NO).

Nitric oxide (NO) is formed within cells from the amino acid arginine. As a kind of signaling material, it is involved in various physiological activities such as immune action, vasodilation, and signal transmission. In particular, it induces and stimulates various activities of the body, induces the production of cGMP (cyclic guanosine monophosphate), dilates blood vessels, lowers blood pressure to reach a normal level range, and improves the flow of blood supplied to organs. In addition, it prevents blood clots in the cardiovascular system, thereby preventing stroke, in particular, preventing heart attacks such as myocardial infarction.

For the research and development as described above, the present inventors continuously investigated blood circulation-related candidate herbal medicines based on various data and papers, and performed work to derive candidate herbal medicines therefrom. As a result, turmeric ( Curcuma longa ), mulberry (Morus alba), and Eucommia ulmoides Oliver (please check the scientific names of each) were selected as candidate herbal medicines, and their efficacy related to blood circulation improvement was studied.

Turmeric is a perennial plant belonging to the order Ginger. It is mainly cultivated in tropical and subtropical regions around India, and its stems and roots are used for food and medicine. It is widely cultivated in India, China, and Southeast Asia, and in Korea, it is cultivated in Jindo, Jeollanam-do, Jeonnam Haenam, Jeonbuk Buan, Gyeonggi Siheung, and Chungnam Cheongyang. It is used as a colorant, spice, and dye to dye clothes. As a pharmacological action, it is a powerful antioxidant that strengthens immunity, has excellent anti-inflammatory effects, and promotes pain relief, skin protection, liver health and metabolism. center

Mulberry is a mulberry fruit or a dried medicine, and is also called heartache or heartache. It has been used as a medicine since the Tang Dynasty. Its medicinal properties are mild, and its taste is sweet and sour. As for pharmacological action, it is known to have diuretic, antitussive, and tonic effects. It is also effective for those who are hypersensitive due to nervous breakdown, and it is also used when the head is heavy and dizzy due to arteriosclerosis or high blood pressure. To the extent that Donguibogam explains that it is good for diabetes and anti-aging, it has effects of suppressing aging, treating diabetic retinopathy, improving eyesight, antioxidant action, anti-diabetes, growth and maintenance of the body, and lowering cholesterol content.

Eucommia is mainly used as a medicine by removing the epidermis from the stem bark of the Eucommia tree, on the other hand, the leaves and flowers of Eucommia are also used for medicinal purposes. Pharmacological actions include lowering blood pressure, anti-aging, lowering cholesterol, anti-inflammation, sedation, pain relief, immune regulation, blood coagulation, uterine contraction, anti-allergy, antibacterial action, improvement of sexual function, diuretic action, and strengthening of muscles and bones.

As described above, although various pharmacological efficacies are known for each of turmeric, mulberry, and Eucommia, no specific study has been conducted on the effect of improving blood circulation by a mixture thereof. That is, research results on how these mixtures affect blood flow improvement and vasodilation through nitric oxide (NO) release have not been reported.

Therefore, in the present invention, turmeric + mulberry extract mixture, mulberry + wormwood extract mixture, turmeric + wormwood extract mixture, or turmeric + mulberry + wormwood extract mixture as components showing medicinal effects of blood circulation improvement and / or blood flow improvement Various experiments and evaluations were performed with respect to the method, and a method for exhibiting optimal effects in applications in the field of medicine or food was derived and the present invention was reached.

An object of the present invention is to provide a functional composition with blood circulation improving efficacy comprising a mixture of two or more herbal extracts selected from the group of turmeric, mulberry, and eucommia as a main component exhibiting blood circulation and/or blood flow improvement efficacy. In particular, the present invention is intended to provide a composition that is effective in increasing nitric oxide (NO) release in HUVEC cells and improving vasoconstrictor relaxation in blood vessels of SD rats.

The present invention provides a functional composition having blood circulation improving efficacy comprising a mixture of two or more extracts selected from the group consisting of extracts of turmeric, mulberry and eucommia as a main component exhibiting blood circulation improvement and/or blood flow improvement efficacy.

The functional composition may include the main component and conventional components necessary for the functional composition.

Each extract included in the mixture of the extracts is mixed in the same mass ratio.

The composition enhances nitric oxide (NO) release in cells.

The composition improves vasoconstrictor relaxation.

The curcuma, mulberry or Eucommia extract is prepared by extracting the lyophilized powder in an extraction solvent, removing solids from the extraction product to obtain a supernatant, and freeze-drying the supernatant to obtain an extract.

In the extraction step, one or more extraction solvents selected from organic solvents including water and methanol, ethanol, butanol, ethyl acetate, and nucleic acids are used.

Preferably, the extraction solvent is 40 to 70% ethanol.

Preferably, the composition comprises the extract mixture at a concentration of 50 to 100 μg/ml.

The composition may be food or pharmaceutical.

The composition may be provided in the form of a solution, suspension, tablet, granule or powder.

According to the present invention, as a composition effective for improving blood circulation, a composition comprising a mixture of two or more extracts selected from the group consisting of extracts of turmeric, mulberry, and Eucommia as a main component exhibiting efficacy in improving blood circulation and/or improving blood flow can be provided. Such a composition has an effect of increasing nitric oxide (NO) release in cells and improving vasoconstrictor relaxation of blood vessels. Therefore, the composition of the present invention can be expected to have a therapeutic effect for people with blood circulation-related diseases or cerebrovascular diseases, and a preventive effect of stroke and heart attack for those at high risk of these diseases.

Figure 1 is a single extract of turmeric, mulberry and Eucommia to HUVEC; and mixtures of extracts; It shows the amount of NO emission during treatment.
Figure 2 is a single extract of turmeric, mulberry and Eucommia in the aortic ring of rats; and mixtures of extracts; It shows the vasoconstrictor relaxation power during treatment.

The present invention provides a composition with blood circulation improving efficacy comprising a mixture of two or more extracts selected from the group consisting of extracts of turmeric, mulberry, and Eucommia as a main component exhibiting blood circulation improvement and/or blood flow improvement efficacy.

The composition is effective in improving blood flow through vasodilation, and specifically, exhibits an effect of increasing nitric oxide (NO) release from cells and improving vasoconstrictor relaxation.

The mixture of extracts included in the composition may be, for example, a mixture of turmeric + mulberry extract, a mixture of turmeric + wormwood extract, a mixture of mulberry + wormwood extract, or a mixture of turmeric + mulberry + wormwood extract.

The mixture of the extracts shows superior results in terms of blood circulation improvement effect than single extracts. Therefore, the present invention provides a composition characterized in that it does not contain the turmeric, mulberry or Eucommia extract alone, but in the form of a mixture of extracts by mixing two or more.

Each extract included in the extract mixture is preferably mixed in the same mass ratio for a synergistic effect.

Cells related to NO release in the present invention are vascular endothelial cells, and when NO is released from vascular endothelial cells, physiological activities such as vasodilation and signal transmission are increased. In other words, it induces the production of cGMP to dilate blood vessels, maintains blood pressure at a normal level, and improves the flow of blood supplied to organs. In addition, it prevents blood clots in the cardiovascular system, thereby preventing stroke, in particular, preventing heart attacks such as myocardial infarction. In addition, when blood vessels are dilated, blood circulation can be improved, which is related to the contraction and relaxation of blood vessels. That is, when the vasoconstriction and relaxation force is improved, elasticity is generated in the vascular muscles, so that the blood vessels can be easily expanded, thereby improving blood circulation.

Since the composition of the present invention has the effect of improving blood circulation by the above mechanism, it is ultimately effective in treating people with brain and cardiovascular diseases related to blood circulation and in preventing stroke and heart attack in people with high risk of these diseases. can be expected

The extract of the present invention is obtained by extracting the lyophilized powder in an extraction solvent, removing solids from the extraction product to obtain a supernatant, and freeze-drying the supernatant to obtain an extract. are manufactured

In the extraction step, one or more extraction solvents selected from water and organic solvents including methanol, ethanol, butanol, ethyl acetate and nucleic acids are used. Preferably, 40 to 70% ethanol is used as an extraction solvent. Depending on the concentration of the extraction solvent, there is a difference in cell viability, active oxygen scavenging ability and NO release amount of each extract, and when 40 to 70% of ethanol is used as an extraction solvent, it shows the highest effect at low cytotoxicity.

In the step of removing the solid content from the extraction product and obtaining the supernatant, the solid content may be removed by centrifugation.

온도에서 24시간 동안 건조한 것으로 한다.Next, lyophilization is performed to obtain the final extract. Freeze-drying condition is -70

It is dried for 24 hours at room temperature.

In the present invention, the turmeric, mulberry, and Eucommia extracts obtained in this way are used as a mixture mixed in the same mass ratio, and preferably treated at a concentration of 50 to 100 μg/ml. It is confirmed that it does not exhibit cytotoxicity in the above concentration range, and the effect of increasing NO emission and improving vasoconstrictor relaxation is shown.

Therefore, when the present invention is provided as a functional composition of various types as follows, it is preferable for the effect of improving blood circulation to be included in the above concentration range.

The composition of the present invention may be food or pharmaceutical. In addition, the composition may be provided in various forms such as aerosols, solutions, suspensions, tablets, granules or powders.

The present invention will be described in more detail through the following examples. However, it should not be considered that the present invention is limited thereto.

Example

1. Preparation of extracts of turmeric, mulberry and Eucommia

Turmeric, mulberry and Eucommia were powdered using a grinder. After adding 900 mL of 40% or 70% ethanol to 100 g of the powder, leaching and extracting twice at 25 ° C. for 24 hours, and then using a centrifuge at 3000 rpm for 10 minutes, the solid content was removed. Only the centrifuged supernatant was collected, concentrated under reduced pressure, and freeze-dried. Through this extraction process, extracts of each component were obtained.

2. NO emission measurement

2-1. HUVEC cell culture

Human Umbilical Vein Endothelial Cell (HUVEC) culture is “Aging Cell. 2020 Dec;19(12):e13279”. That is, cells were cultured in Endothelial Cell Growth Basal Medium 2 (EBM-2) supplemented with Endothelial Cell Growth Medium 2 (EGM-2).

2-2. Cell viability measurement

Human umbilical vein endothelial cells (HUVEC) were cultured in a culture medium supplemented with endothelial cell growth medium 2 (EGM-2) at 5% CO ₂ and humidified at 37 ° C, and the number of cells was adjusted to 5 × 10 ⁴ /well. Cells were seeded in each well. The cells were tested by adding 100L of culture medium per well to a 96-well culture plate, and the plate was cultured in a 5% CO ₂ humidified and 37°C incubator.

After the cells reached ~80% cell filling rate in the well, the cells were treated with the extracts of turmeric, mulberry, and Eucommia, and mixtures thereof in distilled water at concentrations of 50 and 100 μg/ml.

2-3. NO emission measurement

70% mulberry: mulberry extract extracted using 70% ethanol

40% Turmeric: Turmeric extract extracted using 40% ethanol

Eucommia 70%: Eucommia extract extracted using 70% ethanol

(1) Curcuma + mulberry extract mixture: a mixture obtained by mixing the turmeric and mulberry extracts in the same mass ratio

(2) Turmeric + Eucommia extract mixture: A mixture obtained by mixing the turmeric and Eucommia extracts in the same mass ratio

(3) Eucommia + Mulberry Extract Mixture: A mixture obtained by mixing the extracts of Eucommia and Mulberry in the same mass ratio.

(4) Curcuma + Mulberry + Eucommia Extract Mixture: A mixture obtained by mixing the extracts of Curcuma, Mulberry and Eucommia in the same mass ratio.

NO release from cells is Aging Cell. 2020 Dec;19(12):e13279 as determined by the Griess reaction. After the cells reached ~80% cell filling rate in the well, the cells were treated with the extracts of Curcuma, Mulberry and Eucommia, and their mixtures at concentrations of 50 and 100 μg/ml in each well. After 48 hours, in order to measure the amount of NO released from the cells, the cell culture medium was collected and reacted by mixing with an equal volume of nitrate/nitrite analysis kit (Sigma, St Louis, MO, USA), and the nitrite standard concentration was determined by the manufacturer ( Sigma, St Louis, MO, USA) was prepared and used as directed.

As for the reaction principle, Azo coupling is formed by the reaction of NEDHC, Sulfanilamide and NO ₂ ^- , and these two ring types (the higher the NO content, the brighter red) have the maximum absorbance value at a wavelength of 540 nM. Therefore, by measuring this value, the amount of NO produced is indirectly quantified by comparing it with the standard.

The results are shown in Figure 1. As shown in Figure 1, the amount of NO released from vehicle, which is a cell without any treatment, is set to 1, and the amount of NO released from cells treated with an extract and a mixture thereof is shown. As a result, NO emission was higher when the mixtures of mulberry + turmeric, turmeric + wormwood, and mulberry + worm + turmeric extracts were treated than when the mixture was treated with the extract mixture of mulberry, turmeric, or Eucommia alone.

3. Evaluation of vasoconstrictor relaxation

The rat's aortic ring was carefully dissected and the isolated descending aorta was cut into rings (3-4 mm in length). Modified Krebs buffer (118 mM NaCl, 1.2 mM MgCl ₂ , 11.2 mM NaH ₂ PO ₄ , 4.7 mM KCl, 1.2 mM Na ₂ SO ₄ , 25 mM NaHCO ₃ , 10 mM N-[2-hydro-ethyl]-piperazine -N'-[2-ethanesulfonic acid] (HEPES) and 11.1 mM glucose; pH 7.4) and changes in isometric tension were recorded. Blood vessels were constricted using phenylephrine (PE), and the condition of the blood vessels and vasodilator were first checked by increasing the concentration of Acetylcoline and then the blood vessels were constricted, and then they were contracted using PE, and the blood vessels were relaxed using each extract and mixture was confirmed, and vasodilation % (vasodilation) was measured and expressed. The first PE contraction and relaxation ability of Acetylcoline were set to 100%, and the final relaxation ability using each extract and mixture was shown as % on the bar graph.

The results are shown in Figures 2a and 2b. As shown in Figures 2a and 2b, it shows that the vasoconstrictor relaxation ability increases when the mixture thereof is administered rather than the single extract of turmeric, mulberry or Eucommia.

Claims (11)

A functional composition with blood circulation improving efficacy, comprising a mixture of two or more extracts selected from the group consisting of extracts of turmeric, mulberry, and Eucommia, as a main component exhibiting blood circulation improvement and/or blood flow improvement efficacy.
In paragraph 1,
Each extract contained in the extract mixture is characterized in that mixed in the same mass ratio, functional composition.
In paragraph 1,
The composition is a functional composition, characterized in that to enhance the amount of nitric oxide (NO) released in cells.
In paragraph 1,
The composition is characterized in that to improve the vasoconstrictor relaxation, functional composition.
In paragraph 1,
The turmeric, mulberry or Eucommia extract is prepared by extracting the lyophilized powder in an extraction solvent, removing solids from the extraction product to obtain a supernatant, and freeze-drying the supernatant to obtain an extract. To, a functional composition.
In paragraph 5,
In the extraction step, water and methanol, ethanol, butanol, ethyl acetate and one or more extraction solvents selected from among organic solvents including nucleic acids are used, the functional composition.
In paragraph 6,
The extraction solvent is characterized in that 40 to 70% ethanol, functional composition.
In paragraph 1,
The composition is characterized in that the extract mixture is included in a concentration of 50 to 100 μg / ml, functional composition.
In paragraph 1,
The composition is a functional composition, characterized in that food or pharmaceutical.
In paragraph 9,
The composition is characterized in that it comprises a conventional component for food or medicine in addition to the main component, functional composition.
In paragraph 1,
The functional composition, characterized in that provided in the form of an aerosol, solution, suspension, tablet, granule or powder.

Images