COMPOSITION FOR PREVENTING OR TREATING HYPERTENSION

Abstract

The present invention relates to a composition for preventing or treating hypertension, the composition comprising, as an active ingredient, a complex extract of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus. A pharmaceutical composition or food composition according to the present invention can be used to effectively prevent, ameliorate, or treat hypertension or hypertension-related diseases.

Claims

1. A composition for preventing or treating hypertension or a hypertension-related disease, the composition comprising a complex extract of at least five species of herbal medicines selected from the group consisting of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus.

2. The composition of claim 1, wherein the complex extract comprises any one of the following: (a) a complex extract of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, and Coicis Semen; (b) a complex extract of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, and Schisandrae Fructus; (c) a complex extract of Puerariae Radix, Platycodonis Radix, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus; (d) a complex extract of Puerariae Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus; (e) a complex extract of Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus; and (f) a complex extract of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus.

3. The composition of claim 1, wherein the mixing weight ratio of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus in the complex extract is 2:2:2:1:1:1.

4. The composition of claim 1, wherein the extract is an extract with a polar organic solvent.

5. The composition of claim 4, wherein the polar organic solvent is water, a C1-C4 anhydrous or hydrous lower alcohol, acetic acid, or a mixture thereof.

6. The composition of claim 1, wherein the hypertension is essential hypertension or secondary hypertension.

7. The composition of claim 1, wherein the hypertension-related disease is postmenopausal hypertension, pulmonary arterial hypertension, stroke, dementia, erectile dysfunction, coronary artery disease, renal failure, myocardial infarction, arrhythmias, vascular aneurysm, heart failure, hypertensive retinopathy, aortic dissection, angina, and pregnancy induced hypertension.

8.-9. (canceled)

10. A method for prevention, alleviation, or treatment of hypertension or a hypertension-related disease comprising: administering a composition to a subject in need thereof, the composition comprising a complex extract of at least five species of herbal medicines selected from the group consisting of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus.

11. The method of claim 10, wherein the complex extract comprises any one of the following: (a) a complex extract of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, and Coicis Semen; (b) a complex extract of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, and Schisandrae Fructus; (c) a complex extract of Puerariae Radix, Platycodonis Radix, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus; (d) a complex extract of Puerariae Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus; (e) a complex extract of Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus; and (f) a complex extract of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus.

12. The method of claim 10, wherein the mixing weight ratio of Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus in the complex extract is 2:2:2:1:1:1.

13. The method of claim 10, wherein the extract is an extract with a polar organic solvent.

14. The method of claim 13, wherein the polar organic solvent is water, a C1-C4 anhydrous or hydrous lower alcohol, acetic acid, or a mixture thereof.

15. The method of claim 10, wherein the hypertension is essential hypertension or secondary hypertension.

16. The method of claim 10, wherein the hypertension-related disease is postmenopausal hypertension, pulmonary arterial hypertension, stroke, dementia, erectile dysfunction, coronary artery disease, renal failure, myocardial infarction, arrhythmias, vascular aneurysm, heart failure, hypertensive retinopathy, aortic dissection, angina, and pregnancy induced hypertension.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0076] FIG. 1 shows hypertension alleviating effects of single herbal medicine extracts and a complex herbal medicine extract of the present disclosure in the hypertension-induced mouse model according to Test Example 1.

[0077] FIG. 2 shows hypertension alleviating effects of complex herbal medicine extracts excluding one species of herbal medicine of the present disclosure in the hypertension-induced mouse model according to Test Example 2.

DETAILED DESCRIPTION

[0078] Hereinafter, the present disclosure will be described in more detail with reference to exemplary embodiments. These exemplary embodiments are provided only for the purpose of illustrating the present disclosure in more detail, and therefore, according to the purpose of the present disclosure, it would be apparent to a person skilled in the art that these examples are not construed to limit the scope of the present disclosure.

EXAMPLES

Preparation Example 1: Preparation of Composite Herbal Medicine Extract Through Extraction with Aqueous Ethanol Solution

[0079] After washed and dried Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus were mixed at a weight ratio (w/w) of 2:2:2:1:1:1, a 70% aqueous ethanol solution (L) corresponding to 10 times the weight (kg) of the mixture was added thereto, followed by extraction with favorable stirring at 20° C. for 72 hours. The extract was filtered, concentrated under reduced pressure at 45-50° C., and then freeze-dried, to thereby obtain a complex herbal medicine extract powder. The yield thereof is shown in Table 1.

TABLE-US-00001 TABLE 1 Classification Kind of herbal medicine Yield (%) Preparation Puerariae Radix, Platycodonis Radix, 19.08 Example 1-1 Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus (2:2:2:1:1:1)

Comparative Example 1: Preparation of Single Herbal Medicine Extracts

[0080] As for each of washed and dried Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus, a 70% aqueous ethanol solution (L) corresponding to 10 times the weight of each herbal medicine was added thereto, followed by extraction with favorable stirring at 20° C. for 72 hours. Each herbal medicine extract was filtered, concentrated under reduced pressure at 45-50° C., and then freeze-dried, to thereby obtain a total of six single herbal medicine extract powders. The yields thereof are shown in Table 2.

TABLE-US-00002 TABLE 2 Classification Kind of herbal medicine Yield (%) Comparative Example 1-1 Puerariae Radix 18.80 Comparative Example 1-2 Platycodonis Radix 18.85 Comparative Example 1-3 Liriopis Tuber 26.49 Comparative Example 1-4 Dioscoreae Rhizoma 12.37 Comparative Example 1-5 Coicis Semen 2.36 Comparative Example 1-6 Schisandrae Fructus 32.90

Comparative Example 2: Preparation of Extracts of Complex Herbal Medicines Extracts Excluding One Species of Herbal Medicine

[0081] After mixtures of five species of herbal medicines among washed and dried Puerariae Radix, Platycodonis Radix, Liriopis Tuber, Dioscoreae Rhizoma, Coicis Semen, and Schisandrae Fructus were obtained by weight ratios (w/w) shown in Table 3, a 70% aqueous ethanol solution (L) corresponding to of 10 times the weight (kg) of each of the mixtures was added thereto, followed by extraction with favorable stirring at 20° C. for 72 hours. The extracts were filtered, concentrated under reduced pressure at 45-50° C., and then freeze-dried, to thereby obtain a total of six complex herbal medicine extract powders. The yields thereof are shown in Table 3.

TABLE-US-00003 TABLE 3 Puerariae Platycodonis Liriopis Dioscoreae Coicis Schisandrae Yield Classification Radix Radix Tuber Rhizoma Semen Fructus (%) Comparative 2 2 2 1 1 — 19.54 Example 2-1 Comparative 2 2 2 1 — 1 23.33 Example 2-2 Comparative 2 2 2 — 1 1 23.22 Example 2-3 Comparative 2 2 — 1 1 1 19.98 Example 2-4 Comparative 2 — 2 1 1 1 22.16 Example 2-5 Comparative — 2 2 1 1 1 20.93 Example 2-6

Test Example 1: Comparison of Blood Pressure Increase Inhibitory Effect Between Complex Extract and Single Herbal Medicine Extracts in L-NAME-Induced Mouse Hypertension

[0082] For comparative evaluation of the blood pressure increase inhibitory effect between the complex extract and the single herbal medicine extracts, N(G)nitroLarginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, was used to induce hypertension in mice, and then the blood pressure of the tail was measured.

[0083] The hypertension was induced in 8-week-old female ICR mice by providing 1 mg/mL L-NAME dissolved in drinking water, for one week, and during the same period, a complex extract (Preparation Example 1-1) and single extracts (Comparative Examples 1-1, 1-2, 1-3, 1-4, 1-5, and 1-6) were orally administered at a dose of 200 mg/kg daily. Distilled water was administered for a normal group and a negative control (an induced group).

[0084] To measure the systolic blood pressure (SBP) of a tail part without anesthesia in mice (n=6-7 per group) that have been administered, a CODA High Throughput Noninvasive Blood Pressure system (CODA, Kent Scientific Co., USA) were used. After a tail cuff was placed on the tail of the mouse, a volume pressure recording (VPR) sensor was installed and the mice were stabilized for 30 to 40 min. Then, an average value of results of 15-20 repeated measurements was used. The results are shown in Table 4 and FIG. 1.

TABLE-US-00004 TABLE 4 Blood pressure Blood Activity compared increase compared pressure with complex Test SBP with normal increase herbal medicine Test Group L-NAME substance (mmHg) group (%) extract, % Normal group X Distilled 121.0 ± — — — water 4.1 Negative ◯ Distilled 164.7 ± 43.7 100 — control group water 3.8 (induced group) Complex herbal ◯ Preparation 128.5 ± 7.5 17.0 100 medicine extract Example 1-1 6.2 (Preparation Example 1-1) Puerariae ◯ Comparative 151.8 ± 30.8 70.4 35.7 Radix extract Example 1-1 4.5 (Comparative Example 1-1) Platycodonis ◯ Comparative 164.8 ± 43.8 100.2 −0.3 Radix extract Example 1-2 4.8 (Comparative Example 1-2) Liriopis ◯ Comparative 153.7 ± 32.7 74.8 30.3 Tuber extract Example 1-3 6.0 (Comparative Example 1-3) Dioscoreae ◯ Comparative 163.0 ± 42.0 96.0 4.9 Rhizoma extract Example 1-4 5.7 (Comparative Example 1-4) Coicis ◯ Comparative 165.9 ± 44.9 102.6 −3.2 Semen extract Example 1-5 4.6 (Comparative Example 1-5) Schisandrae ◯ Comparative 163.0 ± 42.0 96.0 4.9 Fructus extract Example 1-6 2.6 (Comparative Example 1-6)

[0085] When 1 mg/mL L-NAME was administered through drinking water for one week, the systolic blood pressure increased by 43.7 mmHg compared with the normal group as shown in Table 4. As for the groups receiving the complex extract or single extracts at a dose of 200 mg/kg, the complex herbal medicine extract (Preparation Example 1-1) showed an 83% inhibition of the blood pressure increase, whereas the Puerariae Radix extract (Comparative Example 1-1) showed a 29.6% inhibition, the Liriopis Tuber extract (Comparative Example 1-3) showed a 25.2% inhibition, the Dioscoreae Rhizoma extract (Comparative Example 1-4) and Schisandrae Fructus extract (Comparative Example 1-6) showed only a 4% inhibition, and the Puerariae Radix extract (Comparative Example 1-2) and Coicis Semen extract (Comparative Example 1-5) showed no effects. Therefore, the complex extract of six species of herbal medicines of Preparation Example 1-1 showed a significantly excellent effect.

Test Example 2: Comparison of Blood Pressure Increase Inhibitory Effect Between Complex Extract and One Herbal Medicine-Excluded Extracts in L-NAME-Induced Mouse Hypertension

[0086] The hypertension was induced in 8-week-old female ICR mice by providing 1 mg/mL L-NAME dissolved in drinking water for one week, and during the same period, a complex extract (Preparation Example 1-1) and one herbal medicine-excluded extracts (Comparative Examples 2-1, 2-2, 2-3, 2-4, 2-5, and 2-6) were orally administered at a dose of 200 mg/kg daily. Distilled water was administered for a normal group and a negative control (an induced group).

[0087] To measure the systolic blood pressure (SBP) of a tail part without anesthesia in mice (n=6-7) that have been administered, a CODA High Throughput Noninvasive Blood Pressure system (CODA, Kent Scientific Co., USA) were used. After a tail cuff was placed on the tail of the mouse, a volume pressure recording (VPR) sensor was installed and the mice were stabilized for 30 to 40 min. Then, an average value of results of 15-20 repeated measurements was used. The results are shown in Table 5 and FIG. 2.

TABLE-US-00005 TABLE 5 Blood pressure Blood Activity compared increase compared pressure with complex Test SBP with normal increase herbal medicine Test Group L-NAME substance (mmHg) group (%) extract, % Normal group X Distilled 113.7 ± — — — water 4.1 Negative ◯ Distilled 183.4 ± 69.7 100.0 — control group water 6.6 (induced group) Complex herbal ◯ Preparation 137.0 ± 23.3 33.4 100 medicine extract Example 1-1 6.3 (Preparation Example 1-1) Schisandrae ◯ Comparative 164.3 ± 50.6 72.6 41.1 Fructus excluded Example 2-1 10.8 (Preparation Example 2-1) Coicis Semen ◯ Comparative 162.4 ± 48.7 69.8 45.3 excluded Example 2-2 5.2 (Preparation Example 2-2) Dioscoreae ◯ Comparative 174.8 ± 61.1 87.6 18.7 Rhizoma- Example 2-3 9.1 excluded (Preparation Example 2-3) Liriopis Tuber ◯ Comparative 150.5 ± 36.8 52.7 71.0 excluded Example 2-4 7.8 (Preparation Example 2-4) Platycodonis ◯ Comparative 150.2 ± 36.5 52.3 71.7 Radix excluded Example 2-5 6.3 (Preparation Example 2-5) Puerariae ◯ Comparative 150.8 ± 37.1 53.2 70.3 Radix excluded Example 2-6 4.7 (Preparation Example 2-6)

[0088] As shown in Table 5 and FIG. 2, when 1 mg/mL L-NAME was administered through drinking water for one week, the systolic blood pressure increased by 69.7 mmHg compared with the normal group as shown in Table 5. As for the groups receiving 200 mg/kg complex extract or one herbal medicine-excluded extracts, the complex herbal medicine extract (Preparation Example 1-1) showed a 66.6% inhibition of the blood pressure increase, and the Schisandrae Fructus-excluded extract (Comparative Example 2-1) showed a 27.4% inhibition, the Coicis Semen-excluded extract (Comparative Example 2-2) showed a 30.2% inhibition, the Liriopis Tuber-excluded extract (Comparative Example 2-4) showed a 47.3% inhibition, the Platycodonis Radix-excluded extract (Comparative Example 2-5) showed a 47.7% inhibition, and the Puerariae Radix-excluded extract (Comparative Example 2-6) showed a 46.8% inhibition, showing excellent effects. However, the Dioscoreae Rhizoma-excluded extract (Comparative Example 2-3) showed only a 12.4% inhibition.

[0089] The blood pressure increase inhibition rates (blood pressure increase inhibitory activities) of the single herbal medicine extracts and the complex extracts of five and six species of herbal medicines in Tables 4 and 5 were compared with the blood pressure increase inhibition rate (100%) of the complex extracts of six species of herbal medicines of Preparation Example 1-1. As a result, the Puerariae Radix extract had the highest activity among the single herbal medicine extracts in Table 4, and all the complex extracts of five and six species of herbal medicines except for the Dioscoreae Rhizoma-excluded extract (Comparative Example 2-3) in Table 5 had higher activity than the activity (35.7%) of the Puerariae Radix extract compared with the complex extract of six herbal medicines.

[0090] It was identified from the above results that the complex extracts of five species of herbal medicines excluding Dioscoreae Rhizoma-excluded extract (Comparative Examples 2-1, 2-2, 2-4, and 2-6) and the complex extract of six species of herbal medicines (Preparation Example 1-1) of the present disclosure were considered to have an excellent synergistic effect compared with the single herbal medicine extracts, and especially, the complex extracts of six species of herbal medicines showed a significantly excellent blood pressure increase inhibitory effect.