KR19990039368A - Blood pressure lowering composition containing hesperidin - Google Patents

Abstract

The present invention relates to a blood pressure lowering composition comprising hesperidin, wherein the composition of the present invention includes a pharmaceutical and food composition. Since the composition of the present invention lowers blood pressure in the animal body, it may be usefully used as a therapeutic agent for hypertension or as a component of a health food.

Description

Blood pressure lowering composition containing hesperidin

The present invention relates to a blood pressure lowering composition comprising hesperidin (C ₂₈ H ₃₄ O ₁₅ , molecular weight 610.55).

Cardiac circulatory disease currently accounts for more than 30% of all deaths, and in developed countries, in some cases, up to 40% mortality occurs. In particular, hypertension is the predominant cause of heart disease and is the leading cause of high mortality. Hesperidin is present in citrus fruits such as oranges and tangerines, and has been reported to be effective in preventing and treating cerebral anemia, retinal hemorrhage, and purpura as a vitamin that lowers permeability of capillaries.

The present inventors found that hesperidin isolated from citrus peel, which is also commonly used as a medicinal herb in Korea, was useful in lowering blood pressure while searching for ingredients that could prevent high blood pressure from edible sources and were not toxic.

It is an object of the present invention to provide a composition for lowering blood pressure containing hesperidin.

In the present invention, there is provided a blood pressure-lowering pharmaceutical composition comprising hesperidin as an active ingredient with a pharmaceutically acceptable carrier, and a blood pressure-lowering food composition comprising hesperidin.

Hesperidin can be extracted from citrus fruits or synthesized by known synthetic methods. Citrus fruits in the present invention refers to tangerine, orange, lemon, grapefruit, citron or tanza. Many methods of extracting hesperidin from citrus fruits have been published in the literature and patents such as the Merck Index.

Hesperidin has been shown to lower blood pressure in rats, and its toxicity studies have shown little toxicity when administered orally to mice at a dose of 1,000 mg / kg. In addition, hesperidin shows no adverse effects on the function of organs, including the liver.

Hesperidin showed significant hypotensive activity when administered to rats in an amount of 1.0 to 9.0 g / kg.

In order to lower blood pressure, hesperidin may be mixed with a pharmaceutically acceptable carrier as an active ingredient to prepare a blood pressure lowering agent composition. The pharmaceutical composition may further include conventionally used excipients, disintegrants, sweeteners, lubricants, flavoring agents and the like, and by conventional methods tablets, capsules, powders, granules, suspensions, emulsifiers, syrups, solutions Or in dosage unit forms or as multi-dose pharmaceutical preparations, such as preparations for parenteral administration.

The antihypertensive composition containing hesperidin as an active ingredient may be parenterally or orally administered as desired, and the amount of hesperidine 0.1 to 10 g, preferably 0.5 to 3 g per 1 kg of body weight per day may be 1 to several times. Can be administered in divided doses. Dosage levels for a particular patient may vary depending on the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, severity of the disease, and the like.

Hesperidin may also be added to food for the purpose of lowering blood pressure. Foods to which hesperidin can be added for the development of dietary supplements include, for example, various foods, meats, beverages, chocolates, snacks, confectionery, pizzas, ramen noodles, other noodles, gums, ice creams, alcoholic beverages, vitamins. Complexes, dietary supplements, and the like.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following Examples are only for illustrating the present invention, and the scope of the present invention is not limited to these.

Example 1: Confirming the blood pressure control effect of hesperidin

Congenital hypertensive rats (SHR) were purchased from Charles River, Japan. Male Sprague-Dawley rats were 4 weeks old at the Korea Institute of Chemistry and were raised in the absence of specific pathogens (SPF). 12 weeks of age and 350-weight weight, respectively, were fed to feed and water freely in a normal breeding room (12 hours, 12 hours cancer cycle) maintained at a constant temperature (22 ℃) and humidity (55 ± 5%). When 450g was used for the experiment.

100 mg deoxycorticosterone acetate pellets (Innovative Research of America, USA) were implanted into the right femoral subcutaneous of Sprague Dawley rats and sutured with autoclips. After four weeks of oral administration of 1% NaCl to the rats to establish DOCA / saline hypertensive rats, rats with elevated mean arterial pressure above 170 mmHg were used for the evaluation of hypotensive action.

Meanwhile, another Sprague Dawley rat (350-450 g) was anesthetized with ether, incised about 1 cm in the left abdomen, and carefully separated the renal artery near the abdominal aorta with a suture (4/0 sterile surgical silk, Ethicon). The renal artery was completely ligated and the muscle layer and skin were sutured with a suture with needle. After 6-8 days of ligation, animals with systolic blood pressure greater than 180 mmHg were used in the experiments as a model of renal hypertensive rat (RHR).

DOCA / saline hypertensive rats, SHR and RHR rats prepared as described above were anesthetized by intraperitoneal administration of ketamine hydrochloride in an amount of 125 mg / kg, followed by PE10 to polyethylene tubing 50 (PE50). A cannula was inserted into the femoral artery by filling a heparinized saline solution in a catheter connected to the catheter. The other end of the catheter was pulled behind the neck subcutaneously and fixed. After the rats were stabilized in the blood pressure measuring cage, a cannula was inserted into the femoral artery of the animal that awoke from the anesthesia the next day. blood pressure and heart rate were measured using a processing center (Modular, USA). After confirming that the blood pressure was stabilized for about 1 hour, a solution in which hesperidin (Sigma Chemical Co.) was suspended in 0.5% carboxymethylcellulose (CMC) was administered orally by dose. Blood pressure and heart rate were measured up to 24 hours after administration at regular intervals, and the results were expressed as the rate of change of blood pressure and heart rate before drug administration.

The results are shown in Tables 1, 2 and 3, and hesperidin showed a significant hypotensive effect in DOCA and RHR model mice.

Effect of Hesperidin on Blood Pressure and Heart Rate in DOCA Rats Average blood pressure (%) time Control 1 g / kg hesperidin 3 g / kg hesperidin 0 0.00 0.00 0.00 10 minutes 0.30 -2.00 -0.70 20 minutes -0.20 -3.90 -3.30 30 minutes 0.20 -3.60 -7.30 60 mins -3.10 -6.50 -13.30 90 mins -1.30 -14.10 -14.80 2 hours -6.00 -17.20 -17.40 4 hours -6.60 -17.30 -20.00 6 hours -7.20 -16.50 -27.60 22 hours -3.20 -17.20 -25.00 24 hours -6.40 -21.00 -31.00 Baseline (mmHg) 144.00 161.00 158.00

Average heart rate (%) time Control 1 g / kg hesperidin 3 g / kg hesperidin 0 0.00 0.00 0.00 10 minutes 0.00 6.90 4.10 20 minutes 2.00 4.80 3.40 30 minutes 2.80 3.40 3.20 60 mins -1.50 1.90 -3.10 90 mins -2.80 -2.80 -3.10 2 hours -4.70 -4.80 -2.30 4 hours -1.80 2.30 -4.20 6 hours -5.00 -8.00 -14.40 22 hours -11.90 -20.60 -24.30 24 hours -12.00 -18.90 -21.40 Baseline (mmHg) 284.00 296.00 313.00

Effect of Hesperidin on Blood Pressure and Heart Rate in SHR Average blood pressure (%) time Control 1g / kg Hesperidin 0 0.00 0.00 10 minutes -0.20 3.70 20 minutes -1.90 2.10 30 minutes -3.20 3.00 60 mins -2.30 -1.20 90 mins -3.00 -4.20 2 hours -1.00 -2.30 4 hours -0.60 -7.20 6 hours -0.90 -6.60 22 hours -9.00 24 hours -0.10 -7.20 Baseline (mmHg) 150.00 143.00

Average heart rate (%) time Control 1 g / kg hesperidin 0 0.00 0.00 10 minutes 8.40 5.10 20 minutes 7.10 1.70 30 minutes 2.50 4.40 60 mins -0.50 0.30 90 mins 1.70 -1.30 2 hours -0.80 -0.50 4 hours -5.00 -0.10 6 hours -7.50 -1.50 22 hours -9.40 24 hours -10.10 -5.80 Baseline (mmHg) 366.00 308.00

Effect of Hesperidin on Blood Pressure and Heart Rate in RHR Average blood pressure (%) 20 minutes -0.60 -7.70 -2.50 30 minutes -0.30 -7.60 -0.30 60 mins -1.20 -7.70 3.20 90 mins 1.80 -8.80 -0.30 2 hours 3.00 -9.90 -0.60 4 hours -3.10 -9.60 -3.50 6 hours -4.30 -11.70 -5.20 22 hours -1.50 -28.80 -7.70 24 hours -0.20 -30.60 -11.00 Baseline (mmHg) 182.00 187.00 169.00

Average heart rate (%) time Control 3 g / kg hesperidin 9 g / kg hesperidin 0 0.00 0.00 0.00 10 minutes 5.90 3.80 -4.30 20 minutes 6.50 3.80 -5.20 30 minutes 2.00 2.30 -4.70 60 mins -0.10 1.50 2.10 90 mins 0.10 5.00 1.30 2 hours 5.80 8.40 3.60 4 hours 5.10 12.10 -4.70 6 hours -2.20 4.60 -5.40 22 hours 0.80 8.10 1.40 24 hours -5.80 6.00 -0.40 Baseline (mmHg) 393.00 373.00 360.00

Example 2: Oral Toxicity Test of Hesperidin

Specific pathogens free of 7-8 weeks of age, 6 females weighing 25-29 g and 6 males weighing 34-38 g, temperature 22 ± 1 ° C, humidity 55 ± 5%, illumination 12L / 12D was bred in the animal room. Mice were allowed to acclimate for about a week before being used for the experiment. Feed for experimental animals (Jeil Jedang Co., Ltd., mice and rats) and drinking water were supplied after sterilization and free ingestion.

Hesperidin was prepared at a concentration of 100 mg / ml using 0.5% Tween 80 as a solvent, followed by oral administration of 0.2 ml per 20 g of mouse body weight. Samples were administered orally once and observed for side effects or lethality for 10 days after administration. That is, on the day of dosing, changes in general symptoms and the presence or absence of dead animals were observed at least once in the morning, at least 1 pm, 4 hours, 8 hours, 12 hours, and the next day until the 10th day of administration. In addition, the animals were killed and dissected at 10 days of administration, and the internal organs were visually examined. The change in body weight was measured at the interval of 1 day from the day of administration to observe the weight loss phenomenon of the animal by hesperidin.

The purpose of this study was to provide information on available doses in general pharmacology and drug efficacy tests and to derive basic data on toxicity by identifying the degree of acute toxicity in the oral route of hesperidin. Got it.

For acute oral toxicity, no lethal animals were observed for 10 days at a dose of 1,000 mg / kg of hesperidin. An autopsy of the surviving animals was performed 10 days later, and there were no gross lesions, and normal body weight gain was observed without any weight loss for 10 days from the day after the administration.

In conclusion, hesperidin was not toxic upon oral administration at the above concentrations.

The following formulation examples are merely illustrative of the formulation of the present invention and do not limit the scope of the invention.

My example

Hard gelatin capsules were prepared using the following ingredients:

Amount (mg / capsule)

Active ingredient (hesperidin) 1,000

Dry starch 160

Magnesium Stearate 40

Total 1,200 mg

Since the composition of the present invention containing hesperidin lowers blood pressure in the animal body, it can be usefully used as a therapeutic agent for hypertension or as a component of a health food.

Claims (4)

An antihypertensive composition comprising an effective amount of hesperidin as an active ingredient with a pharmaceutically acceptable carrier. The method of claim 1, A composition wherein the effective amount of hesperidin is 0.1 to 10 g / kg body weight / day. A blood pressure lowering food composition comprising an effective amount of hesperidin as an active ingredient. The method of claim 3, wherein A composition wherein the effective amount of hesperidin is 0.1 to 10 g / kg body weight / day.