KR100833705B1 - Extracts from Orira, Gboigboi, Osusu and these partitions - Google Patents

Abstract

The present invention relates to a blood circulation or vasodilator containing an extract of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .) Or Osusu ( Drypetes molunduana) having an excellent vasorelaxant effect. More specifically, blood containing an extract extracted from the roots of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .) And Osusu ( Drypetes molunduana) native to Africa with organic solvents and fractions fractionated with organic solvents. Circulators or vasodilators.

Orira * Gboiboi * Osusu * Vascular Relaxation * Blood Circulation * 5-HT

Description

Extracts from Orira, Gboigboi, Osusu and these partitions}             

1 is a graph showing the 5-HT-induced thoracic aortic contraction effect.

Figure 2 is a polygraph of the vasorelaxant effect of Oriria, Gboigboi, Osusu root extract against 5-HT-induced vasoconstriction.

Figure 3 is a graph showing the vasorelaxant effect of Oriria, Gboigboi, Osusu root extract against 5-HT-induced vasoconstriction.

Figure 4 shows the fractionation process of Osusu.

5 is a polygraph of the vasorelaxation response by Osusu root fraction.

Figure 6 is a graph showing the vasorelaxant effect of Osusu fraction on thoracic aorta.

7 is a graph showing the vasorelaxant effect of Osusu fraction on the abdominal aorta.

The present invention relates to a blood circulation or vasodilator containing an extract of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .) Or Osusu ( Drypetes molunduana) having an excellent vasorelaxant effect. More specifically, the extract of the roots of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .) And Osusu ( Drypetes molunduana) native to Africa with organic solvents and fractions fractionated with organic solvents are 5-HT. The present invention has been found to exhibit excellent blood circulation and vasorelaxant effects on inducible vasoconstriction, and to provide a blood circulation or vasodilator using the same.

In general, vascular relaxant is the most essential prescription for the prevention and treatment of diseases such as hypertension, cerebral hemorrhage, arteriosclerosis, blood circulation disorder, neuralgia, sexual dysfunction, memory impairment caused by disorders of the circulatory system. Therefore, a number of vascular relaxants have been developed all over the world so far, and recently, a number of drugs have been developed that are limited to overcoming sexual dysfunction such as Viagra. Such vasodilators can be roughly classified into chemicals and herbal medicines.

Studies recently demonstrating that estrogens have a beneficial effect on the risk of cardiovascular disease development when taken alone or in combination with methoxyprogesterone acetate or micronized progesterone with the above chemicals (Writing group for the PEPI trial, JAMA 273; 199,1955). However, these estrogens are known to exhibit side effects on the endometrium and possibly breast tissue by increasing the frequency of malignancies in these areas after sustained treatment.                         

On the other hand, 5-HT is mainly present in enterochromaffin cells of the gastrointestinal tract, and is one of the factors that regulate the contraction of blood vessels in most parts of the human body, such as platelets and the central nervous system. In fact, 5-HT acts on the thoracic aorta and abdominal aorta of rats. Indicates. Drugs such as fenfluramine and dexfenfluramine that inhibit the nervous system action of 5-HT, drugs such as ephedrine and caffeine through the noradrenaline nervous system, and drugs such as sibutramine that act on the noradrenaline nervous system are commercially available. However, drugs such as fenfluramine, which have been used conventionally, have been banned due to side effects such as primary pulmonary hypertension or heart valve lesions, and other drugs also have problems such as blood pressure reduction or lactic acidosis, which lead to heart failure and kidney disease. There is a problem that can not be used in the patient. Therefore, there is a need for a new compound that exhibits an excellent vasorelaxant effect of estrogen but does not cause significant effects on the reproductive organs.

On the other hand, traditional herbal medicine among the herbal medicine as a vasodilator is a result of a natural long-term clinical trials can be said to have almost no fatal side effects. For example, ginsenosides of Korean ginseng according to the Republic of Korea Patent Publication No. 99-201585, although side effects such as endothelial damage and hemolysis may occur, as can be seen in vascular relaxants whose main components are saponin. In some cases, such side effects are not reported, such as vascular relaxants mainly composed of Rg3 and Rg5. As described above, in the case of herbal medicines in general, the side effects may be much reduced than in the case of chemical drugs.

Therefore, the development of new drugs using natural products as a side effect of chemical synthesis drugs has been attracting attention from around the world, and the study of bioefficiency is being actively conducted in various countries around the world. The products currently on the market are organic compounds and have many side effects. Therefore, their countermeasures are urgently needed, and the development of a new concept of medicinal plants without side effects is required from medicinal plants that have been delivered as private medicines.

Recently, many studies have been conducted on the effect of vasodilation using natural products, among which water extracts of thorny ogapi (Kang, Bon-seok et al., 2001; 16; 13-18) are effective for the relaxation of blood vessels in rats. Water extracts of ginkgo biloba leaves (Jungsu et al. 2001; 16; 8-12) also showed a strong relaxation effect on the thoracic aorta of rats contracted with 5-HT and PE. In addition, Korean Patent Publication No. 2001-0049156 (name of the invention: pine needle extract and its use) after making a pine needle extract using a water extraction method, water-alcohol extraction method, alcohol extraction method, hypertension, coronary artery It has been described for use in heart disease, angina pectoris, arrhythmia, diabetes, hyperlipidemia, high blood viscosity, high blood aggregation, atherosclerosis, cerebral infarction, cerebral atherosclerosis, senile dementia, and sudden deafness. In addition, Korean Patent Publication No. 2001-0099197 (the name of the invention: the development of functional products of natural herbs and silk peptides using silk peptides and blood circulation promoting functional products) has a strong and unique physiology based on natural materials. A method of producing a special functional food related to the blood circulation of women by describing the activity of blood circulation and promoting blood circulation by adding a certain ratio of silk medicinal herbs as an active ingredient and silk peptide and amino acid in a proportion is described. have.

Therefore, the present inventors studied and reviewed a material showing excellent vasorelaxant effect without side effects as a herbal medicine, and Orira, a healthy plant native to Port-Harcout and Warri, which is southwestern Africa, especially in southwestern Nigeria ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ) extract was found to exhibit an excellent vasorelaxant effect, respectively, to complete the present invention.

Accordingly, it is an object of the present invention to provide extracts and fractions thereof of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ), which exhibits excellent vasorelaxant effect.

Another object of the present invention is to provide a vasodilator or blood circulation agent containing the extract of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ) and fractions thereof.

In order to achieve the above object, in the present invention, Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ) roots extracted with a solvent, and then filtered, concentrated and dried to obtain Orira ( Anogeissus leiocarpus ) , Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ) is characterized in that it provides an extract.

In the present invention, the solvent used for the extraction of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ) is an organic solvent, preferably methanol, the concentration of methanol is about 80% It is suitable.

The present invention also provides a blood circulation or vasodilator containing at least one of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ).

In addition, the extract may be prepared in the form of liquids, powders, emulsions, suppositories, liposomes, transdermal scaffolds, sustained release, skin grafts, tablets, etc. by known methods. It can be administered more than.

Meanwhile, Orira (Anogeissus leiocarpus), Gboigboi (Cnestis sp.), Osusu (Drypetus molunduana) extract of the present invention includes a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient, a carrier or excipient acceptable as a food ingredient It may be contained in a health supplement food composition. For example, when Orira (Anogeissus leiocarpus), Gboigboi (Cnestis sp.), Osusu (Drypetus molunduana) extract of the present invention is used in health food, the routine 2 ~ 20g, Osusu extract 0.1 ~ 50g, Vitamin E in 100g of the composition It consists of 0.05 ~ 2g, Vitamin B1 0.012 ~ 1g, Vitamin B2 0.001 ~ 1g, Vitamin C 0.01 ~ 10g, Chlorophyll 0.01 ~ 10g, Plant Fiber 10 ~ 40g. In addition, when using the extract of the present invention in soft capsules, etc. Osusu extract 0.01 ~ 50g, beta carotene 1.5 ~ 5g, green tea extract 1 ~ 10g, ginkgo leaf extract 1 ~ 10g, Vitamin C 0.1 ~ 1g, Vitamin E 0.05 ~ 0.2mg, It consists of 40-50 g of soybean oil, 1-2 g of refined palm oil, 1-2 g of lecithin, 3-8 g of refined palm oil, and 0.5-1 g of lead.

In addition, in the composition of the health food or soft capsule, as well as Osusu extract, it can be prepared using Orira and Gboigboi, it is also possible to use a mixture of the Orira, Gboigboi, Osusu extract.

Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ) of the present invention is at least one selected from the group consisting of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetus molunduana ) The composition or the dietary supplement may be contained by a method known by those skilled in the art, and the pharmaceutical composition may be used alone or in combination with a known vasodilator.

Extracts of the present invention can be administered in a variety of oral and parenteral formulations in actual clinical administration, when formulated using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. commonly used Can be prepared.

First, solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may be at least one natural product and at least one excipient such as starch, calcium carbonate, sucrose, or It can be prepared by mixing lactose, gelatin and the like. Liquid preparations for oral administration include suspensions, solvents, emulsions, and syrups, and include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water, liquid, and paraffin. Can be.

On the other hand, preparations for parenteral administration include sterilized demand solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable esterol such as ethyl oleate, and the like can be used. In addition, as the base of the preparation, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol, gelatin and the like can be used.

On the other hand, the vascular tissue section used in the experiment in the present invention was excised and lethal in the carotid artery of the rat, extracted the thoracic aorta and abdominal aorta and put in oxygen-saturated physiological salt solution (PSS), oxygen While continuing to supply the ring section by cutting horizontally to the length of about 1.5 ~ 2mm to use the vascular endothelial cells removed.

In addition, the physiological salt solution (PSS) serves to maintain vascular smooth muscle normally, and the composition is NaCl 130mM, KCl 4.7mM, NaH ₂ PO ₄ 1.18mM, MgSO ₄ 1.6mM, CaCl ₂ 1.6mM And NaHCO ₃ 14.9 mM, and glucose (5.5 mM) and maintained at pH 7-8, preferably at pH 7.38.

Hereinafter, the present invention will be described in more detail with examples, but the present invention is not limited only to these examples.

Preparation Example 1 Extraction and Fractionation of Osusu, Orira and Gboigboi

Extract 100 g of roots of African native plants Osusu, Orira and Gboigboi, respectively, with 80% methanol solution, filter with filter paper, and concentrate under reduced pressure at 60 ℃ with a vacuum concentrator (Osusu-1, Orira-1, Gboigboi-1). Got. Next, in order to fractionate the extract, Osusu methanol extract (Osusu-1) was dissolved in water, and then hexane (Hexane) was added to the same amount, shaken and left to stand. Got. Next, the same amount of chloroform (Chloroform) was added to the water layer and shaken vigorously to obtain a chloroform fraction (Osusu-C). Ethyl acetate (butanol) and butanol (Ethyl acetate) and butanol (Osusu-E) and butanol fraction (Osusu-B) were sequentially obtained in the water layer. Finally, the remaining water layer fraction (Osusu-W) was used in the experiment, and the extraction and fractionation steps are shown in FIG. 1.

Preparation Example 2 Preparation of Physiological Nutrient Solution and Vascular Tissue Section

First of all, the animals were supplied with Sprague-Dawley male rats (Semtaco experimental animals, Korea) of about 250 ~ 300g and fed solid foods (mixed feed, experimental animals, Semtaco feed, Korea) and water for more than 2 weeks. Used after adapting to the environment. In addition, physiological salt solution (PSS) for the normal maintenance of vascular smooth muscle is NaCl 130mM, KCl 4.7mM, NaH ₂ PO ₄ 1.18mM, MgSO ₄ 1.17mM, CaCl ₂ 1.6mM, NaHCO ₃ 14.9mM, and glucose Glucose was prepared in a composition of 5.5 mM and the pH was maintained at 7.38.

On the other hand, the vascular tissue section was first excised and killed in the carotid artery of the rat, and then opened along the abdominal central line, and the thoracic aorta (TA) and abdominal aorta (AA) were extracted to the oxygen-saturated physiological nutrient solution. I put it. Next, the adipose tissue and connective tissue was removed while the oxygen was continuously supplied, and then cut horizontally to have a length of 1.5 to 2 mm to prepare a ring section. Finally, rub the inside of the vascular ring with a cotton swab to remove vascular endothelial cells, and then the vessel contains 0.3% of 3- [3- (chloramidopropyl) -dimetyl-ammonio] -1-propane sulfonate (CHAPS) The vascular tissue sections were prepared by shaking for 10 seconds in the PSS and washing with fresh PSS.

Test Example 1 Isotonic Shrinkage Measurement

Isotonicity was measured to confirm the vasorelaxant effect according to Preparation Example 1. First, to measure isotonicity, one part of the blood vessel was hung on a ring installed at the bottom of an organ chamber containing 37 ° C PSS (5 ml) saturated with 95% O ₂ -5% CO ₂ , and the other The side was hung on a force-displacement transducer and the results recorded in a polygraph. Prior to drug testing, 2 g of thoracic aorta and 1.5 g of abdominal aorta were loaded with baseline tension and allowed to equilibrate for 90 minutes with fresh PSS changed every 20 minutes. Next, when the baseline was maintained, PSS containing 100 mM KCl was confirmed to confirm the size of the contraction, and 1 μM of acetylcholine was administered to determine the presence of endothelial cells. At this time, it was determined that endothelial cells were not damaged when relaxation by acetylcholine exceeded 50% or more of contraction by KCl. After 60 minutes after the experiment, the contraction response was measured by treating the vasoconstriction drug 5-HT (5-hydroxytryptamine) by concentration. The results are shown in Figure 1 below.

In order to examine the effects of vascular endothelial cells on vascular contraction, the effects of vascular endothelial cell removal and vascular endothelial cell removal were recorded on a physiological recorder. Then, after inducing contractility with 5-HT, the induced vascular tissue was treated with Osusu and its fractions at 0.1, 0.3, 1, 3, 10 mg / ml to observe the vasorelaxant effect by dose-accumulation method. It was. The results are shown in FIGS. 2-3 and 5-7. At this time, the size of vascular relaxation was calculated as a percentage of the contraction height caused by 5-HT, and if the contraction height was not maintained for a certain time or the tissue was damaged, the sections were removed and retested. In addition, the experimental results were expressed as the mean value ± standard error, and when testing the difference between the control group and the experimental group, it was determined by the Student's t- test to have a statistically significant difference when the P value was less than 0.05.

As can be seen in Figure 1, 5-HT showed a concentration-dependent contraction response to the thoracic aortic section of the rat. The maximum contractile response to 5-HT 1x10 ^-5 M in the thoracic aorta was 98.7 ± 8.3% of the maximum contractile response to KCl. In addition, the abdominal aorta showed a concentration-dependent contraction response, and the 5-HT 1x10 ^-5 M maximum contraction response was 152.5 ± 9.9%.

In addition, as can be seen in Figures 2 and 3 below, the relaxation response of 80% methanol extract of Osusu, Orira and Gboigboi on 5-HT-induced vasoconstriction was observed regardless of the presence or absence of endothelial cells in the thoracic aorta of rats. -HT 10 ^-4 M Induced maximum contraction was found to have a relaxation effect. Among the most effective 80% Osusu methanol extracts, the relaxation effect for each dose of 0.01, 0.03, 0.1, 0.3 g / mL was 0.0 %, 16.7%, 32.3% and 100%. At this time, the maximum relaxation was observed in 0.3 g / ㎖ Osusu methanol extract.

In addition, as can be seen in Figures 5 to 6, Osusu, Oriria, Osbo fractionation of the largest vascular relaxation effect on the maximum contractile force of 5-HT 1x10 ^-4 M of Gboigboi fraction by vascular relaxation for each fraction As a result of the experiment, the vasorelaxant effect on the thoracic aorta was observed in the Osusu-C, Osusu-E, and Osusu-W fractions at the maximum dose of 10 mg / ml for 0.1, 0.3, 1, 3, and 10 mg / ml. The relaxation reactions were 7.2%, 16.8%, 18.7%, and the maximum relaxation reactions of Osusu-1, Osusu-H, and Osusu-B fractions were 44.5%, 56.4%, and 54.9%.

In addition, as can be seen in Figure 7, the vasorelaxant effect on the abdominal aorta is the vascular relaxation effect of the fraction of Osusu on 5-HT 1x10 ^-4 M maximal contractile force has a maximum relaxation effect at a dose of 3 mg / ㎖ It confirmed that it was shown.

As described above, the present invention is an extract extracted from the roots of Orira ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp .), Osusu ( Drypetes molunduana ), native to Africa, with 80% methanol and Osusu fraction having the greatest effect. The polygraphs of the vascular relaxation of the thoracic and abdominal aorta of rats were measured with polygraphs. The results showed that the new natural products Osusu, Oriria and Gboigboi were caused by vasoconstriction such as myocardial infarction, cerebral infarction and hypertension. It can be provided as a raw material to be utilized as a natural vasodilator, such as a disease.

Claims (5)

Five liras (Orira, Anogeissus leiocarpus), that show the visible (Gboigboi, Cnestis sp.) And ohsusu circulation characterized in that it contains the selected at least one from the group consisting of an extract of (Osusu, Drypetus molunduana) agent or vascular relaxant . The extract of claim 1, wherein the extract is extracted from the roots of Oryra (Anogeissus leiocarpus ), Gboigboi, Cnestis sp. , And sewage (Osusu, Drypetus molunduana ) with methanol, followed by filtration and concentration. Blood circulation or vasodilator, characterized in that obtained by drying. Five liras (Orira, Anogeissus leiocarpus), that show the visible (Gboigboi, Cnestis sp.) And ohsusu (Osusu, Drypetus molunduana) of the blood vessel, characterized in that it contains at least one selected from the group consisting of extracts Lee Wan - yong pharmaceutical composition. 4. A pharmaceutical composition according to claim 3, which is prepared in the form of a liquid, powder, emulsion, suppository, liposome, transdermal patch, sustained release, skin graft, tablet, and the like. A dietary supplement comprising at least one member selected from the group consisting of extracts of Oryra ( Anogeissus leiocarpus ), Gboigboi ( Cnestis sp. ) And sewage (Osusu, Drypetus molunduana ).

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