KR102087033B1 - Compositions for reducing weight comprising Oenothera extract or its fraction as effective component - Google Patents

Abstract

The present invention relates to a composition for weight loss containing an Oenothera tetraptera extract or a fraction thereof as an active component. The composition for weight loss according to the present invention contains the Oenothera tetraptera extract or the fraction thereof as the active component, so as to induce weight loss through subcutaneous and intramuscular fat reduction in a short period, for a day or so, without cytotoxicity while maintaining the reduced weight for a long time. Especially, since the composition has a distinct effect by a water fraction of the extract, so as to be used without toxicity. Therefore, the composition of the present invention can be usefully used as a pharmaceutical composition, a health functional food composition, and a feed additive composition for preventing, treating or alleviating obesity.

Description

Composition for reducing weight comprising Oenothera extract or its fraction as effective component

The present invention relates to a composition for weight loss comprising evening primrose extract or a fraction thereof as an active ingredient.

In recent years, overweight and obesity, which are rapidly increasing due to high fat, high calorie diet, and inactive lifestyle, are one of the most important independent risk factors for prevalence and mortality worldwide in place of existing malnutrition and infectious diseases.

Obesity refers to the accumulation of excess fat tissue, but the accumulation of fat tissue increases the risk of developing metabolic syndrome, such as hypertension and diabetes, and is associated with the development of cardiovascular disease. Recently, metabolic disorders as well as increased oxidative stress have been known to increase the risk of neurological dysfunction and tumor development.

In particular, excessive body fat in women affects onset of menstruation, ovulation disorders, luteal defects, and postmenopausal health due to the induction of high blood hormone and female hormones, resulting in prematurity, menstrual disorders, infertility, polycystic ovary syndrome, and females. This may increase your risk of hormone-dependent cancer.

As obesity patients increase due to dietary changes and abnormal reasons due to genetic reasons or stress, social problems are emerging, and various methods such as diet, exercise therapy, and diet for treating obesity have been proposed.

Weight loss through exercise is known to be the most effective way without side effects, but in busy modern life it is very difficult to regularly exercise long enough to treat obesity. As another method, drug therapy is used, but the drug therapy is often not known exactly about side effects, so there is a disadvantage that it is difficult to take a long time for at least several weeks.

In relation to the treatment of obesity with drug therapy, the use of non-selective sympathetic anti-nausea drugs that promote weight loss by promoting energy metabolism has been proposed, but side effects on the cardiovascular system and long-term use in obese patients with heart disease There is a problem that resistance is not suitable for the treatment of obesity, there was an attempt to induce a decrease in body fat by administering a red ginseng complex agent to the experimental animals, but it has been reported that the effect appears slightly when administered over four weeks.

Treatment of obesity using a diet has the disadvantage that it is difficult to patiently carry out long-term administration of at least several months with the inconvenience of carefully selecting and preparing various foods.

As obesity is increasing, various drugs, surgery, exercise, diet, and behavioral modifications are flooded, and oriental medical clinics offer prescription-based herbal medicine, acupuncture, acupuncture stimulation, and herbal acupuncture. Through the use of systemic obesity, partial obesity is being treated.

Considering the disadvantages or difficulties of the conventional methods used in the treatment of obesity, it is possible to reliably obtain the effect of obesity treatment without side effects, and can be easily applied without the need for special effort obesity treatment method or There is a need for development of the composition.

Evening primrose is an annual herb, and belongs to the needle family. The height reaches 1 meter and the stem stands straight and hardly prunes. There are short hairs all over the body and the leaves are offset from each other at narrow intervals. Leaves are long, lanceolate, pointed at the end, and have some sawtooth at edges. There are about 80 species of needle flower and evening primrose in the whole world, and many species are naturalized and grow in our country. Long-leaf evening primrose, big evening primrose, and evening primrose are growing.

In the herbal medicine, the root of evening primrose is used as a medicine called woldogcho (月見草), when the fever is high and a sore throat is put into the water and taken over the moon, and the seeds are used for hyperlipidemia as woldogja (月 見 子). In general, antipyretic and anti-inflammatory effects are known to have a therapeutic effect on colds, sore throat, bronchitis, dermatitis. Evening primrose oil has long been a folk medicine applied to Indians by inflammation and rashes, and has been given to whites as an asthma pill, and in the UK it has been called the king's panacea. In recent years, evening primrose oil has been in the spotlight as a medicine and health food because it has been found that unsaturated fatty acid called gamma linolenic acid, which is rich in evening primrose oil, is the mother of a physiologically active substance called prostaglandin. Prostaglandins have a wide range of physiological effects such as vasoconstriction of blood vessels, bronchial muscle contraction and relaxation, inhibition of gastric juice secretion, uterine muscle contraction, water excretion, induction or inhibition of platelet aggregation. Evening primrose oil reduces the amount of cholesterol significantly and improves circulatory disorders and heart diseases such as myocardial infarction, arteriosclerosis, high blood pressure, and angina pectoris. In addition, it is effective in allergic skin diseases. Especially, the experiments in children with atopic dermatitis and atopic eczema have shown a clear improvement in symptoms in the intake group, and it has recently been known to be effective in preventing skin aging and whitening. It is also widely used in cosmetics such as cosmetics and soap.

Under the above technical background, the present inventors earnestly studied about a substance capable of maintaining an excellent weight loss effect in a short period of time and maintaining a weight loss for a long time. As a result, an evening primrose extract or a fraction thereof has an excellent weight loss in a short period of about one day. It was confirmed that there is an effect of inducing and maintaining a weight loss, and completed the present invention.

Korean Patent Registration No. 10-1888471

An object of the present invention is to provide a composition for weight loss that can exhibit an excellent weight loss effect in a short period of time by using the Evening Primrose extract or a fraction thereof as the main raw material.

In order to solve the above problems, Oenothera genus Evening Primrose extract or a fraction thereof provides a composition for weight loss comprising as an active ingredient.

The present invention also provides a pharmaceutical composition for the prevention or treatment of obesity, including Oenothera evening primrose extract or a fraction thereof as an active ingredient.

In addition, the present invention provides a food composition for preventing or improving obesity, including Oenothera Evening Primrose extract or a fraction thereof as an active ingredient.

In addition, the present invention provides a feed additive composition for preventing or improving obesity, including Oenothera evening primrose extract or a fraction thereof as an active ingredient.

The composition for weight loss according to the present invention includes evening primrose extract or fractions thereof as an active ingredient, without cytotoxicity, induces weight loss through subcutaneous and intramuscular fat reduction in a short period of about one day and at the same time can maintain a reduced weight for a long time have. Therefore, the composition according to the present invention can be usefully used as a pharmaceutical composition, nutraceutical composition and feed additive composition for the prevention, treatment or improvement of obesity.

1 is a graph showing the weight loss effect of evening primrose starch extract.
Figure 2 is a schematic diagram showing the process of obtaining a fraction of evening primrose starch extract.
3 is an image of a fraction of the evening primrose starch extract obtained according to FIG.
Figure 4 shows the fractions of five evening primrose starch extract obtained according to Figure 2 (Hexane, Chloroform, Ethyl acetate, Butyl alcohol, Distilled water) and cisplatin as an anticancer agent to A549 cells for up to 96 hours, Lactate dehydrogenase (LDH) The results of quantitative measurement of cytotoxicity by the release assay are shown.
5 is a graph showing the weight loss effect of the butanol fraction and water fraction of Evening Primrose extract.
Figure 6 is a graph showing the results of measuring the effect of water fraction of Evening Primrose Outpost extract according to the present invention on weight loss in mice overweight induced through high fat feed.
7 is a graph showing the results of measuring the effect of the water fraction of Evening Primrose Outpost extract according to the present invention on the quantitative change of body weight, BMI, fat, muscle (lean).

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

The present inventors earnestly studied about a substance that can maintain an excellent weight loss effect in a short period of time and at the same time maintain a weight loss, evening primrose extract or fractions thereof induces an excellent weight loss in a short period of about a day and lose weight It was confirmed that there is an effect to maintain, to complete the present invention.

The present invention provides a composition for weight loss comprising the evening Primrose Oenothera extract or a fraction thereof as an active ingredient.

At this time, the evening primrose extract may be any one or more extracts selected from the group consisting of flowers, leaves, branches, roots, fruits, shells, outposts and mixtures of evening primrose, more specifically, may use the evening primrose outpost .

In addition, the evening primrose may be a long-leaf evening primrose (Oenothera odorata or Oenothera stricta).

In addition, the evening primrose extract may be extracted with any one or more solvents selected from the group consisting of water, organic solvents and mixed solvents thereof.

In this case, the organic solvent may be a polar solvent such as alcohol having 1 to 5 carbon atoms, ethyl acetate, acetone and a non-polar solvent such as ether, chloroform, benzene, hexane, dichloromethane, or a mixed solvent thereof. In addition, the alcohol may be selected from methanol (methyl alcohol), ethanol, propanol, butanol, isopropanol and the like, more specifically may be methanol.

In addition, the evening primrose extract may be included in the weight loss composition at a concentration of 0.001 to 10 mg / kg.

The term "extract" of the present invention also encompasses fractions which additionally fractionate the extract. That is, the evening primrose extract includes not only one obtained by using the above-described extraction solvent, but also one obtained by additionally applying a purification process thereto. In addition, fractions obtained by passing the extract or fraction through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. Evening fractions and hydrothermal extracts obtained through various purification methods are included in the evening primrose extract of the present invention.

More preferably, the fraction may be obtained by fractionating the evening primrose extract with a solvent selected from the group consisting of hexane, chloroform, ethyl acetate, butanol, water and a mixed solvent thereof, most preferably the fraction is It may be a butanol fraction or a water fraction of evening primrose extract.

The term "evening primrose extract" of the present invention includes the preparation of the evening primrose extract as well as the crude extract obtained by treating the evening primrose with the extraction solvent. For example, evening primrose extract may be prepared in powder form by additional processes such as distillation under reduced pressure and lyophilization or spray drying.

The present invention also provides a pharmaceutical composition for the prevention or treatment of obesity, including Oenothera evening primrose extract or a fraction thereof as an active ingredient.

In this case, the pharmaceutical composition may further include a pharmaceutically acceptable carrier, excipient or diluent.

The term "pharmaceutically acceptable" of the present invention means to exhibit properties that are not toxic to cells or humans exposed to the composition. The carrier may be used without limitation as long as it is known in the art such as buffers, preservatives, analgesics, solubilizers, isotonic agents, stabilizers, bases, excipients, lubricants. Examples of pharmaceutically acceptable carrier excipient diluents that may be used in the pharmaceutical compositions of the invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin Calcium phosphate, calcium silicate, calcium carbonate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidine, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. have.

The pharmaceutical compositions of the present invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories, and sterile injectable solutions according to conventional methods. . When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants are usually used. Typically available surfactants that facilitate migration across the membrane are those derived from steroids, but N- [1- (2,3-dioleoyl) propyl-N, N, N-trimethylammonium chloride] (DOTMA Cationic lipids, or cholesterol hemisuccinate. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like. One or more excipients such as starch, calcium carbonate, sucrose or lactose, gelatin and the like are mixed to prepare. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of liquids 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 and liquid paraffin. Can be. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

In addition, the present invention provides a health functional food composition for the prevention or improvement of obesity comprising Oenothera genus Evening Primrose extract or a fraction thereof as an active ingredient.

Specifically, the evening primrose extract or fractions thereof according to the present invention may be added to food or beverages for the purpose of weight loss, prevention or improvement of obesity, the food type is not particularly limited, for example, confectionery, bread, Various foods such as noodles, water, soft drinks, drinks such as fruit drinks, gum, tea, vitamin complexes, seasonings, health functional foods and the like. At this time, the amount of the evening primrose extract or its fraction in the food or beverage can be added to 0.01 to 15% by weight, preferably 0.1 to 5% by weight of the total food weight of the health functional food composition of the present invention, The beverage composition may be added at a ratio of 0.01 to 50 g, preferably 0.01 to 10 g, based on 100. The health functional food of the present invention thus obtained is a food which can fully utilize the effect of weight loss, obesity prevention or improvement possessed by the evening primrose extract or a fraction thereof, according to the present invention.

The health functional food of the present invention may be prepared by the process of adding the evening primrose extract of the present invention or a fraction thereof during the manufacturing process of the base food or the process of adding the evening primrose extract of the present invention or a fraction thereof after the preparation of the food. It can be manufactured easily. At this time, a taste and odor correction agent may be added as needed.

In addition, the health functional food is a variety of nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the health functional food of the present invention may contain fruit flesh for the production of natural fruit juice and fruit juice beverage and vegetable beverage. Such components may be used independently or in combination. The proportion of such additives is generally selected within the range of about 20 parts by weight or less per 100 parts by weight of the health functional food of the present invention.

In addition, the present invention provides a feed additive composition for preventing or improving obesity, including Oenothera evening primrose extract or a fraction thereof as an active ingredient.

Feed additive composition in the present invention may be a feed additive composition for pets and livestock, the livestock is not limited thereto, for example, cattle, horses, sheep, pigs, deer, chickens, ducks, geese, turkeys , Quail, ostrich, pheasant, and other animals determined by the Ministry of Agriculture, Food and Rural Affairs, preferably ruminant.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. However, these examples and the like are intended to describe the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited thereto.

Example  1. Evening primrose extract and its Fraction  Produce

Evening Primrose flower extract obtained by repeating 10-minute sonication and 2 hours stop at 45 ° C for 10 minutes using methyl alcohol 99.9% (HPLC grade) as an extraction solvent in long-leaved Evening Primrose was collected from Korea Plant Extract Bank. Used as a sample.

In addition, the Evening Primrose extract was commissioned by the Korea Plant Extract Bank with five solvents of Hexane, Chloroform, Ethyl acetate, Butyl alcohol, Distilled water to obtain a fraction, which was used as a sample of this experiment (Fig. 2 and Fig. 3). ).

Experimental Example  1. Measurement of Weight Loss Effect of Evening Primrose Extract

First, the lyophilized Evening Primrose Outpost extract obtained from the Korea Plant Extract Bank was dissolved in 50% DMSO to make an extract solution of 200 mg / mL. Body weight changes were measured daily for about 7 days after injection, starting about 2 to 3 days before the injection of evening primrose extract and control group 10 to 14 weeks old C57BL6 / J mice. Evening primrose extract was diluted 20-fold (10 mg / mL) and 200-fold (1 mg / mL), respectively, using PBS before injection into mice, and 200 μL of diluted evening primrose starch extract was injected once into the abdominal cavity of a mouse using a 1 cc syringe. . 0.25% and 2.5% DMSO solutions were used as controls.

1 is a graph showing the weight loss effect of evening primrose starch extract. As a control, DMSO (Dimethyl sulfoxide) was used to dissolve the extract. Two different concentrations of Evening Primrose Outpost (1mg / mL and 10mg / ml) were injected into the abdominal cavity of 10-14 week-old mice. In the case of the weight loss of about 4.4 ~ 9.8% was observed between the 1st and 2nd day after the injection, through which it was confirmed that the Evening Primrose extract according to the present invention shows an excellent weight loss effect in a short time. However, about 3 days after the injection of Evening Primrose extract, it was confirmed that the body weight began to increase again.

Experimental Example  2. Evening primrose extract and its Fraction  Cytotoxicity Study by Treatment

First, A549 cells, a cell line obtained from human lung cancer tissue, were mixed with 10% fetal bovine serum in RPMI-1640 medium and cultured at 37 ° C. and 5% CO ₂ . Next, the fractions of five evening primrose starch extracts (Hexane, Chloroform, Ethyl acetate, Butyl alcohol, Distilled water) and cisplatin, an anticancer agent, were treated with A549 cells for up to 96 hours, followed by Lactate dehydrogenase (LDH) release assay. Toxicity was measured quantitatively, and the results are shown in FIG. 4. At this time, hydrogen peroxide was used as a positive control and saline (phosphate-buffered saline) was used as a negative control.

As a result, the toxicity of Chloroform, Ethyl acetate, Butyl alcohol and Distilled water fractions in fractions were as low as negative control level. However, Chloroform and Ethyl acetate fractions induce morphological changes in A549 cells. Finally, Butyl alcohol and Distilled water fractions were the most suitable.

Experimental Example  3. Evening Primrose Extract Fraction  Weight loss effect measure

Butaneol and water fractions of the lyophilized Evening Primrose Outpost extract were dissolved in 50% DMSO to prepare 500 mg / mL fraction solution. Each fraction solution was diluted 500-fold with PBS, followed by injection of 200 uL of butanol fraction (1 mg / ml) and water fraction (1 mg / ml) into an average 15-week-old C57BL6 / J mouse abdominal cavity using a 1 cc syringe. , As in Experiment 1, starting from about 2 to 3 days before injection of the fraction and the control, the weight change was measured every day for about 7 days after the injection, and DMSO was used as a control.

5 is a graph showing the weight loss effect of the butanol fraction and water fraction of Evening Primrose extract. Through this, as in the evening primrose starch extract, both butanol and water fractions showed a weight loss effect from the 1st day after injection, the effect is 5.7 ~ 10.5% was confirmed to be superior to the evening primrose starch extract. In addition, unlike the Evening Primrose Outpost extract, it was observed that the weight loss of the extract fraction was maintained well until the 7th day after one injection. Through this, the Evening Primrose Extract fraction according to the present invention showed excellent weight loss effect in a short time. At the same time it was confirmed that the effect of maintaining a weight loss is excellent.

Experimental Example  4. Evening Primrose Extract Water for Overweight-induced Mice Fraction  Weight loss effect measure

To investigate whether evening primrose extract is effective in normal-weight mice as well as overweight-induced mice, the average diet (fat content, 15%) was replaced with 45% fat content in high-fat diets on average 6-week-old C57BL / 6J mice. Afterwards, weight change was measured daily. Body weight changes were measured daily up to 34 days after injection of 200 μL of Evening Primrose Extract (1 mg / mL) into the abdominal cavity at 27 days, 28.5 days, 30 days and 31.5 days after high fat diet.

Figure 6 is a graph showing the results of measuring the effect on the weight loss of the fraction of Evening Primrose according to the present invention for mice overweight induced via high fat feed.

As a result, it was confirmed that the mice gained about 4 weeks of high fat diet gained about 30% in weight. The mice gained in weight gained 200 ul of water fraction (1 mg / ml) four times every 36 hours. As a result of injection into the abdominal cavity, unlike the control group, the body weight of the mice injected with the water fraction of Evening Primrose extract according to the present invention was continuously reduced, and it was confirmed that about 14% of the body weight was lost 7 days after the injection. In addition, the weight loss of 10% was observed only 36 hours after administration, and no side effects such as decreased appetite, dehydration, stress, stamina or toxicity were observed after weight loss.

Experimental Example  5. Evening Primrose Extract Water In fractions  by BMI  Measure

Body weight by the water fraction of the Evening Primrose Outpost extract according to the present invention using the same mouse used in FIG. 6 to investigate which part of the Evening Primrose Extract water fraction acts on muscle and fat to induce weight loss induction effect, Quantitative changes in BMI, fat and muscle were measured by DEXA scan.

As can be seen in Figure 7, the treatment group injected with 200 ul of water fraction (1mg / ml) in the mouse, unlike the control group after injection of the water fraction of evening primrose extract according to the present invention the final weight of the mouse is about 1 week It was confirmed that the weight was reduced by 14%. In addition, the BMI index was observed to decrease by about 25%. It was observed that the decrease in the BMI index was due to fat loss of about 33%, as muscle mass did not seem to decrease.

Through this, it was confirmed that the evening primrose extract and fractions thereof according to the present invention can induce weight loss by maintaining subcutaneous and intramuscular fat in a short period of time without side effects and at the same time maintain a reduced weight. Therefore, the composition according to the present invention is expected to be usefully used as a pharmaceutical composition, nutraceutical composition and feed additive composition for weight loss, prevention, treatment or improvement of obesity.

Claims (10)

The evening primrose (Oenothera odorata) containing butanol fraction or water fraction of the methanol extract as an active ingredient, weight loss and weight loss composition for weight maintenance. delete delete delete delete delete delete A pharmaceutical composition for preventing or treating obesity, comprising butanol fraction or water fraction of an Evening Primrose (Oenothera odorata) outpost methanol extract. Evening Primrose (Oenothera odorata) Health care food composition for the prevention or improvement of obesity comprising a butanol fraction or water fraction of methanol extract as an active ingredient. A feed additive composition for preventing or improving obesity, comprising butanol fraction or water fraction of evening primrose (Oenothera odorata) starch methanol extract.

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