KR102376806B1 - Compositions for reducing weight comprising Oenothein B analogs as effective component - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the treatment or prevention of obesity and/or obesity complications, and a food composition or feed composition for anti-obesity or weight loss or body fat reduction, comprising an oenotein B analog.

Description

Compositions for reducing weight comprising Oenothein B analogs as effective component

The present invention relates to a composition comprising an oenotein B analogue as an active ingredient, which is effective for anti-obesity or weight loss, and more preferably, body fat loss, and a use thereof.

Worldwide, overweight and obesity are rapidly increasing due to an increase in high-fat, high-calorie diets and inactive lifestyles, and these overweight and obesity act as risk factors for increasing morbidity and mortality. Obesity refers to a state of excess accumulation of adipose tissue, but excess accumulation of adipose tissue increases the risk of metabolic syndrome such as hypertension and diabetes, and is also associated with cardiovascular disease.

Recently, it has been known that an increase in oxidative stress as well as these metabolic disorders increases the risk of neurological dysfunction and tumor development. In particular, excess body fat in women induces high androgen status in the blood, and increase in female hormones affects early onset of menstruation, ovulation disorders, luteal phase defects, postmenopausal health, and precocious puberty, menstrual irregularities, infertility, polycystic ovary syndrome And it can increase the risk of various diseases such as female hormone-dependent cancer.

As interest in obesity increases, various exercise therapy, diet, drug therapy, and surgery therapy have been proposed to treat obesity. Weight loss through exercise is known as the most effective method without side effects, but it is very difficult to regularly and long-term exercise sufficient to treat obesity in busy modern life. The treatment of obesity using a diet that requires careful selection and preparation of various foods also has a disadvantage in that it is difficult to carry out long-term use for at least several months with patience. Another method is drug therapy, which also needs to be administered for a long period of time to have some effect or, depending on the drug, drug resistance may develop, which is not suitable for obesity treatment. On the other hand, oriental medicine clinics treat not only general obesity but also partial obesity through prescription-based herbal medicine therapy, acupuncture, electrical stimulation, and medicinal acupuncture treatment, but there are cases where people feel fear or rejection of acupuncture treatment. . Considering the disadvantages or difficulties of conventional methods used to treat obesity, the effect of obesity treatment can be reliably obtained without side effects, and obesity treatment methods or novel anti-obesity methods that can be conveniently applied without special effort There is a need to develop active ingredients.

KR 10-2014-0021401 KR 10-2018-7001716

An object of the present invention is to provide a pharmaceutical composition for the treatment or prevention of obesity, obesity complications, or both, comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object to be solved by the present invention is to provide a food composition for improving obesity, weight loss or body fat loss, comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof.

Another object to be solved by the present invention is to provide an animal feed composition for alleviating or preventing obesity, obesity complications, or both, including an oenotein B analog compound or a pharmaceutically acceptable salt thereof.

Another object to be solved by the present invention is to provide a low-fat-containing livestock feed composition comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof.

In order to solve the above problems, the present invention provides a pharmaceutical composition for treating or preventing obesity, complications of obesity, or both, comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the pharmaceutical composition for the treatment or prevention of obesity, obesity complications, or both may be to reduce the amount of body fat.

In the present invention, the composition may reduce the amount of one or more fats selected from abdominal fat, visceral fat, intramuscular fat, and blood fat.

In addition, the present invention provides a food composition for improving obesity, weight loss or body fat reduction, comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof.

In the present invention, the food composition may be a health functional food, but is not limited thereto.

In addition, the present invention provides an animal feed composition for alleviating or preventing obesity, obesity complications, or both, comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof.

In the present invention, the animal may be one or more animals selected from mammals and birds.

In addition, the present invention provides a low-fat-containing livestock fattening feed composition comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof.

The composition comprising the oenotein B analogue compound or a pharmaceutically acceptable salt thereof according to the present invention exhibited an effective weight loss effect in normal or obese animal models, and the weight loss can reduce fat without loss of muscle mass. Since it did not show side effects such as dehydration symptoms, stress, decreased physical strength, or toxicity even after weight loss, it is used as a pharmaceutical composition, food composition, feed composition, etc. for weight loss, body fat loss, obesity treatment, improvement or prevention. It can be usefully applied. When the composition comprising the oenotein B analogue compound or a pharmaceutically acceptable salt thereof according to the present invention is applied to the livestock industry, the fat content can be reduced in edible livestock such as broilers in which the fat layer accumulated in the muscle is a problem, useful as

1 is an experimental result confirming the change in body weight according to Oenotein B treatment in a normal-weight animal model.
2 is an experimental result confirming the change in body weight according to Oenotein B treatment in an obese animal model.
3 is an experimental result confirming the change in abdominal fat mass according to Oenotein B treatment in an obese animal model.
4 shows 3T3-L1 preadipocytes in vitro differentiated into adipocytes, treated with various concentrations of oenotein B, and Oil Red O It is the result of measuring the change in neutral triglyceride and lipid content by staining with
5 shows the results of confirming the presence or absence of cytotoxicity of oenotein B.

As a result of intensive research to find a novel natural substance-derived substance capable of reducing obesity, particularly body fat, the present invention confirmed the pharmacological effect of an oenotein B analogue compound or a pharmaceutically acceptable salt thereof on anti-obesity. was completed.

Hereinafter, the present invention will be described in more detail.

The present invention provides a pharmaceutical composition for the treatment or prevention of obesity, obesity complications, or both, comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the term "obesity complications" refers to various diseases having a prevalence due to excessive accumulation of fat, and the complications include metabolic syndromes such as hypertension, diabetes, and hyperlipidemia. Also included are herniated discs, osteoarthritis (eg, osteoarthritis of the ankle, knee joint, hip joint, etc.). Also included are gastroesophageal reflux disease, hernia, and stress incontinence due to abdominal obesity. Also included are sleep apnea and nonalcoholic fatty liver, which is caused by a decrease in the space in the throat due to obesity. Also included are cardiovascular diseases such as angina pectoris, myocardial infarction, and heart failure. In addition, cerebrovascular diseases such as stroke and cerebral infarction are included. In addition, the neurological function is reduced due to the increase in oxidative stress. In addition, various diseases such as early onset of menstruation, ovulation disorder, luteal phase defect, postmenopausal health, precocious puberty, menstrual irregularity, infertility, polycystic ovary syndrome, and female hormone-dependent cancer caused by an increase in female hormones due to excessive body fat in women Included. As described above, there are various complications appearing due to obesity, but is not limited thereto.

Preferably, the obesity complications are hypertension; diabetes; hyperlipidemia;

Herniated disc; degenerative arthritis;

reflux esophagitis, hernia or stress incontinence due to abdominal obesity;

sleep apnea; nonalcoholic fatty liver;

angina pectoris; myocardial infarction; heart failure;

stroke; cerebral infarction;

Early menarche caused by increased female hormones due to excess body fat in women; ovulation disorders; precocious puberty; irregular menstruation; sterility; polycystic ovary syndrome and the like.

The oenotein of the present invention has four benzoic acids attached to glucose as a basic monomer, and oenoteins A, B, C, D, F, and G exist, which are structurally very similar and In the present invention, it is included in the term “oenotein B analog” (Phytochemistry 40:555-561, 1995). Oenotein B (CAS# 104987-36-2) is a dimeric ellagitannin composed of C68H48O44 having a molecular weight of 1569.08. It was first discovered in the leaves of Oenothera erythrosepala (J. Chem. Soc. Perkin Trans. 1, 2735-2743, 1990), may be represented by the following formula (3). Subsequently, the genus Oenothera (Phytochem Anal. 23(6):582-587, 2012) or Epilobii angustifolli herba (J Chromatogr A. 1173(1-2):146-150, 2007) or Eucalyptus globulus (Phytochem Anal. 24(2) ):162-170, 2013) were also found in several plants.

According to the present invention, the oenotein B analogue is a monomer or dimer compound of a compound represented by the following formula (1); or a pharmaceutically acceptable salt thereof:

[Formula 1]

R ₁ is any one selected from the group consisting of OH, CH ₃ , COOH, CHO, =O, NH ₂ and the like,

R ₂ is (CH ₂ ) _n , where n is an integer from 1 to 6,

R3 is any one selected from the group consisting of -O-, -CH ₂ - and -O(CH ₂ ) _m -, wherein m is an integer from 1 to 6,

R ₄ , R ₄ ', R ₅ and R ₆ are the same as or different from each other, and each independently H, (C _1-3 )alkyl, (C _1-3 )alkenyl, (C _1-3 )alkynyl , cyano, halo, nitro, thio, phenyl, hydroxyl, (C _1-3 )alkoxy, (C _2-4 )acyloxy, (C _1-3 )carboxamino, phenoxy, phenylmethoxy, etc. Any one selected from the group consisting of,

In the case of a monomer, R ₇ and R ₈ are —OH.

According to the present invention, when the oenotein B analog is a dimer of the compound represented by the above formula (1), R ₇ and R ₈ are condensed with R ₄ , respectively. In this condensation, R ₇ and R ₈ and R ₄ and each condensation may be connected to any one selected from the group consisting of -O-, -CH ₂ - and -O(CH ₂ ) _p -, where p is an integer from 1 to 6.

In the case of the dimer compound of the compound of Formula 1, it may be a compound represented by the following Formula 2 or a pharmaceutically acceptable salt thereof:

[Formula 2]

In the formula,

R ₁ is any one selected from the group consisting of OH, CH ₃ , COOH, CHO, =O, NH ₂ and the like,

R ₂ is (CH ₂ ) _n , where n is an integer from 1 to 6,

R ₃ is any one selected from the group consisting of -O-, -CH ₂ - and -O(CH ₂ ) _m -, wherein m is an integer from 1 to 6,

R ₄ , R ₄ ', R ₅ and R ₆ are the same as or different from each other, and each independently H, (C _1-3 )alkyl, (C _1-3 ) _alkenyl , ( _{C 1-3 )} alkynyl , cyano, halo, nitro, thio, phenyl, hydroxyl, (C _1-3 )alkoxy, (C _2-4 ) _acyloxy , ( _{C 1-3 ) carboxamino} , phenoxy, phenylmethoxy, etc. Any one selected from the group consisting of, and

R ₇ ' and R ₈ ' are each independently selected from the group consisting of -O-, -CH ₂ -, and -O(CH ₂ ) _p -, wherein p is an integer of 1 to 6.

The compound according to the present invention may be a compound represented by the following formula (3) or a pharmaceutically acceptable salt thereof:

[Formula 3]

In the present invention, the pharmaceutically acceptable salt means a salt commonly used in the pharmaceutical industry, for example, inorganic ionic salts prepared from calcium, potassium, sodium and magnesium, hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, iodine Inorganic acid, perchloric acid, tartaric acid and sulfuric acid, acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid , galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc. organic acid salts, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p -There are sulfonic acid salts prepared from toluenesulfonic acid and naphthalenesulfonic acid, amino acid salts prepared from glycine, arginine, lysine, etc., and amine salts prepared from trimethylamine, triethylamine, ammonia, pyridine, picoline, etc. The types of salts in the present invention are not limited by these listed salts.

According to the present invention, the composition may be to treat or prevent obesity by reducing the amount of body fat.

According to the present invention, the composition may treat or prevent obesity, obesity complications, or both by reducing the amount of one or more fats selected from abdominal fat, visceral fat, intramuscular fat, and blood fat.

Abdominal obesity or visceral obesity is a symptom of the accumulation of fat in the subcutaneous or internal organs of the abdomen and is known to accompany various complications. The composition according to the present invention can also be used for the treatment or prevention of the above-mentioned complications of obesity.

The composition according to the present invention can selectively reduce fat without loss of muscle mass, and has very low cytotoxicity, so it is effective in treating or preventing obesity, obesity complications, or both.

In addition, the composition according to the present invention has excellent effects in that it reduces neutral triglyceride and lipid content without toxicity in the human body, and exhibits a weight loss effect and an effect on reducing abdominal fat.

In the present invention, the term "treatment" refers to both the action of alleviating the symptoms caused by obesity and obesity complications by administering the composition, and the disease, the symptoms of the disease, the secondary disease of the disease or disease, or To a subject (human or animal) having a disease, a symptom of a disease, a secondary disease of a disease or disorder, or a predisposition thereto, for the purpose of treating, alleviating, alleviating, remedy, or ameliorating a predisposition It is defined as the application or administration of the composition.

The pharmaceutical composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight of the oenotein B analog compound or a pharmaceutically acceptable salt thereof, based on the total weight of the composition.

According to one embodiment of the present invention, the oenotein B analog compound or a pharmaceutically acceptable salt thereof is mixed with a conventional carrier, adjuvant or diluent and formulated in a conventional formulation method for oral or parenteral administration. It can be prepared in any suitable form.

The carrier, adjuvant or diluent may include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, poly vinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

In addition, in the case of formulation, conventional fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. may be further included, and lubricants such as magnesium stearate and talc may be further added.

In the case of oral administration, it can be prepared in the form of tablets, capsules, solutions, syrups, suspensions, etc., and in the case of parenteral administration, it is suitable for intravenous, intrauterine, intraperitoneal, subcutaneous, intramuscular, transdermal and intracerebrovascular injection. It can be prepared in the form of an injection for

The pharmaceutical composition of the present invention is an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human as considered by a researcher, veterinarian, doctor or other clinician, that is, the amount of the symptom of the disease or disorder being treated. It can be administered in a therapeutically effective amount, which is an amount inducing remission. It is apparent to those skilled in the art that the therapeutically effective dosage and frequency of administration for the pharmaceutical composition of the present invention will vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the content of active ingredients and other ingredients contained in the composition, the type of formulation, the age, weight, and general health of the patient. , sex and diet, administration time, administration route and secretion rate of the composition, treatment period, and various factors including concurrently used drugs. The pharmaceutical composition of the present invention may be administered to an individual by various routes. For example, intravenous, intraperitoneal, intramuscular, intraarterial, buccal, intracardiac, intramedullary, intrathecal, transdermal, enteral, subcutaneous, sublingual or topical administration may be administered, but not limited thereto.

The pharmaceutical composition of the present invention may be administered in an amount of 1 to 10,000 mg/kg/day, preferably 1 to 200 mg/kg/day, and may be administered once a day or divided into several administrations .

In addition, another object to be solved by the present invention is to provide a food composition for improving obesity, weight loss, or weight loss, comprising an oenotein B analogue compound or a pharmaceutically acceptable salt thereof.

In addition, the present invention provides a food composition for improving obesity or reducing body fat containing oenotein B.

The food composition of the present invention can be used as a health functional food. The term "health functional food" means a food manufactured and processed using raw materials or ingredients useful for the human body in accordance with the Health Functional Food Act, and "functionality" refers to the structure and function of the human body. It refers to ingestion for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological effects.

The food composition of the present invention may contain conventional food additives, and the suitability as the "food additive" is determined according to the general rules and general test methods of food additives approved by the Ministry of Food and Drug Safety, unless otherwise specified. It is judged according to the standards and standards related to the item.

The items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; Mixed preparations such as sodium L-glutamate preparation, noodle-added alkali agent, preservative agent, and tar color agent can be mentioned.

The food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight of the oenotein B analogue compound or a pharmaceutically acceptable salt thereof, based on the total weight of the composition.

In addition, the food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of improving obesity, weight loss or body fat loss.

For example, the health functional food in tablet form is granulated with a mixture of oenotein B analogues, excipients, binders, disintegrants, and other additives in a conventional manner, followed by compression molding by adding a lubricant, etc.; The mixture can be directly compression molded. In addition, the health functional food in the form of tablets may contain a mating agent, etc., if necessary, and may be coated with a suitable skinning agent if necessary.

Among health functional foods in the form of capsules, hard capsules can be prepared by filling conventional hard capsules with a mixture of oenotein B analogues and additives such as excipients, or their granules or coated granules. can be prepared by filling a mixture of an oenotein B analogue and an additive such as an excipient into a capsule base such as gelatin. The soft capsule formulation may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.

A health functional food in the form of a ring can be prepared by molding a mixture of oenotein B analogues, excipients, binders, disintegrants, etc. in an appropriate way, and if necessary, the skin is coated with sucrose or other suitable skinning agent, or starch, talc, or You can also dress the gown with a suitable material.

The health functional food in the form of granules can be prepared in a granular form by a suitable method of a mixture of oenotein B analogues, excipients, binders, disintegrants, etc., and may contain flavoring agents, flavoring agents, etc. if necessary. For health functional foods in granular form, use No. 12 (1680 μm), No. 14 (1410 μm), and No. 45 (350 μm) sieves to pass all the sieves in the next particle size test, and the remaining amount in No. 14 sieves 5.0% or less and passing through No. 45 may be less than 15.0% of the total amount.

The term definitions for the excipients, binders, disintegrants, lubricants, flavoring agents, flavoring agents, etc. are described in documents known in the art and include those having the same or similar functions (Explanation of the Korean Pharmacopoeia, Moonseongsa, Korea) Association of Colleges of Pharmacy, 5th ed., p33-48, 1989).

There is no particular limitation on the type of the food. Examples of foods to which the oenotein B analogue of the present invention can be added include beverages, gums, vitamin complexes, drinks, and the like, and include all health functional foods in a conventional sense.

The food composition may contain food supplement additives, and the food products include, for example, beverages, gum, tea, vitamin complexes, health supplements, etc., capsules, tablets, powders, granules, liquids, pills, slices, pastes. It can be used in the form of phases, syrups, gels, beverages, jellies or vines.

The content of the oenotein B analogue may be contained in an amount of 0.01 to 15% by weight based on the total weight of the health functional food, and in the case of a health beverage composition, 0.02 to 10 g, preferably 0.3 to 1, based on a total of 100 g g may contain.

The food supplement additives include food additives conventional in the art, for example, flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like. In addition, the health drink composition is an essential ingredient in the indicated ratio, and there is no particular limitation on the ingredients added other than the oenotein B analog. there is. Examples of the natural carbohydrate include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; polysaccharides such as dextrins, cyclodextrins; and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatine, stevia extract (eg rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. there is.

In addition to the above, food compositions, diet supplements, or health functional foods containing an oenotein B analogue compound or a pharmaceutically acceptable salt thereof include various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors. Flavoring, coloring and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages It may contain topics and the like.

In addition, the present invention provides an animal feed composition for improving or preventing obesity and obesity complications, comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof.

In the present invention, the animal may be one or more selected from mammals and birds, and preferably, the wild habits defined in Article 2, No. 1 of the Livestock Livestock Act and Article 2 of the Enforcement Rule of the same Act, and are suitable for breeding. And it can be a livestock that can contribute to an increase in farm household income. The livestock may be cattle, horses, mules, donkeys, goats, goats, sheep, deer, pigs, rabbits, poultry, etc., and poultry includes chickens, turkeys, ducks, ostriches, geese, quails, etc., preferably chickens, If it is suitable for breeding and obtaining livestock products, it is not limited thereto. The above "livestock products" are meat, milk, eggs, honey and their processed products, raw hides (including raw fur), raw wool, and other livestock products, which are defined by Article 2, 3 of the Livestock Act, as determined by the Ordinance of the Ministry of Agriculture and Forestry. means that In addition, it may be a dog, a cat, etc., including companion animals, but is not limited thereto.

The term "feed" in the present invention means any natural or artificial diet, meal, etc., or a component of said meal, intended for or suitable for being eaten, consumed, and digested by an animal. In one embodiment, the composition for feed containing the oenotein B analogue compound of the present invention or a pharmaceutically acceptable salt thereof may include a concentrated feed, forage and/or special feed.

In the enriched feed, seed fruits containing grains such as wheat, oats, and corn, bran containing rice bran, bran, barley bran, etc. Fish-soluble, meat powder, which is a concentrated product of fish meal, fish waste, and fresh liquids obtained from fish meal, fish waste, and residual starch, which is the main component of starch residue, which is the remainder of starch residue obtained by subtracting starch from sweet potatoes and potatoes. , animal feed such as dried whey, yeast, chlorella, seaweed, etc., which are dried whey, which is the remainder of the production of casein from milk, cheese, and casein from skim milk.

For roughage, raw grass feed such as wild grasses, grasses, and green cuttings, turnips for feed, beets for feed, root vegetables such as ruther beargers, a type of turnip, raw herbs, green crops, grains, etc. are placed in a silo. There are silage, which is stored feed fermented with lactic acid, wild grass, hay dried after cutting grass, straw for breeding crops, and leaves from legumes. Special feed includes mineral feed such as oyster shell and rock salt, urea feed such as urea or its derivative diureide isobutane, and supplementation of ingredients that are likely to be lacking when only natural feed ingredients are blended or added to formulated feed to increase feed storage. There are feed additives, which are substances added in trace amounts.

In addition, the present invention provides a low-fat-containing livestock fattening feed composition comprising an oenotein B analog compound or a pharmaceutically acceptable salt thereof.

According to the present invention, the oenotein B analog can be usefully applied as an additive to a low-fat-containing livestock fattening feed composition because it reduces the body fat content without loss of muscle mass.

Hereinafter, preferred examples are presented to help the understanding of the present invention, but the following examples are merely illustrative of the present invention, and it will be apparent to those skilled in the art that various changes and modifications are possible within the scope and spirit of the present invention, It goes without saying that such variations and modifications fall within the scope of the appended claims.

Example

reagent

The reagents and solvents mentioned below were purchased from Sigma-Aldrich, TCI or Alfa aesar, unless otherwise specified, and HPLC grade was used.

test example 1. In a normal-weight animal model Oenotein B weight loss effect

Oenotein B was dissolved in sterile distilled water to prepare a solution of 20 mg/mL. After diluting the prepared solution 20-fold with saline, 200 μL of oenotein B (1 mg/mL) was injected into the abdominal cavity of C57BL6/J mice with an average age of 13 weeks using a 1 cc syringe on days 1 and 3 of the experiment. The injections were made at time intervals, and body weight changes were measured daily for 5 days after injection, starting one day before the injection of oenotein B solution. Distilled water was used as a control, and normal feed and water having a fat content of 15% were provided during the experiment.

1 shows a graph showing the weight loss effect of oenotein B. Arrows indicate the time of injection of oenotein B. After the first injection of oenotein B, a weight loss effect was observed, and 1.5 to 8.5% of the body weight was lost after the first injection, and 1.5 to 6% of the body weight was lost after the second injection. These results suggest that oenotein B exhibited an excellent weight loss effect in a short period of time, and that the weight loss was maintained.

test example 2. Obesity in animal models Oenotein B weight loss effect

The weight loss effect of oenotein B in an obese animal model was confirmed using overweight-induced mice. C57BL/6J mice of an average age of 12 weeks were fed after changing the general diet (fat content 15%) to a high-fat diet containing 45% fat, and the change in body weight was measured daily. After feeding the high-fat feed, on the 21st, 23rd, and 25th days, 200 μL of oenotein B (1 mg/mL) was injected into the abdominal cavity of the mice, and body weight changes were measured every day until the 27th day, and the control group was injected with distilled water.

As shown in FIG. 2 , it was confirmed that the body weight of the mice receiving the high-fat feed for 3 weeks increased by about 16.3% on average. As a result of intraperitoneal injection of 200 μL of oenotein B (1 mg/mL) three times at 48 hour intervals to mice with increased body weight, there was no significant change in body weight in the control group, but the body weight of mice injected with oenotein B was It continued to decrease, and about 12.9% of the body weight was lost on the 6th day after injection. In addition, 9% of the weight was lost within 72 hours after administration. After weight loss, there was no decrease in appetite, no signs of dehydration, no stress, deterioration of physical strength, and no side effects such as toxicity. .

test example 3. Obesity in animal models Oenotein B weight loss effect

In order to determine whether the weight loss by oenotein B in the overweight-induced mouse was due to the reduction in fat, the weight of abdominal fat was measured using the same mouse used in Test Example 2, and the results are shown in FIG. .

In the case of mice administered oenotein B, compared to the control group, it was confirmed that an average of about 44% of abdominal fat was reduced. These results show that the weight loss by the administration of oenotein B is due to the decrease in fat mass.

test example 4. Oil red O staining

Oil red O is a dye used to stain neutral triglycerides and lipids. After 3T3-L1 preadipocytes were differentiated into adipocytes, the degree of fat reduction was investigated by treatment with oenotein B at a concentration of 20 and 40 μg/ml four times, which is shown in FIG. 4 .

4 shows the staining results. Unlike the control group, it was confirmed that the amount of stained fat was reduced by up to 50% in the group treated with oenotein B.

test example 5. Cytotoxicity Assessment

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 conditions. Next, after treating A549 cells with Oenotein B, lactate dehydrogenase (LDH) release assay was performed to quantitatively measure cytotoxicity, and the results are shown in FIG. 5 . Hydrogen peroxide was used as a positive control, and phosphate-buffered saline was used as a negative control.

As shown in FIG. 5 , it was confirmed that the toxicity of oenotein B was as low as the level of the negative control.

The above results show that the oenotein B analog according to the present invention can induce weight loss by reducing body fat in a short period of time without side effects such as cytotoxicity, and can maintain the weight loss for a long time. Based on these results, the composition containing the oenotein B analog according to the present invention is a pharmaceutical composition, a food composition for weight loss, treatment, prevention or improvement of obesity and obesity complications, in particular, health for weight loss or body fat loss It can be usefully applied as a functional food, a feed composition, and further can be usefully used as a feed composition for fattening livestock containing low fat.

Claims (15)

delete delete A pharmaceutical composition for the prevention or treatment of obesity comprising an oenotein B compound represented by the following formula (3) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 3]

4. The method of claim 3,
The oenotein B compound will reduce the amount of body fat at least one selected from abdominal fat, visceral fat, intramuscular fat and blood fat. delete delete delete A food composition for the prevention or improvement of obesity comprising an oenotein B compound represented by the following formula (3) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 3]

9. The method of claim 8,
The food composition is a health functional food, food composition. delete delete An animal feed composition for preventing or improving obesity comprising oenotein B represented by the following formula (3) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 3]

delete delete delete

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