Composition for preventing or treating obesity or related metabolic disease, comprising 1,1-diethoxyethane as active ingredient

Abstract

The present invention relates to a composition for preventing or treating obesity or a related metabolic disease, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. More specifically, the present invention relates to a pharmaceutical composition, a cosmetic composition, a food composition, or a feed composition for preventing or treating obesity, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), or sleep apnea, the composition comprising 1,1-diethoxyethane as an active ingredient.

Description

A composition for the prevention or treatment of obesity or related metabolic diseases containing 1,1-diethoxyethane as an active ingredient

[0001] The present invention relates to a composition for the prevention or treatment of obesity or related metabolic diseases comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. More specifically, the present invention relates to a pharmaceutical composition, cosmetic composition, food composition, or feed composition for the prevention or treatment of obesity, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea comprising 1,1-diethoxyethane as an active ingredient.

[0002] In modern society, while rapid economic development and nutritional affluence have led to a significant decrease in physical activity, the prevalence of metabolic syndrome—characterized by the complex combination of two or more conditions such as obesity, diabetes, hypertension, hypertriglyceridemia, hypercholesterolemia, and arteriosclerosis—is on the rise. Consequently, heart disease and stroke resulting from this are increasing to the point where they rank as the second and third leading causes of death among Koreans. These diseases manifest as symptoms that lead to a loss of bodily function, as metabolic waste products and toxins accumulate in the body due to an imbalance in metabolism. As a result, metabolic syndrome can progress to insulin resistance syndrome and act as a cause of cardiovascular and cerebrovascular diseases.

[0003] Metabolic syndrome can cause damage to the coronary arteries, leading to heart disease or stroke; it reduces the kidneys' ability to remove salt, causing high blood pressure; and increases triglyceride levels, which are a cause of cardiovascular disease. Furthermore, it can cause various problems, such as increasing the risk of blood clots and leading to damage to the eyes, kidneys, and nerves due to increased insulin resistance caused by type 2 diabetes.

[0004] Drugs for the effective treatment of metabolic syndrome have not yet been developed, and medications used to treat diabetes, dyslipidemia, and hypertension are currently being used to treat metabolic syndrome. Currently available drugs for treating metabolic syndrome include the diabetes medication metformin, thiazolidinediones (TZD) class drugs, glucosidase inhibitors, and dipeptidyl peptidase-IV inhibitors (DDP), along with antihypertensive drugs and dyslipidemia medications, which are receiving attention. However, there are limitations to fundamentally improving metabolic syndrome with these drugs.

[0005] It is known that factors related to the causes and treatment of metabolic syndrome, such as exercise, dietary habits, body weight, blood glucose, triglycerides, cholesterol, insulin resistance, adiponectin, leptin, AMP-activated protein kinase (AMPK) activity, sex hormones such as estrogen, genetic factors, and in vivo levels of malonyl-CoA, have a direct or indirect influence.

[0006] Accordingly, for the effective management or treatment of metabolic syndrome, it is ideal to develop substances capable of maintaining normal blood sugar levels while simultaneously addressing obesity, the underlying cause of the syndrome. However, research and development for such treatments has been lacking to date.

[0007] Prior art literature

[0008] [비특허문헌 1] Marcq, P. and P. Schieberle, Characterization of the Key Aroma Compounds in a Commercial Fino and a Commercial Pedro Ximenez Sherry Wine by Application of the Sensomics Approach. J Agric Food Chem, 2021. 69(17): p. 5125-5133.

[0009] [비특허문헌 2] Moreno, J., et al., Use of a flor velum yeast for modulating colour, ethanol and major aroma compound contents in red wine. Food Chem, 2016. 213: p. 90-97.

[0010] [비특허문헌 3] Tan, C., et al., The Effects of Ultrasonic and Gamma Irradiation on the Flavor of Potato Wines Investigated by Sensory Omics. Foods, 2023. 12(15).

[0011] [비특허문헌 4] Dunkel, A., et al., Nature's chemical signatures in human olfaction: a foodborne perspective for future biotechnology. Angew Chem Int Ed Engl, 2014. 53(28): p. 7124-43.

[0012] [Non-patent Document 5] Kawaguchi, D., H. Ogihara, and H. Kurokawa, Upgrading of Ethanol to 1,1-Diethoxyethane by Proton-Exchange Membrane Electrolysis. ChemSusChem, 2021. 14(20): p. 4431-4438.

[0013]

[0014] The inventors investigated the effects of 1,1-diethoxyethane (1,1-DEE) on body weight gain, blood glucose control, insulin resistance, liver damage, and fat production in high-fat diet (HFD)-induced obesity and metabolic disease models. After confirming that 1,1-DEE can inhibit body weight gain, improve blood glucose and insulin resistance, alleviate liver damage and fat production, and reduce the amount of LDL-cholesterol in the blood in HFD mice, they went on to complete the present invention.

[0015]

[0016] Accordingly, the present invention aims to provide a pharmaceutical composition for the prevention or treatment of obesity or related metabolic diseases comprising 1,1-diethoxytain (1,1-DEE) as an active ingredient.

[0017] The present invention also aims to provide a cosmetic composition for preventing or improving cellulite comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient.

[0018] The present invention also aims to provide a food composition for preventing or improving obesity or related metabolic diseases, comprising 1,1-diethoxytain (1,1-DEE) as an active ingredient.

[0019] The present invention also aims to provide a feed composition for preventing or improving obesity or related metabolic diseases, comprising 1,1-diethoxytain (1,1-DEE) as an active ingredient.

[0020] However, the problems that this invention seeks to solve are not limited to those mentioned above, and other unmentioned problems will be clearly understood by those skilled in the art from the description below.

[0021] The present invention discloses a pharmaceutical composition, cosmetic composition, food composition, or feed composition for the prevention, treatment, or improvement of obesity or related metabolic diseases comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient.

[0022] In the present invention, the 1,1-diethoxyethane (1,1-DEE) has the molecular formula C6H 14 It is represented by the following structural formula 1 as O2, and is also called acetaldehyde diethyl acetal or ethyllidene diethyl ether.

[0023] [Structural Formula 1]

[0024]

[0025] According to one embodiment,

[0026] A pharmaceutical composition for the prevention or treatment of obesity or related metabolic diseases comprising 1,1-diethoxytaine as an active ingredient is disclosed.

[0027] In the present invention, the obesity-related metabolic diseases may include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

[0028] In the present invention, the pharmaceutical composition may be administered by one or more methods of administration selected from the group consisting of oral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, epithelial administration, local administration, vaginal administration, pulmonary administration, rectal administration, sublingual administration, buccal administration, transdermal administration, ocular administration, inhalation, intracavernous injection, intrathecal injection, epidural injection, oral mucosal administration, bronchial administration, lymphatic administration, head and neck administration, cardiac administration, and rectal administration.

[0029] In the present invention, the pharmaceutical composition may be carried on a carrier, and the carrier may include one or more selected from virus particles, vesicles, nanoparticles, microparticles, liposomes, transposons, micelles, antibodies, and exosomes.

[0030]

[0031] According to another embodiment,

[0032] A cosmetic composition for preventing or improving cellulite comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient is disclosed.

[0033] In the present invention, the cosmetic composition may be formulated into one or more selected from the group consisting of a solution, an external ointment, a cream, a foam, a nourishing lotion, a softening lotion, a perfume, a pack, a softening water, a lotion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleansing product, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, a body lotion, a hand cream, a massage cream, a hair tonic, a foot cream, a body scrub, a facial mask, a serum, a hair mask, a toner, a mist, and a spray.

[0034]

[0035] According to another embodiment,

[0036] A food composition for preventing or improving obesity or related metabolic diseases is disclosed, comprising 1,1-diethoxytain (1,1-DEE) as an active ingredient.

[0037] In the present invention, the obesity-related metabolic diseases may include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

[0038] In the present invention, the food may include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, coffee beverages, stamina drinks, alcoholic beverages, vitamin complexes, fruit juices, desserts, health supplements, instant foods, seasonings and sauces, and processed meat products.

[0039]

[0040] According to another embodiment,

[0041] A feed composition for preventing or improving obesity or related metabolic diseases is disclosed, comprising 1,1-diethoxytain (1,1-DEE) as an active ingredient.

[0042] In the present invention, the obesity-related metabolic diseases may include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

[0043] In the present invention, the feed may include powder feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, wet feed, snacks, special feed, functional feed, dry feed, rice and grain feed, natural feed, or raw feed.

[0044] 1,1-diethoxyethane (1,1-DEE) according to the present invention can provide the following effects.

[0045] (1) 1,1-diethoxyethane was found to reduce body weight gain and improve fat accumulation in eWAT and iWAT in obese mice induced by a high-fat diet (HFD), and 1,1-DEE was found to improve glucose tolerance and improve insulin sensitivity.

[0046] (2) 1,1-diethoxyethane has been shown to reduce the risk of fat accumulation and atherosclerosis by reducing ALT, AST, and LHD, which are biomarkers of liver damage induced by HFD, and by improving TG and LDL-C levels.

[0047] Accordingly, the composition containing 1,1-diethoxyethane according to the present invention is expected to be usefully utilized as a pharmaceutical composition, food composition, cosmetic composition, or feed composition for the prevention, treatment, or improvement of obesity, diabetes, fatty liver, and related metabolic diseases.

[0048]

[0049] Meanwhile, the scope of the present invention is not limited by the effects described above.

[0050] Figure 1 shows the protocol for creating an HFD-induced obesity model and the administration plan for 1,1-DEE.

[0051] Figure 2 evaluates the effects of 1,1-DEE on body weight change and fat accumulation in an HFD-induced obesity model, showing (A) representative mouse appearance of each treatment group, (B) body weight change, (C) food intake change, (D) eWAT fat accumulation change, (E) iWAT fat accumulation change, F) heart weight change, (G) liver weight change, and (H) colon length change.

[0052] Figure 3 shows the effect of 1,1-DEE on inhibiting body weight gain in HFD mice. Eight-week-old male mice were divided into six groups and administered different diets. The groups were as follows: ND (normal diet), ND+1,1-DEE (treated with 1,1-DEE 100 mg / kg), HFD (high-fat diet), HFD+1,1-DEE (treated with 1,1-DEE 100 mg / kg), HFD+Met (treated with metformin 100 mg / kg), and HFD+1,2-DEE (treated with 1,2-DEE 100 mg / kg) (n=7 per group). After 4 weeks of treatment, the following parameters were measured: (A) change in body weight over 4 weeks for each treatment group, (B) comparison of body weight at week 12, and (C) food intake. Data were expressed as mean ± SEM, and statistical significance was evaluated using the unpaired two-tailed Student's t-test (nsp > 0.05, **p ≤ 0.01).

[0053] Figure 4 evaluates the effects of 1,1-DEE on blood glucose and insulin sensitivity in HFD-induced obese mice, showing (A) data on random changes in blood glucose levels, (B) changes in fasting blood glucose levels, (C) glucose tolerance test, (D) changes in serum insulin levels, and (E) results of insulin tolerance test.

[0054] Figure 5 shows the results of evaluating the effect of 1,1-DEE on improving liver damage and fat production in HFD-induced obese mice, including (A) changes in ALT levels, (B) changes in AST levels, (C) changes in LHD levels, (D) changes in ALP levels, (E) changes in T-Bil levels, (F) changes in Alb levels, (G) changes in TG levels, (H) changes in T-chol levels, (I) changes in HDL-C levels, (J) changes in LDL-C levels, and (K) changes in LDL-C levels.

[0055] Hereinafter, a composition for the prevention or treatment of obesity or related metabolic diseases comprising 1,1-diethoxyethane as an active ingredient according to a specific embodiment of the invention will be described in detail. However, this is presented as one example of the invention and does not limit the scope of the invention, and it is obvious to those skilled in the art that various modifications to the embodiment are possible within the scope of the invention. Throughout this specification, unless otherwise specifically stated, "includes" or "contains" refers to the inclusion of any component (or constituent) without any particular limitation and should not be interpreted as excluding the addition of other components (or constituents).

[0056] As used herein, the term "treatment" means any form of treatment or prevention that provides effects, including improvement of the individual's condition, delay of disease progression, delay of symptom onset, or slowing of symptom progression, to an individual who suffers from a disease or is at risk of developing a disease. Accordingly, the term "treatment" includes preventive treatment of the individual that prevents the onset of symptoms. Furthermore, the terms "treatment" and "prevention" are not intended to mean the cure or complete elimination of symptoms.

[0057] As used in this specification, the term "improvement" may mean any action that at least reduces parameters related to the alleviation or treatment of a condition, such as the degree of symptoms.

[0058] As used herein, the term “object” means an animal including animals such as cattle, monkeys, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, rabbits, or guinea pigs. For example, the object may be a mammal, particularly a human.

[0059]

[0060] 1. Pharmaceutical composition

[0061] The present invention

[0062] We intend to provide a pharmaceutical composition for the prevention or treatment of obesity or related metabolic diseases comprising 1,1-diethoxyethanein as an active ingredient.

[0063] In the pharmaceutical composition according to the present invention, the obesity-related metabolic disease may include, but is not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

[0064] In the pharmaceutical composition according to the present invention, the pharmaceutical composition may be administered by one or more methods of administration selected from the group consisting of oral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, epithelial administration, local administration, vaginal administration, pulmonary administration, rectal administration, sublingual administration, buccal administration, transdermal administration, ocular administration, inhalation, intracavernous injection, intrathecal injection, epidural injection, oral mucosal administration, intrabronchial administration, lymphatic administration, head and neck administration, intracardiac administration, and rectal administration. When administered orally, for example, the pharmaceutical composition may be formulated as a tablet, or the active agent may be coated or protected from degradation in the stomach. Additionally, the composition may be administered by any device capable of delivering the active substance to target cells. The route of administration may vary depending on the general condition and age of the subject being treated, the nature of the treatment condition, and the selected active ingredient.

[0065] In the pharmaceutical composition according to the present invention, the pharmaceutical composition may be carried on a carrier, and the carrier may include one or more selected from virus particles, vesicles, nanoparticles, microparticles, liposomes, transposons, micelles, antibodies, and exosomes, but is not limited thereto.

[0066] In the pharmaceutical composition according to the present invention, the suitable dosage of the pharmaceutical composition varies depending on factors such as the formulation method, the mode of administration, the patient's age, body weight, sex, pathological condition, food, time of administration, route of administration, excretion rate, and response sensitivity, and a physician of ordinary skill can easily determine and prescribe a dosage effective for the desired treatment or prevention. For example, the pharmaceutical composition may be administered as a single or multiple doses, or divided into 1 to 4 doses per day. For example, the pharmaceutical composition may contain 0.01 mg / kg to 100 mg / kg, preferably 0.02 mg / kg to 90 mg / kg, and more preferably 0.03 mg / kg to 80 mg / kg per adult.

[0067] In the pharmaceutical composition according to the present invention, the pharmaceutical composition may be prepared in a unit dose form or contained in a multi-dose container by formulation using a pharmaceutically acceptable carrier and / or excipient according to a method that can be easily carried out by a person skilled in the art to which the invention pertains. In this case, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or in the form of an extract, powder, granule, tablet, or capsule, and may additionally include a dispersant or a stabilizer. Furthermore, the pharmaceutical composition may be administered in the form of a suppository, spray, ointment, cream, gel, inhalant, or skin patch. Additionally, the pharmaceutical composition may be prepared for administration to mammals, more preferably for administration to humans.

[0068] In the pharmaceutical composition according to the present invention, the pharmaceutically acceptable carrier may be a solid or a liquid and may be one or more selected from excipients, antioxidants, buffers, bacteriostatic agents, dispersants, adsorbents, surfactants, binders, preservatives, disintegrants, sweeteners, flavoring agents, lubricants, release regulators, wetting agents, stabilizers, suspending agents, and lubricants. Additionally, the pharmaceutically acceptable carrier may be selected from saline solution, sterile water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures thereof.

[0069] In one embodiment, suitable fillers may include, but are not limited to, sugars (e.g., dextrose, sucrose, maltose and lactose), starch (e.g., corn starch), sugar-alcohols (e.g., mannitol, sorbitol, maltitol, erythritol and xylitol), starch hydrolysates (e.g., dextrin and maltodextrin), cellulose or cellulose derivatives (e.g., microcrystalline cellulose).

[0070] In one embodiment, suitable binders may include, but are not limited to, povidone, copovidone, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, gelatin, gums, sucrose, starch, or mixtures thereof.

[0071] In one embodiment, suitable preservatives may include, but are not limited to, benzoic acid, sodium benzoate, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorbutol, gallate, hydroxybenzoate, EDTA, or mixtures thereof.

[0072] In one embodiment, suitable disintegrant may be sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked carboxymethylcellulose, starch, microcrystalline cellulose, or a mixture thereof, but is not limited thereto.

[0073] In one embodiment, suitable sweeteners may include, but are not limited to, sucralose, saccharin, sodium or potassium or calcium saccharin, acesulfame potassium or sodium cyclamate, mannitol, fructose, sucrose, maltose, or mixtures thereof.

[0074] In one embodiment, suitable glidant may be silica, colloidal silicon dioxide, talc, etc., but is not limited thereto.

[0075] In one embodiment, suitable lubricants may include, but are not limited to, long-chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glyceride wax, or mixtures thereof.

[0076]

[0077] 2. Cosmetic composition

[0078] The present invention

[0079] We intend to provide a cosmetic composition for preventing or improving cellulite comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient.

[0080] As used in this specification, the term "cellulite" refers to the appearance of fat protruding in places, particularly on the thighs or buttocks, due to circulatory disorders caused by the accumulation of excessive fat and waste products. The cause of cellulite is fundamentally due to an increase or hypertrophy of fat cells. Therefore, the term "prevention or improvement of cellulite" may mean reducing the volume of cellulite, lowering the height of cellulite, removing cellulite, or flattening cellulite and its surroundings.

[0081] 1,1-diethoxyethane (1,1-DEE) according to the present invention has the effect of inhibiting fat accumulation, thereby preventing or improving cellulite. In addition, due to this effect, the composition has a body slimming effect. The term "body slimming" may mean promoting the even redistribution of fat in a body line that appears bumpy due to uneven subcutaneous fat distribution, reducing the volume of the body or a part of the body, eliminating swelling to consequently reduce the volume of a part of the body, improving localized obesity, breaking down and expelling fat within fat cells, and reducing the accumulation of triglycerides and fluids within fat cells.

[0082] In the cosmetic composition according to the present invention, the cosmetic composition may additionally include a dermatologically acceptable carrier. The dermatologically acceptable carrier may include, but is not limited to, purified water, oil, wax, fatty acid, fatty acid alcohol, fatty acid ester, surfactant, hygroscopic agent, thickener, antioxidant, viscosity stabilizer, chelating agent, buffer, preservative, lower alcohol, etc., and its type and concentration may vary and may include parts that a person skilled in the art can modify within the scope of the present invention.

[0083] In the cosmetic composition according to the present invention, in addition to the active ingredient of the present invention, the cosmetic composition may include functional substances as needed, such as whitening agents, moisturizers, anti-inflammatory agents, antibacterial agents, antifungal agents, vitamins, sunscreens, antibiotics, anti-acne agents, perfumes, and dyes, and these may be included in the cosmetic composition according to the present invention in amounts commonly used in the field of cosmetics. To enhance the functional effect, the cosmetic composition of the present invention may additionally contain one or more moisturizing active ingredients exhibiting the same or similar functions.

[0084] In the cosmetic composition according to the present invention, the cosmetic composition may be prepared in the form of a general emulsion formulation and a solubilizing formulation. Cosmetics in the form of an emulsion include nourishing lotions, creams, essences, etc., and cosmetics in the form of a solubilizing formulation include softening lotions. In addition to the active ingredient of the present invention, the cosmetic composition may also be prepared in the form of an adjuvant for topical or systemic application commonly used in the art by containing a dermatologically acceptable medium or base. Suitable cosmetic formulations may be provided, for example, in the form of a solution, gel, solid or paste anhydrous product, an emulsion obtained by dispersing an oil phase in an aqueous phase, a suspension, a microemulsion, a microcapsule, a microgranulocyte, or an ionic (liposome) or non-ionic vesicular dispersant, or in the form of a cream, skin toner, lotion, powder, ointment, spray, or conceal stick. Additionally, it may be prepared in the form of a foam or an aerosol composition further containing a compressed propellant.

[0085] In the cosmetic composition according to the present invention, the cosmetic composition may be formulated into one or more selected from the group consisting of a solution, an external ointment, a cream, a foam, a nourishing lotion, a softening lotion, a perfume, a pack, a softening water, a lotion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleansing product, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, a body lotion, a hand cream, a massage cream, a hair tonic, a foot cream, a body scrub, a facial mask, a serum, a hair mask, a toner, a mist, and a spray.

[0086]

[0087]

[0088] 3. Food composition

[0089] As used in this specification, the term “food” refers to a natural product or processed product containing one or more nutrients, preferably one that has undergone some degree of processing to become ready for direct consumption, and in a conventional sense may include food, food additives, functional foods, and beverages.

[0090] As used in this specification, the terms “functional food” or “health functional food” refer to a group of foods to which added value has been added to the food by using physical, biochemical, or biotechnological methods to act or manifest the function of the food for a specific purpose, or to foods designed and processed to sufficiently express in vivo regulatory functions regarding the regulation of biological defense rhythms, disease prevention, and recovery, which are inherent in the food composition; specifically, they may be health functional foods. The functional food may include food science-acceptable food additives and may further include appropriate carriers, excipients, and diluents commonly used in the manufacture of functional foods. The types of health functional foods may include, but are not limited to, powder, granules, tablets, capsules, or beverage forms.

[0091] According to one embodiment,

[0092] The present invention aims to provide a food composition for preventing or improving obesity or related metabolic diseases, comprising 1,1-diethoxytain (1,1-DEE) as an active ingredient.

[0093] In the food composition according to the present invention, the obesity-related metabolic disease may include, but is not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

[0094] In the food composition according to the present invention, the food is characterized by including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, coffee beverages, stamina drinks, alcoholic beverages, vitamin complexes, fruit juices, desserts, health supplements, instant foods, seasonings and sauces, and processed meat products.

[0095] In the food composition according to the present invention, the food composition may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice beverages, or vegetable beverages. These ingredients may be used independently or in combination.

[0096] In the food composition according to the present invention, the term “functional food or health functional food” refers to a group of foods to which added value is imparted by using physical, biochemical, or biotechnological methods to make the function of the food act or manifest for a specific purpose, or a food processed by designing it to sufficiently express in the body the in vivo regulatory functions regarding the regulation of biological defense rhythms, disease prevention, and recovery possessed by the food composition; specifically, it may be a health functional food. The functional food may include food-scientifically acceptable food auxiliary additives and may further include appropriate carriers, excipients, and diluents commonly used in the manufacture of functional foods.

[0097]

[0098] 4. Feed composition

[0099] According to one embodiment,

[0100] The present invention aims to provide a feed composition for preventing or improving obesity or related metabolic diseases, comprising 1,1-diethoxytain (1,1-DEE) as an active ingredient.

[0101] In the feed composition according to the present invention, the obesity-related metabolic disease may include, but is not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

[0102] In the feed composition according to the present invention, the feed comprises nutrients such as energy, protein, lipids, vitamins, and minerals required by animals, and may be a plant-based feed such as grains, root vegetables, food processing by-products, algae, fibers, oils, starches, meal, grain by-products, or animal-based feed such as proteins, inorganic substances, oils, minerals, oils, and single-cell proteins, but is not limited thereto.

[0103] In the feed composition according to the present invention, the feed may be powder feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, wet feed, snacks, special feed, functional feed, dry feed, rice and grain feed, natural feed, or raw feed, but is not limited thereto.

[0104] In the feed composition according to the present invention, the feed composition may include binders, emulsifiers, preservatives, etc. added to prevent quality degradation, and the feed composition may include feed additives. To increase utility, amino acid preparations, vitamin preparations, enzyme preparations, flavoring agents, non-protein nitrogen compounds, silicate preparations, buffering agents, extractants, oligosaccharides, etc. may be added to the feed. In addition, feed mixing agents, etc. may be additionally included, but are not limited thereto.

[0105]

[0106] 5. Treatment methods for diseases related to insulin resistance

[0107] The present invention aims to provide a method for preventing or treating obesity or related metabolic diseases, comprising the step of administering to an individual a pharmaceutical composition of Item 1, which contains the above-mentioned 1,1-diethoxyethane (1,1-DEE) as an active ingredient.

[0108] In a method for preventing or treating obesity or related metabolic diseases according to the present invention, the obesity-related metabolic diseases may include, but are not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

[0109] In a method for preventing or treating obesity or related metabolic diseases according to the present invention, the individual may include, but is not limited to, a human, a cow, a monkey, a horse, a sheep, a pig, a chicken, a turkey, a quail, a cat, a dog, a mouse, a rat, a rabbit, or a guinea pig.

[0110] In the method for preventing or treating obesity or related metabolic diseases according to the present invention, the route of administration, dosage, and frequency of administration of the pharmaceutical composition may be administered to the subject in various ways and amounts depending on the patient's condition and the presence or absence of side effects, and the optimal method of administration, dosage, and frequency of administration may be selected within an appropriate range by a person skilled in the art. In the present invention, the preferred dosage of the exosome or pharmaceutical composition may be in the range of 0.001 mg / kg to 100 mg / kg per day for adults, depending on the patient's condition, body weight, gender, age, severity of the patient, and route of administration. Administration may be performed once a day or divided into several times. Such dosage shall not be interpreted as limiting the scope of the present invention in any aspect.

[0111]

[0112] Various embodiments are presented below to aid in understanding the invention. The following embodiments are provided merely to facilitate a better understanding of the invention and do not limit the scope of protection of the invention to the following embodiments.

[0113]

[0114] Materials and Methods

[0115] 1. Animal Model and Oral Administration of 1,1-DEE

[0116] Eight-week-old male C57BL-6J mice were purchased from Damool Science (Daejeon, Korea). The mice were divided into four groups (n=5) and provided with various diets, including a normal diet (ND) group, an ND group administered 1,1-DEE, a high-fat diet (HFD) group, and an HFD group administered 1,1-DEE (Fig. 1). The ND diet contained 10 kcal% fat, 70 kcal% carbohydrates, and 20 kcal% protein, while the HFD diet contained 60 kcal% fat, 20 kcal% carbohydrates, and 20 kcal% protein. Mice were orally administered 100 mg / kg of 1,1-DEE every other day, while the control group consumed the same amount of water. After 8 weeks of treatment, the mice were used for glucose tolerance and insulin tolerance tests. After 10 weeks of treatment, the mice were sacrificed, blood samples were collected, and stored at room temperature (RT) for 30 minutes. Liver, WAT, colon, and heart tissues were collected, rapidly immersed in liquid nitrogen, and stored at -80°C for further investigation.

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[0118] 2. Serum Chemistry Analysis

[0119] After coagulating the blood at RT, the blood samples were centrifuged at 3,000 rpm at 4°C for 20 minutes, and the serum samples were transferred to Eppendorf tubes. Serum chemistry analysis was performed using an automated blood chemistry analyzer (Duyeol Biotech Company, Seoul, Republic of Korea), which included markers for AST, ALT, ALP, lactate dehydrogenase (LDH), total bilirubin (T-Bili), total cholesterol (T-chol), triglycerides (TG), albumin (Alb), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C). Plasma insulin levels were measured using a mouse insulin ELISA kit (#292-89401, FUJIFILM Wako Pure Chemical Corporation, Japan).

[0120]

[0121] 3. Intraperitoneal Glucose Tolerance Test (IGTT) and Insulin Resistance Test (IITT)

[0122] To test glucose tolerance, mice were transferred to a new cage without food overnight for 12 hours. Fasting blood glucose was measured using a glucose meter. Subsequently, 2 g / kg of D-glucose was injected intraperitoneally into the mice. Blood glucose levels were measured at 15, 30, 60, 90, and 120 minutes after the glucose injection. To test insulin tolerance, mice were starved for 4 hours. Insulin (Humulin R) was injected intraperitoneally into the mice at a dose of 0.6 U / kg. Blood glucose levels were recorded using a glucose meter at 15, 30, 60, 90, and 120 minutes after the insulin injection.

[0123]

[0124] 4. Histological analysis

[0125] Liver, fat, colon, and heart tissues were collected from each mouse and fixed in 4% paraformaldehyde. The tissues were sliced ​​to a thickness of 5 mm and embedded in paraffin. The paraffin sections were stained with hematoxylin and eosin (H&E).

[0126]

[0127] 6. Western Blot Analysis

[0128] The tissue was lysed using NP-40 lysis buffer (RIPA, 1% NP-40, 10 mM NEM). The tissue extract was stored on ice for 1 hour and then centrifuged at 13,000 rpm for 30 minutes. The supernatant was collected, and protein concentrations were measured using a BCA kit. Reducing and non-reducing sample buffers were added to prepare corresponding protein samples. Western blots were performed to investigate the protein expression of phosphorylated AMPK, phosphorylated ACC, and β-actin.

[0129]

[0130] 7. Statistical Analysis

[0131] Statistical analysis was performed using GraphPad Prism. Data were expressed as mean ± standard error of the mean (SEM). Statistical significance was analyzed using two-way analysis of variance, and a p-value ≤ 0.05 was considered statistically significant.

[0132]

[0133] <Result>

[0134] 1. Evaluation of the weight gain inhibitory effect of 1,1-DEE

[0135] (1) Evaluation of the effect of 1,1-DEE on inhibiting body weight gain in high-fat diet (HFD) mice

[0136] In this study, the effects of 1,1-DEE on body weight gain in a high-fat diet (HFD)-induced obesity model were investigated (Fig. 1). For the experiment, 8-week-old mice were orally administered HFD supplemented with 1,1-DEE at a concentration of 100 mg / kg every other day for 8 weeks. Fig. 2A shows representative mice from each group. As a result, the HFD group showed distinct body weight gain compared to the normal diet (ND) group, but the group administered 1,1-DEE significantly inhibited HFD-induced body weight gain (Fig. 2B). Meanwhile, there was no difference in body weight change between the ND group and the ND group supplemented with 1,1-DEE (Fig. 2B). Furthermore, while 1,1-DEE increased food intake in the ND group, food intake remained similar in the HFD group and the HFD+1,1-DEE group (Fig. 2C). These results suggest that 1,1-DEE induces appetite in mice. Additionally, post-sacrifice tissue analysis showed that 1,1-DEE had an effect on reducing HFD-induced eWAT and iWAT body weight (Figs. 2D-E). No significant differences were observed in the weight and length of the heart, liver, and large intestine (Figs. 2F-H).

[0137]

[0138] (2) Evaluation of weight control through comparison of 1,1-DEE and metformin

[0139] In addition, this study conducted additional experiments to compare the anti-obesity effects of 1,1-DEE and metformin. First, in a high-fat diet (HFD) mouse model, 1,1-DEE rapidly inhibited body weight gain from the beginning of administration, and the weight loss effect was consistently maintained compared to the HFD group for 4 weeks. On the other hand, the metformin-treated group showed a slight increase in body weight during the initial week, but the rate of weight gain was subsequently regulated gradually. In normal diet (ND) mice, the administration of 1,1-DEE did not affect changes in body weight. In particular, in the HFD+D100 group, mice treated with 1,1-DEE showed increased food intake compared to the HFD group, suggesting that 1,1-DEE may exert its effects on body weight control through exercise mimetic action rather than appetite suppression. These results demonstrate that 1,1-DEE can inhibit body weight gain more rapidly compared to metformin (Fig. 3). Therefore, it was confirmed that 1,1-DEE can be utilized as a useful candidate substance for the prevention and treatment of obesity and diabetes-related metabolic diseases.

[0140]

[0141] 2. Evaluation of the effects of 1,1-DEE on blood glucose control and insulin resistance improvement

[0142] To evaluate the effects of 1,1-DEE on glucose and insulin metabolism, random blood glucose measurements were taken every two weeks. As a result, blood glucose levels were significantly lower in the group administered 1,1-DEE compared to the HFD group (Fig. 4A). After 8 weeks of treatment, fasting blood glucose measured after a 12-hour fast was higher in the HFD group than in the ND group, and fasting blood glucose decreased upon administration of 1,1-DEE (Fig. 4B). Furthermore, the HFD group supplemented with 1,1-DEE showed lower GTT (AUC) values ​​compared to the HFD group, confirming improved glucose tolerance (Fig. 4C). This suggests that 1,1-DEE has a positive effect on glucose metabolism. After 8 weeks, serum insulin levels were higher in the HFD group compared to the ND group, and insulin levels improved in the 1,1-DEE-treated group (Fig. 4D). In the Insulin Resistance Test (ITT) to evaluate insulin resistance, the 1,1-DEE administration group also showed improved insulin sensitivity with a lower AUC value (p=0.2427, Fig. 4E). Therefore, it was confirmed that 1,1-DEE can improve glucose metabolism and insulin sensitivity in hyperglycemia and insulin resistance conditions.

[0143]

[0144] 3. Evaluation of the effects of 1,1-DEE on improving liver damage and lipogenesis

[0145] To evaluate whether 1,1-DEE improves liver damage and lipid production in HFD mice, serum biomarkers were analyzed. Liver damage-related biomarkers such as ALT, AST, and LHD were relatively increased in the HFD group, but these levels decreased in the 1,1-DEE-treated group (Figs. 5A-C). No significant differences were found in serum ALP, T-Bil, and Alb levels (Figs. 5D-F). Furthermore, when serum biomarkers such as TG, T-chol, HDL-C, and LDL-C were examined, 1,1-DEE showed a decrease in TG levels in the HFD group (Fig. 5G), and HFD-induced HDL-C and LDL-C levels decreased after 1,1-DEE treatment (Figs. 5H-K). In particular, 1,1-DEE demonstrated that it can reduce the risk of atherosclerosis by improving HFD-induced LDL-C levels (Fig. 5K). These results suggest that 1,1-DEE can improve liver damage and fat production in HFD-induced obese mice.

[0146]

[0147] Project ID: 2018R1D1A1B06051438

[0148] Ministry Name: Ministry of Science and ICT

[0149] Research Management Agency: National Research Foundation of Korea

[0150] Research Project Title: Regulation of the Cancer Suppressor Protein PTEN by Alcohol

[0151] Organizing Institution: Chonnam National University

[0152] Participating Company: Lux Anima Co., Ltd.

[0153] Research Period: 2023.03.01.–2024.02.29

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[0155] Project ID: 2022M3A9E4017151

[0156] Ministry Name: Ministry of Science and ICT

[0157] Research Management Agency: National Research Foundation of Korea

[0158] Research Project Title: Development of Heart Failure Control and Treatment Technologies Based on the MyHeart Platform

[0159] Organizing Institution: Chonnam National University

[0160] Participating Company: Lux Anima Co., Ltd.

[0161] Research Period: January 2024 – December 2024

[0162]

[0163] Department Name: Jeonnam Technopark Foundation

[0164] Research Project Name: Hwasun Vaccine Industry Special Zone Intellectual Property Capacity Building Support Project

[0165] Research Project Title: IP-R&D

[0166] Organizer: Lux Anima Co., Ltd.

[0167]

[0168] Specific parts of the present invention have been described in detail above. It is evident to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the invention. Accordingly, the actual scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A pharmaceutical composition for the prevention or treatment of obesity or related metabolic diseases comprising 1,1-diethoxytaine as an active ingredient.

2. In Paragraph 1, A pharmaceutical composition characterized in that the above obesity-related metabolic diseases include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

3. In Paragraph 1, The above pharmaceutical composition is characterized by being administered by one or more methods of administration selected from the group consisting of oral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, epithelial administration, local administration, vaginal administration, pulmonary administration, rectal administration, sublingual administration, buccal administration, transdermal administration, ocular administration, inhalation, intracavernous injection, intrathecal injection, epidural injection, oral mucosal administration, bronchial administration, lymphatic administration, head and neck administration, cardiac administration, and rectal administration.

4. In Paragraph 1, A pharmaceutical composition wherein the above pharmaceutical composition may be carried on a carrier, and the carrier comprises one or more selected from virus particles, vesicles, nanoparticles, microparticles, liposomes, transposons, micelles, antibodies, and exosomes.

5. A cosmetic composition for preventing or improving cellulite comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient.

6. In Paragraph 5, The cosmetic composition is characterized by being formulated into one or more selected from the group consisting of a solution, an external ointment, a cream, a foam, a nourishing lotion, a softening lotion, a perfume, a pack, a softening water, a lotion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleansing product, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, a body lotion, a hand cream, a massage cream, a hair tonic, a foot cream, a body scrub, a facial mask, a serum, a hair mask, a toner, a mist, and a spray.

7. A food composition for preventing or improving obesity or related metabolic diseases, comprising 1,1-diethoxytain (1,1-DEE) as an active ingredient.

8. In Paragraph 6, A food composition characterized in that the above obesity-related metabolic diseases include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

9. In Paragraph 6, The above food composition comprises meat, sausage, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, coffee beverages, stamina drinks, alcoholic beverages, vitamin complexes, fruit juices, desserts, health supplements, instant foods, seasonings and sauces, and processed meat products. 10.1,1-diethoxytain (1,1-DEE) as an active ingredient. Feed composition for preventing or improving obesity or related metabolic diseases.

11. In Paragraph 10, A feed composition characterized in that the above obesity-related metabolic diseases include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea.

12. In Paragraph 10, The above feed composition is characterized by including powdered feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, wet feed, snacks, special feed, functional feed, dry feed, rice and grain feed, natural feed, or raw feed.

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