WO2023214716A1

WO2023214716A1 - Pharmaceutical composition and health functional food for preventing or obesity comprising garcinia cambogia extract

Info

Publication number: WO2023214716A1
Application number: PCT/KR2023/005272
Authority: WO
Inventors: 최진원
Original assignee: (주)초이스메디케어
Priority date: 2022-05-02
Filing date: 2023-04-19
Publication date: 2023-11-09
Also published as: KR102461437B1

Abstract

The present invention relates to a pharmaceutical composition and health functional food for preventing or obesity, comprising a Garcinia cambogia extract. Particularly, the pharmaceutical composition and the health functional food comprise, as an active ingredient, a Garcinia cambogia extract, L-arginine, L-carnitine, or the like, which are natural substances that reduce side effects caused by conventional synthetic medicines and can replace these medicines, and thus have excellent efficacy in the prevention and treatment of obesity while minimizing side effects.

Description

Obesity prevention or pharmaceutical composition and health functional food containing Garcinia cambogia extract

The present invention relates to an obesity prevention or pharmaceutical composition and health functional food containing Garcinia cambogia extract.

Recently, as the death rate due to adult diseases has increased, attention has been focused on obesity. Accordingly, various health supplements with anti-obesity effects are being released one after another not only in Korea but also in the global pharmaceutical industry. In addition, the consumption status is good due to economic growth. As the number of obese people increases rapidly and lack of exercise becomes more serious, the resulting increase in adult diseases is emerging as a social problem. Additionally, as the dietary habits of Korean people become westernized, the number of chronic lifestyle diseases such as adult diseases will increase in the future. As we enter an aging society, demand for silver foods targeting the elderly is expected to increase.

Obesity occurs when excessive energy accumulation occurs due to metabolic imbalance when the supply of energy is much greater than the demand for energy. Clinically, it is involved in the development of various diseases or worsens them. Diseases related to obesity include high blood pressure and camellia sclerosis. , diabetes, fatty liver, and cholelithiasis. In particular, endometrial cancer, gallbladder cancer, cervical cancer, ovarian cancer, and breast cancer occur frequently in women, and in the case of endometrial cancer, the increase in incidence and mortality due to obesity is reported to be the most significant compared to other cancer diseases. Additionally, the mortality rate of obese people is reported to be 1.3 times higher than that of normal weight people.

Strategies for the treatment of obesity and related disorders include dietary restrictions, increased physical activity, pharmacological approaches, and even surgery, which depend at least in part on the degree of weight loss an individual is attempting to achieve, as well as the severity of obesity exhibited by the subject. is selected according to For example, for individuals who are only mildly overweight, treatments such as a low-calorie, low-fat diet and/or regular exercise are often appropriate. However, the difficulty in maintaining long-term weight loss through dietary and behavioral modifications has led to increased interest in other treatment options, especially pharmacotherapy.

Traditional pharmacological interventions typically induce weight loss of 5 to 15 kilograms; When drug treatment is discontinued, resumption of weight gain often follows. Surgical treatment is quite successful and is reserved for patients with extreme obesity and/or serious medical comorbidities.

The treatment can be enhanced by the controlled use of over-the-counter appetite suppressants such as caffeine, ephedrine and phenylpropanolamine (Acutrim, Dexatrim). Moreover, amphetamines, diethylpropion (Tenuate), mazindol (Mazanor, Sanorex), phentermine (Fastin, Ionamin), phenmetrazine ( Preludin), Phendimetrazine (Bontrol, Plegine, Adipost, Dital, Dyrexan, Melfiat, Prelu- Prescription medications, including Prelu-2 (Prelu-2), Rexigen Forte), benzphetamine (Didrex), and fluoxetine (Prozac), are often used in severely overweight and/or obese subjects or Used in patient treatment.

Society has seen vast progress in the field of pharmaceuticals, but, of course, there are drawbacks to the administration of any given drug. Often, the disadvantages or “side effects” are severe enough to preclude administration of therapeutically effective amounts of a particular agent. Additionally, many agents within the same therapeutic class exhibit similar side effect profiles, meaning that patients may have to suffer varying degrees of side effects that precede or are associated with the selected drug treatment.

Topiramate (2,3,4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose sulfamate) is approved by the FDA and many others for the treatment of certain seizure disorders and for the prevention of migraines. It is a broad-spectrum neurotherapeutic agent approved by national regulatory agencies (E. Faught et al. (1996) Neurology 46:1684-90]; [Karim et al. (1995) Epilepsia 36 (S4):33]; [ S. K. Sachdeo et al. (1995) Epilepsia 36(S4):33]; [T. A. Glauser (1999) Epilepsia 40 (S5):S71-80]; [R. C. Sachdeo (1998) Clin. Pharmacokinet. 34:335-346] ). Additionally, topiramate is effective in treating diabetes (U.S. Patent Nos. 7,109,174 and 6,362,220), nervous system disorders (U.S. Patent No. 6,908,902), depression (U.S. Patent No. 6,627,653), psychosis (U.S. Patent No. 6,620,819), headache (U.S. Patent No. No. 6,319,903) and high blood pressure (U.S. Patent No. 6,201,010). However, there are adverse effects associated with the use of topiramate in humans, such as cognitive dulling and word-finding difficulties, which may dissuade many obese patients from taking this drug.

Phentermine was approved by the FDA as an appetite suppressant in 1959, and phentermine hydrochloride has been used as a weight loss agent since the 1970s, for example, Adipex-P®, Fastin® , Zantril® It has been used under brand names such as. Regarding combining phentermine with a second active agent following reports of heart and lung problems associated with the "Fen-Phen" product (wherein phentermine was combined with fenfluramine and then with a related drug, dexfenfluramine) Although the FDA warns, it is safe and effective to lose weight by combining phentermine with an active agent that reduces the side effects of phentermine and allows administration of much lower doses of phentermine than "phentermine" (containing 30 mg or 37.5 mg of phentermine hydrochloride). It was discovered that weight loss treatment was available.

In relation to this, recently, a lower dose combination product of topiramate and phentermine is being sold domestically and internationally under the trademark Qsymia ^TM .

However, topiramate and phentermine included in Qsymia products are also synthetic substances and are known to have side effects such as paresthesia, alopecia, parosmia, amenorrhea, and aphasia. There is ([Korean J Obes 2015 March;24(1):17-27, Innov Clin Neurosci. 2011 Aug; 8(8): 14-16.]).

Accordingly, the present inventor discovered a composition that can eliminate or reduce the side effects of conventional obesity prevention and treatment compositions and replace them, and thus treat and prevent obesity containing natural substances that can minimize side effects as active ingredients. The purpose is to provide a pharmaceutical composition for.

A number of studies are in progress to replace conventional synthetic medicines with natural substances. Among these, Garcinia cambogia, which is known to be effective in suppressing obesity, is a tropical fruit tree of the Guttiferae family and is obtained by extracting the pericarp of Garcinia cambogia fruit. It is known that the resulting product is used to prevent or treat obesity. This Garcinia cambogia extract contains HCA (hydroxy citric acid). The HCA is a compound that is very similar to citric acid but has a hydroxyl group attached to it. It inhibits the process of converting citrate to acetyl-Co-A in vivo, inhibiting the synthesis of fatty acids, promoting oxidation, and converting to glucogen synthesis. increases energy production. In addition, HCA is known to have various physiologically active functions, such as suppressing appetite and promoting fat decomposition.

Research and development are currently being conducted to ensure sufficient effectiveness in improving obesity and reducing blood sugar levels by reducing body fat using Garcinia cambogia extract, and also provide pharmaceutical compositions and health functional food compositions for preventing or treating obesity with better effects. There is a need for development of food additive compositions.

One object of the present invention is to provide a pharmaceutical composition for preventing or treating obesity containing Garcinia cambogia extract, L-Arginine, and L-Carnitine.

Another object of the present invention is to provide a health functional food for preventing or treating obesity containing the above composition.

However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

According to one embodiment of the present invention, a combination preparation; Branched chain amino acids (BCAAs) containing at least one selected from the group consisting of leucine, isoleucine and valine; Calcium pantothenate; Nicotinic acid amide; crystalline cellulose; Magnesium stearate; hydroxypropylmethylcellulose; and carboxymethylcellulose calcium; a pharmaceutical composition for preventing or treating obesity, wherein the combination preparation includes an active ingredient, the combination preparation has a structure of a core and a shell formed on the core, and the active ingredient is Garcinia cambogia extract obtained by extracting Garcinia cambogia with an extraction solvent, contains L-Arginine and L-Carnitine in a weight ratio of 1:0.01 to 0.1:0.1 to 0.5, and the core contains the Garcinia cambogia. It contains the extract and the L-Carnitine, the shell contains the L-Arginine, and the ratio of the outer diameter of the composite preparation to the outer diameter of the core is 1:0.6 to 1:0.95. Provided is a pharmaceutical composition for preventing or treating obesity that satisfies the above.

In the present invention, Catechin, Cathinone, Tryptamine, P-Octopamine, P-Tyramine, Synephrine and Ephedrine It provides a pharmaceutical composition for preventing or treating obesity further comprising at least one selected from the group consisting of.

The present invention provides a pharmaceutical composition for preventing or treating obesity, comprising the Garcinia cambogia extract, L-Arginine, and L-Carnitine in a weight ratio of 1:0.017:0.25. .

In the present invention, a pharmaceutical composition for preventing or treating obesity is provided, comprising 40 parts by weight or more and 70 parts by weight or less of the combination preparation based on 100 parts by weight of the pharmaceutical composition for preventing or treating obesity.

According to another embodiment of the present invention, the pharmaceutical composition for preventing or treating obesity contains the L-arginine ( L-Arginine) is in the range of 40 to 45% of the total weight of the active ingredient after 1 hour, and the Garcinia Cambogia extract and L-Carnitine are in the range of 5 to 15% of the total weight of the active ingredient after 1 hour. Provided is a pharmaceutical composition for preventing or treating obesity that satisfies a dissolution profile.

In the present invention, the extraction solvent is water, C1-C4 alcohol, n-hexane, ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, ethyl acetate, benzene, and mixtures thereof. Provided is a pharmaceutical composition for preventing or treating obesity, which is selected from the group consisting of solvents.

In the present invention, the extraction solvent is modified alkylene glycol; and a solvent having a boiling point of 90°C or lower, wherein the extraction solvent includes 80 parts by weight or more and 95 parts by weight or less of the modified alkylene glycol; and 5 parts by weight or more and 20 parts by weight or less of a solvent having a boiling point of 90°C or lower.

Finally, a health functional food containing the pharmaceutical composition for preventing or treating obesity according to the present invention is provided.

The pharmaceutical composition for preventing or treating obesity provided by the present invention contains Garcinia cambogia extract, L-Arginine, and L-Carnitine, and exhibits effects in preventing and treating obesity.

In particular, the pharmaceutical composition of the present invention reduces the side effects caused by conventional synthetic drugs and contains natural substances that can replace them, such as garcinia cambogia extract, L-arginine, and L-carnitine, as active ingredients to minimize side effects and reduce obesity. It has excellent efficacy in the prevention and treatment of.

Among them, the pharmaceutical composition of the present invention has a composite preparation containing the above-mentioned active ingredients, and the composite preparation is composed of a core and shell structure, and the ratio of the outer diameter of the composite preparation to the outer diameter of the core is 1:0.6 to 1: It is characterized by satisfying 0.95.

In other words, based on the entire complex preparation as described above, the outer diameter ratio of the core satisfies a certain range (i.e., by adjusting the ratio of the core and shell), so it has the feature of effectively controlling the amount of active ingredient dissolved within a certain time. do. In other words, the three substances included as active ingredients are not eluted at once, but are prepared in the form of a complex preparation to satisfy the specific structure of the core-shell, so the required composition is eluted in high content within a certain period of time and the 3 substances are continuously released thereafter. It was confirmed that it showed superior obesity prevention and treatment effects by eluting with .

In addition, the pharmaceutical composition of the present invention has anti-obesity and anti-inflammatory properties as well as antioxidant and toxin removal, that is, detox effects.

However, it is not limited to the above-described effects, and should be understood to include all effects that can be inferred from the configuration of the invention described in the detailed description or claims.

Figure 1 is a diagram schematically showing a combination preparation according to an embodiment of the present invention.

Figure 2 is a graph showing cell survival rate treated with compositions according to one embodiment of the present invention.

Figures 3 to 10 show images taken under a microscope at 20x magnification showing the results of inhibiting intracellular adipocyte differentiation when 3T3-L1 cells were treated with compositions according to embodiments of the present invention.

Figure 11 is a graph schematically illustrating the results of inhibiting intracellular adipocyte differentiation when treated with compositions according to embodiments of the present invention.

Hereinafter, the present invention will be described in detail through examples to aid understanding. However, the following examples only illustrate the content of the present invention, and the scope of the present invention is not limited to the following examples. Examples of the present invention are provided to more completely explain the present invention to those skilled in the art. The present invention is not limited to the embodiments presented herein and may be embodied in other forms.

According to one embodiment of the present invention, a combination preparation; Branched chain amino acids (BCAAs) containing at least one selected from the group consisting of leucine, isoleucine and valine; Calcium pantothenate; Nicotinic acid amide; crystalline cellulose; Magnesium stearate; hydroxypropylmethylcellulose; and carboxymethylcellulose calcium; a pharmaceutical composition for preventing or treating obesity, wherein the combination preparation includes an active ingredient, the combination preparation has a structure of a core and a shell formed on the core, and the active ingredient is Garcinia cambogia extract obtained by extracting Garcinia cambogia with an extraction solvent, contains L-Arginine and L-Carnitine in a weight ratio of 1:0.01 to 0.1:0.1 to 0.5, and the core contains the Garcinia cambogia. It contains the extract and the L-Carnitine, the shell contains the L-Arginine, and the ratio of the outer diameter of the composite preparation to the outer diameter of the core is 1:0.6 to 1:0.95. It relates to a pharmaceutical composition for preventing or treating obesity that satisfies the above.

As used in the present invention, the term “compound” refers to a result obtained by performing fractionation to separate a specific component or specific group of components from a mixture containing various various components.

The separation method for obtaining the above compound in the present invention is not particularly limited and may be performed according to methods commonly used in the art. A non-limiting example of the separation method may be a method of obtaining a compound from a natural substance extract by treating it with a predetermined solvent.

In the present invention, the term "extracted material" or "extract" refers to an extract obtained by extraction treatment, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a crude product or purified product of the extract, or a mixture thereof. etc., includes the extract itself and all formulations of the extract that can be formed using the extract.

The extract in this specification follows the dictionary definition and may mean a liquid substance extracted from a specific substance or condition.

The extract of this specification follows the dictionary definition and is obtained by concentrating a specific component in the extract. The specific active ingredient is separated with an appropriate solvent, the solvent is completely or mostly evaporated, and the remaining lump or powder is adjusted according to the standard. In this specification, extract can be used to include all three types: semifluid or syrup, pill dealer or solid, dried powder, etc. there is.

In the present invention, drying of the extract can be done by a known method as long as useful components from the collected natural material are not destroyed, for example, by natural drying in the shade. In addition, crushing or pulverization can be performed to a degree that the useful components of the plant can be sufficiently extracted during the subsequent extraction process. The drying and crushing or pulverizing processes can be performed in reverse order or repeatedly as needed.

In the extraction of the present invention, the extraction method is not particularly limited, and extraction may be performed according to a method commonly used in the art. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, and reflux extraction, which may be performed alone or by combining two or more methods.

In particular, the type of extraction solvent used to extract natural substances in the present invention is not particularly limited, and any solvent known in the art can be used.

Garcinia cambogia is known to be effective in suppressing obesity, and it is known that the result obtained by extracting the pericarp of Garcinia cambogia fruit, a tropical fruit tree of the Guttiferae family, is used for the prevention or treatment of obesity.

The Garcinia cambogia extract contains hydroxycitric acid (HCA), an inhibitor of enzymes involved in fatty acid and cholesterol synthesis, and provides the function of inhibiting fat synthesis, suppressing appetite, and promoting fat decomposition. The HCA is a compound that is very similar to citric acid but has a hydroxyl group attached. It inhibits the process of converting citrate to acetyl-coenzyme A (acetyl-coenzyme A) in vivo, thereby inhibiting the synthesis of fatty acids. It promotes oxidation and conversion to glycogen synthesis, increasing energy production. In addition, HCA is known to have various physiologically active functions, such as suppressing appetite and promoting fat decomposition.

In other words, Garcinia Cambogia extract acts as a factor that blocks the synthesis of excess carbohydrates in the spleen and interferes with fat synthesis, thereby prolonging energy production in the body and increasing total energy production. In particular, Garcinia cambogia extract reduces acetyl-Co-A in the human body, resulting in increased liver and glycogen synthesis rates.

As a result, when excess glycogen accumulates, the hypothalamus of the brain recognizes that enough energy needed by the body has been accumulated, so the consuming person reduces further energy intake. That is, when consuming the pharmaceutical composition, health functional food composition, or health functional food additive composition for preventing or treating obesity according to the present invention, appetite is naturally suppressed and weight loss occurs.

The Garcinia cambogia extract is in powder form by freeze-drying the peel of the Garcinia cambogia fruit, pulverizing it to 100 mesh or less, extracting it at a temperature of 80°C or higher with 70% extraction solvent, concentrating and freeze-drying.

In the present invention, Garcinia cambogia extract obtained by extracting Garcinia cambogia with an extraction solvent is used.

In the present invention, the extraction solvent is water, C1-C4 alcohol, n-hexane, ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, ethyl acetate, benzene, and mixed solvents thereof. Provided is a pharmaceutical composition for preventing or treating obesity, which is selected from the group consisting of.

Among them, the extraction solvent for making the Garcinia cambogia extract according to the present application includes modified alkylene glycol; and a solvent having a boiling point of 90°C or lower, wherein the extraction solvent includes 80 parts by weight or more and 95 parts by weight or less of the modified alkylene glycol; and 5 parts by weight or more and 20 parts by weight or less of a solvent having a boiling point of 90°C or lower.

In general, glycol refers to a compound having two hydroxy groups (-OH), and alkylene glycol refers to a substance having two hydroxy groups (-OH) functional groups in a straight-chain or branched alkyl group. it means. Among these, in the case of modified alkylene glycol as in the present application, it may refer to a substance obtained by reacting at least one of the hydroxy groups to replace another compound.

In an exemplary embodiment of the present application, the alkylene group may include methylene, ethylene, propylene, butylene, etc., and the appropriate number of alkyl groups may include an alkylene group having 1 to 30 carbon atoms, more preferably may be an alkylene group having 1 to 20 carbon atoms, most preferably an alkylene group having 1 to 5 carbon atoms.

In an exemplary embodiment of the present application, the modified alkylene glycol may include propylene glycol monomethyl ether.

In an exemplary embodiment of the present application, the solvent having a boiling point of 90° C. or lower may be used without limitation as long as the boiling point range among widely known solvents satisfies the above range.

More preferably, the solvent having a boiling point of 90°C or lower may include at least one selected from the group consisting of acetone and ethyl acetate.

In the case of organic solvents according to the present application, modified alkylene glycols; and a solvent having a boiling point of 90°C or lower, wherein 80 parts by weight or more and 95 parts by weight or less of the modified alkylene glycol; And it may include 5 parts by weight or more and 20 parts by weight or less of a solvent having a boiling point of 90°C or lower.

In the case of organic solvents according to the present application, modified alkylene glycols; and a solvent having a boiling point of 90°C or lower, including 80 parts by weight or more and 95 parts by weight or less of modified alkylene glycol, preferably 85 parts by weight or more and 95 parts by weight or less, more preferably 90 parts by weight or more and 95 parts by weight or less. may be included.

In the case of organic solvents according to the present application, modified alkylene glycols; and a solvent having a boiling point of 90°C or lower, wherein the amount of the solvent having a boiling point of 90°C or lower is 5 parts by weight or more and 20 parts by weight or less, preferably 5 parts by weight or more and 15 parts by weight or less, more preferably 5 parts by weight or more and 10 parts by weight or less. may be included.

The inventor of the present application discovered that the extraction solvent for making Garcinia cambogia into an extract as described above has the above composition, and that when it satisfies the above extraction solvent composition, it is effective in extracting Garcinia cambogia extract from the skin of Garcinia cambogia fruit.

The L-Arginine is one of the amino acids that make up protein and belongs to the protein protamine present in fish sperm. As a semi-essential amino acid required for the growth of children and animals, it has been reported that ingestion of L-arginine promotes the secretion of glucagon, which directly accelerates the decomposition of fat tissue in the human body (Kalkhoff RK, et al. , N Engl J Med 289: 465-467).

The L-carnitine has the chemical name of β-hydroxy-γ-N-trimethylaminobutyrate, and is an amino acid-like substance structurally similar to choline. However, strictly speaking, L-carnitine is not an actual vitamin because part of the body's requirements can be met through biosynthesis, but it can be said to be a nutrient in the form of a vitamin such as choline, taurine, inositol, etc.

The most important biological mechanism of L-carnitine is its role as an essential cofactor in fatty acid metabolism and as a transport molecule that smoothly transports fatty acids into mitochondria in the body and converts fat into cellular energy. This role improves intracellular fatty acid and sugar metabolism.

In particular, long-chain fatty acids are activated in the mitochondrial outer membrane and oxidized in the mitochondrial matrix. The long-chain fatty acids cannot pass through the inner membrane of mitochondria without a special transport mechanism, and in this case, the transport mechanism is L-carnitine. In this way, long-chain fatty acids activated in the mitochondrial outer membrane temporarily bind to the hydroxyl group of L-carnitine to form long-chain fatty acid acyl-carnitine, which is transported into the mitochondria and metabolized.

In addition, L-carnitine has been proven to reduce lipid accumulation in the blood and tissues in various conditions in the body for weight loss, and improves cardiac function and oxygen intake by supplying energy essential for muscle work. It provides effects such as increasing body weight, maintaining physical strength, and reducing fat.

The L-carnitine may be L-carnitine tartrate, which has improved preservability by combining tartrate.

The pharmaceutical composition for preventing or treating obesity of the present invention includes a combination preparation, and the combination preparation includes an active ingredient, and the active ingredient is Garcinia cambogia extract, L-Arginine (L-Arginine) and L-carnitine ( L-Carnitine) may be included in a weight ratio of 1:0.01 to 0.1:0.1 to 0.5.

For example, the Garcinia cambogia extract, the L-arginine and the L-carnitine are used at a weight ratio of 1:0.015 to 0.05:0.05 to 0.4, preferably, 1:0.015 to 0.05:0.25 to 0.3, for example , may be included in a weight ratio of 1:0.017:0.25.

The Garcinia cambogia extract and the L-arginine may be included in a weight ratio of 1:0.01 to 0.1, and if the content of the L-arginine is less than 0.01 times that of the Garcinia cambogia extract, the effect of inhibiting adipocyte differentiation is reduced, If it exceeds twice the amount, palatability decreases rapidly due to the unique taste and smell, and problems such as stomach pain, vomiting, diarrhea, and nausea may occur.

The Garcinia cambogia extract and the L-carnitine may be included in a weight ratio of 1:0.1 to 0.5, and if the content of the L-carnitine is less than 0.1 times the content of the Garcinia cambogia extract, there is almost no effect of inhibiting adipocyte differentiation, and 0.5 If it exceeds twice the amount, palatability decreases rapidly due to the unique taste and smell, and problems such as stomach pain, vomiting, diarrhea, and nausea may occur.

That is, the first feature of the present invention is that the combination preparation contains an active ingredient and the active ingredient satisfies the above composition and content, resulting in a more effective obesity prevention effect.

The composite preparation according to the present application has a structure of a core and a shell formed on the core, wherein the core contains the Garcinia cambogia extract and the L-Carnitine (L-Carnitine), and the shell contains the L-arginine (L -Arginine).

That is, the above-described composite preparation satisfies the above-described composition and content and is formed in a core-shell structure, each containing a specific composition in the core and shell parts.

At this time, the ratio of the outer diameter of the composite preparation to the outer diameter of the core may satisfy 1:0.6 to 1:0.95.

In another embodiment, the ratio of the outer diameter of the composite preparation to the outer diameter of the core is 1:0.6 to 1:0.95, preferably 1:0.65 to 1:0.85, more preferably 1.0.70 to 1:0.80. can be satisfied, and more preferably, the range of 1:0.75 can be satisfied.

At this time, the outer diameter of the combination preparation and the outer diameter of the core can be confirmed in detail in Figure 1. Specifically, Figure 1 is a diagram schematically showing a combination preparation according to an exemplary embodiment of the present invention. The outer diameter of the combination preparation may be indicated by B, and in this case, the outer diameter of the core may be indicated by A. That is, the outer diameter can be expressed as the radius of a sphere or circle.

That is, by satisfying the outer diameter range of the above-described combination preparation, the pharmaceutical composition for preventing or treating obesity contains the above-mentioned composition contained in the water eluate at 37°C, pH 4.0, and water according to the Korean Pharmacopoeia Dissolution Test Method 2 (Paddle Method). L-Arginine accounts for 40 to 45% of the total weight of the active ingredient after 1 hour, and the Garcinia Cambogia extract and L-Carnitine account for 5 to 15% of the total weight of the active ingredient after 1 hour. The dissolution profile dissolving in the range of % is satisfied.

In an exemplary embodiment of the present application, the composite preparation satisfies a certain outer diameter range, and specifically, the outer diameter ratio of the core and the shell satisfies a certain range. Accordingly, in the early stages after administration, the content of L-Arginine contained in the shell is high, and the Garcinia Cambogia extract and L-Carnitine contained in the core are eluted to a minimum extent, especially It is effective in managing obesity.

That is, when the outer diameter is outside the above range, the elution amount of Garcinia cambogia extract, L-Arginine, and L-Carnitine cannot be controlled, so it is not effective in managing obesity. However, the combination preparation according to the present application is not effective in managing obesity. The second feature of the present invention is that the dissolution amount of the three components can be adjusted over time by satisfying the outer diameter range as described above, maximizing the effect, even without including a separate release control mechanism.

The composition of the present invention contains Catechin, Cathinone, Tryptamine, P-Octopamine, P-Tyramine, Synephrine and Ephedrine ( Ephedrine) may further include any one or more of these substances, which are norepinephrine releasing substances. Norepinephrine acts as a neurotransmitter in the nerve junctions of the brain and muscles and regulates fuel metabolism in the liver and muscles. It means acting as a hormone.

In the present invention, the pharmaceutical composition for preventing or treating obesity may be a compound that stimulates the hypothalamus to increase norepinephrine secretion. Specifically, it increases the concentration of norepinephrine at the synapse and activates hypothalamic POMC neurons to suppress appetite and provide energy. It may be a compound that increases consumption.

The catechin can be extracted from Camellia sienesis and inhibits COMT (catechol O-methyltransferase) enzyme to increase norepinephrine in the synaptic gap, thereby increasing energy activity, thereby preventing and treating obesity. It can act as a substance ([Korean J Clin Pharm 2018;28(4):342-346, ARYA Atheroscler. 2014 Jan; 10(1): 55-58.]).

The cathinone can be extracted from Catha edulis (Khat) and, like amphetamine, catecholamines such as dopamine and norepinephrine through TAAR1 activation. ), releases epinephrine, and acts on α and beta adrenergic receptors (Alpha, beta Adrenergic receptors), showing an appetite suppressing effect. The cathinone has a greater CNS activation effect than amphetamine ([Cathinone (Khat) and Methcathinone (CAT)in Urine Specimens: A Gas Chromatographic-Mass Spectrometric Detection Procedure], [MECHANISM OF ACTION OF CATHINONE: THE ACTIVE INGREDIENT OF KHAT (CATHA EDULIS)]).

The tryptamine can be extracted from Vachellia aroma , and increases insulin in the pancreas through the TAAR1 receptor, thereby reducing fasting blood sugar in the liver and delaying food evacuation time from the stomach. By increasing GLP-1&PYY, it can act as a substance for the prevention and treatment of obesity through a complex mechanism including the effect of reducing the extracorporeal excretion of glucose ([Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges], [ Pharmacology & Therapeutics, Volume 180, December 2017, Pages 161-180]).

The P-Octopamine can be extracted from Bitter Orange ( Citrus aurantium ), and has the effect of increasing the feeling of satiety by increasing the release of Serotonin through the TAAR1 receptor, thereby reducing food intake. As a result, it can act as a substance for the prevention and treatment of obesity. In addition, P-octopamine acts on the Beta 3 Adrenergic receptor in adipocytes to activate Beta 3 Adrenergic receptor, and induces the conversion of white fat into brown fat through the binding activation of Norepinephrine and activation of UCP-1 protein in adipocytes. It can act as a substance for the prevention and treatment of obesity by showing the effect of increasing energy consumption through thermogenesis by brown fat ([Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges], [Pharmacology & Therapeutics, Volume 180, December 2017, Pages 161-180]).

The P-Tyramine can be extracted from Bitter Orange ( Citrus aurantium ) or Musa sapientum L , and increases insulin in the pancreas through the TAAR1 receptor, thereby increasing fasting blood sugar level in the liver. It can act as a substance for the prevention and treatment of obesity through a complex mechanism including the effect of reducing the extracorporeal excretion of glucose by increasing GLP-1&PYY by delaying the gastric food excretion time ([Pharmacology of human trace amine -associated receptors: Therapeutic opportunities and challenges], [Pharmacology & Therapeutics, Volume 180, December 2017, Pages 161-180]).

The synephrine can be extracted from Bitter Orange ( Citrus aurantium ), releases catecholamines through TAAR1 activation, binds to the β 3 adrenergic receptor, activates lipolysis, and It can act as a substance for the prevention and treatment of obesity by increasing epinephrine (norepinephrine) and showing efficacy in energy activation ([Phytother Res. 2017 Oct; 31(10): 1463-1474.]).

The ephedrine is ephedra sinica ), it mainly acts on α and β adrenergic receptors, stimulates sympathetic nerves, increases norepinephrine in the synaptic gap, and is effective in energy activation, thereby acting as a substance for the prevention and treatment of obesity. ([Anesth Prog. 2012 Winter; 59(4): 159-169.]).

The pharmaceutical composition of the present invention preferably contains catechin as a norepinephrine release substance.

The pharmaceutical composition for preventing or treating obesity of the present invention may include the Garcinia cambogia extract, L-arginine, L-carnitine, and catechin in a weight ratio of 1:0.01 to 0.1:0.1 to 0.5:0.5 to 2.

The Garcinia cambogia extract and the catechin may be included in a weight ratio of 1:0.5 to 1:2, and if the content of the catechin is less than 0.5 times that of the Garcinia cambogia extract, the effect of inhibiting adipocyte differentiation is reduced, and if the content of the catechin is more than 2 times. In this case, a problem of cytotoxicity occurs.

For example, the composition may be included in a weight ratio of 1:0.015 to 0.05:0.05 to 0.4:0.1 to 0.2 in order to maximize the effect of inhibiting adipocyte differentiation while preventing or minimizing cytotoxicity.

In the present invention, the composition includes branched-chain amino acids (BCAA) containing at least one selected from the group consisting of leucine, isoleucine, and valine, calcium pantothenate, nicotinic acid amide, crystalline cellulose, magnesium stearate, hydroxypropylmethylcellulose, and It may contain calcium carboxymethylcellulose.

The branched-chain amino acid (BCAA) is one of the essential amino acids that is closely related to muscles, and the calcium pantothenate (molecular formula C ₁₈ H ₃₂ O ₁₀ N ₂ Ca) is a white powder with an odor. It is a calcium salt fortifier with a slightly bitter taste that acts as a coenzyme in the body and is necessary for normalizing tissue function, physical growth, and maintaining health.

The nicotinic acid amide is a type of vitamin, which is added to suppress obesity and diet, and includes vitamins B1, B2, B6, B12, C, D3, and nicotinic acid amide. Vitamins B, C, D, and nicotinic acid amide act as coenzymes in the TCA cycle, which breaks down glucose to create energy. At this time, if there are no vitamins, this process cannot proceed and the nutrients cannot be consumed as energy and are converted to body fat and accumulated in the body. In other words, if you do not have enough vitamins, the food you eat cannot be used as energy and accumulates in the body, ultimately leading to obesity.

The crystalline cellulose is an additive used as an anti-caking agent, stabilizer, emulsifier, and dietary fiber in foods, and the magnesium stearate provides mineral components by supplying magnesium, and the hydroxypropylmethylcellulose (hypromellose, HPMC), The carboxymethylcellulose calcium serves as a viscosity regulator.

Additionally, the composition may further include additives such as zinc oxide and silicon dioxide.

In the present invention, the term “prevention” refers to all actions that suppress or delay obesity, and the term “treatment” refers to all actions that improve or beneficially change the symptoms of an individual suspected of or suffering from obesity. Additionally, the pharmaceutical composition may contain the active ingredient alone or may be provided as a pharmaceutical composition including one or more pharmaceutically acceptable carriers, excipients, or diluents. In the above, 'pharmacologically acceptable' refers to a composition that is physiologically acceptable and does not usually cause allergic reactions or similar reactions when administered to humans.

Furthermore, the pharmaceutical composition may be provided by mixing with conventionally known obesity treatment substances. That is, the pharmaceutical composition can be administered in combination with a known compound that has the effect of preventing or treating obesity.

The term "administration" means introducing a predetermined substance into an individual by an appropriate method, and "individual" refers to all animals such as rats, mice, and livestock, including humans, that have or may develop obesity. As a specific example, it may be a mammal, including humans.

Additionally, in the present invention, “obesity” refers to something caused by energy imbalance, and the causes of obesity are complexly related to hormonal changes, genetics, mental health problems, socioeconomic factors, etc. Specifically, it means that it can be caused by energy imbalance, genetic factors, neuroendocrine factors, and environmental factors.

The route of administration of the pharmaceutical composition is not limited to these, but is oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, or Includes workplace.

The pharmaceutical composition can be administered orally or parenterally, and when administered parenterally, it is preferable to select the injection method by external injection through the skin or intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. , but is not limited to this, and oral administration may be preferably selected from the viewpoint of selecting a more effective absorption route.

In the case of a formulation for oral administration, the composition of the present invention can be formulated into powder, granule, tablet, pill, powder, sugar-coated tablet, capsule, solution, gel, syrup, slurry, suspension, etc. using methods known in the art. It can get angry. For example, oral preparations can be prepared by combining the active ingredient with solid excipients, grinding them, adding suitable auxiliaries and processing them into a granule mixture to obtain tablets or dragees. Examples of suitable excipients include sugars including lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol and maltitol, starches including corn starch, wheat starch, rice starch and potato starch, cellulose, Fillers such as cellulose, including methyl cellulose, sodium carboxymethylcellulose, and hydroxypropylmethyl-cellulose, gelatin, polyvinylpyrrolidone, calcium carbonate, etc. may be included. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, syrups, etc. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. . Additionally, in some cases, cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may be added as a disintegrant. Furthermore, the pharmaceutical composition of the present invention may further include anti-coagulants, lubricants, fragrances, emulsifiers, and preservatives.

In the case of preparations for parenteral administration, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories are included. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurel, glycerogeratin, etc. can be used. In addition, it can be formulated in the form of injections, creams, lotions, external ointments, oils, moisturizers, gels, aerosols, and nasal inhalants by methods known in the art. These formulations are described in Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour, a generally known text in all pharmaceutical chemistry.

The preferred dosage of the pharmaceutical composition varies depending on the patient's condition and weight, degree of disease, drug form, administration route and period, but can be appropriately selected by a person skilled in the art. However, for desirable effects, the pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the severity of the disease. Preferably, a preferred total dosage of the composition of the present invention may be about 0.01 μg to 1,000 mg per kg of patient body weight per day, most preferably 0.1 μg to 100 mg per kg of patient body weight per day. However, the dosage of the composition is determined by considering various factors such as the route of administration and number of treatments of the pharmaceutical composition, as well as the patient's age, weight, health status, gender, severity of the disease, diet, and excretion rate. Therefore, taking this into consideration, anyone with ordinary knowledge in the art will be able to determine an appropriate effective dosage according to the specific use of the composition as a preventive or therapeutic agent for obesity. The pharmaceutical composition according to the present invention is not particularly limited in its formulation, administration route, and administration method as long as it exhibits the effects of the present invention. When formulating the pharmaceutical composition, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

In addition, the pharmaceutical composition of the present invention can be used not only in the form of a medicine for humans, but also in the form of an animal medicine. Here, animals are a concept that includes livestock and pets.

According to another embodiment of the present invention, a health functional food containing the pharmaceutical composition for preventing or treating obesity according to the present application is provided.

The health functional food may be formulated with one selected from the group consisting of tablets, pills, powders, granules, powders, capsules, and liquid formulations, further including one or more of carriers, diluents, excipients, and additives. Foods to which the above acteoside or its foodologically acceptable salt can be added include various foods, powders, granules, tablets, capsules, syrups, beverages, gum, tea, vitamin complexes, nutritional supplements, health functional foods, and Food additives, etc.

Additives that may be further included in the health functional food include natural carbohydrates, flavors, nutrients, vitamins, minerals (electrolytes), flavors (synthetic flavors, natural flavors, etc.), colorants, fillers (cheese, chocolate, etc.) , pactic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, antioxidants, glycerin, alcohol, carbonating agents and pulp. there is.

Examples of such natural carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, natural flavoring agents (thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. In addition, various Nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, It may contain pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated drinks, etc. In addition, the health functional food may contain pulp for the production of natural fruit juice and vegetable drinks. These ingredients can be used independently or in combination.

Specific examples of the carriers, excipients, diluents and additives include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, erythritol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium phosphate, calcium. Silicates, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, sugar syrup, methylcellulose, methyl hydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate. It is preferred that at least one selected from the group consisting of mineral oil is used.

When formulating the health functional food, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Hereinafter, for a more detailed explanation, examples will be given in detail.

실시예Example

<< 가르시니아garcinia 캄보지아cambogia 추출액의 제조> Preparation of extract>

Garcinia cambogia extract was obtained by freeze-drying the peel of the Garcinia cambogia fruit, pulverizing it to 100 mesh or less, and extracting it at a temperature of 80°C or higher with 70% extraction solvent. At this time, the extraction solvent below was used, Accordingly, Garcinia Cambogia Extract-1 and Garcinia Cambogia Extract-2 were prepared.

At this time, Garcinia cambogia extract-1 was extracted using extraction solvent 1, and Garcinia cambogia extract-2 was extracted using extraction solvent 2.

- Extraction solvent 1: An extraction solvent was prepared to satisfy 5 parts by weight of acetone, 5 parts by weight of ethyl acetate, and 90 parts by weight of propylene glycol monomethyl ether based on 100 parts by weight of the total extraction solvent.

- Extraction solvent 2: An extraction solvent was prepared to satisfy 75 parts by weight of acetone, 20 parts by weight of ethyl acetate, and 5 parts by weight of propylene glycol monomethyl ether based on 100 parts by weight of the total extraction solvent in an Erlenmeyer flask.

<복합제제의 제조><Manufacture of combination preparation>

A core-shell structure was formed with a composite preparation that satisfied the composition, content, and outer diameter of Table 1 below.

	코어core			쉘shell
	가르시니아 캄보지아 추출액Garcinia Cambogia Extract	상기 L-카르니틴(L-Carnitine)The L-Carnitine (L-Carnitine)	외경outer diameter	L-아르기닌(L-Arginine)L-Arginine	복합제제 외경External diameter of complex preparation
실시예 1Example 1	추출액-160gExtract - 160g	1.02g1.02g	30nm30nm	15g15g	40nm40nm
실시예 2Example 2	추출액-160gExtract - 160g	1.02g1.02g	38nm38nm	15g15g	40nm40nm
실시예 3Example 3	추출액-160gExtract - 160g	1.02g1.02g	24nm24nm	15g15g	40nm40nm
실시예 4Example 4	추출액-260gExtract - 260g	1.02g1.02g	30nm30nm	15g15g	40nm40nm
비교예 1Comparative Example 1	추출액-160gExtract - 160g	10g10g	24nm24 nm	15g15g	40nm40nm
비교예 2Comparative Example 2	추출액-160gExtract - 160g	1.02g1.02g	24nm24nm	40g40g	40nm40nm
비교예 3Comparative Example 3	추출액-160gExtract - 160g	1.02g1.02g	22nm22nm	15g15g	40nm40nm
비교예 4Comparative Example 4	추출액-160gExtract - 160g	1.02g1.02g	39.5nm39.5nm	15g15g	40nm40nm

<비만 예방 또는 치료용 약학적 조성물의 제조><Manufacture of pharmaceutical composition for preventing or treating obesity>

As additional mixing ingredients in the composition containing the above complex preparation, 0.1 g of BCAA mix, 0.1 g of calcium pantothenate, 0.1 g of nicotinic acid amide, 18 g of crystalline cellulose, 2 g of magnesium stearate, 1 g of hydroxypropyl methyl cellulose, and 3 g of calcium carboxymethyl cellulose are added. The final compositions were prepared by mixing.

제조예Manufacturing example 1. INS-1 세포 배양 1. INS-1 cell culture

Rat pancreatic β-cells (INS-1) purchased from Biohermes (Shanghai, China) were supplemented with 11mM D-glucose, 10% fetal bovine serum, and 1% penicillin/streptomycin. Penicillin/streptomycin (Invitrogen Co., Grand Island, NY, USA), 0.05mM2-mercaptoethanol, 2mM L-glutamine, 10mM hydroxyethylpiperazineethane The cells were cultured in RPMI-1640 (Cellgro, Manassas, VA, USA) containing sulfonic acid (HEPES) and 1 mM sodium pyruvate at 37°C, 5% CO ₂ and 95% humidity.

제조예Manufacturing example 2. 3T3-L1 cell 배양 2. 3T3-L1 cell culture

3T3-L1 preaidpocyte cells purchased from ATCC (American Type Culture Collection, USA) are subcultured in DMEM (containing 10% Bovine Serum, 100 units/ml penicillin, 100ug/ml streptomycin) medium and used to induce adiocyte differentiation and adipogenesis. .

Preadipocyte cells were used as a normal group, and as a control group, preadipocyte cells cultured to a post-confluent state after seeding were induced to differentiate for 3 days using Zenbio DM medium according to Zenbio manual, and then cultured once every two days using Zenbio AM medium. The adipocytes were exchanged and maintained for 4 days.

The experimental group was treated with Hispidulin, Synephrine, and P-Octopamine (Octopamine hydrochloride) at concentrations of 0, 5, 10, 20, or 40 μM each time DM and AM medium were treated, respectively, under the same culture conditions as the control group.

실험예Experiment example 1. One. 세포생존력실험Cell viability experiment

Using 3T3-L1 cells, which are adipogenic cells derived from mice, we evaluated whether Hispidulin, Synephrine, and P-Octopamine (Octopamine hydrochloride) affect cell viability as follows.

The normal group, 3T3-L1 preadipocyte cells of the preparation example, were dispensed into a 96-well plate at 1Х10 ⁴ per well and cultured under the same conditions for 24 hours to stabilize the cells.

Thereafter, the compositions of Examples 1 to 4 and Comparative Examples 1 to 4 (compositions before mixing additional mixing ingredients) at a concentration of 200 ug/ml were cultured under the same conditions for 24 hours after each treatment. Afterwards, EZ-Cytox cell viability assay solution (100 μL; Daeil Lab Service Co., Ltd., Seoul) was added to the plate and incubated for 40 minutes. Next, the absorbance of the samples in the well plate was measured using a PowerWave

Figure 2 is a graph showing the survival rate results of 3T3-L1 cells treated with the compositions of Examples 1 to 4 and Comparative Examples 1 to 4 at a concentration of 200ug/ml.

According to Figure 2 and Table 2 below, it was confirmed that there was no significant difference in the number of 3T3-L1 cells between the compositions of Examples 1 to 4 and Comparative Examples 1 to 4. Therefore, it can be confirmed that the compositions of Examples 1 to 4 and Comparative Examples 1 to 4 are all non-toxic to 3T3-L1 cells.

실시예Example	세포생존율 (%)Cell survival rate (%)
실시예 1Example 1	97.2±3.197.2±3.1
실시예 2Example 2	96.5±2.596.5±2.5
실시예 3Example 3	98.1±2.798.1±2.7
실시예 4Example 4	95.2±4.295.2±4.2
비교예 1Comparative Example 1	95.6±1.995.6±1.9
비교예 2Comparative Example 2	98.2±2.398.2±2.3
비교예 3Comparative Example 3	94.5±3.494.5±3.4
비교예 4Comparative Example 4	96.9±2.396.9±2.3

실험예Experiment example 2. 지방세포 분화 억제 2. Inhibition of adipocyte differentiation 효과effect

3T3-L1 cells were treated with the compositions of Examples 1 to 4 and Comparative Examples 1 to 4 each time they were treated with DM medium and AM medium under the same culture conditions as the control group in the preparation example. Then, to confirm the effect of the compositions of Examples 1 to 4 and Comparative Examples 1 to 4 on fat accumulation, the culture medium of each group of cells was removed and the amount of fat accumulated in the cells was compared and confirmed through the Oil red O test.

Figures 3 to 10 show images taken under a microscope at 20x magnification showing the results of intracellular fat accumulation (adipocyte differentiation inhibition rate) when 3T3-L1 cells cultured in a post confluent state were treated with compositions according to embodiments of the present invention. admit. Figure 11 is a graph schematically illustrating the results of inhibiting intracellular adipocyte differentiation when treated with compositions according to embodiments of the present invention.

Specifically, Figures 3 to 10 are images of 3T3-L1 cells treated with the compositions of Examples 1 to 4 and Comparative Examples 1 to 4 of the present invention at a concentration of 200ug/ml, and Figure 11 is an image of Figures 3 to 10. This is a graph showing the results of intracellular fat accumulation (adipocyte differentiation inhibition rate), and Table 3 below shows the results of the graph in Figure 11 in a table.

실시예Example	Oil Red O (%)Oil Red O (%)
실시예 1Example 1	38.1±3.638.1±3.6
실시예 2Example 2	42.3±2.842.3±2.8
실시예 3Example 3	38.9±4.138.9±4.1
실시예 4Example 4	42.7±1.942.7±1.9
비교예 1Comparative Example 1	68.2±2.468.2±2.4
비교예 2Comparative Example 2	71.5±3.571.5±3.5
비교예 3Comparative Example 3	65.8±1.565.8±1.5
비교예 4Comparative Example 4	65.2±2.365.2±2.3

According to Figure 11, it can be seen that when treated with the compositions of Examples 1 to 4 of the present invention, the effect of inhibiting adipocyte differentiation is suppressed by about 50% or more, and up to 60% or more. However, unlike this, when treated with the compositions of Comparative Examples 1 to 4, it can be seen that the effect on inhibiting adipocyte differentiation is weak, at about 20 to 30%. In particular, it can be confirmed that the composition of Example 1 has an effect of inhibiting adipocyte differentiation by about 62%.

When treated with Examples 1 to 4, it was confirmed that the effect in inhibiting differentiation of 3T3-L1 cells was approximately twice that of Comparative Example 4, which had the highest rate of inhibiting adipocyte differentiation among the comparative examples.

Among them, Example 1 of the present invention satisfies the weight ratio of the Garcinia cambogia extract, L-Arginine and L-Carnitine of 1:0.017:0.25, and the outer diameter: core of the composite preparation It was confirmed that the ratio of the outer diameter satisfied the ratio of 1:0.75, which was the most effective.

Additionally, although evaluated better than Comparative Examples 1 to 4, in Example 4, the extraction solvent was changed to a different composition, so less effective substances were extracted into the extracted Garcinia cambogia extract, and Example 4 among Examples 1 to 4 was The inhibition rate of adipocyte differentiation was the poorest.

The above results correspond to the fact that the composite preparation satisfies the structure of the core and shell, and especially satisfies a certain composition and outer diameter ratio.

Comparative Example 1 and Comparative Example 2 each satisfied the outer diameter ratio of the present invention, but did not satisfy the composition ratio, and it was confirmed that the effect of inhibiting adipocyte differentiation was only insignificant, about 30%.

Comparative Examples 3 and 4 correspond to cases where the composition ratio of the present invention is satisfied but the external diameter ratio is not satisfied. That is, in Comparative Example 3, the outer diameter of the core is less than the range of the present invention, and in Comparative Example 4, the outer diameter of the core is greater than the range of the present invention. In this case, Garcinia cambogia extract, L-Arginine, and L-Carnitine are included in the eluate at 37°C, pH 4.0, and water according to the Korean Pharmacopoeia Dissolution Test Method 2 (Paddle Method) After 1 hour, the L-Arginine accounts for 40 to 45% of the total weight of the active ingredient, and the Garcinia Cambogia extract and the L-Carnitine account for 5% of the total weight of the active ingredient after 1 hour. Since the range of ∼15% was not satisfied, it was confirmed that the effect of inhibiting adipocyte differentiation was only minimal, around 30%.

Ultimately, in Comparative Example 3, the core was formed too thin and the Garcinia cambogia extract and the L-Carnitine did not elute in the desired amount even after a certain time, and in Comparative Example 4, the core was formed too thick. This is the result of the Garcinia Cambogia extract and the L-Carnitine being eluted at too high a dose before a certain period of time.

In other words, the main purpose of the present invention is to discover a composition that has an excellent obesity suppression rate when the combination preparation satisfies a certain outer diameter ratio and at the same time satisfies a specific composition and content range.

In the foregoing, exemplary embodiments of the present invention have been described, but the present invention is not limited thereto, and those skilled in the art will understand the scope without departing from the concept and scope of the following claims. You will be able to understand that various changes and modifications are possible.

Claims

combination preparation; Branched chain amino acids (BCAAs) containing one or more selected from the group consisting of leucine, isoleucine and valine; Calcium pantothenate; Nicotinic acid amide; crystalline cellulose; Magnesium stearate; hydroxypropylmethylcellulose; A pharmaceutical composition for preventing or treating obesity containing calcium carboxymethylcellulose,

The combination preparation contains an active ingredient,

The combination preparation has a structure of a core and a shell formed on the core,

The active ingredient includes Garcinia cambogia extract obtained by extracting Garcinia cambogia with an extraction solvent, L-Carnitine, and L-Arginine in a weight ratio of 1:0.017:0.25,

The core includes the Garcinia cambogia extract and the L-Carnitine,

The shell contains the L-Arginine,

A pharmaceutical composition for preventing or treating obesity, wherein the ratio of the outer diameter of the combination preparation: the outer diameter of the core satisfies 1:0.6 to 1:0.95.
According to paragraph 1,

From the group consisting of Catechin, Cathinone, Tryptamine, P-Octopamine, P-Tyramine, Synephrine and Ephedrine. A pharmaceutical composition for preventing or treating obesity further comprising one or more selected substances.
According to paragraph 1,

A pharmaceutical composition for preventing or treating obesity comprising 40 parts by weight or more and 70 parts by weight or less of the combination preparation based on 100 parts by weight of the pharmaceutical composition for preventing or treating obesity.
According to paragraph 1,

The pharmaceutical composition for preventing or treating obesity is 37°C, pH 4.0, and the L-Arginine contained in the water eluate according to the Korean Pharmacopoeia Dissolution Test Method 2 (Paddle Method) after 1 hour. 40-45% of the total weight of active ingredients,

A pharmaceutical composition for preventing or treating obesity, wherein the Garcinia cambogia extract and the L-carnitine (L-Carnitine) satisfy a dissolution profile in which 5 to 15% of the total weight of the active ingredient is eluted after 1 hour.
According to paragraph 1,

The extraction solvent is a group consisting of water, C1-C4 alcohol, n-hexane, ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, ethyl acetate, benzene, and mixed solvents thereof. A pharmaceutical composition for preventing or treating obesity, which is any one selected from .
The method of claim 5, wherein the extraction solvent is modified alkylene glycol; And a solvent with a boiling point of 90°C or lower,

The extraction solvent is

80 parts by weight or more and 95 parts by weight or less of the modified alkylene glycol; and

A pharmaceutical composition for preventing or treating obesity comprising 5 parts by weight or more and 20 parts by weight or less of a solvent having a boiling point of 90°C or lower.
A health functional food comprising the pharmaceutical composition for preventing or treating obesity according to any one of claims 1, 2, and 4 to 7.