KR102672768B1 - Pharmaceutical composition for preventing or treating obesity having oriental medicine mixture and injection having the same - Google Patents

Abstract

The present invention relates to obesity prevention or pharmaceutical compositions and injections containing a mixture of herbal medicines.

Description

Obesity prevention or pharmaceutical composition containing a mixture of herbal medicines and an injection containing the same {PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING OBESITY HAVING ORIENTAL MEDICINE MIXTURE AND INJECTION HAVING THE SAME}

The present invention relates to obesity prevention or pharmaceutical compositions and injections containing a mixture of herbal medicines.

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 occurrence 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 on 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. Sachdeo (1998) Clin. Pharmacokinet. ). 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 has discovered a composition that can eliminate or reduce the side effects of conventional obesity prevention and treatment compositions and replace them, and has discovered a composition for the treatment and prevention of obesity that contains natural substances that can minimize side effects as active ingredients. The purpose is to provide a pharmaceutical composition for.

Research and development are currently being conducted to ensure sufficient effectiveness in improving obesity and reducing blood sugar levels by reducing body fat using a mixture of herbal medicines, and in order to have better effects, pharmaceutical compositions for preventing or treating obesity are directly injected as injections. I'm doing it.

At this time, in order to achieve a more certain effect, the above-mentioned pharmaceutical composition for preventing or treating obesity is administered through an intravenous injection with good absorption, but in the case of intravenous injection, embolism is also a problem if air bubbles are included.

Therefore, research is needed on injections that can ensure effectiveness and minimize side effects when administering pharmaceutical compositions for preventing or treating obesity as injections.

Patent Document 1: Republic of Korea Patent Publication No. 10-2004-0097813

One object of the present invention is an active ingredient; Branched chain amino acids (BCAA) containing at least one selected from the group consisting of leucine, isoleucine and valine; A pharmaceutical composition for preventing or treating obesity comprising a foam remover, wherein the active ingredients include a mixture of herbal medicines, L-Arginine, L-Carnitine, and calcium pantothenate. The object is to provide a pharmaceutical composition for preventing or treating obesity, wherein the viscosity is 100 cPs or more and 1000 cPs or less, and the bubble remover is 0.1 part by weight or more and 0.5 parts by weight or less based on 100 parts by weight of the composition.

Another object of the present invention is to provide an injectable agent for preventing or treating obesity comprising the composition described above.

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, an active ingredient; Branched chain amino acids (BCAA) containing at least one selected from the group consisting of leucine, isoleucine and valine; A pharmaceutical composition for preventing or treating obesity comprising a foam remover, wherein the active ingredients include a mixture of herbal medicines, L-Arginine, L-Carnitine, and calcium pantothenate. The object is to provide a pharmaceutical composition for preventing or treating obesity, wherein the viscosity is 100 cPs or more and 1000 cPs or less, and the bubble remover is 0.1 part by weight or more and 0.5 parts by weight or less based on 100 parts by weight of the composition.

In one embodiment of the present invention, the foam remover provides a pharmaceutical composition for preventing or treating obesity, which includes a non-polar oil or a polar oil.

In one embodiment of the present invention, the non-polar oil includes at least one selected from mineral oil and silicone-based oil, and the polar oil includes at least one selected from the group consisting of fatty alcohols, fatty acids, and alkyl amines. Provided is a pharmaceutical composition for preventing or treating obesity.

In one embodiment of the present invention, the active ingredient is a mixture of herbal medicine, L-Arginine, L-Carnitine, and calcium pantothenate at a ratio of 1:0.01 to 0.1:0.1 to 0.5:0.1 to 0.4. It provides a pharmaceutical composition for preventing or treating obesity, comprising a weight ratio of:

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.

In the present invention, a pharmaceutical composition for preventing or treating obesity is provided, wherein the active ingredient contains 20 parts by weight or more and 40 parts by weight or less based on 100 parts by weight of the pharmaceutical composition for preventing or treating obesity.

In the present invention, the herbal medicine mixture is prepared by precipitating and drying at least one selected from the group consisting of Rehmannia glutinosa, Hyssopia, Angelica root, Hwangbaek, Chrysanthemum, Astragalus, Schisandra chinensis, White ginseng, Baekchul, Sanyak, Euchung, Goji berry and Tosaja. Provided is a pharmaceutical composition for preventing or treating obesity.

In the present invention, the herbal medicine mixture provides a pharmaceutical composition for preventing or treating obesity, which is prepared by precipitating and drying Schisandra chinensis and Tosaja and pulverizing it into fine powder.

Lastly, an injection 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 a mixture of herbal medicines, L-Arginine, L-Carnitine, and calcium pantothene as active ingredients, and has the effect of preventing and treating obesity. represents.

In particular, the pharmaceutical composition of the present invention reduces the side effects caused by conventional synthetic drugs and contains herbal medicine mixture, L-arginine, L-carnitine, etc., which are natural substances that can replace them, as active ingredients, thereby minimizing side effects and preventing obesity. It has excellent efficacy in prevention and treatment.

Among them, firstly, the pharmaceutical composition of the present invention is characterized by premixing the above-mentioned active ingredients. In other words, premixing the active ingredient is not simply mixing the composition contained in the active ingredient, but rather is characterized by adjusting the viscosity to the above-mentioned range through premixing.

When the viscosity is adjusted by premixing the active ingredients as described above, problems such as bacterial infection can be solved, and thus the obesity prevention effect can be secured more stably.

Additionally, secondly, the pharmaceutical composition of the present invention is characterized by containing a certain amount of a specific anti-foaming agent. In the case of the pharmaceutical composition of the present invention, it is used as an injection rather than oral administration, especially for intravenous injection. In the case of intravenous injection, the active ingredients are injected directly through the blood vessels, and the absorption rate is better than that of oral or other intramuscular injections, so the effect appears immediately. However, if the injection solution is injected into the vein and contains air bubbles, severe side effects such as embolism may occur.

In the case of the pharmaceutical composition according to the present application, the above-mentioned bubble remover is included in the above content, so that air bubbles can be removed when the injection is administered, thereby eliminating the problem of embolism, and also has the feature of securing the effect of preventing obesity. do.

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.

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, an active ingredient; Branched chain amino acids (BCAA) containing at least one selected from the group consisting of leucine, isoleucine and valine; A pharmaceutical composition for preventing or treating obesity comprising a foam remover, wherein the active ingredients include a mixture of herbal medicines, L-Arginine, L-Carnitine, and calcium pantothenate. The object is to provide a pharmaceutical composition for preventing or treating obesity, wherein the viscosity is 100 cPs or more and 1000 cPs or less, and the bubble remover is 0.1 part by weight or more and 0.5 parts by weight or less based on 100 parts by weight of the composition.

In an exemplary embodiment of the present application, the herbal medicine mixture can play a role in facilitating the basic metabolism of the human body and improving the absorption rate and function of the ingested product in the human body. By performing this role, the basic metabolism of the human body becomes smooth, and the effect of preventing obesity is revealed.

In the present application, the herbal medicine mixture is prepared by precipitating and drying at least one selected from the group consisting of Rehmannia glutinosa, Achyranthes root, Angelica root, Hwangbaek, Chrysanthemum, Astragalus, Schisandra chinensis, White ginseng, Baekchul, Sanyak, Euchung, Goji berry and Tosaja. It could be.

More preferably, the herbal medicine mixture may be prepared and dried and then ground into fine powder.

In the present application, Schisandra chinensis (Turcz.) Baill. belongs to the genus Schisandra and is one of the traditional medicinal plants with various therapeutic properties. Previous studies have confirmed that Schisandrae Fructus extract and its components have various beneficial pharmacological effects, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, immunomodulatory and antitumor effects. In addition, Schisandra chinensis has the effect of smoothing the basic metabolism of the human body.

In this application, "Cuscutae Semen" is the seed of Saesam, an annual vine plant belonging to the Convolvulaceae family. It is sweet and very tasty and has a flat nature. It contains resinous glycosides, amylase, about 40 mg% of provitamin A, and sugar. It is mainly known as a medicinal herb that protects the liver and kidneys, brightens the eyes, helps positive energy, and strengthens kidney function. Rather than being effective in preventing obesity, it is included as a medicine and plays a role in supplementing kidney function.

In the present application, based on 100 parts by weight of the herbal medicine mixture, Schisandra chinensis may include 80 parts by weight or more and 90 parts by weight or less, and Tosaja may include 10 parts by weight or more and 20 parts by weight or less.

In another embodiment, based on 100 parts by weight of the herbal medicine mixture, Schisandra chinensis may be 80 parts by weight or more and 85 parts by weight or less, and Tosaja may be 15 parts by weight or more and 20 parts by weight or less. Specifically, Schisandra chinensis may be 85 parts by weight; Sediment may contain 15 parts by weight.

When included in the above range, the obesity prevention effect can be maximized, and at the same time, no matter how natural the extract is, it can cause strain on the kidneys and liver. To prevent this, this problem was solved by including the tosajja in the above-mentioned content.

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 improves preservability by combining tartrate.

The pharmaceutical composition for preventing or treating obesity of the present invention includes an active ingredient, and the active ingredient may include a herbal medicine mixture, L-Arginine, L-Carnitine, and calcium pantothenate. .

In an exemplary embodiment of the present application, the active ingredient is a mixture of herbal medicine, L-Arginine, L-Carnitine, and calcium pantothenate at a ratio of 1:0.01 to 0.1:0.1 to 0.5:0.1 to 0.4. It provides a pharmaceutical composition for preventing or treating obesity, comprising a weight ratio of:

Specifically, the active ingredient is a mixture of herbal medicine, L-Arginine, L-Carnitine, and calcium pantothenate in a weight ratio of 1:0.01 to 0.1:0.1 to 0.5:0.1 to 0.4, preferably , may be included in a weight ratio of 1:0.015 to 0.05:0.25 to 0.3:0.2 to 0.3, for example, 1:0.02:0.25:0.25.

The herbal medicine mixture 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 herbal medicine mixture, the effect of inhibiting adipocyte differentiation is reduced, and if it is more than 0.1 times. In this case, palatability decreases rapidly due to the unique taste and smell, and problems such as stomach pain, vomiting, diarrhea, and nausea may occur.

The herbal medicine mixture 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 that of the herbal medicine mixture, there is almost no effect of inhibiting adipocyte differentiation, and if it is more than 0.5 times. In this case, palatability decreases rapidly due to the unique taste and smell, and problems such as stomach pain, vomiting, diarrhea, and nausea may occur.

In an exemplary embodiment of the present application, the viscosity of the active ingredient may be 100 cPs or more and 1000 cPs or less, preferably 150 cPs or more and 800 cPs or less, and more preferably 200 cPs or more and 500 cPs or less.

Among them, firstly, the pharmaceutical composition of the present invention is characterized by premixing the above-mentioned active ingredients. In other words, premixing the active ingredient is not simply mixing the composition contained in the active ingredient, but rather is characterized by adjusting the viscosity to the above-mentioned range through premixing.

When the viscosity is adjusted by premixing the active ingredients as described above, problems such as bacterial infection can be solved, and thus the obesity prevention effect can be secured more stably.

In an exemplary embodiment of the present application, a Garcinia cambogia extract obtained by extracting Garcinia cambogia with an extraction solvent may be further included.

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 refers to all three forms: semi-fluid or syrup, pill or solid, dried powder, etc. can be used

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 technical field. 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 of the commonly known solvent 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.

In an exemplary embodiment of the present application, the composition includes a bubble remover, and the bubble remover is provided in an amount of 0.1 part by weight or more and 0.5 part by weight or less based on 100 parts by weight of the composition.

In another embodiment, the composition includes a bubble remover, and the bubble remover is present in an amount of 0.1 part by weight or more and 0.5 part by weight or less, preferably 0.1 part by weight or more and 0.3 part by weight or less, more preferably, based on 100 parts by weight of the composition. may include 0.2 parts by weight.

In certain embodiments, the defoaming agents include non-polar oils such as mineral oils, silicone-based oils, polar oils such as fatty alcohols, fatty acids, alkylamines, and hydrophobic oils such as treated silica, aluminum oxide, and polypropylene. Solids, alkyl sulfates, alkyl ethoxylate sulfates, alkyl aryl sulfonates, phosphate esters, quaternary ammonium compounds, fatty amine salts. , fatty acid amides, alkyl phenol ethoxylates, ethoxylate-propoxylate polymers, acrylate esters, fatty alcohol ethoxylates. may be selected from surfactants such as alcohol ethoxylates and combinations thereof.

In an exemplary embodiment of the present application, the foam remover includes a non-polar oil or a polar oil, the non-polar oil includes one or more selected from mineral oil and silicone-based oil, and the polar oil includes fatty alcohol. It provides a pharmaceutical composition for preventing or treating obesity, comprising at least one selected from the group consisting of fatty acids and alkyl amines.

In the case of the pharmaceutical composition of the present invention, it is used as an injection rather than oral administration, especially for intravenous injection. In the case of intravenous injection, the active ingredients are injected directly through the blood vessels, and the absorption rate is better than that of oral or other intramuscular injections, so the effect appears immediately. However, if the injection solution is injected into the vein and contains air bubbles, severe side effects such as embolism may occur. In the case of the pharmaceutical composition according to the present application, the above-mentioned bubble remover is included in the above content, so that air bubbles can be removed when the injection is administered, thereby eliminating the problem of embolism, and also has the feature of securing the effect of preventing obesity. do.

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 to increase 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 can be extracted from Ephedra sinica , and mainly acts on α and β adrenergic receptors and stimulates sympathetic nerves to increase norepinephrine in the synaptic gap, thereby showing efficacy in energy activity, thereby reducing obesity. It can act as a substance for the prevention and treatment of ([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 herbal medicine mixture, 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 herbal medicine mixture and the catechin may be included in a weight ratio of 1:0.5 to 1:2. If the content of the catechin is less than 0.5 times that of the herbal medicine mixture, the effect of inhibiting adipocyte differentiation is reduced, and if it is more than 2 times. A problem of cytotoxicity arises.

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, and the vitamin 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 in the case of the present application, it is used as an injection, especially for intravenous injection.

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 a desirable effect, 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, an injection containing the pharmaceutical composition for preventing or treating obesity according to the present application is provided.

When formulating the above injection, 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.

Example

<Preparation of herbal medicine mixture>

The peel of Schisandra chinensis fruit was freeze-dried, ground to 100 mesh or less, and extracted with 70% extraction solvent (water) at a temperature of 80°C or higher.

Tosaja (purchased from Dusonae herbal medicine) was freeze-dried, ground to 100 mesh or less, and extracted with 70% extraction solvent (water) at a temperature of 80°C or higher.

Schisandra chinensis and Tosaja were mixed in a ratio of 85:15 to form a herbal medicine mixture.

<Manufacture of active ingredients>

Active ingredients satisfying the composition, content, and viscosity shown in Table 1 below were prepared. At this time, the composition was pre-mixed and the viscosity was adjusted as follows.

herbal medicine mixture L-Arginine L-Carnitine Calcium Pantothenate Viscosity (cPs) Example 1 100g 2g 25g 25g 350 Example 2 100g 2g 25g 25g 360 Comparative Example 1 100g 2g 25g 25g 90 Comparative Example 2 100g 2g 25g 25g 1500 (no pre-mixing) Comparative Example 3 100g 2g 25g 25g 350 Comparative Example 4 100g 2g 25g 25g 350 Comparative Example 5 100g 2g 25g 25g 350

<Manufacture of pharmaceutical composition for preventing or treating obesity>

A pharmaceutical composition for preventing or treating obesity was prepared by mixing 0.1 g of BCAA mix as an additional mixing ingredient with the composition containing the above active ingredients.

At this time, in Examples 1, 2, Comparative Examples 1 and 2, a non-polar oil, mineral oil: silicone oil = 1:1 based on 100 parts by weight of the pharmaceutical composition for preventing or treating obesity. 0.2 parts by weight of the bubble remover was included.

In Comparative Example 3, 0.05 parts by weight of the foam remover was included, in Comparative Example 4, 1 part by weight of the foam remover was included, and in Comparative Example 5, the foam remover was not included.

Preparation Example 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.

Preparation Example 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.

Experimental Example 1. Cell viability test and inhibitory effect on adipocyte differentiation

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 2 and Comparative Examples 1 to 5 (compositions before mixing additional mixing components) 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

It was confirmed that the compositions of Examples 1 to 2 and Comparative Examples 1 to 5 did not have a significant difference in the number of 3T3-L1 cells. Therefore, it can be confirmed that the compositions of Examples 1 to 2 and Comparative Examples 1 to 5 are all non-toxic to 3T3-L1 cells.

In addition, 3T3-L1 cells were treated with the compositions of Examples 1 to 2 and Comparative Examples 1 to 5 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 2 and Comparative Examples 1 to 5 on fat accumulation, the culture medium of each group of cells was removed, and then the amount of fat accumulation in the cells was compared and confirmed through the Oil red O test in Table 2. .

Example Cell survival rate (%) Oil Red O (%) Example 1 96.5±2.5 32.1±3.2 Example 2 98.1±2.7 43.3±2.1 Comparative Example 1 96.1±2.7 66.3±2.2 Comparative Example 2 94.5±3.4 49.2±2.3 Comparative Example 3 95.6±1.9 47.6±2.1 Comparative Example 4 94.5±3.4 65.3±2.2 Comparative Example 5 95.6±1.9 44.3±2.6

Experimental Example 2. Stability evaluation

The compositions of Examples 1 to 2 and Comparative Examples 1 to 5 were evaluated for factors related to bacterial infection 20 hours after storage, and the results are shown in Table 3 below. In addition, Table 3 below shows whether the composition causes embolism when administered to rats purchased from Biohermes (Shanghai, China). At this time, the injection of the injectable agent generally underwent the same pretreatment to remove air bubbles.

Example Bacterial infection rate (%) Embolism incidence rate (%) Example 1 0.2±0.03 0.1±0.06 Example 2 0.18±0.03 0.15±0.03 Comparative Example 1 0.2±0.03 0.2±0.06 Comparative Example 2 14.1±0.02 0.15±0.03 Comparative Example 3 0.2±0.03 12.6±2.1 Comparative Example 4 0.21±0.04 0.1±0.06 Comparative Example 5 0.22±0.02 29.3±2.6

It was confirmed that when the injections of Examples 1 and 2 were administered intravenously, the desired obesity prevention effect was achieved, as well as safety (embolism, bacterial infection).

In the case of Comparative Example 1, the viscosity was below the range of the present application, so problems with bacterial infection or embolism did not occur, but the active ingredient did not have sufficient viscosity and was not absorbed well into the blood vessels when injected intravenously, so fat accumulation was different. It was confirmed that it was higher than the examples and comparative examples.

In the case of Comparative Example 2, the viscosity was formed high because the active ingredient was not premixed, and it was confirmed that due to the increase in the viscosity of the active ingredient itself, the rate of bacterial infection increased and side effects occurred.

In Comparative Example 3, a small amount of the bubble remover was added, and in Comparative Example 5, the bubble remover was not included. It was confirmed that the embolism incidence rate increased in both Comparative Examples 3 and 5. This is a result of the problem of bubbles in the composition.

In Comparative Example 4, a rather large amount of bubble remover was added, which may be effective in removing bubbles, but as can be seen in Table 2, the amount of fat accumulation was measured to be higher than that of other examples. This corresponds to the result that the content of other active ingredients is low due to the inclusion of the foam remover.

In the above, exemplary embodiments of the present invention have been described, but the present invention is not limited thereto, and a person skilled in the art will understand the invention within the scope and spirit of the following claims. You will be able to understand that various changes and modifications are possible.

Claims (9)

active ingredient; Branched chain amino acids (BCAAs) containing one or more selected from the group consisting of leucine, isoleucine and valine; A pharmaceutical composition for preventing or treating obesity comprising a foam remover,
The active ingredients include herbal medicine extract mixture, L-Arginine, L-Carnitine, and calcium pantothenate,
The viscosity of the active ingredient is 100 cPs or more and 1000 cPs or less,
The herbal medicine extract mixture is an extraction mixture of Schisandra chinensis and Tosa chinensis extracts mixed in a ratio of 85:15,
The defoaming agent includes a non-polar oil,
The non-polar oil is a mixture of mineral oil and silicone oil in a ratio of 1:1,
A pharmaceutical composition for preventing or treating obesity, wherein the bubble remover is present in an amount of 0.1 part by weight or more and 0.5 part by weight or less based on 100 parts by weight of the composition. delete delete In claim 1,
The active ingredient is a herbal medicine extract mixture, L-Arginine, L-Carnitine, and calcium pantothenate in a weight ratio of 1:0.01 to 0.1:0.1 to 0.5:0.1 to 0.4. Pharmaceutical composition for prevention or treatment. delete According to paragraph 1,
A pharmaceutical composition for preventing or treating obesity, wherein the active ingredient contains 20 parts by weight or more and 40 parts by weight or less based on 100 parts by weight of the pharmaceutical composition for preventing or treating obesity. delete delete An injectable agent for preventing or treating obesity comprising the pharmaceutical composition for preventing or treating obesity according to any one of claims 1, 4, and 6.